Textbook of Sports Medicine: Basic Science and Clinical Aspects of Sports Injury and Physical Activity - PDF Free Download (2024)

Textbook of Sports Medicine Basic Science and Clinical Aspects of Sports Injury and Physical Activity Edited by Michael Kjær, Michael Krogsgaard Peter Magnusson, Lars Engebretsen Harald Roos,Timo Takala Savio L-Y Woo

Blackwell Science

Textbook of Sports Medicine

Textbook of Sports Medicine Basic Science and Clinical Aspects of Sports Injury and Physical Activity Edited by Michael Kjær, Michael Krogsgaard Peter Magnusson, Lars Engebretsen Harald Roos,Timo Takala Savio L-Y Woo

Blackwell Science

©  by Blackwell Science Ltd a Blackwell Publishing company Blackwell Science, Inc.,  Main Street, Malden, Massachusetts -, USA Blackwell Publishing Ltd,  Garsington Road, Oxford, Ox DQ Blackwell Science Asia Pty Ltd,  Swanston Street, Carlton South, Victoria , Australia Blackwell Wissenschafts Verlag, Kurfürstendamm ,  Berlin, Germany The right of the Authors to be identified as the Authors of this Work has been asserted in accordance with the Copyright, Designs and Patents Act . All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act , without the prior permission of the publisher. First published  ISBN --- Catalogue records for this title are available from the British Library and the Library of Congress Set in ‒/ pt Ehrhardt by SNP Best-set Typesetter Ltd., Hong Kong Printed and bound in India by Thomson Press (India) Commissioning Editor: Stuart Taylor Managing Editor: Rupal Malde Production Editor: Jonathan Rowley Production Controller: Kate Charman For further information on Blackwell Science, visit our website: http://www.blackwellpublishing.com

Contents Editors and Contributors, ix Preface, xv Introduction, 

Part 1: Basic Science of Physical Activity and Sports Injuries: Principles of Training .

Cardiovascular and respiratory aspects of exercise — endurance training,  Sigmund B. Strømme, Robert Boushel, Bjørn Ekblom, Heikki Huikuri, Mikko P. Tulppo & Norman L. Jones

.

Metabolism during exercise — energy expenditure and hormonal changes,  Jan Henriksson & Kent Sahlin

.

Skeletal muscle: physiology, training and repair after injury,  Michael Kjær, Hannu Kalimo & Bengt Saltin

.

Neuromuscular aspects of exercise — adaptive responses evoked by strength training,  Per Aagaard & Alf Thorstensson

.

Biomechanics of locomotion,  Erik B. Simonsen & Paavo V. Komi

.

Connective tissue in ligaments, tendon and muscle: physiology and repair, and musculoskeletal flexibility,  Peter Magnusson, Timo Takala, Steven D. Abramowitch, John C. Loh & Savio L.-Y. Woo

.

Cartilage tissue — loading and overloading,  Karola Messner, Jack Lewis, Ted Oegema & Heikki J. Helminen

.

Bone tissue — bone training,  Peter Schwarz, Erik Fink Eriksen & Kim Thorsen

Part 2: Aspects of Human Performance .

Recovery after training — inflammation, metabolism, tissue repair and overtraining,  Jan Fridén, Richard L. Lieber, Mark Hargreaves & Axel Urhausen

.

Principles of rehabilitation following sports injuries: sports-specific performance testing,  Malachy McHugh, Jens Bangsbo & Jan Lexell

v

vi

Contents

.

Physical activity and environment,  Peter Bärtsch, Bodil Nielsen Johannsen & Juhani Leppäluoto

.

Nutrition and fluid intake with training,  Leif Hambræus, Stefan Branth & Anne Raben

.

Ergogenic aids (doping) and phamacological injury treatment,  Ulrich Fredberg, Timo Säppälä, Rasmus Damsgaard & Michael Kjær

Part 3: Physical activity: Health Achievements vs. Sports Injury .

Epidemiology and prevention of sports injuries,  Roald Bahr, Pekka Kannus & Willem van Mechelen

.

Exercise as disease prevention,  Ilkka Vuori & Lars Bo Andersen

.

Physical activity in the elderly,  Stephen Harridge & Harri Suominen

.

Exercise in healthy and chronically diseased children,  Helge Hebestreit, Oded Bar-Or & Jørn Müller

.

Disabled individuals and exercise,  Fin Biering-Sørensen & Nils Hjeltnes

Part 4: Exercise in Acute and Chronic Medical Diseases .

Cardiovascular and peripheral vessel diseases,  Mats Jensen-Urstad & Kerstin Jensen-Urstad

.

Exercise and infectious diseases,  Bente Klarlund Pedersen, Göran Friman & Lars Wesslén

.

Osteoarthritis,  L. Stefan Lohmander & Harald P. Roos

.

Exercise in the treatment of type  and  diabetes,  Hannele Yki-Järvinen & Flemming Dela

.

Asthma and chronic airway disease,  Malcolm Sue-Chu & Leif Bjermer

.

Amenorrhea, osteoporosis, and eating disorders in athletes,  Michelle P. Warren, Jorun Sundgot-Borgen & Joanna L. Fried

Contents .

Physical activity and obesity,  Pertti Mustajoki, Per Björntorp & Arne Astrup

.

Gastrointestinal considerations,  Frank Moses

Part 5: Imaging in Sports Medicine .

Imaging of sports injuries,  Inge-Lis Kanstrup, Hollis G. Potter & Wayne Gibbon

Part 6: Sports Injury: Regional Considerations. Diagnosis and Treatment .

Lower leg, ankle and foot,  Jon Karlsson, Christer Rolf & Sajkari Orava

.

Knee,  Lars Engebretsen, Thomas Muellner, Robert LaPrade, Fred Wentorf, Rana Tariq, James H.-C. Wang, David Stone & Savio L.-Y. Woo

.

Hip, groin and pelvis,  Per Hölmich, Per A.F.H. Renström & Tönu Saartok

.

Head,  Liying Zhang, King H. Yang, Albert I. King & Lars Engebretsen

.

Spine,  Jens Ivar Brox

.

Shoulder,  Michael R. Krogsgaard, Richard E. Debski, Rolf Norlin & Lena Rydqvist

.

Elbow, wrist and hand,  Nicholas B. Bruggeman, Scott P. Steinmann, William P. Cooney & Michael R. Krogsgaard

.

Practical sports medicine,  Sverre Mæhlum, Henning Langberg & Inggard Lereim

.

Multiple Choice Answers,  Index, 

vii

Editors and Contributors Per Aagaard Team Denmark Test Center, Sports Medicine Research Unit, University of Copenhagen, Bispebjerg Hospital, Copenhagen, DK-N, Denmark Steven Abramowitch Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA , USA

Lars Bo Anderson Institute of Exercise and Sports Science, University of Copenhagen, DK-N, Denmark Arne Astrup Research Department of Human Nutrition, Royal Veterinarian and Agricultural University, DKF, Frederiksberg, Denmark Roald Bahr The Norwegian University of Sport and Physical Education, Oslo, N-, Norway Jens Bangsbo Laboratory for Human Physiology, August Krogh Institute, University of Copenhagen, DK-Ø, Denmark

Oded Bar-Or Children’s Exercise and Nutrition Centre, McMaster University, West Hamilton, Ontario, CANL L, Canada

Peter Bärtsch Division of Sports Medicine, Department of Internal Medicine, University of Heidelberg, DE-, Heidelberg, Germany Fin Biering-Sørensen Clinic for Spinal Cord Injuries, Rigshospitalet, University of Copenhagen, DK-Ø, Denmark

Leif Bjermer Department of Lung Medicine, University Hospital, Norwegian University of Science and Technology, Trondheim, N-, Norway

Per Björntorp Department of Heart and Lung Diseases, University of Gothenburg, Sahlgrenska Hospital, SE- , Sweden

Robert Boushel Department of Exercise Science, Concordia University, Montreal, Quebec, CAN-HB R, Canada

Stefan Brauth Department of Medical Sciences, Uppsala University Hospital, SE-, Sweden Jens Ivar Brox Department of Orthopaedics, Section for Physical Medicine and Rehabilitation, Rikshhospitalet, Oslo, N-, Norway Nicholas Bruggeman Department of Orthopaedic Surgery, Mayo Clinic, Rochester, MN , USA William P. Cooney Department of Orthopaedic Surgery, Mayo Clinic, Rochester, MN , USA Rasmus Damsgaard Copenhagen Muscle Research Centre, Rigshospitalet, Copenhagen, DK-Ø, Denmark Richard E. Debski Musculoskeletal Research Center, University of Pittsburgh Medical Center, Pittsburgh, PA , USA

Flemming Dela Department of Medical Physiology, Panum Institute, University of Copenhagen, DK-N, Denmark

ix

x

Editors and Contributors

Bjorn Ekblom Department of Physiology and Pharmacology, Karolinska Institute, University of Stockholm, SE, Sweden

Lars Engebretsen Department of Orthopaedic Surgery, University of Oslo, Ullevål Hospital, NO-, Norway Erik Fink Eriksen Department of Endocrinology, Aarlus University Hospital, DK-C, Denmark Ulrich Fredberg Department of Medicine, Silkeborg Central Hospital, DK-, Denmark Jan Fridén Department of Hand Surgery, Sahlgrenska University Hospital, SE-, Göteborg, Sweden Joanna L. Fried Department of Obstetrics and Gynaecology, Columbia University, New York, NY , USA Göran Friman Department of Medical Services, Section of Infectious Diseases, Uppsala University Hospital, SE, Sweden

Wayne Gibbon Department of Sports Medicine, University of Leeds, LS NL, UK Leif Hambraeus Department of Medical Sciences, Nutrition Unit, Uppsala University, SE-, Sweden Mark Hargreaves Department of Exercise Physiology, School of Health Sciences, Deakin University, Burwood, AUS-, Australia

Steve Harridge Department of Physiology, Royal Free & University College Medical School, London, NW PF, UK

Helge Hebestreit Pneumologie/Sportsmedizin, Universitäts-Kinderklinik, Würzburg, DE-, Germany Heikki Helminen Department of Anatomy, University of Kuopio, FIN-, Finland Jan Henriksson Department of Physiology and Pharmacology, Karolinska Institute, University of Stockholm, SE, Sweden

Nils Hjeltness Department of Spinal Cord Injury, Sunnaas Hospital, Nesoddtangen, Norway Per Hölmich Department of Orthopaedic Surgery, Amager Hospital, University of Copenhagen, DK-S, Denmark

Heikki V. Huikuri Department of Medicine, Division of Cardiology, University of Oulo, FIN-, Finland Kerstin Jensen-Urstad Department of Clinical Physiology, Karolinska Hospital, Stockholm, SE-, Sweden

Mats Jensen-Urstad Department of Cardiology, Karolinska Hospital, Stockholm, SE-, Sweden Norman L. Jones Department of Medicine, McMaster University, Hamilton, Ontario, CAN-LN Z, Canada Hannu Kalimo Department of Pathology, Turko University Hospital, Turko, FIN-, Finland Pekha Kannus Accident and Trauma Research Center, UKK Institute, Tampere, FIN-, Finland Inge-Lis Kanstrup Department of Clinical Physiology, Herlev Hospital, University of Copenhagen, DK-, Denmark

Jon Karlsson Department of Orthopaedics, Sahlgrenska University Hospital/Östra, Gothenburg, SE-, Sweden

Albert I. King Bioengineering Center, Wayne State University, Detroit, MI , USA

Editors and Contributors

xi

Michael Kjær Sports Medicine Research Center, University of Copenhagen, Bispebjerg Hospital, Copenhagen, DK- NV, Denmark

Pavo Komi Department of Biology of Physical Activity, University of Jyväskylä, FIN-, Finland Michael Krogsgaard Department of Orthopaedic Surgery, Bispebjerg Hospital, University of Copenhagen, DK NV, Denmark

Henning Langberg Sports Medicine Research Unit, Bispebjerg Hospital, Copenhagen, DK- NV, Denmark Robert F. La Prada, Sports Medicine and Shoulder Divisions, Department of Orthopaedic Surgery, University of Minnesota, MN , USA

Juhani Leppäluoto Department of Physiology, University of Oulo, FIN-, Finland Ingard Lerein Department of Orthopaedic Surgery, Region Hospital of Trondhjem, NO-, Norway Jack Lens Department of Orthopaedic Surgery, University of Minnesota, MN , USA Jan Lexell Brain Injury Unit, Neuromuscular Research Laboratory, Department of Rehabilitation, Lund University Hospital, SE-, Sweden

Richard L. Lieber Department of Orthopaedics and Bioengineering, University of California and V.A. Medical Center, La Jolla, CA -, USA John C. Loh Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA , USA

Stefan Lohmander Department of Orthopaedics, University Hospital, Lund, SE-, Sweden Sverre Mæhlum Norsk Idrettsmedisinsk Institutt (NIMI), University of Oslo, NO-, Norway Peter Magnusson Team Denmark Test Center, Sports Medicine Research Unit, University of Copenhagen, Bispebjerg Hospital, Copenhagen, DK- NV, Denmark Willem van Mechelen Department of Social Medicine, Vreie Universität, Amsterdam, NL-, The Netherlands

Karola Messner Department of Neuroscience and Locomotion, Division of Sports Medicine, Faculty of Health Sciences, Linköping, SE-, Sweden Malachy McHugh Nicholas Institute of Sports Medicine and Athletic Trauma, Lenox Hill Hospital, New York, NY , USA

Frank Moses Gastroenterology Service, Walter Reed Army Medical Center, Washington DC, -, USA Thomas Muellner Department of Orthopaedic Surgery, University of Vienna, Austria Jørn Müller Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, DK-Ø, Denmark

Pertti Mustajoki Department of Medicine, Helsinki University Central Hospital, FIN-, Finland Bodil Nielsen Johansen Institute of Exercise and Sports Science, August Krogh Institute, University of Copenhagen, DK-Ø, Denmark

Rolf Norlin Linköping Medical Center, SE-, Linköping, Sweden

xii

Editors and Contributors

Ted Oegena Department of Orthopaedic Surgery, University of Minnesota, MN , USA Sakari Orava Tohturitalo Hospital, Turka, Fin-, Finland Bente Klarlund Pedersen Finsencentret, Department of Infectious Diseases, University of Copenhagen, DKØ, Denmark

Hollis Potter Department of Radiology and Imaging, Hospital for Special Surgery, New York, NY , USA Anne Raben Research Department of Human Nutrition, Centre for Advanced Food Studies, Royal Veterinarian and Agricultural University, DK-F, Denmark

Per Renström Section of Sports Medicine, Department of Orthopaedics, Karolinska Hospital, Stockholm, SE, Sweden

Christer Rolf Centre of Sports Medicine, University of Sheffield, S TA, UK Harald Roos Department of Orthopaedic Surgery, Helsingborg Hospital, Helsingborg, SE-, Sweden Lena Rydqvist Linköping Medical Center, SE-, Linköping, Sweden Kent Sahlin Department of Physiology and Pharmacology, Karolinska Institute, University of Stockholm, SE, Sweden

Bengt Saltin Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, DK-Ø, Denmark

Tönu Saartok Section of Sports Medicine, Department of Orthopaedics, Karolinski Hospital, Stockholm, SE , Sweden

Peter Schwartz Department of Endocrinology, Rigshospitalet, University of Copenhagen, DK-N, Denmark Erik Simonsen Institute for Medical Anatomy, Panum Institute, University of Copenhagen, DK-N, Denmark Scott Steinman Department of Orthopaedic Surgery, Mayo Clinic, Rochester, MN , USA David Stone Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA , USA

Sigmund B. Strømme The Norwegian University of Sport and Physical Education, Oslo, NO-, Norway Malcolm Sue-Chu Department of Lung Medicine, University Hospital, Norwegian University of Science and Technology, Trondheim, N-, Norway Jorun Sundgot-Borgen Norwegian University of Sport and Physical Education, Oslo, NO-, Norway Harri Snominen Department of Health Sciences, University of Jyväskylä, FIN-, Finland Timo Säppälä National Public Health Institute, Helsinki, FIN-, Finland Timo Takala Department of Biology of Physical Activity, University of Jyväskylä, FIN-, Finland Rana Tariq Department of Radiology, Ulleval University Hospital, Oslo, N-, Norway Kim Thorsen Department for Sports Medicine, Norrland University Hospital, Umeå University, SE-, Sweden

Alf Thorstensson Department of Sport and Health Sciences, University College of Physical Education and Sports, Department of Neuroscience, Karolinska Institute, Stockholm, SE-, Sweden

Editors and Contributors

xiii

Mikko P. Tulppo Merikoski Rehabilitation and Research Centre, University of Oulu, FIN-, Finland Axel Urhausen Institute of Sports and Preventitive Medicine, Department of Clinical Medicine, University of Saarland, D-, Saarbruecken, Germany

Ilkka Vuori UKK Institute for Health Promotion Research, Tampere, FIN-, Finland James H.-C. Wang Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA , USA Michelle Warren Department of Obstetrics and Gynaecology, Colombia University, College of Physicians and Surgeons, New York, NY , USA Fred Wentort Department of Orthopaedic Surgery, University of Minnesota, Minneapolis, MN , USA Lars Wesslén Department of Medical Sciences, Section of Infectious Diseases, Uppsala University Hospital, Uppsala, Sweden

Savio L.-Y. Woo Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA , USA

King H. Yang Bioengineering Center, Wayne State University, Detroit, Michigan, MI , USA Hannele Yki-Järvinen Department of Medicine, University of Helsinki, FIN-, Helsinki, Finland Liying Zhang Bioengineering Center, Wayne State University, Detroit, Michigan, MI , USA

Preface

In past decades the number of exercising individuals and the area of sports medicine have grown considerably. Sports medicine has developed both in terms of its clinical importance with appropriate diagnosis and adequate rehabilitation following injury as well as its potential role in the promotion of health and prevention of life-style diseases in individuals of all ages. Furthermore, lately the medical field has gained improved understanding of the use of physical activity as a treatment modality in patients with a variety of chronic diseases and in rehabilitation after disabilities, injuries and diseases. Common to these advancements is the fact that a certain amount of clinical experience has to be coupled with sound research findings, both basic and applied, in order to provide the best possible recommendations and treatments for patients and for the population in general. There is a tradition in Scandinavia for an interaction between exercise physiology and clinical medicine and surgery, and it is apparent that both areas have hypotheses, inspiration and possible solutions to offer each other. It is therefore apparent that a textbook on sports medicine must attempt to incorporate all of these aspects to be comprehensive. A historical or classical reference has been selected as an introduction to each chapter to reflect the impact that a specific scientific work has had on that field. Having several authors collaborating on each chapter in the book ensures both diversity and a degree of consensus in the text, which will hopefully make the book usable as a reference book, and as a textbook both at the pre- and postgraduate levels. It has been our goal to address each topic within sports medicine in a scientific way, highlighting both where knowledge is well supported by research, as well as areas where the scientific support is minimal or completely lacking. It is the intention that the book will help the people who work clinically within the area of sports medicine in their daily practice, and that it will also provide the basis for further research activity within all areas of sports medicine. Moreover, we wish to highlight where knowledge and methodologies from different, and often distant, areas can interact to create a better understanding of, for example, the mechanisms behind development of tissue injury and its healing. The editorial group has been delighted that some of the world’s leading experts have agreed to participate in this project, and they have all contributed with informative and very comprehensive chapters. I greatly appreciate their contribution and that of the editorial group who worked hard on the completion of the book. Additionally, I wish to acknowledge all other contributors who have helped with the practical procedures of this project. Finally, I hope the reader of this book will share the research dreams, the clinical interest, and the enthusiasm in relation to the sports medicine topics with that of the authors and the entire editorial group. Michael Kjaer Copenhagen, September 

xv

Introduction MICHAEL KJ ÆR MICHAEL KROGSGA ARD PETER MAGNUS S ON LARS ENGE B RE TSE N HARALD ROOS TIMO TAK A LA SAVIO L-Y WOO

The exercising human: an integrated machine Physiological boundaries have fascinated man for a long time, and achievements like climbing up to more than  m above sea level without oxygen supply or diving down to more than  m in water without special diving equipment are at the limit of what textbook knowledge tells us should be possible for humans. Likewise, athletes continue to set new standards within sports performance, and patients with chronic diseases master physical tasks of a very challenging nature, like marathon running, that hitherto were thought impossible. Muscles, tendons and bone are elegantly coupled together to provide an efficient system for movement, and together with joint cartilage and ligaments they allow for physical activity of various kinds. In order to provide energy to contracting muscles, ventilation often rises –-fold and cardiac pump function can increase up to -fold during strenuous exercise in welltrained individuals in the attempt to deliver sufficient oxygen to allow for relevant oxidative processes that can be initiated within seconds. In addition, working skeletal muscles can by training achieve substantial increases in their capacity to both store energy and to extract and utilize oxygen. With regards to endurance capacity, humans are still left with the fact that the size of the heart relative to the skeletal muscle is relatively small — even in top-class runners — compared to basically all other animal species. To drive the human machinery, local as well as dis-

tant substrate stores provide fuel for energy combustion, allowing for very prolonged exercise bouts. A controlled interplay between exercise intensity, energy metabolism and regulatory hormones takes place, and intake of different food stores can cause the muscle to adjust its fuel combustion to a large degree. The initiation of signals from motor centers to start voluntary movement and afferent signals from contracting muscle interact to achieve this and several signalling pathways for circulatory and metabolic control are now identified. The brain can make the muscles move, and can at the same time use substances for fuel that are released from muscle. Furthermore, intake of different food sources can cause the muscle to adjust its fuel combustion to a large degree. Training can cause major tissue and organ adaptation and it is well known that this to a large degree depends upon both genetic and trainable factors (Table ). More recent studies on identical twins have allowed for a discrimination of these two factors in relation to exercise and have shown that between  and % of the variation in parameters like maximal oxygen uptake or muscle strength are likely to be attributed to genetic factors. Rather than discourage humans from starting training on this background, it is fascinating to identify factors responsible for training improvements in, for example, muscle tissue. It is evident that contractile force can elicit transcription and translation to produce relevant changes in the amount of contractile or mitochondrial proteins, but the underlying mechanism in both muscle and connective

Introduction

Table  The capacity of various tissues and systems, and their ability to adapt to physical activity or inactivity. Decrease in function or maximal load with 3–4 weeks of inactivity (%)

Function

Increase during single bout of physical activity ultimate tensile strength

Improvement with training (%)

Cardiorespiratory Ventilation CO O2 extraction VO2

35-fold 6-fold 2–3-fold 12–18-fold

0 90 25 50–60

Muscle metabolism Glycogen/fat stores Oxidative capacity

– –

100 300

Connective tissue Tendon Ligament Bone Cartilage

100 MPa 60–100 MPa 50–200 MPa 5–40 MPa

20 20 5–10 5–10

100–200

60

– –

40 80

20 30

Muscle Strength Fibre CSA Type I Type II

Time required for adaptation Months–years

40 30 40 Weeks–months 50 40–100 Months–years 30 30 30 30 Months–years

CO: cardiac output;VO2: whole body oxygen uptake; CSA: cross-sectional area.

tissue is not understood. Interestingly, substances are now being identified (e.g. mitogenactivated protein kinases) where subtypes are differentially activated by either metabolic stress or by the degree of contractile stress, to cause either increased cell oxidative capacity or muscle cell hypertrophy, respectively. We are therefore at a point where we can begin to master the study of the adaptation of the human body not only to acute exercise, but also to loading and overloading, and this will provide us with prerequisites for study of the ultimate adaptation potential that the human organism achieves, and thereby better describe also on an individual level why tissue becomes overloaded and injured.

The delicate balance between training adaptation and injury — the dilemma of rehabilitation It is important for the clinician who treats the recreational or elite athlete to have a thorough understanding of the injury, and also the ability of the affected tissue to adapt to immobilization, remobilization and

training. One example is the considerable plasticity that skeletal muscle tissue displays. While strength is lost (up to %) rapidly within a few weeks of immobilization, it can be regained over the next couple of months, and strength can be augmented up to -fold with training for extended periods (months/year). Bone loss also (up to %) occurs rapidly within weeks of immobilization and is subsequently regained in the following months of rehabilitation. However, somewhat in contrast to muscle, extended training periods have a relatively modest impact on bone tissue augmentation. Connective tissue loss in tendon is also comparable to muscle and bone; however, in contrast, its slower metabolism requires perhaps up to  months or more before complete tissue recovery from an injury and subsequent inactivity. Thus, an injury that demands a limb to be immobilized for a given length of time may require different time periods for the various tissues to return to their preinjury levels. In this context it is important for the clinician to note that the cardiovascular system recovers the fastest after

Introduction  a period of relative inactivity, which may create a dilemma: the athlete wants to take the rehabilitation and training program to new and challenging levels, but the different tissues may not be able to withstand the associated loads, and re-injury or a new so-called ‘overload injury’ may result. Thus, a thorough understanding of how tissues adapt to physical activity or lack thereof is paramount for the effective treatment and rehabilitation of the injured person. While acute injury during exercise may intuitively be somewhat easy to understand, it may be more challenging to grasp the insidious and frequent ‘overuse’ injuries that occur with training. Some important observations in the field of sports medicine have been made in recent decades that have improved our understanding of these injuries. An awareness of the subject’s loading pattern is important, of course. The recreational athlete who runs  km/week may subject each lower limb to approximately  landings and take-offs in that time period. In contrast, the long distance runner who runs  km/week may subject each lower limb to approximately   landings and takeoffs. Clearly, a certain degree of appropriate tissue adaptation has already taken place to withstand these vastly different loads, but nevertheless, injuries may be sustained by both the recreational and elite athlete and therefore remains an enigma. Interestingly, the weekly loading of tissue induced by sports participation is equivalent to that established by national authorities as the upper limits for what is tolerable for manual labour, suggesting that perhaps there is an inherent tissue limitation to loading. Disadvantageous alignment, like severe pes planus or genu valgus, for example, may be important factors in determing who can withstand a given loading pattern, although such internal factors cannot entirely explain overuse injury. It has become generally accepted that it takes appreciable time for tissues like connective tissue to adapt to a new or increasing demand, even for the most genetically fortuitous. Therefore, any desired progression or change in a training program should be gradual. However, more detailed information with respect to the training frequency, duration and intensity that is required to avoid an injury is currently lacking, and thus preventative efforts in this respect remain difficult. At the same time, it is becoming increasingly

appreciated that tissues need restitution periods to ‘adapt’ to the previous bout of physical activity. This is put into practice, for example, by the tri-athlete who loads the cardiovascular system considerably on a daily basis, but stresses the musculo-skeletal system alternately by training either cycling, running or swimming, which may help to avoid injury. It is during the restitution period that tissues are allowed to recover, or further adapt to an increasing demand by either expanding their quantity or improving their quality. It is likely that in years to come researchers will furnish new and improved measurement techniques that will yield important detailed information about tissue adaptation to physical activity and restitution.

Sports injuries and development of treatment: from recreational sports to elite athletes In many situations the transformation from overload symptoms to a sports injury is poorly defined and understood. Intensified research in anatomy, biochemistry, physiology and mechanisms of tissue adaptation to mechanical loading is needed to provide the basic understanding of overload injury pathogenesis. Although this in itself represents a paramount challenge, it seems even more difficult to understand an individual’s disposition for developing symptoms. Why does one individual develop severe Achilles tendon pain in connection with a certain amount of running, while others do not? Why are overhead activities very painful for some athletes but not for others? Why is the functional stability of a cruciate ligament deficient knee or a mechanically unstable ankle joint different between persons despite the same activity level? Obviously it would be essential to identify the weakest link in each individual case, but knowledge of the individual specific factors is very incomplete. Could there be physiologically different levels for initiation of symptoms in different individuals? It is well known that persons with decreased sensory inputs, for example caused by diabetic polyneuropathy, have a high rate of overload injuries like tendonitis or stress fractures, simply because the natural alarm system is out of order. If a physiological difference in, for example, the threshold of sensory inputs exists in otherwise healthy people, the difference between a

Introduction

mechanical load that causes symptoms and one that results in tissue damage would vary from person to person. Treatment of sports injuries represents major challenges. First, the aim to reduce symptoms is demanded by the athlete, and several pharmacological treatments will work well at rest, but will not provide pain relief when the individual is exercising. Secondly, when surgical treatment is indicated to repair irreversible changes of tissues (e.g. rupture of anterior and posterior cruciate ligaments of the knee) or to change biomechanical inferior or insufficient movement patterns (e.g. multidirectional instability in the shoulder) the procedures need to be minimally invasive in order to leave the remaining tissue as intact as possible and to allow for a quick regeneration process. Thirdly, the rehabilitation procedures and time allowed for recovery will be challenged. This is because athletes are eager to return to their sports. In this aspect, similarities can be drawn to occupational and rehabilitation medicine, which aims towards getting the patient back to the functional level that is required to perform a certain labour task. In contrast to the little which is known about the individual-based factors, there is increasing knowledge about injury mechanisms in athletic performance. A number of specific pathological entities have been recognized, especially during the past two decades, e.g. secondary impingement and internal impingement of the shoulder in overhead athletes. On the basis of recognizing certain common patterns of injury and understanding their pathogenesis, specific treatments — surgical as well as nonsurgical — have been developed. Probably the first injury to be recognized as a specific lesion connected to sports performance was the Bankart lesion of the shoulder, described in , and the way to repair the lesion was obvious once the pathoanatomical background was established. Similarly, when the SLAP lesion of the labrum in the shoulder was described for the first time about  years ago, the surgical treatment options could be defined (for further details see Chapter 6.5). Arthroscopy, which was introduced for knee disorders back in  and developed for the treatment of shoulder, elbow and ankle disorders in the s, has made direct visualization of joint movement and intra-articular structures possible, and has increased

the understanding of many intra-articular sports injuries. For the individual athlete it has resulted in a much more specific diagnosis and treatment, and consequently rehabilitation has become faster and easier than after open surgery. Furthermore, the invention and development of magnetic resonance imaging in the early s, and the refinement and general availability of ultrasound investigation during the late s, has increased the spectrum of diagnostic tools significantly. What still requires specific attention is the relative use of these para-clinical supplements as compared with a good clinical examination and judgement. There is no doubt that the new ‘machine-tools’, developed to help the sports medicine practitioner, tend to be ‘over-used’ in the initial phase, which is often followed by a more balanced phase in which it becomes evident that patient history and clinical examination can never be replaced by para-clinical tools, but that the latter provides a fruitful supplement in the process of diagnosis in sports medicine. The collection of clinical information on symptomatic conditions in athletes can lead to identification of uniform patterns and logically based treatment modalities. Series of treated patients can also give information about the success rate of certain treatments, whereas only randomized studies can identify the best treatment strategy in a specific condition. Unfortunately, there are very few randomized studies in sports medicine and especially within traumatology. This is often due to a high demand for treatment to ensure fast recovery and return to sports participation, and it is unlikely that more than a small part of the surgical and nonsurgical treatment modalities will ever be evaluated by randomized studies. Even though more than  anterior cruciate ligament (ACL) reconstructions are performed every year in the USA, it is unknown which treatment strategy is the most advantageous. There are different factors influencing the decision to perform ACL reconstruction: the chance to get back to sports, prevention of secondary meniscus and cartilage injury, prevention of giving-way or subluxation episodes, risk for anterior knee pain or other operative complications, or timing of surgery. There is no evidence for how these factors should be weighted, and it is unknown if routine reconstruction in all patients shortly after an ACL injury would reduce the risk of late complications and increase activity level better

Introduction  than a more conservative approach with rehabilitation as primary treatment. It is very important to perform randomized trials at the same time as new treatments are introduced, as it is almost impossible to return to such studies later. Most rehabilitation programs are based on individual, clinical experience and theoretical principles. Just as with surgical treatment, evidence is still lacking on the effect of a number of general treatment principles. Rehabilitation is very costly, and it is desirable with further development of evidence-based rehabilitation strategies. New technologies will probably influence the treatment of sports injuries in the near future. Local availability of growth factors may reduce repair and remodelling time after injury or surgery. Scaffolds can be used to introduce a specific architecture. These can be taken over by living tissue, and in combination with controlled gene expression, injured tissue can possibly be restored completely. This will contribute to an avoidance of reconstruction with replacement tissue and accompanying suboptimal recovery, as well as ensure the absence of scar tissue otherwise seen in repair. In the recreational athlete, many overload conditions are often self-limiting. Nature’s alarm system works: overloading of tissues often results in symptoms (pain) long before irreversible changes of the tissue structures happen. With a gradual reduction of activity, symptoms and overloading disappears, and the athlete can resume normal activity again. Tennis elbow is a good example of this mechanism. During one season about % of middle-aged persons per-

forming recreational racquet sports will experience symptoms of tennis elbow. The majority of these cases resolve without specific treatment. The interesting phenomenon is, why humans often carry on with exercise despite symptoms and signs of overuse. Interestingly, inflammatory reactions within and around tendons are seen in humans and in a few animal species that are forced to run like race-horses, whereas almost all other species (like mouse, rat or rabbit) do not show signs of tendinitis or peritendinitis despite strenuous activity regimens. Elite athletes can be motivated to continue peak performance despite pain or other symptoms, and it can be difficult or impossible for the natural repair processes to take place. Not enough is known about tissue repair and rehabilitation to define the maximum activity in each individual that is compatible with a full and fast repair. The boundary between trivial, reversible conditions and irreversible, disabling injuries still has to be defined in many sports. As an example, there is an ongoing discussion about the risk for chronic brain damages in boxing. Furthermore, nearly nothing is known about the long-term effect of continued elite sports activity on degenerative changes in the knee after ACL reconstruction. With this lack of evidence about physical consequences of sports injuries, ethical considerations have a central place in advice and planning. The influence of psychological factors such as competition (matches only take up less than % of the active playing time in elite handball, more than % of the ACL injuries happen there), self-confidence and acceptance of personal limits have to be acknowledged and further knowledge is warranted.

Table  Motivation and needs in different individuals with physical training.

Patient Recreational sports Elite athletes

Performance motivation

Disease-effect motivation

Prevention motivation

Guidelines for training

Tolerable amounts of training

+ + (function) + + + + (competition)

+++ – –

++ +++ (+)

+++ ++ +++

+ ++ +++

The motive for performing physical training can primarily be based upon a wish of increased performance either in sports or in everyday life, or be related to a wish of increased health and disease prevention.All three groups of individuals display an individually varying degree of which for achieving mental well-being in relation to exercise.The tolerable amount of training depends on the ability of the body to withstand loading and varies therefore significantly between athletes and patients, whereas both patients and athletes share a large request for specific guidelines in relation to the training they perform.

Introduction

Regular physical training: benefits and drawbacks For more than  years, systematic exercise or sports have been carried out worldwide, and one can easily consider the average individual living today as being much more inactive than they were in the past. It is becoming more and more scientifically documented that physical inactivity is a major risk factor for disease and premature death, and that the magnitude of this lies on the level of other risk factors like smoking, obesity or drinking. Studies have uniformly concluded that being active or beginning physical activity even at an advanced age, will positively influence risk factors for development of inactivity-associated diseases. In spite of the fact that acute training is associated with a transient increased risk of cardiac arrest, taken in the population as a group, as well as the costly treatment of sports injuries, socio-economic calculation has found that, for the recreational athlete, these drawbacks are far outweighed by the cost-saving benefits of physical training such as lower incidence of diseases, faster hospital recovery after disease in general, as well as a lower frequency of infection and time away from work due to sickness. The field of sports medicine is therefore facing a major challenge in improving the level of physical activity in the general population, and for setting up overall guidelines.

Physical training and patients with chronic diseases Acute and chronic diseases are associated with both organ specific manifestations as well as by more general disturbances in function due to physical inactivity and sometimes even additional hormonal and cytokine-related catabolism. In general, physical training can counteract the general functional disturbances, and maybe even affect or prevent the primary manifestations of disease. It is important to note that the motivational aspects, as well as the requirements for supervision and guidelines, in the patient with a present disease differ markedly from healthy exercising individuals (Table ). In principle, most diseases can be combined with a certain degree of physical activity, but the amount of restrictions put upon the patient differs considerably between diseases (Table ). Certain diseases have been shown to be influenced greatly from physical activity

Table  Effects of physical training upon different diseases. Diseases in which physical training will act preventively in disease development and positively upon primary disease manifestations Ischemic heart disease Recovery phase of acute myocardial infarction Hypertension Type-2 diabetes Obesity (most pronounced with respect to prevention) Osteoporosis Age-related loss of muscle mass (sarcopenia) Osteoarthritis (most likely only the prevention) Back pain Cancer (prevention of colon and breast cancer) Depression and disturbed sleep pattern Infectious diseases (prevention of upper respiratory tract infection) Diseases in which moderate or no direct effect can be demonstrated upon the primary disease manifestations, but where exercise will positively affect both health associated risk factors and the general disturbances in overall body function Peripheral vascular diseases (arterial insufficiency) Type-1 diabetes Bronchial asthma Chronic obstructive lung disease Chronic kidney disease Most forms of cancer Most acute and chronic liver diseases Rheumatoid arthritis Organ transplanted individuals Spinal cord injured individuals Most neurological and mental diseases Diseases in which much caution has to be taken or where exercise is to be discouraged, and where physical training often can have a worsening effect upon primary disease manifestations or may lead to complications Myocarditis or perimyocarditis Acute heart conditions (e.g. unstable angina, acute AMI, uncontrolled arrhythmia or third degree AV-block) Acute infectious diseases associated with fever (e.g. upper respiratory tract infection) Mononucleosis with manifest splenomegaly Aorta stenosis (chronic effect) Acute severe condition of many diseases mentioned above (e.g. severe hypertension, ketoacidosis in diabetes) Acute episodes of joint swelling (e.g. rheumatoid arthritis) or severe muscle disease (e.g. myositis)

Introduction  (e.g. ischemic heart disease, type- diabetes), whereas other diseases are known to be relatively insensitive to exercise when it comes to primary disease manifestations (e.g. chronic lung disease, type- diabetes). In the later group of diseases, it should, however, be noted that physical training can still have a beneficial effect on health-related parameters that can be achieved by individuals in general. This effect is achievable even in the absence of any worsening of the primary chronic disease. This emphasizes the importance of also encouraging individuals with chronic (and not necessarily fatal) diseases to train on a regular basis from a general health perspective. In addition, almost all diseased individuals can exercise in order to counteract the general loss in function that their disease-related inactivity has caused. In very few cases, extreme caution has to be taken when performing exercise (e.g. acute infectious diseases) (Table ). In spite of current knowledge of the effect of physical training on diseases, the exact mechanisms behind this are still only partially described. To find such bio-

chemical and physiological pathways will be important not only for addressing which type and dose of physical training should be prescribed for the individual patient, but also for identifying more general ‘health-pathways’ by which muscular contractions can influence the health status of the individual. Especially in relation to disease, the influence of training on such pathways either by itself or in combination with pharmaceutical drugs will potentially play a role in treatment of disease and maintenance of health into old age. Specific identification of health-related pathways in our genes will furthermore provide insight into the genetic polymorphism and help to explain the interindividual variation in training responses and healthrelated outcome of these. Evidently, this will also open possibilities for genetic treatment of inherited disorders with regards to tissue and organ adaptability to training, and at the same time inadvertently provide opportunities for misuse of gene therapy in relation to doping, a question that will challenge the sports medicine field ethically.

Part 1 Basic Science of Physical Activity and Sports Injuries: Principles of Training

Chapter 1.1 Cardiovascular and Respiratory Aspects of Exercise — Endurance Training SIGMUND B. S TRØMME , ROBE RT BOUSHE L , BJØRN EKBLOM, HE I KKI HUI KURI , MIKKO P. TUL PPO & NORMA N L. J ONE S

Classical reference Krogh, A, Lindhard, J The regulation of respiration and circulation during the initial stages of muscular work. J Physiol (Lond) 1913; : –. This paper demonstrated changes in respiration and heart rate with the transition from rest to bicycle exercise. The investigators did experiments on themselves, and Fig. .. shows the changes in tidal air and heart rate at the onset of exercise. As will be noted, a very rapid increase in both ventilation and heart rate was observed, and this led to the conclusion that motor center activity in parallel with activation of skeletal muscle caused an increased stimulation of respiratory centers as well as the heart. This was called cortical irradiation, and has later been referred to as central command or feed-forward, and has become an important topic in the discussion of respiratory, circulatory, and hormonal changes during exercise.

Cardiovascular adaptation Cardiac output The pumping capacity of the heart is a critical determinant of endurance performance in exercise events such as running, cycling, rowing, swimming, etc., where a large fraction of total body muscle mass is contracting dynamically. Because of the large dependence on oxidative metabolism for the total energy turnover in exercise activities sustained for longer than  min,

Fig. .. A recording of the tidal air on a spirometer (constructed by Krogh) at rest and at the beginning of exercise.

performance level is, as will be discussed later, largely dependent on the capacity for O2 delivery, and thus on the magnitude of maximal cardiac output. Maximal aerobic power (V˙2 max) is a classic measure of the capacity to perform endurance exercise, and may be described physiologically as the product of cardiac output and the extraction of O2 by muscle. For almost a century it has been recognized that a linear relationship exists between maximal oxygen uptake and cardiac output, and this relationship is also observed in other species [–]. It is estimated that –% of the interindividual difference in V˙2 max is



 Chapter . 35

Cardiac output (L /min)

30 25 20 15 10 5

1

2

3 . VO2max (L /min)

4

attributable to the level of maximal cardiac output []. Looked at another way, during whole body exercise, only ~–% of maximal mitochondrial respiratory capacity is exploited because of the limits of O2 delivery [–]. Endurance training augments skeletal muscle oxidative capacity and O2 extraction, but the principal variant for improvements in V˙2 max is maximal cardiac output [–] (Fig. ..). On the other hand, differences in athletic performance amongst competitive athletes with similar V˙2 max are linked to peripheral mechanisms [], such as running economy. The basic question as to what limits maximal aerobic power (V˙2 max) will be discussed later in this chapter.

Cardiac structure The increase in maximal cardiac output (Q max) following endurance training results from a larger cardiac stroke volume (SV), whereas maximal heart rate (HRmax) is unchanged or even slightly reduced. While heart size is a function of total body size as well as genetic factors, the higher SV achieved by endurance training is attributed to enlargement of cardiac chamber size and to expansion of total blood volume []. On the basis of cross-sectional studies in both

5

Fig. .. Relationship between increases in cardiac output and maximal oxygen uptake in heart failure patients (circles), healthy males after  days’ bedrest (squares), the same subjects before bedrest (inverted triangle), the same subjects after endurance training (upright triangle), and endurance athletes (diamonds).

female and male endurance-trained athletes, total heart volume is generally –% larger than sedentary size-matched controls, with morphologic differences seen in both the ventricles and the atria []. Chamber enlargement is also observed in endurance-trained paraplegics compared to sedentary matched controls []. There is a close relationship between cardiac volume and physical performance []. However, the cardiac hypertrophy is dependent on the type of sport carried out. There are two main types of myocardial hypertrophy. In weight lifters and other strengthtraining athletes heart wall thickness is increased, with only minor increases in heart cavity diameters, while endurance athletes have increased heart volume and cavity diameter with a proportional increase in wall muscle thickness []. The ratio of wall thickness to cavity diameter is unchanged in the endurancetrained individual but increased as a result of strength training []. The left ventricular hypertrophy in the endurancetrained individual is due to volume overload (‘eccentric’ hypertrophy), while the hypertrophy due to strength training develops as a consequence of pressure overload (‘concentric’ hypertrophy). Rowing, for

Cardiovascular and Respiratory Responses to Exercise instance, represents a mixture of volume and pressure overloading. In the former sarcomeres are added in series to increase cavity diameter, while in the latter sarcomeres are mainly added in parallel, causing wall thickening []. Both these are reversible processes since deconditioning from elite sport reduces cardiac size and volume towards what is normal for age and gender []. The cardiac morphology of the female athlete heart is the same as in men but the dimensions are in general smaller []. Structural and functional echocardiographic indices characterizing the normal limits of the athletic heart are shown in Table ... Whether or not cardiac hypertrophy (‘athlete’s heart’) predisposes the athlete to future cardiac problems has been discussed for many years [,]. However, the number and severity of cardiac arrhythmias seem to be the same in young athletes compared to untrained individuals of the same age and gender [], but increased in active elderly athletes []. However, a fast regression of ventricular hypertrophy through physical inactivity may cause some temporary increase in the number of arrhythmias [].

Table .. The upper normal healthy limits of cardiac dimensions associated with exercise training. From Urhausen & Kindermann, Sports Med ; : –.

Heart volume (mL/kg) Heart weight (g/kg) LV muscle mass (g/m2) LV mass/V·O2 max (g.min/L) LVED diameter (mm) Septum, LV post wall thickness Septum/LV post wall thickness Hypertrophic index (%)* Fractional shortening (%) Early/late transmitral flow velocity Left atrium thickness (mm)

Men

Women

20 7.5 170 80 63 (67a) 13

19 7 135 80 60 (63a) 12

1.4

1.3

48 >(22-) 27; ≠ exercise >1.0

45 >(22-) 27; ≠ exercise >1.0

43 (47a)

43 (45a)

*Hypertrophic index (%) = septum + LV thickness (mm)/LVED diameter (mm).



Functional adaptations In addition to structural adaptations, endurance training produces functional improvements in cardiac performance during exercise []. Most notable is a more rapid early and peak ventricular filling rate during diastole. An enlarged blood volume, together with greater ventricular compliance and distensibility, and a faster and more complete ventricular relaxation are important factors allowing stroke volume to increase even at high heart rates during exercise [,]. Improved myocardial relaxation allows for a more rapid lowering of ventricular pressure, optimizing the left atrial/ventricular pressure gradient for enhanced filling []. At the same time, the cardiac output is distributed more selectively to activated regions of skeletal muscle, from where the muscle pump facilitates venous return. As a result of an enlarged end-diastolic volume, left ventricular systolic performance is improved mainly by way of the Frank–Starling mechanism []. During submaximal exercise, myocardial work and O2 consumption are reduced in those who are endurance trained due to a lower heart rate at a given cardiac output as well as a reduced afterload attributable to lower peripheral resistance []. The enhanced diastolic filling and reduced afterload ensure that stroke volume is maintained or even progressively increased from submaximal to maximal exercise [], as compared to the sedentary person whose stroke volume plateaus at submaximal intensities and may fall as maximal exertion is approached [].

Myocardial vascularization and perfusion In a comparison of the cross-sectional area of proximal coronary arteries from endurance-trained and sedentary humans it has been suggested that coronary vascular volume may be increased by training []. It remains unresolved whether in humans endurance training increases coronary vascular dimensions beyond the vascular proliferation that accompanies normal training-induced cardiac hypertrophy. On the basis of studies in rats, endurance training has been shown to increase myocardial capillary density expressed as capillary/fiber ratio []. However, in larger animals, there is little evidence for increased capillary proliferation per fiber, nor is there evidence for proli-

 Chapter .

Heart rate At the beginning of dynamic exercise, heart rate increases rapidly due to the inhibition of parasympathetic tone. If the exercise is light (heart rate <  beats/min), the sympathetic activity applied to the heart and the vasculature does not increase and tachycardia occurs solely due to the reduction in parasympathetic tone []. As the workload increases, heart rate increases due to further vagal withdrawal and concomitant sympathetic activation (Fig. ..) []. The increase in sympathetic activation may be due to arterial baroreflex resetting, the muscle metaboreflex or muscle mechanoreceptor activation []. During heavy exercise, parasympathetic activity wanes and sympathetic activity increases in such a way that, at a workload corresponding to maximal oxygen consumption, little or no parasympathetic tone remains []. The analysis of heart rate variability (HRV) has become a frequently used tool for providing information on cardiovascular autonomic regulation at various phases of exercise, and also on the effects of physical training on cardiovascular autonomic regulation. The most commonly used HRV methods are time and frequency domain analysis techniques. The standard deviation of all normal-to-normal R–R intervals over

ct

ffe

Vagal blockade

he

at

p ym

e tic

S Heart rate

feration of collateral coronary vessels in the healthy non-ischemic heart. Commensurate with the reduction in myocardial work and O2 consumption at rest and during submaximal exercise after endurance training, coronary blood flow per unit myocardial mass is reduced []. However, studies in animals have shown that endurance training can increase maximal coronary perfusion per unit mass of the myocardium []. There are only modest increases in myocardial O2 extraction from rest to maximal exercise since extraction is very high even in the untrained state. However, there is evidence that exercise training elicits changes in vascular tone leading to an optimized distribution of blood flow, whereby more capillaries are recruited without a change in capillary density [,]. This is probably due to specific endothelium-mediated vasodilatation. Results from animal studies suggest that increased endothelial cell nitric oxide synthase, an enzyme that synthesizes nitric oxide from -arginine, contributes to such an adaptation [,].

ct

ffe

g Va

Rest

Sympathetic blockade

e al

. Max VO2

Fig. .. Schematic diagram showing the relative contributions of the sympathetic and parasympathetic systems to cardioacceleration at various levels of exercise. Comparisons are between the control state (broken line) and parasympathetic or sympathetic blockade. (Modified from [].)

an entire recording (SDNN) is a simple time domain method. This variable is considered to reflect both parasympathetic and sympathetic influences on the heart. The power spectrum of R–R intervals reflects the amplitude of heart rate fluctuations present at different oscillation frequencies. The different power spectral bands reveal different physiologic regulatory mechanisms; e.g. an efferent vagal activity is a major contributor to the high frequency component (see Fig. ..). A distinct cardiovascular adaptation to endurance training is a lowering of the heart rate at rest and during submaximal exercise. Maximal heart rate is unchanged or in some cases may be slightly reduced. The lowering of resting and submaximal heart rate is mediated by alterations in the autonomic nervous system, and by changes in the intrinsic automaticity of the sinus node and right atrial myocytes [,]. Both cross-sectional and longitudinal studies involving pharmacologic autonomic blockade and analysis of HRV indicate that increases in cardiac parasympathetic (vagal) tone make an important contribution to resting bradycardia [,]. The chronic increase in parasympathetic tone occurs within a few weeks after beginning regular training and this occurs independently of a lower intrinsic heart rate. In crosssectional studies, aerobic fitness and/or long-term

Cardiovascular and Respiratory Responses to Exercise (a) 1.5



Time (s)

HR = 55 beats/min, SDNN 88 ms

0.5 (b)

(c) 1.5

4

0 0.0

R–Rn+1 (s)

Power 103 (ms2)

Fig. .. Representative examples of R–R interval tachogram (a) and corresponding power spectra (b) and two-dimensional vector analyses of Poincaré plot (c) at rest ( min recording).

HF = 1727 ms2 LF = 1526 ms2 VLF = 2544 ms2

SD1 = 52 ms SD2 = 110 ms 0.1

0.2 0.3 Frequency (Hz)

aerobic training have been suggested to be associated with increased HRV, especially with vagally mediated respiratory sinus arrhythmia, at rest [,]. Some studies, however, have failed to show such an association [,]. The results from most longitudinal studies reveal decreased resting heart rate and increased vagal activity at rest after aerobic training [,]. During exercise in the trained, a given increase in cardiac output requires less increase in heart rate due to the maintenance of a larger stroke volume. Studies focusing on autonomic and endocrine responses to training indicate that heart rate is reduced during submaximal exercise (absolute load) in the trained due to a lower intrinsic heart rate, a reduction in sympathetic activity and circulating catecholamines, and a greater parasympathetic influence [,,]. Tulppo and colleagues [] found that higher levels of physical fitness were associated with an augmentation of cardiac vagal function during exercise, whereas aging resulted in more evident impairment of vagal function at rest. The lower sympathetic activity to the heart at a given submaximal work rate stems in part from diminished reflex signals originating from skeletal muscle due to less metabolite accumulation and attenuated discharge of metaboreceptors [].

0.4

0.5 0.5

R–Rn (s)

1.5

The mechanisms underlying the training-induced increase in vagal tone are thought to be greater activation of the cardiac baroreceptors in response to the enlargement of blood volume and ventricular filling [,], as well as changes in opioid [] and dopaminergic modulation of parasympathetic activity []. It is not fully resolved whether a lowering of intrinsic heart rate is a true adaptation to endurance training, but it appears that an intensive and lengthy training period may be necessary for this adaptation []. Primates with larger hearts have lower intrinsic heart rates and it has therefore been hypothesized that training-induced cardiac enlargement accounts for the lower intrinsic heart rate with training. A plausible mechanism for reduced intrinsic heart rate is that atrial enlargement reduces the stretch–depolarization stimulus, and thereby alters resting automaticity.

Blood pressure There is general agreement that endurance training elicits small reductions in resting blood pressure [,]. In addition, long-term exercise training has the beneficial effect of preventing the normal agerelated increase in blood pressure. A pressurelowering effect of endurance training has been shown to occur within  days after initiating an exercise

 Chapter . program []. Reduced adrenal medullary catecholamine output during exercise at a given absolute work rate may be of importance for the blood pressure lowering effect of training, as well as changes in sympathetic and renal dopaminergic activity. The reduction in resting diastolic blood pressure with training is significantly related to the increase in exercise capacity, which suggests that high-intensity training may be important. Attention is currently focused on determining the effectiveness of various training regimens which induce both reductions in resting blood pressure and significant improvements in functional capacity. During exercise at a given submaximal load, blood pressure and vascular resistance are reduced after endurance training. This adaptation is associated with reduced sympathetic activation and lower circulating catecholamines. At high exercise intensities and at maximal exercise, blood pressure is generally similar before and after training. Yet a given blood pressure is achieved by a lower vascular resistance and a higher cardiac output in the endurance trained.

Blood volume Blood volume (BV) is kept remarkably constant in many different situations and hyper- and hypovolemia are corrected fairly rapidly through the mechanism of renal absorption of sodium. Cross-sectional studies show that there is a close relationship between V˙2 max on the one hand and BV and total amount of hemoglobin (but not the hemoglobin concentration [Hb]) on the other. Exercise training increases blood volume. Plasma volume usually increases after a few days of training, while the expansion of erythrocyte volume takes longer []. The central venous compartment of blood volume is an important factor for cardiac output. The increased blood volume with physical training is regarded as a requisite for increased Qmax, although it may be that the blood volume increases in parallel with the increased V˙2 max. Acute plasma volume expansion (using Macrodex®) increases SV during submaximal and maximal exercise in well-trained individuals [,]. The explanation is that the enhanced BV causes an enhanced diastolic filling pressure (preload), which through a direct Frank–Starling mechanism increases

end-diastolic volume. End-systolic volume remains unchanged or decreases. Consequently SV is increased []. Since peak HR also remains unchanged, Qmax is increased. This increase in the well-trained athletes is just about enough to compensate for the reduced [Hb] and arterial oxygen content (Ca2), so that the V˙2 max is mainly unchanged compared to control experiments. However, in untrained or moderately trained individuals a corresponding plasma volume expansion may increase Qmax by a greater amount than that needed to compensate for the reduction of [Hb] during maximal exercise and, thus, increase V˙2 max [].

Peripheral vascular adaptations Regular physical activity results in peripheral vascular adaptations which enhance perfusion and flow capacity. Thus it has been shown that total leg blood flow during strenuous exercise increases in parallel with the rise in maximal aerobic power. In addition, the muscle arteriovenous oxygen difference is significantly greater after conditioning. Such adaptations may arise from structural modifications of the vasculature and alterations in the control of vascular tone [,]. The increase in capillary density of the muscle seems to be the major factor responsible for the rise in maximal oxygen extraction. Both cross-sectional and longitudinal studies have shown greater muscle capillary density in trained than in untrained individuals, and that physical inactivity is associated with reduced capillary density [,,]. Both capillary density and blood flow seem to increase in proportion with the rise in maximal aerobic power during long-term physical conditioning [,]. The rise in peak muscle blood flow appears to be achieved by enhanced endothelium-dependent dilatation (EDD) in the muscle which increases its vasodilator capacity in parallel with expanded oxidative capacity. Accordingly, the rise in cardiac output can occur without any rise in arterial pressure. An enhanced peak hyperemic blood flow appears to be an early adaptation to regular exercise [,]. A near % increase in flow-mediated EDD of the brachial artery after  weeks of aerobic and anaerobic training was shown by Clarkson et al. []. Furthermore, a high correlation between maximal aerobic power and peripheral vasodilator capacity, measured by vascular conductance, has been demonstrated [,]. King-

Cardiovascular and Respiratory Responses to Exercise well et al. [] found a near % greater reduction in forearm vascular resistance to an endotheliumdependent stimulus in endurance athletes as compared to sedentary subjects. This reduction was directly related to maximal aerobic power. In endurance-trained older people a significantly greater EDD, as compared with age-matched sedentary subjects, has also been observed []. Additionally, Rinder et al. [] found that abnormal EDD discovered in older, otherwise healthy individuals could be improved with long-term endurance training. They also noted a significant and reasonably good correlation between maximal aerobic power and EDD. The mechanisms behind the enhanced endothelial function associated with physical training may involve exercise-induced increases in shear stress and pulsatile flow. According to Niebaur and Cooke [] chronic increases in blood flow induced by training may exert their effect on EDD by modulating the expression of endothelial cell nitric oxide synthase (NOS). It has been shown that endothelium-derived nitric oxide (NO) may influence vascular tone in the periods between exercise bouts. In animal studies, reactivity to stimuli which mediate their effects via NO is increased by training in coronary circulation, as mentioned previously in this chapter [,]. Human studies have produced evidence for a role of NO in the regulation of muscle blood flow [,]. NOS exists in several isoforms. Consequently, endothelial NOS is named eNOS. Another isoform, called neuronal NOS (nNOS), is located in the sarcolemma and cytosol of human skeletal muscle fibers, in apparent association with mitochondria []. Frandsen and coworkers [] have shown that endurance training may increase the amount of eNOS in parallel with an increase in capillaries in human muscle, while the nNOS levels remain unaltered.

Respiratory adaptation As there are many variables that contribute to the achievement of V˙2 max, it may be difficult to identify which mechanism is ‘limiting’. This applies particularly to respiratory responses, which are generally considered as non-limiting or ‘submaximal’ during maximal exercise. Ventilation at maximal exercise is not as high as the maximal achievable ventilation (MAV), but MAV (or maximal breathing capacity,



MBC) is usually measured over – s, and falls progressively by about % after – min. Thus whilst some athletes may achieve an MAV of –  L/min, their sustainable maximal ventilation is – L/min, a value frequently achieved during maximal exercise. Of course, such values are accompanied by severe dyspnea, and it may be more helpful to understand factors contributing to limiting dyspnea, than to judge whether a ‘limiting’ ventilation has been reached. Trained individuals experience much less dyspnea than the untrained. Indeed, early in their experience of exercise, athletes may sense that they are able to exercise with much less dyspnea than their struggling peers, leading them to take up their sport in a serious way. The study and quantitative measurement of the intensity of dyspnea had to wait firstly for the introduction of the field of psychophysics by Stevens [], and secondly for the development of appropriate psychophysical techniques by Borg and Noble []. The application of these techniques has allowed the assessment of the separate contributions of many factors to dyspnea during exercise in health and disease, and provided some answers as to why the sense of effort in breathing is so much less in trained than in untrained individuals. Studies employing neurophysiologic techniques have suggested that the sense of dyspnea represents the conscious appreciation of the central outgoing command to the respiratory muscles []. Thus, consideration of all the factors contributing to the sensation spans the metabolic demands for ventilation; mechanical capacity to meet the demand; adopted patterns of breathing; pulmonary gas exchange efficiency; central control of breathing; respiratory muscle function; and sensory mechanisms by which the effort of breathing is appreciated. Furthermore, all these physiologic links are interdependent and capable of adaptation, apparently with the overall objective of minimizing discomfort and thereby enhancing performance.

Ventilatory demands of exercise The major demand on ventilation is CO2 production (V2); although this is closely related to metabolic oxygen consumption and pulmonary intake, many studies have dissociated the two and shown close corre-

 Chapter . Before After

Ventilation (L/min)

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2 CO2 output (L/min)

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Fig. .. Reductions in ventilation at two power outputs in five subjects, before and after training; reductions in VE are closely · related to reductions in V2 (there was no change in V 2 at either power output) []. Open and filled symbols denote before and after training, respectively.

lation between V2 and ventilation (VE). At a given power or ATP turnover, V2 is quantitatively related to the balance between fat and carbohydrate as fuels, and the amount of lactate accumulating in the blood; increases in fat oxidation [] and reductions in lactate accumulation [,] may account for as much as a halving of VE at a given power in trained as against untrained subjects. Higher activities of fat metabolizing enzymes [], greater mitochondrial surface area [] and more efficient oxygen delivery mechanisms [] all contribute to the metabolic changes. Training-related reductions in VE closely parallel reductions in both V2 (Fig. ..) and plasma lactate concentrations [,,]. Thus, at a given power output, an increase of % in fat utilization will reduce ventilation by approximately %, and a reduction in plasma lactate concentration of  mmol/L will be accompanied by a further, up to %, reduction. In some athletes changes may be much larger; moreover, when accompanied by the other changes described below, such small effects are magnified, so that ventilation in some athletes may be half that observed in untrained subjects exercising at comparable power [].

Ventilatory capacity In terms of dimensions, the maximal breathing capacity is a function of the total lung volume and the maxi-

mal flow rates in inspiration and expiration; volume is related to thoracic volume, and flow rates to airway cross-sectional area. For a given stature and weight both volume and maximal flow tend to be larger in athletes, but studies in twins suggest that this has a genetic basis, and that training has little influence []. Within these constraints, athletes employ a larger volume, by being able to achieve both a smaller endexpiratory and larger end-inspiratory volume. They also employ larger flow rates in both inspiration and expiration; indeed some athletes are capable of using virtually all their maximal flow-volume loop during exercise [,]. It seems likely that this is because of stronger and more fatigue-resistant respiratory muscles (see below). In older subjects there is a loss of elastic recoil; this reduces flow at low lung volumes and prevents them from achieving a reduction in endexpiratory volume, and contributes to an increase in respiratory effort in older athletes [].

Pulmonary gas exchange Pulmonary gas exchange efficiency is broadly related to ventilation–perfusion (V/Q) matching in the lungs, and to diffusion across the alveolar capillary membrane. In general, in healthy subjects larger lungs imply greater alveolar volume and surface area and larger pulmonary capillary volume. The range of V/Q ratios extends from zero (representing anatomic pathways between the right and left sides of the heart, or ‘shunt’) to infinity (representing anatomic airway dead space); areas in the lungs with a low V/Q ratio contribute to the alveolar–arterial P2 difference (A– a D2), and those with high V/Q to physiologic dead space (VD/VT). Both A–a D2 and VD/VT are minimized by increases in tidal volume. However, healthy untrained subjects as well as athletes appear to reach similar minimal values for both, and at higher levels of V˙2 there is no further reduction [,]. This phenomenon has been carefully studied, especially for A–a D2; in some athletes very wide A–a D2 have been observed, leading to arterial P2 values as low as  mmHg (Fig. ..) []. When associated with a ‘rightward shift’ of the oxygen dissociation curve due to low arterial pH, such low Pa2 values translate into arterial O2 saturations of % or less. The cause of this ‘arterial desaturation’ and ‘failure of gas exchange’ has been debated, but

Cardiovascular and Respiratory Responses to Exercise

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Fig. .. Increasing exercise is associated with progressive increases in pulmonary blood flow; pulmonary capillary blood volume increases to a maximum of  mL. Capillary mean transit time falls, and at maximum exercise approaches values as short as . s. From Dempsey [].

VO2 (L/min, STPD) Fig. .. Arterial blood gases and pH at rest and during submaximal and maximal treadmill exercise in a group of untrained [*] and three groups of trained subjects. One group of trained subjects (l) showed a significant fall in arterial P2, associated with higher P2 at maximal exercise. From Dempsey [].

remains unresolved []. There is no doubt that it occurs especially in elite athletes exercising at high V˙2, leading to theories that include relatively high venous P2, low venous O2 contents and very short pulmonary capillary transit times (Fig. ..) contributing to incomplete O2 diffusion. Interstitial pulmonary edema occurs in animal models of exercise but has never been shown in humans. Other possible factors include incomplete equilibration for CO2 in blood traversing the lung [] combined with low blood pH, leading to incomplete oxygenation of hemoglobin. The limiting process in CO2 equilibration appears to be the erythrocyte chloride exchanger which has a half-equilibration time that is in excess of pulmonary capillary transit time in heavy exercise [,].

Pattern of breathing Athletes breathe more slowly and deeply than nonathletes, and a slower breathing rate is one of the effects

of training. The volumes and flows determine the tidal volume and frequency of breathing during exercise; all other matters being equal, larger tidal volumes and slower frequencies lead to greater efficiency in breathing with lower values for the VD/VT ratio. Some subjects entrain breathing frequency with their pedaling or running cadence [], but there is scope for wide variation in such responses ( strides/breath vs.  strides/breath, for example), so that the entrainment never dominates the pattern. Although the use of a given pattern of breathing is often assumed to be a selfoptimizing response to minimize the oxygen cost of breathing, it seems more likely that patterns are adopted consciously or unconsciously to minimize the sense of effort in breathing [].

Control of breathing Whilst the mechanisms responsible for the control of breathing during exercise remain a topic of continuing research [] beyond the scope of the present chapter, there is general agreement that increases in ventilation are a closely related function of the body’s CO2 production. Many have studied the ventilatory responses to increases in arterial P2 (VE/P2), in athletes and untrained subjects. The findings may be summarized as follows.

 Chapter .  There is a wide range in both VE/P2 (.– . L/mmHg) and VE/V2(– L/L) in trained and untrained individuals [,].  There is a relationship between the two indices: low responders to P2 have a low response to exercise [].  There is a strong genetic component determining VE/P2 [].  Training does not seem to change either VE/V2 or VE/P2 [,]. One might interpret these findings as indicating no influence of ventilatory control on performance. However, the effect of the variations in VE/V2 is substantial, even when associated with the normal range of variation in arterial P2. At an exercise power accompanied by a V2 of . L/min, ventilation may range from  to  L/min in normal subjects [], with a corresponding variation in breathing effort. A child taking up competitive swimming is presumably more likely to persist if she experiences little breathlessness compared to her panting friends. The ventilatory responses to hypoxia and P2 are closely correlated []; this fact may contribute to the lack of response to a falling P2, but also may be important in athletes at high altitude. A low ventilatory responsiveness might be seen to predispose to dangerous hypoxia; however, what has emerged from studies simulating the ascent of Mount Everest is that low responders are more likely to reach the summit and are less likely to suffer the deleterious cerebral and pulmonary effects of altitude []; these effects appear to be mediated by reductions in arterial P2 and associated alkalosis. In athletes who because of their sport have to breath hold for long periods of time, such as synchronized swimmers, the ventilatory response to hypoxia is blunted and breath hold times prolonged [].

The respiratory muscles As first systematically studied by Ringqvist [], the respiratory muscles show considerable variation in strength and endurance, in relation to stature, age and sex, with fairly obvious implications for the capacity to achieve and maintain ventilation during exercise [], and also for the sense of effort experienced in breathing. Subjects with stronger respiratory muscles achieve higher tidal volumes (and thus lower breathing

frequencies), and experience less dyspnea than those with weaker muscles []. The actions of the respiratory muscles differ; expiratory flow is mainly dependent on the elastic recoil of the respiratory system with only a minor contribution from expiratory muscle contraction until very high expiratory flows are recruited. Expiratory muscle contraction mainly acts to reduce end-expiratory lung volume and thus recruit the inspiratory recoil of the thorax and increase the precontraction length of the inspiratory muscles; in this way, they tend to ‘unload’ the inspiratory muscles []. The latter have to generate inspiratory flow against the lung recoil pressure, and thus carry the major responsibility for ventilatory work. Inspiratory muscle training mainly accompanies other aspects of endurance training, but resistive training is known to improve inspiratory muscle strength and endurance []. These considerations have important implications in aging athletes in whom there is the normal decline in lung elasticity; end-expiratory lung volume cannot be reduced to the same extent as in the young, forcing the inspiratory muscle to carry a greater proportion of the respiratory work during exercise []. Johnson et al. [] found that reductions in elastic recoil and increases in end-expiratory volume paralleled reductions in V˙2 max in a group of older ( ±  years) people; such subjects are likely to have been limited by dyspnea.

Sensation of dyspnea Respiratory muscle oxygen consumption was once thought to increase disproportionately at high levels of ventilation, and thus contribute to a limitation of maximal oxygen intake, but more recent estimates suggest that patterns of breathing are adopted mainly to minimize dyspnea []. Because exercise is a voluntary activity, conscious humans stop exercise when the sensation of excessive effort and weakness in exercising muscle or of dyspnea becomes intolerable. A number of sensations related to breathing can be discriminated and scaled [], including inspiratory muscle tension and displacement, a sense of ‘satiety’ or appropriateness related to increases in arterial P2 [,], and a sense of effort related mainly to central outgoing command [] (Fig. ..). Both effort and dyspnea are less in trained compared



Cardiovascular and Respiratory Responses to Exercise Sense of APPROPRIATENESS

Central motor drive

Sense of EFFORT

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Effective intrapulmonary pressure Sense of IMPEDANCE

Impedance (elastance, resistance)

CONTROL

Fig. .. Mechanisms contributing to sensations related to breathing during exercise. Whilst the changes in tension developed and displacement of inspiratory muscles can be discriminated and scaled, contributors to the sense of effort include difficulty in breathing (sense of impedance), sufficiency of the ventilatory response (‘satiety’), and the outgoing central motor command [].

Sense of DISPLACEMENT

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Sense of SATIETY

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Severe 5 Somewhat severe 4 Moderate 3 Fig. .. Sense of dyspnea during exercise in healthy subjects, grouped according to strength of inspiratory muscles (measured as maximal inspiratory pressure, MIP), into four groups: very weak, MIP < % predicted; weak, –%; strong, –%; very strong, > %. From Hamilton et al. [].

Slight 2 Very slight 1 Just noticeable 0.5 Nothing at all 0

to untrained individuals, enabling them to maintain higher power for longer. The factors accounting for these differences are numerous and interactive. For dyspnea the reasons are mainly that the pressure generated by the respiratory muscles is relatively less in subjects with large lungs (due to lower elastance and resistance), and strong respiratory muscles (Fig. ..). Dyspnea is minimized in trained individuals chiefly through:

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 minimizing V2, through utilization of fat and reduction in lactate production;  maximizing P2, through lower VE/V2;  reducing VD/VT, by increasing VT, a function of lung volume; and  increasing inspiratory muscle strength. At an oxygen consumption of  L/min, the first three factors could theoretically account for a difference in ventilation from  L/min in an unfit individual to  L/min in an elite endurance runner. As the

 Chapter . sustained ventilatory capacity might be as low as  L/min in the former, and as high as  L/min in the latter, the percentage of breathing capacity being used might be as high as % in the untrained and as low as % in the athlete. The associated intensity of dyspnea may thus differ by as much as five-fold []. This example also emphasizes that there is great potential for a reduction in the sense of dyspnea by training, with important implications for elite performers, particularly in distance events.

Maximal aerobic power In elite athletes from endurance sports values for maximal aerobic power (V˙2 max) of > . L/min or >  mL/min/kg body weight are frequently obtained. These extremely high values are primarily due to a large maximal cardiac output (Qmax). Values of more than  L/min have been measured []. Since the arteriovenous oxygen difference (a-v 2 diff) during maximal exercise in these well-trained athletes does not differ from that in less trained individuals but is somewhat larger than in untrained individuals, the main cause for the high Qmax and, thus, V˙2 max in the well-trained athlete is the large stroke volume (SV); values exceeding  mL during maximal exercise are reported []. In well-trained athletes the hemoglobin concentration [Hb] at rest and during exercise is not different from that obtained in untrained individuals of the same sex and age []. Although regular physical training can reduce the oxygen content of the mixed venous blood during maximal exercise in previous untrained individuals [], the [Hb] obviously sets the upper limits of the a-v 2 diff during maximal exercise. Therefore, any changes in [Hb] during exercise will have a direct influence on V˙2 peak, V˙2 max and physical performance. Oxygen transport and utilization includes a series of steps. In the following discussion the different steps of the oxygen cascade from lungs to mitochondria are considered in relation to the basic question: ‘What limits V˙2 max?’ During maximal exercise pulmonary ventilation (Ve) in untrained or moderately trained individuals reaches – L/min. Athletes from endurance events with high V˙2 max can reach a maximal Ve of  L/min and over. In maximal voluntary ventilation

tests at rest (MVV40), when the individual is breathing as much as possible with a fixed breathing frequency ( breaths/min) for – s, the untrained individual may be able to ventilate – and athletes up to – L/min. These volumes far exceed what is used during a maximal exercise test, although they can hardly be maintained for any longer period of time. In addition, most individuals are able to voluntarily increase pulmonary ventilation during a maximal running or cycling test above what is obtained in the test. Furthermore, specific training of the respiratory muscles does not increase either V˙2 max or arterial oxygen saturation (Sa2) during maximal exercise above pretraining values []. The oxygen diffusion capacity of the lung (DL2) depends on many different factors. If DL2 limits V˙2 max then arterial oxygen pressure (Pa2) and Sa2 during maximal exercise will fall, unless alveolar ventilation is increased (to increase Pa2). However, during heavy exercise both Pa2 and Sa2 are mainly maintained unchanged or only slightly reduced compared to rest or submaximal exercise in both elite athletes and untrained individuals [,]. It should be noted that a certain arterial hypoxemia (desaturation) compared to rest has been observed in some well-trained athletes [,]. Whether this is due to hypoventilation, exercise-developed pulmonary edema, insufficient pulmonary capillary transit time, increased blood flow in arterial–venous anastomosis during heavy exercise or other factors is not known []. Another important point in this discussion is related to effects of changes in [Hb] during heavy exercise. If DL2 and/or Ve limit V˙2 max, then an increase in [Hb] would have no or very little effect. However, both an acute increase of [Hb] through ‘blood doping’ [,] and a more ‘chronic’ increase of [Hb] through administration of erythropoietin [] do increase V˙2 max. This speaks against a functional limitation of V˙2 max at the pulmonary level. Arguments have been put forward that factors related to the peripheral blood circulation (such as capillary density), oxygen utilization in the muscle cells (such as mitochondrial mass and enzyme concentrations) and other factors might limit V˙2 max. This is certainly true during heavy exercise carried out with small muscle groups, such as isolated dynamic arm work. In this

Cardiovascular and Respiratory Responses to Exercise situation the ‘peripheral factors’ are of utmost importance for, and certainly do limit, the aerobic energy turnover, performance and endurance []. However, during exercise with large muscle groups, such as running uphill and combined arm and leg exercise, there are several reasons supporting the idea that the ‘periphery’ does not limit V˙2 max.  When a maximal rate of work performed by the legs only is divided into a combination of arm and leg work, neither V˙2 max [,] nor Qmax and arterial blood pressure [] are different from those obtained when using legs only. However, time to exhaustion is much longer when working with arms and legs compared to maximal leg work. For instance, there might be an increase in time to exhaustion from  to  min. This means that during the combined arm and leg work, when the ‘double product’ (HR · BP) is the same as during the work with legs only, the heart has been working for  min beyond the point when the individual would have had to stop the work with legs only. Thus, the endurance capacity of the heart when working with legs only does not limit cardiac performance as has been suggested [].  When comparing trained and untrained individuals there is no relation between V˙2 max and different markers of the peripheral energy turnover such as enzyme activity [,]. Furthermore, endurance training may increase and inactivity reduces mitochondria enzyme concentrations considerably without any or only minor changes in V˙2 max [,].  If ‘central’ (central circulation) and ‘peripheral’ factors (muscle enzyme concentration and mitochondrial volume) are matched, then aerobic energy turnover for a small muscle group would be of the same order of magnitude as that obtained at V˙2 max at the pulmonary level. Measurements of the a-v  2 diff and blood flow over a well-defined muscle group (musculus quadriceps femoris) during maximal exercise and consequent calculations of the maximal aerobic energy turnover for this muscle group show that estimated V˙ 2 peak per kilo muscle mass far exceeds that of the pulmonary V˙2 max per kg muscle mass when working with large muscle groups [,]. Thus, the local muscle capacity for aerobic energy turnover exceeds that which can be maximally obtained as V˙2 max during heavy exercise using large muscle groups.  Changes in Ca2 and arterial oxygen availability will

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ultimately cause corresponding changes in V˙2 max and muscle performance. Reductions of Ca2 through carbon monoxide loading, venesections or hypobaric hypoxia reduce V˙2 max; this, however, could be due to both central and peripheral limiting factors. But, as previously mentioned, both an ‘acute’ [,] and more ‘chronic’ [] increase in Ca2 will increase V˙2 max and physical performance more or less in proportion to the induced changes in Ca2. It seems obvious from these data that the central circulation — mainly the heart function including the blood (BV and [Hb]) — have important roles for both limiting and establishing high values of V˙2 max. Consequently, the next question is: ‘What limits the functional capacity of the heart?’. Since HRmax and Ca2 do not increase with physical training, the only structural factor that can explain individual differences in V˙2 max is the stroke volume (SV). There is a small increase in SV during transition from rest to light submaximal exercise. SV is well maintained or even increased [] during maximal exercise, indicating that the oxygen supply to the heart is adequate. The main cause for the increased SV during exercise is an enlarged end-diastolic volume (EDV) caused by augmented venous ‘filling’ pressure. As mentioned earlier in this chapter, this has been shown in experiments using plasma expanders during exercise. Such plasma expansion increases EDV, and thereby SV and Qmax as compared with peak values obtained before plasma expansion [,]. Although the plasma expansion reduces [Hb], normal peak O2 uptake can still be obtained due to the increased SV and Qmax []. Hammond et al. [] tested the hypothesis that the pericardium restricts heart size and thus limits SV and Qmax. They studied exercising pigs before and after pericardiectomy. During maximal treadmill running Qmax increased by % and V˙2 max by % due to an estimated % increase in EDV. This suggests that the EDV, restricted by the pericardium, sets the upper limit for SV during exercise and thus limits Q max. With advanced age V˙2 max declines due to both reduced Qmax and some reduction in a-v 2 diff. The reason for the former is a reduced peak HR, SV being mainly unchanged. Regarding the a-v 2 diff, there is an increase in oxygen content of mixed venous blood in the elderly, probably due to an inability to shunt blood

 Chapter . to active muscles [], thus reducing a-v 2 diff. The effect of regular physical training in the elderly is essentially the same as in young persons; however, the magnitude is generally smaller. In conclusion, during exercise engaging large muscle groups (running uphill, simultaneous arm and leg work) the V˙2 max is limited by the central circulation. Since HRmax and Ca2 are practically unchanged by physical training, the V˙2 max is basically limited by SV. Thus, the principal variant for improvements in V˙2 max is maximal cardiac output.

Summary The pumping capacity of the heart is a critical determinant of endurance performance. The increased maximal cardiac output following endurance training results from a larger cardiac stroke volume, whereas maximal heart rate is unchanged or even slightly reduced. The higher stroke volume is due to enlargement of cardiac chamber size and to expansion of total blood volume. Plasma volume increases usually after a few days of training while the expansion of erythrocyte volume takes a longer time. Functional improvements in cardiac performance include a more rapid early and peak ventricular filling rate during diastole. The enlarged blood volume, together with greater ventricular compliance and distensibility, and a faster and more complete ventricular relaxation allow stroke volume to increase even at high heart rates. At the same time, the cardiac output is distributed more selectively to activated regions of skeletal muscle, from where the muscle pump facilitates venous return. Endurance training elicits small reductions in resting blood pressure. It remains unresolved whether endurance training increases coronary vascular dimensions beyond the vascular proliferation that accompanies normal training-induced cardiac hypertrophy. Endurance training results in peripheral vascular adaptations, which enhance perfusion and flow capacity in parallel with rise in maximal aerobic power. These adaptations are caused by an increase in capillary density, and alterations in the control of vascular tone. The rise in peak muscle blood flow appears to be achieved by enhanced endothelium-dependent dilatation in parallel with expanded oxidative capacity. Endothelium-derived nitric oxide (NO), synthesized

by nitric oxide synthase (NOS), may contribute to this adaptation. Training-related reductions in ventilation closely parallel reductions in both V2 and plasma lactate concentrations. Although largely genetically determined, a larger volume is exploited by athletes as they are able to achieve a smaller end-expiratory and larger end-inspiratory volume, mainly due to stronger and more fatigue-resistant respiratory muscles. Resistive training improves inspiratory muscle strength and endurance. Subjects with stronger respiratory muscles achieve higher tidal volumes (and thus lower breathing frequencies), and experience less dyspnea than those with weaker muscles, thus enabling them to maintain higher power for longer. The central circulation — mainly the heart function, including the blood volume and hemoglobin concentration — plays an important role in both limiting and establishing high values of maximal aerobic power. During exercise engaging large muscle groups (running uphill, simultaneous arm and leg work) the maximal aerobic power is limited by the central circulation. Since maximal heart rate and arterial oxygen content are practically unchanged by physical training, the maximal aerobic power is basically limited by the stroke volume. Thus, the principal variant for improvements in maximal aerobic power is maximal cardiac output.

Multiple choice questions  Which of the following parameters does not increase appreciably as a response to endurance training: a maximal cardiac output b left ventricular end-diastolic volume c diastolic filling rate d left ventricular end-systolic volume e stroke volume f maximal heart rate.  What is the relationship between cardiac output (CO), total peripheral resistance (TPR) and arterial pressure (BP): a CO = BP/TPR b BP = TPR/CO c CO = BP · TPR d TPR = CO/BP e BP = CO · TPR f TPR = BP/CO.

Cardiovascular and Respiratory Responses to Exercise  Differences in athletic performance amongst athletes with similar V˙o2 max are linked to: a pulmonary gas exchange b hemoglobin concentration c total blood volume d diastolic filling pressure (preload) e work economy f heart rate variability.  Physical training results in peripheral vascular adaptations which improve perfusion and blood flow capacity. Such adaptations may arise from: a increased capillary density b decreased resting heart rate c increased mitochondrial mass d enhanced endothelium-dependent dilatation e changes in endothelium-derived nitric oxide concentration f decreased neuronal nitric oxide synthase.  The sensation of dyspnea is minimized in trained individuals through: a shift of the oxygen dissociation curve to the right b decreased anatomic dead space c minimization of V2, through utilization of fat and reduction in lactate production d increased vital capacity e maximizing P2, through lower VE/V2 f increased pulmonary capillary transit time.

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     

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Cardiovascular and Respiratory Responses to Exercise  Kanstrup I-L, Ekblom B. Acute hypervolemia, cardiac performance and aerobic power during exercise. J Appl Physiol ; : –.  Krip B, Gledhill N, Jamnik V, Warburton D. Effect of alterations in blood volume on cardiac function during maximal exercise. Med Sci Sports Exerc ; : –.  Gledhill N. The influence of altered blood volume and oxygen-transport capacity on aerobic performance. Exerc Sport Sci Rev ; : –.  Ekblom B, Berglund B. Effect of erythropoietin administration on maximal aerobic power in man. Med Sci Sports Exerc ; : –.  Ingjer F. Capillary supply and mitochondrial content of different skeletal muscle fiber types in untrained and endurance-trained men. A histochemical and ultrastructural study. Eur J Appl Physiol ; : –.  Kingwell BA, Jennings GL. The role of aerobic training in the regulation of vascular tone. Nutr Metab Cardiovasc Dis ; : –.  Hepple RT. Skeletal muscle: microcirculatory adaptation to metabolic demand. Med Sci Sports Exerc ; : –.  Ingjer F. Maximal aerobic power related to the capillary supply of the quadriceps femoris muscle in man. Acta Physiol Scand ; : –.  Laughlin MH. Endothelium-mediated control of coronary vascular tone after chronic exercise-training. Med Sci Sports Exerc ; : –.  Sinoway LI, Shenberger J, Wilson J, McLaughlin D, Musch TI, Zelis R. A -day forearm work protocol increases maximal forearm blood flow. J Appl Physiol ; : –.  Clarkson P, Montgomery H, Donald A et al. Exercise training enhances endothelial function in young men. J Am College Cardiol ;  (Suppl.): A.  Martin WH, Kohrt WM, Malley MT, Korte E, Stoltz S. Exercise training enhances leg vasodilatory capacity of year-old men and women. J Appl Physiol ; : –.  Snell PG, Martin WH, Buckey JC, Blomquist CG. Maximal vascular leg conductance in trained and untrained men. J Appl Physiol ; : –.  Kingwell BA, Tran B, Cameron JD, Jennings GJ, Dart AM. Enhanced vasodilatation to acetylcholine in athletes is associated with lower plasma cholesterol. Am J Physiol ;  (Heart Circulation Physiol ): H–.  Rywik TM, Blackman MR, Yataco AR et al. Enhanced endothelial vasoreactivity in endurance-trained older men. J Appl Physiol ; : –.  Rinder MR, Spina RJ, Ehsani AA. Enhanced endotheliumdependent vasodilation in older endurance-trained men. J Appl Physiol ; : –.  Niebaur J, Cooke JP. Cardiovascular effects of exercise role of endothelial shear stress. J Am College Cardiol ; : –.  Duffy SJ, Tran BT, Harper RW, Meredith IT. Relative contribution of vasodilator prostanoids and NO to metabolic vasodilation in the human forearm. Am J Physiol ;  (Heart Circulation Physiol): H–.

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 Rådegran G, Saltin B. Nitric oxide in the regulation of vasomotor tone in human skeletal muscle. Am J Physiol ;  (Heart Circulation Physiol): H–.  Frandsen U, Lopez-Gigueroa MO, Hellsten Y. Localization of nitric oxide synthase in human skeletal muscle. Biochem Biophys Res Comm ; : –.  Frandsen U, Höffner L, Betak A, Saltin B, Bangsbo J, Hellsten Y. Endurance training does not alter the level of neuronal nitric oxide synthase in human skeletal muscle. J Appl Physiol ; : –.  Stevens SS. Psychophysics. Introduction to its Perceptual, Neural, and Social Prospects. John Wiley & Sons Inc, New York .  Borg GAV, Noble B. Perceived exertion. In: Wilmore JH, ed. Exercise and Sports Sciences Reviews, Vol. . New York: Academic Press, : –.  Gandevia SC. Neural control in human muscle fatigue. changes in muscle afferents, motoneurons and motocortical drive. Acta Physiol Scand ; : –.  Coggan AR, Habash DL, Mendenhall LA, Swanson SC, Kien CL. Isotopic estimation of CO2 production during exercise before and after endurance training. J Appl Physiol ; : –.  Casaburi R. Mechanisms of the reduced ventilatory requirement as a result of exercise training. Eur Respiratory Rev ; : –.  Taylor R, Jones NL. The reduction by training of CO2 output during exercise. Eur J Cardiol ; : –.  Gollnick PD, Armstrong RB, Saubert IVCW, Piehl K, Saltin B. Enzyme activity and fiber composition in skeletal muscle of untrained and trained men. J Appl Physiol ; : –.  Hoppeler H, Luthi P, Claassen H, Weibel ER, Howald H. The ultrastructure of the normal human skeletal muscle: a morphometric analysis on untrained men, women and welltrained orienteers. Pflügers Archiv für des Gesamte Physiologie ; : –.  Saltin B, Rowell LB. Functional adaptation to physical activity and inactivity. Fed Proc ; : –.  Casaburi R, Storer TW, Wasserman K. Mediation of reduced ventilatory response to exercise after endurance training. J Appl Physiol ; : –.  Edwards RHT, Jones NL, Oppenheimer EA, Hughes RL, Knill-Jones RP. Interrelation of responses during progressive exercise in trained and untrained subjects. Q J Exp Physiol ; : –.  Weber G, Kartodihardjo W, Klissouras V. Growth and physical training with reference to heredity. J Appl Physiol ; : –.  Grimby G, Saltin B, Wilhelmsen L. Pulmonary flowvolume and pressure-volume relationship during submaximal and maximal exercise in young well trained men. Bull Eur Physiopathol Respiration ; : –.  Johnson BD, Saupe KW, Seow KC, Dempsey JA. Mechanical constraints on exercise hyperpnea in athletes. Am Rev Respiratory Dis ; : A.

 Chapter .  Johnson BD, Reddan WG, Seow KC, Dempsey JA. Mechanical constraints on exercise hyperpnea in a fit aging population. Am Rev Respiratory Dis ; : –.  Dempsey JA, Vidruk EH, Mitchell GS. Pulmonary control systems in exercise: update. Fed Proc ; : –.  Dempsey JA. Is the lung built for exercise ? Med Sci Sports Exerc ; : –.  Jones NL, Heigenhauser GJF. Getting rid of carbon dioxide during exercise. Clin Sci ; : –.  Klocke RA. Velocity of CO2 exchange in blood. Annu Rev Physiol ; : –.  Bechbache RR, Duffin J. The entrainment of breathing frequency by exercise rhythm. J Physiol (Lond) ; : –.  Casan P, Villafranca CC, Kearon MC, Campbell EJM, Killian KJ. Contribution of respiratory muscle oxygen consumption to breathing limitation and dyspnea. Can Respiratory J ; : –.  Killian KJ, Jones NL, Campbell EJM. Control of breathing during exercise. In: Altose MD, Kawakami Y, eds. Control of Breathing in Health and Disease. New York: Marcel Dekker, Inc, : –.  Akiyama Y, Kawakami Y. Clinical assessment of the respiratory control system. In: Altose MD, Kawakami Y, eds. Control of Breathing in Health and Disease. New York: Marcel Dekker, Inc, : –.  Jones NL. Use of exercise in testing respiratory control mechanisms. Chest ; : s–s.  Rebuck AS, Jones NL, Campbell EJM. Ventilatory response to exercise and to CO2 rebreathing in normal subjects. Clin Sci ; : –.  Saunders NA, Leeder SR, Rebuck AS. Ventilatory response to carbon dioxide in youth athletes: a family study. Am Rev Respiratory Dis ; : –.  Hughes RL, Clode M, Edwards RHT, Goodwin TJ, Jones NL. Effect of inspired O2 on cardiopulmonary and metabolic responses to exercise in man. J Appl Physiol ; : –.  Rebuck AS, Campbell EJM. A clinical method for assessing the ventilatory response to hypoxia. Am Rev Respiratory Dis ; : –.  Dempsey JA, Schoene RB. Pulmonary system adaptations to high altitude. In: Bone RC, ed. Pulmonary and Critical Care Medicine. St Louis: Mosby, : –.  Bjurstrom RL, Schoene RB. Control of ventilation in elite synchronized swimmers. J Appl Physiol ; : –.  Ringqvist T. The ventilatory capacity in healthy subjects. An analysis of the causal factors with special reference to the respiratory forces. Scand J Clin Lab Invest (Suppl. ) ; : –.  Freedman S. Sustained maximum voluntary ventilation. Respiratory Physiol ; : –.  Hamilton AL, Killian KJ, Summers E, Jones NL. Muscle strength, symptom intensity, and exercise capacity in patients with cardiorespiratory disorders. Am J Respiratory Crit Care Med ; : –.

 Leblanc P, Summers E, Inman MD, Jones NL, Campbell EJM, Killian KJ. Inspiratory muscles during exercise. a problem of supply and demand. J Appl Physiol ; : –.  Pardy RL, Rivington RN, Despas PJ, Macklem PT. The effects of inspiratory muscle training on exercise performance in chronic airflow limitation. Am Rev Respiratory Dis ; : –.  Johnson BD, Reddan WG, Pegelow DF, Seow KC, Dempsey JA. Flow limitation and regulation of functional residual capacity during exercise in a physically active aging population. Am Rev Respiratory Dis ; : –.  Manning HL, Schwartzstein RM. Dyspnea and the control of breathing. In: Altose MD, Kawakami Y, eds. Control of Breathing in Health and Disease. New York: Marcel Dekker, Inc, : –.  Gandevia SC, Killian KJ, McKenzie DK, Crawford M, Allen GM, Gorman RB et al. Respiratory sensations, cardiovascular control, kinaesthesia and transcranial stimulation during paralysis in humans. J Physiol (Lond) ; : –.  Ekblom B, Åstrand P-O, Saltin B, Stenberg J, Wallström BM. Effect of training on circulatory response to exercise. J Appl Physiol ; : –.  Inbar O, Weiner P, Azgad Y, Rotstein A, Weinstein Y. Specific inspiratory muscle training in well-trained endurance athletes. Med Sci Sports Exerc ; : –.  Dempsey JA, Wagner PD. Exercise-induced arterial hypoxemia. J Appl Physiol ; : –.  Powers SK, Lawler J, Dempsey JA, Dodd S, Landry G. Effects of incomplete pulmonary gas exchange of V˙ 2 max. J Appl Physiol ; : –.  Prefaut C, Durand F, Mucci P, Caillaud C. Exerciseinduced arterial hypoxaemia in athletes. Sports Med ; : –.  Celsing F, Svedenhag J, Pihlstedt P, Ekblom B. Effect of anaemia and stepwise-induced polycythaemia on maximal aerobic power in individuals with high and low hemoglobin concentration. Acta Physiol Scand ; : –.  Saltin B, Nazar K, Costill DLE, Stein E, Jansson B, Essén Gollnick PD. The nature of the training response; peripheral and central adaptations to one-legged exercise. Acta Physiol Scand ; : –.  Bergh U, Kanstrup-Jensen I-L, Ekblom B. Maximal oxygen uptake during exercise with various combinations of arm and leg work. J Appl Physiol ; : –.  Åstrand P-O, Saltin B. Maximal oxygen uptake and heart rate in various types of maximal exercise. J Appl Physiol ; : –.  Stenberg J, Åstrand P-O, Ekblom B, Royce J, Saltin B. Hemodynamic response to work with different muscle groups, sitting and supine. J Appl Physiol ; : –.  Noakes TD. Challenging beliefs: ex Africa semper aliquid novi. Med Sci Sports Exerc ; : –.  Hollozy JO. Biochemical adaptations to exercise. Aerobic metabolism. Exerc Sport Sci Rev ; : –.

Cardiovascular and Respiratory Responses to Exercise  Saltin B, Henriksson J, Nygaard E, Andersen P. Fiber types and metabolic potentials of skeletal muscle in sedentary men and endurance runners. Ann New York Acad Sci ; : –.  Henriksson J, Reitman JS. Time course of changes in human skeletal muscle succinate dehydrogenase and cytochrome oxidase activities and maximal oxygen uptake with physical activity and inactivity. Acta Physiol Scand ; : –.  Örlander J, Kiessling KH, Ekblom B. Time course of adaptation to low intensity training in sedentary men: dissociation of central and local effects. Acta Physiol Scand ; : –.

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 Andersen P, Saltin B. Maximal perfusion of skeletal muscles in man. J Physiol (Lond) ; : –.  Rådegran G, Blomstrand E, Saltin B. Peak muscle perfusion and oxygen uptake in humans: importance of precise estimates of muscle mass. J Appl Physiol ; : – .  Hammond KK, White FC, Bhargava V, Shabetai R. Heart size and maximal cardiac output are limited by the pericardium. Am J Physiol ; : –.  Gerstenblith G, Lakatta EG, Wiesfelt ML. Age changed in myocardial function and exercise response. Prog Cardiovascular Dis ; : –.  Robinson BF et al. Circulation Res ; XIX: –.

Chapter 1.2 Metabolism during Exercise — Energy Expenditure and Hormonal Changes JAN HENRI KSSON & KE NT S AHL I N

Classical references Hohwü Christensen E, Hedman R, Holmdahl I. The influence of rest pauses on mechanical efficiency. Åstrand I, Åstrand P-O, Hohwü Christensen E, Hedman R. Intermittent muscular work. Åstrand I, Åstrand P-O, Hohwü Christensen E, Hedman R. Myohemoglobin as an oxygen-store in man. Acta Physiol Scand ; : –. In this series of three papers, the authors describe the energy expenditure and metabolism resulting from different application of work and rest periods while working on light and heavy workloads. The papers have had a large impact because they were the first, following the initial observations of Karrasch and Müller (Arbeitsphysiologie ; : –), to attract interest to the physiology and metabolism of intermittent work. In the first paper, data are given to support the fact that the energy cost per kJ of work is the same or practically the same whether the work is performed continuously for  h with an easy load or discontinuously with heavier loads. The results disputed the hypothesis of Müller and coworkers that pauses would significantly increase the oxygen demand for a subsequent work period. In the second paper, the authors showed that an extremely heavy workload, when split into short periods of work and rest, was transformed to a submaximal load on circulation and respiration. To explain the low lactate concentrations after intermittent work (work periods of – s), the authors proposed two alternative hypotheses: (i) that the rate of formation of lactic acid during a heavy workload is the same, independent



of the length of the work period, but that lactic acid during the short periods of rest is eliminated almost at the same rate; and (ii) that the formation of lactic acid during the short work periods is reduced to a minimum because it can take place almost aerobically. From the results in the third paper, the authors dismiss the first hypothesis and conclude that approximately . L O2 must have been available in the working muscles at the beginning of each new work period. It is proposed that this amount of oxygen is bound to myohemoglobin (myoglobin) in the muscles and is being ‘reloaded’ during the pauses to constitute approximately half of the amount of oxygen used during a -s work period.

Biochemical pathways of ATP generation Hydrolysis of ATP is the immediate energy source for almost all energy-requiring processes in the cell: ATP + H2O Æ ADP + Pi + energy

()

The store of ATP is limited and must therefore be continuously replenished. Regeneration of ATP occurs through aerobic and anaerobic processes by which energy-rich chemical substances (carbohydrates, fat and phosphocreatine) are transformed into compounds with less stored energy (lactate, H2O, CO2 and creatine). This is achieved by sequences of chemical reactions by which part of the change in free energy is used for the synthesis of ATP through a reversal of reaction (). The ATP–ADP cycle constitutes a basic feature of energy metabolism in all cells and is an intermediate between energy-utilizing and energyconsuming processes.

Metabolism during Exercise Skeletal muscle is a unique tissue in terms of the large variation in energy turnover. Transition from rest to exercise involves a drastic increase in energy demand and the rate of ATP utilization can increase more than  times. This corresponds to a utilization of the whole muscle store of ATP in about – s. To maintain a constant muscle ATP concentration, which is necessary for cellular homeostasis, the rate of ATP regeneration must equal the rate of ATP utilization. To meet the energy requirements skeletal muscle is faced with intricate problems related to supply of fuels and oxygen as well as control of the energetic processes. Adjustment of the rate of ATP regeneration to energy requirements is very precise and involves both feed-forward and feedback control mechanisms. A detailed discussion of the control of energy metabolism is outside the scope of this chapter and the reader is referred to other reviews or textbooks.

Aerobic processes of ATP generation The ultimate process of ATP formation is oxidative phosphorylation during which various substrates are oxidized with oxygen in the mitochondrion. The process is rather complex and will be described only briefly. The fuels for the aerobic processes are mainly pyruvate (derived from carbohydrates) and fatty acids (derived from triglycerides). These fuels are degraded by separate routes to acetyl-CoA within the mitochondrion. The acetyl group of acetyl-CoA is catabolized to CO2 in the TCA cycle (tricarboxylic acid cycle) by which electrons are transferred from the substrates to coenzymes (mainly NAD+). The electrons are transferred from the reduced coenzyme (NADH) to the electron transport chain with oxygen being the final electron acceptor. When electrons pass through the electron transport chain their energy level decreases and part of the energy is used to transfer protons through the mitochondrial membrane. When protons diffuse back through the membrane protein (ATP synthase) ADP is phosphorylated to ATP; the whole process is called oxidative phosphorylation. The efficiency of the aerobic processes in terms of oxygen, i.e. the amount of ATP produced per consumed oxygen (P/O2) is under debate. In textbooks, P/O2 ratio is often considered to be  when carbohydrate (CHO) is oxidized, whereas with free fatty acids (FFA) the P/O2 ratio is about % less. The lower yield of ATP per



oxygen consumed may contribute to the lower power of this process. In this chapter we have used a P/O2 ratio of  to estimate the power and capacity of oxidative phosphorylation. This is probably an overestimate since evidence exists that some of the proton gradient is dissipated by leakage of protons through the inner mitochondrial membrane[]. The extent of this leakage during exercise is uncertain. The efficiency in transforming stored chemical energy into work can be calculated from O2 utilization and performed work. The mechanical efficiency during cycling is about % when calculated from the exercise-induced increase in whole-body O2 uptake and about % when calculated from the O2 uptake by the leg muscles []. In contrast, during static contraction the mechanical efficiency is zero, since no external work is performed. Since more than % of the released energy is transformed to heat, the maintenance of a constant body temperature is a challenge for whole-body homeostasis during exercise.

Anaerobic processes of ATP generation Although the aerobic processes dominate during sustained exercise regeneration of ATP can also occur through anaerobic processes. Three different ATPgenerating anaerobic processes exist: Breakdown of PCr: ADP + PCr + H+ Æ ATP + creatine Glycolysis from glycogen: ADP +  Pi + glucosyl unit Æ ATP +  lactate + H+ ADP fusion: ADP + ADP Æ ATP + AMP

Breakdown of PCr PCr is a high-energy phosphate compound stored in muscle tissue at a concentration three times that of ATP. Creatine kinase (CK) is a highly active enzyme and catalyzes an equilibrium reaction: ADP + PCr + H+ ´ ATP + creatine

()

During exercise there is an increase in ADP, which by a mass action effect stimulates a shift of the reaction to the right (phosphorylation of ADP to ATP at the expense of PCr). During sustained exercise ADP remains elevated and PCr therefore remains low throughout the exercise period. The degree of PCr depletion at a steady state is related to the exercise intensity. PCr decreases even with low-intensity exercise. At

 Chapter . a work rate of % of V˙2max PCr is reduced to % of the initial level and at a work rate of % of V˙2max PCr is reduced to % of the initial level []. During recovery from exercise ADP decreases and the reaction is shifted back to the left. The half-time for PCr resynthesis is about  s and after – min recovery PCr is restored to the initial level. An overshoot in PCr above the pre-exercise level has been observed in fasttwitch muscle fibers after high-intensity exercise [] and in slow-twitch fibers after prolonged exercise at moderate intensity []. The mechanism for this overshoot is not known. The combination of reaction () (ATP hydrolysis) and () (PCr breakdown) results in increased levels of creatine and Pi. An increase in Pi is considered to interact with the contraction process and is a potential factor in fatigue (see below). After the original discovery by Harris et al.[] that supplementation with creatine can augment the muscle store of Cr and PCr by about % there has been great interest in exploring the role of creatine supplementation as an ergogenic aid. Many but not all studies have shown that creatine increases performance during high-intensity exercise especially when it is performed intermittently, whereas there is no documented effect during prolonged exercise. The mechanism for this ergogenic effect is probably related to an increased availability of high-energy phosphates (augmented store of PCr and increased rate of PCr resynthesis) []. Since breakdown of PCr involves uptake of protons the CK reaction has acid–base implications. At the onset of exercise when PCr breakdown is the dominant process an alkalinization of the order of . pH units has been observed, whereas during sustained high-intensity exercise the CK reaction is an important buffer process by which the acidosis incurred by lactate accumulation is counteracted. It has been estimated that the CK reaction accounts for about % of the total intracellular buffer capacity [].

Lactate formation During glycolysis muscle glycogen or blood-borne glucose are partially degraded to pyruvate or lactate in about  well-defined enzymatic steps. Glycolysis from glycogen results in a higher yield of ATP ( moles of ATP per mole of glucosyl unit) than glycolysis from glucose ( moles ATP per mole glucose). Glycolysis to

pyruvate precedes the aerobic combustion of CHO in the mitochondrion and is therefore named aerobic glycolysis. Pyruvate can be transferred to lactate, which is a dead-end metabolite. Glycolysis to lactate is named anaerobic glycolysis, since the process does not require oxygen. However, formation of lactate may also occur in the presence of oxygen. The mechanism of lactate formation during submaximal exercise has been extensively discussed over a number of years and remains a controversial issue. However, it is accepted that lactate is formed by a mass action effect through the near-equilibrium reaction catalyzed by lactate dehydrogenase (LDH) and that increases in pyruvate, NADH/NAD+ ratio or H+ are metabolic changes in the cytosol that will promote lactate formation. Activation of glycolysis in excess of pyruvate oxidation and NADH influx to mitochondria will cause cytosolic increases in pyruvate and NADH and will therefore also lead to lactate formation. Factors such as oxygen deficiency, increased recruitment of fast-twitch fibers and low aerobic training status of the muscle (i.e. low mitochondrial and capillary density) are likely to be of importance for this imbalance. Lactate formation is associated with release of protons and when lactate accumulates the tissue becomes acidotic. Since acidosis may interfere with both the energetic processes and the contraction process lactate formation has become a major interest in exercise physiology.

ADP fusion The adenine nucleotides (AN) are related to each other through an equilibrium reaction catalyzed by adenylate kinase. ADP + ADP ´ ATP + AMP

()

During conditions of energetic deficiency muscle ADP concentration increases and reaction () is shifted to the right. The AN pool can be degraded further through irreversible deamination of AMP to inosine monophosphate (IMP) and ammonia (NH3). AMP Æ IMP + NH3

()

Deamination of AMP enables a further shift of reaction () to the right. The combined effect of ATP hydrolysis, ADP fusion and AMP deamination will lead to a net decrease in the AN pool corresponding to an

Metabolism during Exercise

Not limited

100 75

100 mol ATP

mmol ATP/kg muscle/min

150

50



59

50 25

0 3 mol ATP/min

0.37

0.94

PCr

Lactate

2 1 0 PCr

Glycolysis

CHOox

FFAox

Fig. .. Power of the energy-yielding processes in human skeletal muscle. Power values are based on reported experimental values in humans under the following conditions: PCr breakdown: . s electrical stimulation []; glycolysis:  s cycling []; CHO oxidation: calculated from the following assumptions — O2 utilization by the leg muscles during two-leg · cycling is % of V 2 max ( L/min) [], working muscle mass  kg,  mol of ATP per mole of O2; FFA oxidation: assumed to be % of that of CHO oxidation (see text).

energy equivalent of  moles of ATP per mole of AN. However, the amount of ATP that can be derived by this process is limited (– mmol ATP/kg muscle or about –% of total anaerobic energy release) and is therefore usually neglected as an energetic process during exercise.

Power and capacity of energetic processes There are two inherent limits to the energetic processes: the maximum rate (power) and the amount (capacity) of ATP that can be produced. The power and capacity vary drastically between different energetic processes and will also vary between individuals. Peak values of power and capacity in humans, observed in experimental studies, are shown in Figs .. and ... Factors such as muscle mass, muscle fiber type composition, training status and nutritional factors

CHOox

FFAox

Fig. .. Capacity of the energy-yielding processes in human skeletal muscle. Capacity values have been derived from the following assumptions: the whole store of muscle PCr ( mmol/kg w.wt) is utilized; maximal muscle lactate · formation during exercise at % V 2 max is  mmol/kg w.wt including efflux to blood of %; muscle glycogen content of  mmol/kg w.wt; a working muscle of  kg. Amount of ATP that can be produced from oxidation of FFA is not limited; hence staple bar is cut off.

will be important determinants of the individual profile of power and capacity. The limitations of the energetic processes will set an upper limit for energy production and will consequently be a determinant of exercise capacity. The maximal intensity of the exercise is limited by the combined maximal power of the energetic processes. From the data in Fig. .. one can calculate that the combined power of PCr breakdown, glycolysis and CHO oxidation is . mol ATP/min of which anaerobic power contributes % or . mol ATP/min. Estimates of maximal power during a -s sprint, using a completely different approach (Fig. ..), give an ATP turnover of . mol/min. The difference is expected since the maximal power of oxidative phosphorylation can only be reached after some minutes of delay. Estimated maximal power of energetic processes is very similar to anaerobic energy utilization observed during  s of sprint cycling (. mol/min; recalculated by assuming  kg of active muscles) []. The duration of exercise is limited by the capacity of the recruited energetic processes. For instance with the data shown in Fig. .. oxidative combustion of the whole store of muscle glycogen would result in a total gain of  moles of ATP. During exercise at %

 Chapter .

ATP turnover (mol/min)

4

3

Aerobic Lactate ATP–PCr

2

1

0 Rest

Marathon

5000 m

Running speed:

5.5 m/s

6.4 m/s

Duration:

7610 s 780 s (2h, 7 min) (13 min)

400 m

100 m

9.2 m/s

10.2 m/s

43.5 s

9.8 s

V˙2 max ( L/min), maximal rate of CHO oxidation is . mol ATP/min (Fig. ..). Assuming that the whole energy demand is covered solely by oxidation of CHO the duration of exercise would be  min (/.). However, exercise at % V˙2 max is not limited by muscle glycogen level but by other factors such as accumulation of lactic acid and hence exercise is terminated after – min, long before muscle glycogen depletion. Experiments in humans have shown that exercise at % of V˙2 max results in glycogen depletion after about – min, coinciding with muscle fatigue, and is in a reasonable agreement with the estimates in Figs .. and ...

Breakdown of PCr Breakdown of PCr is the energy source that can sustain the highest rate of ATP production. The maximum rate of PCr breakdown presented in Fig. .. ( mmol ATP/kg muscle/min) was observed during short-term (. s) electrical stimulation of the quadriceps femoris muscle during isometric conditions []. The maximum value is close to Vmax of myosin ATPase activity measured in vitro. It is therefore possible that power during the first few seconds of exercise is limited by the ability to utilize ATP rather than by the rate of ATP regeneration. The amount of energy that can be produced from PCr is limited by the amount of PCr stored. In human skeletal muscle the concentration of PCr is about

Fig. .. ATP turnover at rest and during maximal running of different distances. ATP turnover over  m has · been estimated from an assumed V 2 max of  L/min and  mol of ATP per O2. ATP turnover over other distances has been estimated from the speed of running (assuming that mechanical efficiency remains constant) and the energy required to accelerate to this speed (assumed efficiency of %). Relative recruitment of aerobic processes is from Newsholme et al. []. Relative contributions of ATP-PCr and lactate to energy turnover: -m values are from  s cycling [];  and  m anaerobic ATP formation has been assumed to be limited by the capacity shown in Fig. ...

 mmol/kg w.wt with about a % higher concentration in fast-twitch fibers than in slow-twitch fibers. With the maximal rate of PCr breakdown shown in Fig. .. complete depletion of the PCr store within about  s would be expected. However contribution of ATP from other energy sources and decreased energy expenditure (fatigue) will prolong this time. From thermodynamic considerations the maximal rate of PCr breakdown would be expected to decrease when the PCr content of the muscle decreases. Availability of PCr may therefore be a limiting factor of power output even before the muscle content of PCr is totally depleted. It is well established that due to its high power and rapid recruitment PCr breakdown is an important energy source during high-intensity exercise and at the onset of exercise. However, there is evidence that the CK reaction also has a role in aerobic metabolism. CK is located both in the intermembrane space of the mitochondria (CKmit) and at sites of ATP utilization in the cytosol. During exercise PCr will regenerate ATP at the site of ATP utilization and creatine will diffuse to mitochondria. PCr is then regenerated by CKmit and diffuses back to the sites of ATP utilization. Through the action of this creatine shuttle the concentration of ADP in the vicinity of mitochondria will be high and oxidative phosphorylation will be stimulated. Experiments with permeabilized fibers have shown that creatine is an important activator of mitochondrial

Metabolism during Exercise respiration in cardiac tissue and slow-twitch fibers of skeletal muscle [], and recently creatine supplementation was shown to enhance aerobic metabolism during low-intensity exercise in humans [].

Glycolysis The maximum power of glycolysis in human muscle ( mmol ATP/kg muscle/min, Fig. ..) was obtained from a study of maximal cycling over  s []. Glycogen is the major source of lactate, since the rate of glycolysis of blood-borne glucose is much slower than that of glycogen. The rate of glucose utilization is limited by muscle glucose uptake and by inhibition of glucose phosphorylation by hexose phosphates. During high-intensity exercise muscle glucose uptake increases but increases in hexose phosphates will limit utilization of glucose, which will accumulate in the working muscle []. Intense exercise results in a massive increase in lactate concentration both in muscle tissue and in blood. During cycling to fatigue at % of V˙2 max muscle lactate increased more than -fold (to  mmol/kg w. wt) and muscle pH decreased from . at rest to . at fatigue []. Part of the formed lactate is exported to blood, (about % of total lactate production during this type of exercise []), resulting in increased lactate and decreased pH in blood. The main control of glycogenolysis and glycolysis is exerted by glycogen phosphorylase and phosphofructokinase (PFK), respectively. These enzymes catalyze non-equilibrium reactions and exhibit a complex and diverse mode of control []. The Vmax of glycogen phosphorylase and PFK is close to the observed maximum rate of glycolysis in vivo (for references see Connett & Sahlin []) and may therefore determine the limit of maximum glycolytic power. The activities of PFK and glycogen phosphorylase are reduced by acidosis. The product of glycolysis (lactic acid) can therefore reduce the rate of glycolysis through feedback inhibition and may be regarded as a safety mechanism, by which cellular damage due to excessive lactic acid accumulation is prevented. Both the power and the capacity of glycolysis (i.e. amount of produced lactate) may therefore be limited by product accumulation (i.e. H+). Factors such as muscle buffering capacity and export of lactic acid are likely to modulate the response.



Aerobic processes During two-leg exercise, muscle O2 utilization may increase -fold and with a V˙2 max of  L/min the rate of ATP generation (assuming a P/O2 ratio of ) will be  mmol/kg muscle/min (Fig. ..). It is generally agreed that the major determinant of whole-body maximal aerobic power (V˙2 max) is cardiac output, which sets an upper limit on O2 delivery. It has been estimated that exercise with a muscle mass of  kg is sufficient to tax the maximal cardiac output in a sedentary subject []. The maximal aerobic power of the muscle tissue is therefore not utilized during two-leg exercise where the working muscle mass is about  kg or more. However, during exercise with small muscle groups the rate of aerobic energy production may be limited by peripheral factors (e.g. mitochondrial density or O2 diffusion). During one-leg knee extension the estimated working muscle mass is only about  kg and measured O2 utilization can increase -fold (to  mL/min/kg muscle []). This corresponds to a power of  mmol ATP/kg muscle/min, which is % of the maximum power of glycolysis. Several lines of evidence suggest that oxidation of fatty acids cannot proceed at the same rate as for carbohydrate (CHO) oxidation. First, it has been shown that isolated mitochondria have a lower maximal rate of respiration and at a given energy state (ATP/ADP ratio) a lower submaximal rate of respiration with palmitate compared with pyruvate []. Secondly, it is known that ultradistance running, which results in a depletion of the body storage of carbohydrates and a switch to fat oxidation [], causes a decline in the power output to about % of V˙2 max. The reason for the lower rate of aerobic ATP formation from fat is under debate. Oxidation of FFA provides an approximately % lower yield of ATP per consumed oxygen compared with CHO and will be one significant factor. Combustion of fatty acids may also be limited by the rate of acetyl-CoA formation where one or several links in the chain may limit the process (fuel transport from the fat depots into the muscle fiber; transport of FFA into mitochondria; rate of b-oxidation). In addition, it has long been recognized that CHO availability may be necessary for optimal function of aerobic energy transduction: ‘fat burns in the glow of carbohydrates’ (Albert Szent-Györgyi). The basis for this may be that the function of the tricarboxylic acid (TCA)

 Chapter . cycle depends on pyruvate-dependent anaplerosis (expansion of TCA cycle intermediates). This hypothesis is supported by the finding that (i) prolonged exercise results in glycogen depletion and reduced levels of TCA cycle intermediates [] and (ii) TCA cycle intermediates remained low in McArdle patients where glycogen utilization is blocked []. However, the hypothesis that the level of TCA cycle intermediates may limit maximal TCA cycle flux has recently been questioned []. During prolonged one-legged knee extension exercise it was shown that TCA cycle intermediates decreased but that TCA cycle flux was maintained and PCr increased, and this was considered inconsistent with the hypothesis []. The CHO stores limit the amount of energy that can be produced by CHO oxidation. Cycling or running at intensities of between  and % of V˙2 max can normally proceed for – h before exhaustion and coincide with depletion of the glycogen store in the working muscle. During exercise at low intensities the energy demand is low and can be met by fat oxidation. Since fat is present abundantly the capacity of fat oxidation is very large and metabolic factors will not limit exercise duration.

Influence of muscle mass on power and capacity of whole-body energy production The power of anaerobic energy production appears to be limited by the activities of key enzymes such as myosin ATPase, creatine kinase and PFK. On a wholebody level an increased working muscle mass will result in a proportional increase in the total enzyme activities and therefore an increased anaerobic energy production ability. However, aerobic power is largely limited by cardiac output and will not therefore be influenced by the working muscle mass. The capacity of both aerobic and anaerobic energy production is limited by intrinsic muscular factors such as amount of glycogen, amount of PCr, and the volume available to distribute inhibitory metabolic end-products. An increased working muscle mass will increase the total available amount of glycogen and PCr and will therefore increase the amount of energy that can be produced by these processes. An increased working muscle mass, achieved either by training-induced hypertrophy or by increased recruitment of fasttwitch muscle fibers, will therefore be of advantage

during high-intensity exercise, since both power and capacity of anaerobic processes increase. However, during endurance running an increased muscle mass will be of disadvantage since energy expenditure will increase due to the increase in body weight. The difference in body composition between sprinters and endurance runners is an obvious sign of this basic concept.

Energetics during exercise Estimated whole-body ATP turnover increases from about . mol ATP/min at rest to – mol ATP/min during running. The ATP turnover during  m running is  times higher than that during marathon running, whereas ATP turnover during the  m is only % higher than that during a marathon. The difference in energy demand is reflected by a large difference in the energetic processes used. A mixture of the described energetic processes is normally used but the relative contribution varies considerably. The intensity of exercise is an important factor in determining the relative recruitment of the energy processes. Another factor is the time taken to activate an energetic process. PCr breakdown is instantaneous and is therefore considered to buffer the ATP level both temporally and spatially within the cell. Therefore the first few seconds of exercise always involve PCr utilization. Although most reports demonstrate that glycolysis contributes to ATP generation from the onset of exercise there appears to be a lag of a couple of seconds before maximum rate of glycolysis is achieved []. Aerobic processes reach maximal power (V˙2 max) after – min. The delayed onset of aerobic metabolism is the basis for the incurred O2 deficit during steady-state exercise. In addition to exercise intensity and duration of exercise other factors such as availability of oxygen and fuels, environmental factors and hormonal changes will modify the extent to which the energetic processes are recruited. In Fig. .. the ATP turnover and the estimated contribution of various energetic processes during different running events are shown. The figure does not discriminate between different phases of the exercise (onset of exercise, middle of exercise and spurt) during which both ATP turnover and recruitment will differ from the average values shown. The energetic challenge during exercise will be dif-

Metabolism during Exercise ferent during different running distances. Over  m the time is too short for recruitment of aerobic processes and the muscles rely almost solely on anaerobic processes, which also have the high power required to meet the energy demand. At the end of  m running, muscle PCr will be reduced to about % of the initial level [] and will reduce the power of this energy process. Muscle lactate will accumulate and reach about % of maximal values [] and muscle pH will decrease. Energetic power will for these reasons be reduced and this may explain why speed often decreases at the end of  m. Over  m, the required power exceeds that of the aerobic processes and the duration is too short to reach maximal rates of oxidative energy production. The capacity of the anaerobic processes is insufficient to cover the whole energy demand during  m. The challenge is to maximize the aerobic contribution but to avoid too high a lactate concentration early in the race, which could otherwise impair energetic processes and reduce mechanical efficiency. This metabolic strategy is achieved by a rapid acceleration of speed (which will accelerate oxidative energy release), submaximal running during the middle of the race and a maximal spurt. When the distance is completed the whole energetic capacity of both PCr breakdown and glycolysis should have been used. Normally, the speed decreases at the end of the distance and this is probably related to a reduced power of anaerobic energy release. Over  m, oxidative processes are sufficient to cover the energy requirements. During the race utilization of aerobic processes should be maximized without accumulation of inhibiting amounts of lactate. The high power of anaerobic processes should be saved for the spurt. At the end of the race muscle lactate levels will be high and PCr depleted but due to the high total energy expenditure the relative contribution of anaerobic processes will be low (about %). During the marathon CHO stores are insufficient to cover the energy demand and at the same time the power of FFA oxidation is insufficient. The strategy is to: (i) maximize the CHO stores prior to exercise by CHO loading; (ii) avoid lactate formation since this would rapidly deplete the CHO stores; and (iii) optimize oxidation of FFA. Ideally the glycogen stores should be depleted at the end of the race.



Muscle fatigue and metabolism The cause of muscle fatigue (i.e. inability to maintain a defined exercise intensity) is considered to be multifactorial. The classic hypothesis is that muscle fatigue is caused by failure of the energetic processes to generate ATP at a sufficient rate. The evidence for this hypothesis is that interventions which increase the power (i.e. aerobic training, hyperoxia, blood doping) or capacity (i.e. CHO loading, creatine supplementation, glucose supplementation) of the energetic processes result in increased performance and delayed onset of fatigue. Similarly, factors that impair the energetic processes (i.e. depletion of muscle glycogen, intracellular acidosis, hypoxic conditions, reduced muscle blood flow) have a negative influence on performance. The evidence is, however, circ*mstantial and a direct cause and effect relationship remains to be established. It has been argued that since muscle ATP remains almost unchanged during exhaustive exercise it is unlikely that energetic failure is a cause of fatigue. This line of argument may, however, be too simplistic since temporal and spatial gradients of adenine nucleotides may exist in the contracting muscle. Furthermore, the mechanism may be related to increases in the products of ATP hydrolysis (i.e. ADP, AMP or Pi) rather than to decreases in ATP per se. A small decrease in ATP will cause large relative increases in ADP and AMP, due to much lower concentrations of these compounds. Muscle fatigue is generally associated with increased catabolism of adenine nucleotides, which signifies a condition of energetic stress []. This lends further support to the hypothesis that muscle fatigue under many conditions is caused by energetic deficiency. Decrease in PCr is another hallmark of energetic deficiency and is paralleled by a similar increase in Pi. There is evidence that increases in Pi will interfere with the contraction process and it is considered to be one of the major factors for the decrease in force []. Metabolic factors are likely to play an important role in fatigue and performance during exercise but there is no doubt that conditions exist where fatigue cannot be explained by metabolic changes. Considering the diversity and complexity of exercise this is to be expected.

 Chapter . Energy expenditure and metabolism Energy expenditure during exercise Energy expenditure during exercise varies over a large range. From a basal metabolic rate (BMR) of approximately – kJ/h in men and – kJ/h in women energy expenditure may increase to –  kJ/h during heavy exercise. Assuming a mechanical efficiency of around %, this permits  kJ/h of work to be performed []. During a -s bout of exercise more than  kJ of work may be performed by a highly trained athlete and during a -min bout  kJ []. The total energy expenditure (TEE) of an adult person averages  –  kJ/ h. Individuals with physically very demanding occupations may reach values of  –  kJ/ h. The TEE is made up of three components: the BMR, the dietaryinduced thermogenesis (DIT) and the activitydependent energy expenditure (Table ..). The BMR is normally the largest component of TEE, averaging – kJ/ h in men and – kJ/  h in women. The DIT, which is defined as the extra energy consumption resulting from a meal, normally accounts for one tenth of the TEE. DIT is largest after a protein meal, where it amounts to –% of the energy contained in the meal, but considerably smaller for meals containing carbohydrates (–%) and fat (–%) []. The remaining part of the TEE is the activity-dependent energy expenditure (AEE), which can be calculated based on the . and . kJ of energy released for each liter of oxygen consumed during fat and carbohydrate oxidation, respectively (for further discussion, see below). When the oxygen uptake is unknown, different approximations are often used to assess the activity-dependent energy consumption, e.g. quiet sitting corresponding to an energy consumption of about . ¥ BMR, office work .– . ¥ BMR, standing . ¥ BMR, cycling – ¥ BMR and various sports activities of the order of – ¥ BMR (Table ..) []. The energy cost of running is independent of running speed and of the order of  kJ/km/kg body weight. For walking at a pace of .–  km/h, the corresponding figure is  kJ/km/kg: body weight []. This means, for example, that the energy content of  g fat ( kJ) for a -kg person covers the energy demand of running approximately  km or

Table .. Energy expenditure in adult men and women, given as the total energy expenditure/ h as a multiple of BMR (equal to the physical activity level, PAL). Data from []. BMR = basal metabolic rate (kJ/24 h) DIT = diet-induced thermogenesis (kJ/24 h) AEE = activity-induced energy expenditure (kJ/24 h) TEE = total energy expenditure = BMR + DIT + AEE PAL = physical activity level (includes DIT) = TEE/BMR BMR

18–29 years

30–39 years

40–64 years

Males Females

7500 6200

8200 6000

7000 5800

PAL over 24 h with different living conditions Chair- or bedbound Seated work, low leisure time activity Seated work with moving around, low leisure time activity Standing work, low leisure time activity Strenuous leisure time activity (30–60 min, ≥ 4 times/week) Strenuous work or high activity in leisure time

1.2 1.4–1.5 1.6–1.7 1.8–1.9* +0.3† 2.0–2.4‡

* For example, 8 h sleeping (0.95), 4 h sitting (1.2), 12 h walking around (2.5). † Up to a maximal value of 2.0. ‡ 2.4 is considered to be the highest PAL that can be tolerated other than for short periods of e.g. very intensive training.

walking  km. It is evident that complex nervous and hormonal regulation is required in order to control the utilization of the different energy substrates during exercise with large variations in energy demand.

Exercise metabolism Exercise metabolism is focused on the utilization of biologic energy in order to perform work. Biologic energy is found in the oxidizable substrates in the body, namely glucose, free fatty acids and amino acids, and also lactate and glycerol (and under some circ*mstances ethanol and ketone bodies). In addition to aerobic oxidation, energy is released during the anaerobic degradation of glycogen to lactate. This is the major energy source in some cells and tissues devoid of mitochondria, such as the red blood cells and the kidney tubules, and also in skeletal muscle during short-term, high-intensity exercise. An important issue in metabolic regulation at rest and during exercise is that,

Metabolism during Exercise under non-starving conditions, the central nervous system (as well as the red blood cells and the kidney tubules) is limited to the use of glucose as the sole energy substrate. The supply of glucose to these tissues is therefore highly prioritized. The skeletal muscle cells store energy in the form of glycogen, triglycerides, ATP and phosphocreatine (PCr). Biologic energy can also be delivered to the muscle in the form of bloodborne energy substrates directly originating from the alimentary tract following a meal or, between meals, in the form of blood-borne substrates released from the storage organs, mainly the liver and the adipose tissue. In the previous part of this chapter, a detailed description was given of the biochemical pathways involved in these processes. The energy expenditure during exercise originates from aerobic and anaerobic biochemical processes. The energy expenditure originating from the aerobic combustion of nutrients can be determined with great precision by measuring the oxygen uptake of an individual. Each liter of oxygen consumed corresponds to the release of .–. kJ of energy, depending on the relative proportions of carbohydrates or fat being oxidized. These proportions can be determined from the respiratory quotient (RQ, the ratio between the amount of CO2 exhaled and the amount of O2 taken up). The energy expenditure originating from the anaerobic processes, i.e. glycogen degradation to lactic acid and breakdown of PCr and ATP, can, on the other hand, only be roughly estimated (e.g. based on measurement of the total work performed with subtraction of the aerobic energy delivery). While maximal aerobic power can reach  kJ/min in endurance ath-



letes, athletes in events of – min duration can reach a maximal total anaerobic energy release of  kJ. For an untrained person, aerobic power may reach  kJ/min and maximal total anaerobic energy release  kJ, the former value being limited by the capacity of the heart to eject oxygenated blood into the arterial system and the latter by the total muscle mass that can be recruited in the specific exercise []. During maximal work, anaerobic processes dominate when exercise durations are less than approximately  min, with longer exercise durations aerobic processes will yield the majority of the energy delivery.

Energy sources at rest and during exercise Energy sources at rest At rest, under postabsorptive conditions, fatty acids constitute the primary energy source, accounting for approximately % of energy requirements, leaving about % for carbohydrates and proteins, respectively. Postabsorptive conditions are said to be present when no nutrients are entering the blood from the intestinal tract. The energy liberated per gram of nutrient combusted is  kJ for carbohydrates and proteins and  kJ for fat. Therefore, the demand for fat combustion at rest can be covered by the adipose tissue liberating  g of fatty acids per hour, of which . g is taken up by the liver and  g by skeletal muscle. The carbohydrates are provided by the liver, which releases . g/h of glucose, of which . g is derived from glycogenolysis and  g from gluconeogenesis. This covers mainly the  g/h of glucose which is used

Table .. Typical changes in energy source (g/h) when an individual exercises at successively higher intensity (postabsorptive state) [,].

Glucose, from liver store Glucose, from liver glucose neoformation Glucose, from muscle store Fat, from adipose tissue or muscle

Rest

Exercise 100 W

Exercise 200 W

Exercise 250 W

4.5 3 – 5

16 4 40–45 18

25 5 100 26

40 5 150 22

Values are given in g/h and refer to the postabsorptive state. Exercise metabolism during the absorptive state will vary with meal composition and the time following the meal. Generally, however, more energy will be derived from the blood (glucose, fatty acids, triglycerides) and less from the substrate stores in skeletal muscle and adipose tissue.

 Chapter . by the central nervous system and the red blood cells. Liver glycogenolysis is made possible by the liver store of glycogen (about  g in the fed state), whereas substrates for gluconeogenesis are lactate, glycerol and amino acids taken up by the liver from the blood. The amino acids used for gluconeogenesis derive mainly from net proteolysis in skeletal muscle, which releases around . g amino acids/h. The latter also constitute an important energy substrate for the intestines and the liver []. Absorptive conditions prevail for several hours following each meal, with most nutrients being taken up by the body during the first – h. If it is assumed that the main absorption phase takes place during the first . hours following each meal, with three meals a day, absorptive conditions will prevail for . h/ h, whereas the body during the remaining . h per day is closer to a postabsorptive state. In the absorptive state, the metabolic situation is different in that now carbohydrate oxidation dominates, normally covering three-quarters of total substrate oxidation, while the substrate stores of the body are refilled rather than used. If   kJ/ h is covered by three meals of  kJ each, containing % carbohydrates, % fat and % protein,  g glucose,  g fatty acids and  g amino acids will be made available to the body during the absorptive period after each meal. Due to the shift from predominantly fat to predominantly carbohydrate oxidation during this period, around  g of the  g of carbohydrates taken up by the body will be oxidized, whereas the remaining  g will be used to refill the liver glycogen store ( g) and the glycogen store in skeletal muscles (– g during nonglycogen-depleted conditions) []. The  g of fatty acids from each meal enters the blood in the form of a special lipoprotein, the chylomicron. The chylomicron triglycerides (TGs) are degraded by the enzyme lipoprotein lipase (LPL), which is localized in capillary endothelial cells in most organs of the body, but with especially high levels in adipose tissue, myocardium and skeletal muscles. The fate of the enzymeliberated fatty acids is mainly storage in adipose tissue, but also uptake in liver and skeletal muscle []. In muscle tissue the fatty acids are oxidized and/or used for the restoration of muscle TG stores reduced by exercise []. In the liver, the chylomicron remnants are taken up and fatty acids resynthesized to triglycerides, which are incorporated into very low density lipopro-

tein, exported and finally also stored in adipose tissue. The  g amino acids from each meal are added to the – g of amino acids being formed per  h mainly from the degradation of protein stores of skeletal muscle and liver. Of these amino acids, – g are used for synthesis and approximately  g are used for oxidation in the intestines and the liver [].

Energy sources during exercise in the postabsorptive state During exercise, the energy consumption may be increased by -fold. The primary factor determining whether carbohydrates or fat are preferentially used during exercise is the exercise intensity, the proportion of energy derived from carbohydrates growing progressively larger with increasing intensity. At a moderate exercise level of  W, demanding an oxygen uptake of around . L/min, equalling an energy expenditure of  kJ/h, the proportions might typically change to % carbohydrates and % fat. In this situation, the demand for carbohydrates ( g glucose/h, i.e.  kJ) is met by glycogenolysis (around – g/h) and glucose uptake (around  g/h), whereas the demand for fat is met by lipolysis in adipose tissue and muscle, supplying  g fatty acids (i.e.  kJ). Under normal circ*mstances, protein is not an important metabolic fuel during exercise, and it is considered unlikely that, even during prolonged exercise, protein oxidation can cover more than % of the energy demand of the exercising body []. In spite of this, activation of protein metabolism is an integral part of the acute metabolic response of the body to exercise []. To roughly estimate the RQ during exercise and therefore the relative demand for carbohydrates and fat, Dill and coworkers used an equation, empirically derived from their data: Respiratory quotient during exercise = . + . · oxygen uptake in L/min []. Although obviously not generally applicable, the equation can be used here to illustrate the increasing demand for carbohydrates at increasing exercise intensities. When the exercise intensity is increased to  W (oxygen uptake = . L/min), this formula indicates an RQ value of . (indicating % carbohydrate and % fat oxidation). This corresponds to a combustion of  g carbohydrates and  g fatty acids.

Metabolism during Exercise Similarly, exercise at  W can be calculated to demand combustion of  g carbohydrates and  g fatty acids. It is therefore evident that fat combustion will level off with increasing exercise intensities, when simultaneously carbohydrate oxidation, as well as hepatic and muscular glycogenolysis and muscle glucose uptake, increases exponentially (above the ‘lactate threshold’). When exercise is prolonged, fat combustion increases. This change is most likely secondary to a continuing depletion of the body’s carbohydrate stores. During prolonged exercise at % of V˙2 max in overnight fasted untrained subjects, plasma free fatty acids contributed to % of the fuel demand during the fourth hour of exercise compared to only % during the first hour []. Asmussen and Christensen describe two subjects being able to work at intensities demanding oxygen uptakes of . and . L/min (– W) for  h []. During the first hour, the subjects combusted  g carbohydrates and  g fatty acids; during the third hour the corresponding figures were  g carbohydrates and  g fatty acids. Endogenous glycogen is the dominant fuel during the initial period of moderate to severe exercise, and during sustained exercise at work rates corresponding to –% of V˙2 max, fatigue coincides with the depletion of muscle glycogen [,]. With the continuous depletion of endogenous glycogen, the utilization of plasma-derived glucose increases and has, during prolonged exercise, been reported to cover up to –% of the estimated carbohydrate oxidation by muscle []. The increased glucose uptake by skeletal muscle during heavy exercise must be balanced by a glucose release from the liver of the same magnitude. Because there are only limited possibilities for increasing gluconeogenesis in liver (from  to  g/h [], mainly secondary to increased availability of glycerol due to the increased lipolysis in adipose tissue), the majority of the increased glucose output from the liver has to be derived from glycogenolysis. With liver glycogenolytic rates of  g/h during heavy and  g/h during very heavy exercise, the liver glycogen supply of around  g will be rapidly depleted. However, fatigue due to hypoglycemia can be postponed by the ingestion of glucose. Although it may be difficult to ingest large amounts of glucose during exercise, it has been reported that as much as  g/h of ingested glucose may be taken up by the body [] during heavy exer-



cise of long duration. It has been observed that the total amount of carbohydrate used during a marathon race was higher than could be accounted for by the endogenous glycogen stores in the working muscles and the liver. From this, it was concluded that glycogen reserves in inactive muscle and other tissues must also have been mobilized []. Glycogenolysis with net lactate release from inactive muscle has been demonstrated during exercise []. Relatively little is known about endogenous triglycerides as a potential source of energy for the contracting muscle, but it seems likely to be an important fuel during exercise. During . h of cycle ergometer exercise to exhaustion, it was found that the decrease in thigh muscle triglyceride concentration averaged % []. The authors calculated that % of total oxidized fatty acids originated from endogenous triglycerides, whereas % came from plasma-derived free fatty acids, and that the energy contribution of endogenous triglycerides was % of that of glycogen. During the Swedish -h Wasa ski race, it was calculated that the decrease in muscle triglycerides corresponded to twice as much energy as the decrease in muscle glycogen []. See also the data by Hurley et al. [], which are discussed in the section on training below.

Energy sources during exercise in the absorptive state When exercise is performed in the absorptive state, less energy will be derived from the substrate stores in skeletal muscle and adipose tissue, and more from glucose, fatty acids and triglycerides in blood, although plasma free fatty acids will be less important as an energy fuel than in the postabsorptive state []. In an experimental study, metabolism during  min of forearm exercise after an overnight fast was compared with the same exercise  h following a meal []. In the postabsorptive state, the exercise was fueled by glucose uptake from blood (%) and by intramuscular depots (%). Following the meal, the contribution to exercise metabolism from plasma glucose was similar to that in the postabsorptive state, but the muscular uptake of plasma triglycerides was markedly increased and, if oxidized, could cover around % of the energy demand. This indicates that, following a meal, the contribution of plasma triglycerides to exercise metabolism may be considerably higher than previously realized. Due to the high blood flow during exercise,

 Chapter . arteriovenous differences for VLDL-triglycerides (VLDL-TG) are very difficult to detect accurately, but it has been estimated that, if oxidized, plasma triacylglycerol could cover half of muscle triacylglycerol oxidation during exercise []. However, their slow turnover argues against VLDL-TG as an important fuel for the working muscle. It is likely that muscle lipoprotein lipase may be more active towards chylomicron-TG than VLDL-TG [] and the idea that chylomicron-TG may serve as a fuel for the exercising muscle is further suggested by the fact that postprandial lipidemia is diminished during and after exercise []. There is evidence that physical training, by increasing skeletal muscle lipoprotein lipase activity, while reducing that of adipose tissue, causes a redirection of circulating lipid from storage in adipose tissue to oxidation in muscle.

Energy sources during exercise in the trained state One factor counteracting the low fat combustion at high exercise intensities is the effect of training. It has been convincingly shown that, at a certain exercise intensity, a trained individual uses more fat than an untrained individual. This effect is quite strong and occurs after relatively short periods of training. One group of subjects was studied after  and  days of training for  h daily at a moderately high exercise intensity (% of the pretraining V˙2 max) []. Following  days of training, the total fat oxidation at this intensity had increased by % and after  days of training, the increase was as high as %. The oxidation of carbohydrates during the exercise bout showed the opposite pattern. It is therefore obvious that a good physical fitness level makes it much easier to maintain a high degree of fat combustion during intense exercise []. The source of the increased fat usage during exercise in endurance-trained subjects has been debated, however, since the plasma levels of free fatty acids during exercise are often lower than in untrained individuals []. This is likely to be secondary to the lower sympathoadrenal activation after training [] which, unopposed, would lead to decreased lipolysis of not only adipose tissue, but also intramuscular triglycerides. When male subjects exercised at the same absolute intensity (% of the pretraining V˙2 max)

before and after a -week programme of endurance training, plasma free fatty acid and glycerol concentrations were found to be lower in the trained than in the untrained state []. In spite of this, the respiratory exchange ratio was reduced after training, indicating a greater reliance on fat oxidation. Muscle triglyceride utilization was found to be twice as great and muscle glycogen utilization to be % lower after, as opposed to before, training. It was concluded that the greater utilization of fat in the trained than in the untrained state was fueled by increased lipolysis of intramuscular triglycerides. This conclusion was supported by a study showing a lower turnover of plasma free fatty acids in the trained state []. In fact, Jansson and Kaijser [] also concluded that the reduced reliance on carbohydrate metabolism in their trained, as compared to their untrained, individuals would have been covered by intramuscular triglycerides. They based this conclusion on the finding of no difference between trained and untrained individuals in the ratio of plasma free fatty acid extraction to O2 extraction by the working legs. It is known that increased fat oxidation with training is a local effect since after one-leg training it occurs in the trained leg only [,]. Underlying this training response is an increased mitochondrial density and an increased content of mitochondrial enzymes in aerobically trained muscle, accompanied by increases in the enzymes involved in activation, transfer into the mitochondria and b-oxidation of fatty acids [–]. Holloszy and coworkers have formulated a hypothetical biochemical mechanism whereby a large concentration of mitochondrial oxidative enzymes in trained muscle would lead to a greater reliance on fat metabolism, a lower rate of lactate formation and sparing of muscle glycogen during exercise []. These adaptations in trained skeletal muscle would, at a given exercise intensity, permit the rate of fatty acid oxidation to be higher in the trained than in the untrained muscle, even in the presence of a lower intracellular fatty acid concentration in the trained state.

Exercise and weight regulation Effect of exercise on body weight Weight balance implies that food intake equals food oxidation and most probably also that the oxidation

Metabolism during Exercise of carbohydrates, fat and protein equals the intake of these nutrients. It has therefore been concluded that the quotient between the intake of carbohydrates and fat (described as the food quotient, FQ, i.e. the ratio of carbon dioxide produced to oxygen utilized for the oxidation of the food) over the long term must equal the average RQ over  h (RQ- h) for the individual to maintain weight balance [,]. Most individuals are in weight balance, where their weight only fluctuates by –%. If unusually little food is taken in on a particular day, the RQ will be lowered due to inhibition of glucose oxidation, and fat oxidation will be increased to cover the negative energy balance. Conversely, if more food than usual is taken in during one day, carbohydrate oxidation will be increased (and fat consumption passively decreased to achieve energy balance that day) []. Thus, if the intake decreases it will be covered by stored fat; thereafter all of the lost fat is replenished due to an increased carbohydrate oxidation with high intakes. There seems to be no direct regulatory mechanism whereby fat oxidation is increased with a higher fat intake. However if, over the long term, fat intake is increased, fat oxidation must also be increased in order to achieve weight balance. This may be achieved by expansion of the adipose tissue mass, which increases fat oxidation more than carbohydrate oxidation. However, an increase in  h fat oxidation (i.e. decrease in RQ- h) may also be achieved by exercise []. Therefore, exercise allows weight maintenance to be achieved with less body fat in physically active individuals, where exercise substitutes for an enlarged fat mass in bringing about rates of fat oxidation corresponding with fat intake. This is one conceivable mechanism by which regular exercise tends to keep the fat depots down []. In a meta-analysis by Ballor and Keesey [] based on  scientific studies, it was reported that training reduces the fat mass on average by . kg per week, and to the same extent in men and women.

Hormonal mechanisms at rest and during exercise Hormonal regulation of resting metabolism At rest, insulin and glucagon are the major hormones regulating whether energy fuels are liberated from the storage sites or, conversely, channelled for storage. In



the postabsorptive state, the insulin/glucagon concentration ratio is around , which allows a normal hepatic release of glucose into the blood. Following a carbohydrate-containing meal insulin increases substantially, which in concert with a slight decrease in glucagon concentration causes the insulin/glucagon ratio to increase by more than -fold. This increase is necessary in order to direct glucose for storage in skeletal muscle and liver. With a carbohydratepoor meal, the rise in insulin will be small, whereas plasma glucagon concentration clearly increases. The resulting decrease in the insulin/glucagon ratio serves to maintain a sufficient hepatic release of glucose in order to cover the needs of the central nervous system and erythrocytes in spite of a carbohydrate-poor meal [] (Fig. ..). Insulin stimulates glycogen synthesis in the liver and also promotes liver glucose uptake, but only at an elevated portal vein glucose concentration. Glycogen synthesis in the liver is also directly stimulated by increased vagal nerve activity. Glucagon, on the other hand, stimulates hepatic glycogenolysis as well as lipolysis in adipose tissue. In addition, glucagon stimulates the liver capacity for gluconeogenesis. The effect of glucagon on adipose tissue lipolysis is, however, secondary to the more powerful stimulation by the sympathetic nervous system, cortisol and growth hormone. Several other factors may stimulate hepatic glycogenolysis, including a- and b-adrenergic stimulation and vasoactive intestinal polypeptide, whereas hepatic gluconeogenesis is stimulated by increased precursor (lactate, pyruvate, amino acids, glycerol) availability, secondary to skeletal muscle glycolysis, skeletal muscle proteolysis and adipose tissue lipolysis. During exercise all these processes are stimulated, as well as hepatic extraction of these precursors and gluconeogenetic efficiency [].

Hormonal changes with exercise During exercise, several hormonal systems are activated and increases are seen in plasma concentrations of adrenaline/noradrenaline (epinephrine/ norepinephrine), adrenocorticotrophic hormone (ACTH), cortisol, b-endorphin, growth hormone, renin, testosterone, thyroid hormone and several gastrointestinal hormones (Fig. ..). Arterial levels of glucagon are unchanged or only marginally increased

 Chapter . Liver

Insulin/glucagon = low (epinephrine)

Insulin/glucagon = high

Glucose

Muscle

Contraction Insulin

Availability Fatty acids Insulin Norepinephrine

Plasma–cytoplasmic gradient

Glycogen Contraction Epinephrine Norepinephrine Pyruvate Lactate

Adipose tissue

Fig. .. Schematic illustration of the quantitatively most important hormonal mechanisms in the regulation of carbohydrate and fatty acid metabolism at rest and during exercise. Mechanisms important during exercise are in bold. A low insulin/glucagon ratio is around , a high ratio may be  or higher [,,,–].

by exercise, whereas insulin is decreased []. The decrease in plasma insulin concentration can be quite marked during exercise (< % of values at rest) and is thought to be mediated by an increased activity in sympathetic nerves and by small decreases in the blood glucose concentration during exercise. The latter fact explains why the insulin decrease may be attenuated, and even reversed, by voluntary intake of glucose solutions during exercise. Both insulin and glucagon exert a large part of their effect on the liver and this effect will be underestimated based on hormone concentrations in peripheral arteries, because concentrations in the portal vein, which is the relevant concentration for the liver, are considerably higher. Therefore, it is likely that, although peripheral levels may stay unchanged, the glucagon concentration in the portal vein is increased by exercise []. The catecholamines in plasma increase with exercise intensity in an exponential manner. The source of circulating epinephrine is the adrenal medulla and the

increase with exercise reflects an increased (sympathetic) nerve stimulation of this organ. Norepinephrine also originates to some extent from the adrenal medulla, but the increased norepinephrine concentration in arterial plasma is mainly considered to reflect overflow from postsynaptic sympathetic nerve endings mainly in the heart, but also in the liver and the adipose tissue. The mechanism behind the large sympathetic activation with exercise is not clear, but one important variable is likely to be a decrease in the portal glucose concentration. The two hormones differ in that the plasma concentration of norepinephrine starts to increase at lower rates of exercise and also increases more steeply with increased exercise intensity. At high exercise intensities, or long exercise durations, these hormones may be increased by –-fold. Following exercise, norepinephrine often remains increased for several hours, whereas plasma concentrations of epinephrine return to basal levels within minutes [,].

Metabolism during Exercise Hormonal regulation of carbohydrate metabolism during exercise Changes in insulin and glucagon have been reported to account for practically all of the increase in hepatic glucose output with exercise [,]. It is believed that the decrease in insulin concentration with exercise makes the liver more sensitive to the stimulation by glucagon. Sympathetic nervous stimulation seems to have no role in stimulating hepatic glucose output during exercise in humans, whereas epinephrine has a stimulating effect, additional to that of glucagon, during prolonged exercise, when epinephrine levels are at their highest. In addition, cortisol has an indirect effect on hepatic gluconeogenesis, by increasing the enzymatic potential for this pathway. The catecholamines are important in ‘sensitizing’ skeletal muscle glycogenolysis to the stimulating effect of contraction. With exercise leading to hypoglycemia, the compensatory increase in hepatic glucose output is mainly triggered by epinephrine [].

Hormonal regulation of fat metabolism during exercise The mobilization of free fatty acids from the adipose tissue during exercise is stimulated by catecholamines, mainly norepinephrine synthetized from sympathetic nerves, and inhibited by insulin. In adipose tissue, degradation of triglycerides into glycerol and free fatty acids is to some degree balanced by reesterification of fatty acids, using acyl-CoA and glycolysis-derived glycerol--phosphate. This reesterification has been found to be % of the lipolytic rate at rest, but only % during exercise, a decrease that makes more free fatty acids available to the working muscle during exercise [,].

Effect of training on the hormonal response to exercise In trained individuals, the hormonal responses to exercise are generally decreased. This is true for the increases in norepinephrine, epinephrine, growth hormone, ACTH and glucagon, as well as for the decrease in insulin. This adaptation is especially marked with regard to the sympathoadrenal activation with exercise and occurs rapidly, within the first  weeks of training []. The mechanism behind this change is not fully established, but hormonal activation secondary to



other stressful stimuli, e.g. hypoxia or hypoglycemia is in fact increased in the trained state and it is well known that the secretory capacity of the adrenal medulla is increased by endurance training: ‘sports adrenal medulla’ []. Trained individuals display lower insulin concentrations in plasma, during both basal and glucose-stimulated conditions, secondary to a decreased pancreatic insulin secretory rate [] and an increased peripheral insulin sensitivity []. Training augments the lipolytic capacity of the adipocyte, which serves to maintain a sufficient lipolytic rate in a trained individual, in spite of a reduced sympathetic activation during exercise at a given intensity []. Endurance training also increases the oxidative capacity of the liver as well as the hepatic capacity for gluconeogenesis, although the glucose demand during exercise is clearly decreased in the trained state, as discussed above. This decreased demand is sensed by the body and as little as  days of endurance training has been shown to decrease the hepatic glucose output during  h of exercise by as much as % [].

Summary During exercise, energy consumption may be increased by -fold. The primary factor determining whether carbohydrates or fat are preferentially used during exercise is the exercise intensity, the proportion of energy derived from carbohydrates growing progressively larger with increasing intensity. When exercise is performed in the absorptive state, less energy will be derived from the substrate stores in skeletal muscle and adipose tissue, and more from glucose, fatty acids and triglycerides in blood. A high level of physical fitness results in a higher degree of fat combustion during intense exercise. In addition, regular exercise allows weight maintenance to be achieved with less body fat in physically active individuals. Changes in insulin and glucagon have been reported to account for practically all of the increase in hepatic glucose output with exercise. The mobilization of free fatty acids from adipose tissue during exercise is stimulated by catecholamines, mainly norepinephrine synthesized from sympathetic nerves, and inhibited by insulin. Hydrolysis of ATP is the immediate energy source for practically all energy-requiring processes in the cell. The ultimate process of ATP formation is oxida-

 Chapter . tive phosphorylation during which different substrates are oxidized with oxygen in the mitochondrion. In addition, regeneration of ATP can also occur through anaerobic processes (breakdown of PCr, glycolysis from glycogen and ADP fusion). There are two inherent limits to the energetic processes: the maximum rate (power) and the amount of ATP (capacity) that can be produced. Factors such as muscle mass and fiber type composition, training status and nutritional factors are important determinants of the individual profile of power and capacity. Several lines of evidence suggest that oxidation of fatty acids cannot proceed at the same rate as for carbohydrate oxidation. On a whole-body level an increased working muscle mass will result in a proportional increase in the capacity for anaerobic energy production. In contrast, during two-legged exercise, aerobic power is largely limited by cardiac output and not limited by the working muscle mass.

Multiple choice questions  What is the body’s demand for fatty acids in the postabsorptive state (at rest, VO2 = . L/min): a . g/h b  g/h c  g/h d  g/h e  g/h.  The hepatic glucose output is of the order of . g/h at rest and – g/h during heavy exercise. This is covered by the liver glycogen store of approximately  g and by the synthesis of new glucose in the liver (gluconeogenesis). What is the maximal capacity of the liver for gluconeogenesis during exercise: a  g/h b  g/h c  g/h d  g/h e  g/h.  Which of the following hormones are considered to be the most important in the control of hepatic glucose output during exercise: a epinephrine b cortisol c glucagon d insulin e norepinephrine.

 Breakdown of phosphocreatine in skeletal muscle causes: a pH decrease b buffering of protons c pH increase d release of inorganic phosphate e ADP fusion.  Oxidation of fatty acids cannot proceed at the same rate as for carbohydrate oxidation. This can be explained by: a lower oxygen demand b high rate of acetyl-CoA formation c low b-oxidation capacity d low TCA cycle capacity e low carnitine-palmityl transferase capacity.

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

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Chapter 1.3 Skeletal Muscle: Physiology, Training and Repair After Injury MICHAEL KJ ÆR, HA NNU KA LI MO & BENGT SALTI N

Classical reference

Introduction

Gollnick PD, Armstrong RB, Saltin B, Saubert CW, Sembrowich WL, Shepherd RE. Effect of training on enzyme activity and fiber composition of human skeletal muscle. J Appl Physiol ; : –. This reference was the first to report an enhancing effect of endurance training on muscle oxidative enzymes and fiber types in humans. Individuals trained aerobically for  months performing  h bicycling,  days a week at % (in the early stage) to –% V˙2 max (at the late stage). A significant increase was found in peak pulmonary oxygen uptake rate and this was accompanied by a marked increase in oxidative and glycolytic enzymes (Table ..). Fiber type distribution of type I (ST) and type II (FT) was not altered significantly by training, but in this study no further subdivision into types IIa or IIb was performed. The study demonstrated a marked ability in skeletal muscle to adapt to physical training with regard to metabolic activity.

Table ..

Oxygen uptake · (V O2max) (L/min) Oxidative enzyme (SDH) (mmol/g) Glycolytic enzyme (PFK) (mmol/g)

Before

After

3.81

4.40

13%

4.65

9.10

95%

28.5

59.0

Improvement

117%

PFK, phosphofructokinase; SDH, succinate dehydrogenase.

Skeletal muscle is composed of two main components: specialized contracting cells, myofibers, and a connective tissue framework formed by fibroblasts. Myofibers are long ribbon-shaped cells of various subtypes with different functional properties. They are surrounded by a distinct basal lamina. Each myofiber is ensheathed by a thin layer of collagenous connective tissue named endomysium. A group of myofibers (from a few tens to a couple of hundred) are bound together by another connective tissue sheath named perimysium and form bundles or fascicles of myofibers. Finally a variable number of bundles are ensheathed by a strong epimysium, which forms the bounding fascia for individual muscles and which continues at the ends of muscles into tendons by which the muscles are attached to the surrounding connective tissue. In addition, motor nerve branches penetrate into the muscle and ultimately divide into axon terminals to innervate each individual myofiber. Sensory nerve fibers enter muscle spindles and convey information about the contraction state of the muscle. Nutrients for the active metabolism of muscle are supplied by an abundant vascular network branching into a rich capillary network around individual myofibers. The structural organization of human skeletal muscle and its contractile capacity ensure limb stabilization and weight bearing over joints, and allow for active movement of the body[,]. Around % of total body weight is accounted for by skeletal muscle in an adult human. Skeletal muscle has an amazing ability to adapt to varying workloads, whether increased due to regular physical training, or decreased due to inactivity during injury or disease [].



 Chapter . Presumptive myoblasts

Morphology Muscle cells are derived from mesodermal cells in the somites, which migrate from the parasagittal region into the future sites of individual muscles. These myogenic precursor cells differentiate into myoblasts and begin to synthesize muscle-specific proteins. Important regulators of this process of myogenic differentiation are muscle-specific transcription factors of the myoD family (e.g. MyoD, myogenin and Myf-) [a]. Myoblasts fuse into multinuclear myotubes, which form a basal lamina around themselves and begin to synthesize proteins of the contractile apparatus, which will occupy most of the sarcoplasm. Finally, the nuclei move to the periphery of these elongated cells which then display the morphology of fully differentiated myofibers [] (Fig. ..). It is of great importance that some of the myogenic precursor cells do not differentiate, but become localized between the plasma membrane and basal lamina of the myofibers as so-called satellite cells. These serve as reserve cells and are recruited when growth and/or regeneration after injury of myofibers is needed, controlled by mitogenic factors released during growth or upon muscle cell injury []. Early in development the motor nerves migrate from the anterior horn cells in the spinal cord to regions where muscle tissue is under formation; this migration is dominated by a high degree of specificity although the details are not fully known. When the developed myofiber and axon terminals meet, acetylcholine receptors spread along the sarcolemma are aggregated into the region of the nerve contact and develop further into the motor endplate or neuromuscular junction (NMJ). In fetal life, axons from several motoneurons can form NMJs on a single myofiber, but later on only one single NMJ remains on each muscle fiber, while the other NMJs undergo degeneration after birth []. One motoneuron and the myofibers innervated by its axon terminals form a motor unit, in which myofibers are contracted simultaneously. The number of myofibers which each motoneuron innervates varies considerably depending on the accuracy of movement required. In muscles performing coarse movements like the quadriceps femoris, the number of myofibers per motoneuron is up to , whereas in

Proliferation Clonal distribution Myogenic transcription factor synthesis

Myoblasts

Fusion

Myotubes

Mature muscle cell: Innervation Nuclear migration Myofibrillar synthesis Histochemical differentiation ACh receptor redistribution

Fig. .. Embryonic development and maturation of skeletal muscle cell. Lines illustrate myofibrils, sarcolemma and basal membrane. Nuclei are located intracellularly. Satellite cells are not depicted, but are located outside the sarcolemma and within the basal lamina.

ocular muscles the number is only about  per motoneuron. All muscle fibers within a certain motor unit are of the same fiber type (for the properties of different types of fibers, see below). How this differentiation occurs is only partly understood. In mature myofibers, the firing pattern of the innervating motoneuron is traditionally considered to play an important role in fiber type determination []. It has been demonstrated that cross-innervation of skeletal muscle (i.e. motoneuron axons from a motor unit containing slow contracting muscle fibers transposed to motor units

Skeletal Muscle with fast fibers or vice versa) leads to a change in the fiber type characteristics towards the innervating nerve type. On the other hand, in human fetal muscle fiber types have not yet reached a differentiation level that allows classical fiber type classification. However, more recent molecular biological techniques have demonstrated that even in fetal muscle different types of myoblasts and myotubes exist and thus it is likely that myofibers have already begun their differentiation into fiber types by this stage. These studies demonstrate that during muscle development a selective initial innervation of muscle fibers from specific axons does occur. It is possible that fiber type-specific transmembrane proteins in the sarcolemma can direct axons from spinal motoneurons to muscle cells predisposed to become fast or slow type fibers []. Mature muscle cells, which are specialized in the production of force and movement, account for more than % of skeletal muscle volume. Muscle cells are elongated and ribbon-shaped, i.e. myofibers, with a diameter of – mm and a variable length of up to  mm. Myofibers are multinucleated due to their formation by fusion of myoblasts, the nuclei of which persist in the mature myofibers and become distributed subsarcolemmally along the whole fiber length. Although this indicates that a high degree of internuclear signaling is needed to allow hom*ogenous cell development, experiments have indicated that muscle cell adaptations to, for example, mechanical loading can vary along the length of the muscle cell. These findings suggest that the individual myonuclei have a certain degree of autonomy. The cytoplasm of skeletal myofibers, sarcoplasm, contains — as in other eukaryotic cells — the normal set of organelles but in unusually large numbers reflecting the function of the myofiber as a contractile cell. Most of the sarcoplasm is occupied by cytoskeletal proteins organized into regular sarcomeric structures, which extend the whole length of myofibers and which are composed of the two main contractile filaments myosin and actin and their binding and regulatory proteins (for details see []). The number of ribosomes, the key organelle of protein synthesis, is relatively low compared with the large amount of proteins present in myofibers, which suggests low turnover rates for many muscle proteins. On the other hand, because muscle cells primarily produce proteins which are used locally,



rough endoplasmic reticulum is also a minor component of the sarcoplasm. As the mitochondria are responsible for the major (aerobic) part of energy production in myofibers, they contain the enzymes needed for oxidation of substrates and production of ATP. Because active myofibers consume large amounts of energy mitochondria are numerous, although their size and number can vary substantially during the adaptation of a muscle cell to an altered loading pattern, e.g. at the onset of physical training. Mitochondria can transform from single oval organelles into an almost reticular network along the capillaries in physically very well trained individuals. This contributes to an optimal usage of the delivered oxygen in relation to energy production. In extreme situations in highly oxidative fibers the mitochondria can account for more than % of the total cell volume []. In addition to the aerobic metabolism of substrates, the cytoplasm contains enzymes necessary for the anaerobic formation of ATP from glycogen. Glycogen is stored in abundance in the muscle cell, primarily between myofibrils and adjacent to the sarcoplasmic reticulum []. In addition, small lipid droplets are present in sarcoplasm, most abundantly in fiber types with a high oxidative capacity. Different regions of the sarcomere are named according to their appearance under the microscope. The region that contains myosin is called the A-band (anisotropic appearance in light display) whereas the actin region is called the I-band (isotropic). The region of the A-band where no actin–myosin overlap is present is called the H-band (‘helle’ means ‘light’ in German), the thin band, which divides the I-band into two parts, is called the Z-band (‘zwischen’ means ‘in between’ in German), and the small band dividing the A-band into two is called the M-band. The sarcomere length is defined as the distance from one Z-band to the next, and serially connected sarcomeres comprise the myofibrils of the muscle, which are arranged in parallel to form the muscle fiber [,] (Fig. ..). The architecture of the muscle is important for the development of force and for flexibility, in that the muscle force is proportional to the physiologic crosssectional area of the muscle fibers, whereas the contraction velocity of the muscle is proportional to the muscle length. A more exact description of the

 Chapter . Epimysium

Skeletal muscle

Single muscle fiber Nuclei Perimysium

Integrin Fibronectin Merosin

Capillary

Satellite cell

Sarcolemma Basal lamina

alin ulin, T

, Vinc

Nuclei

Actin

Dystrophin

Myosin thick filament Actin thin filament (+troponin, tropomyosin)

Endomysium Type IV collagen Titin Nebulin

Myofibril

Mitochondrion Desmin

Z-line

M-line H-zone A-band

Z-line

I-band

Fig. .. Schematic representation of a muscle cell with its cellular structures. Actin and myosin filaments are depicted in detail to illustrate the basis for the contraction process.

relationship between the cross-sectional area and force development requires consideration of the muscle fiber angle compared to the axis for force development (pennation angle). It is evident that fibers that run in the direction of contraction contribute maximal force

to the movement, whereas fibers that are at an angle to the work direction will perform a smaller force. However, it has to be taken into account that by angling of the fibers, more fibers are placed within the same muscle bulk, and a larger physiologic cross-sectional area is

Skeletal Muscle thereby reached. This means, for example, that the quadriceps and foot plantar flexors have a high physiologic cross-sectional area, with short fibers, and are thereby well suited for large development of force, whereas the hamstring and dorsal flexors of the foot with long muscle fibers and a smaller cross-sectional area are more suited for large movements and ranges of motion. In addition muscles with high pennation angles often experience smaller increases in intramuscular pressure than other muscles (Fig. ..). Apart from connecting the muscle to bone, tendon structures are important as energy absorbers, improve the functional movement range of the muscle–tendon complex, and are of importance for the release of elastic energy in explosive movements [,]. In skeletal musculature up to % of the total content is collagen tissue, and although studies have demonstrated increased turnover of collagen in response to training, the relative amount or even the total content of collagen does not seem to be influenced. The connective tissue in muscle displays passive resistance to stretching, and human models for evaluation of tendon stiffness and stretch-related energy absorption as well as viscoelastic stress relaxation during the static phase have been developed. Repeated stretching of human ham-

FL ML

ML FL

Fig. .. Muscle architecture in the lower limb. Whereas dorsiflexors (tibialis anterior) have a high fiber length (FL) to muscle length (ML) ratio and thus are suited for high excursions and velocity, plantar flexors (triceps surae) favor large force production due to their low FL : ML ratio.



string muscles results in a shortlived decrease in tissue stiffness. Furthermore, daily stretching exercises over several weeks leads to no change in biomechanical tissue characteristics, but results in an increased range of movement, most likely due to an increased pain tolerance, whereas strength training increases the passive stiffness of the muscle–tendon unit. The load-bearing structures in skeletal muscle during passive stretch are not well defined, and the force transmission is more complicated than previously thought. In addition to the obvious force transmission that occurs in series of muscle–tendon structures, elements of the cytoskeleton are thought to mediate a substantial amount of force transduction in the lateral direction. In support of such a role, individual muscle fibers have been shown not to equal the length of the whole muscle.

Proteins and their function Muscle proteins can be separated into sarcomeric/ myofibrillar, mitochondrial and cytosolic proteins (Table ..). The endosarcomeric proteins are dominated by actin-associated (including both actin and troponin and tropomyosin), myosin heavy chain (MHC) and myosin light chain proteins. These form the two types of contractile filaments. Myosin is an asymmetric molecule with a long twisted root at one end and a more circular arrangement at the other end, and each myosin molecule consists of two heavy and four light chains. Myosin proteins are arranged antiparallel and the molecules are rotated approximately  degrees to each other. This results in the characteristic feather-like structure, with parts of the heavy chains sticking out at the ends. It is at this location that the actin binding regions are found, and the myosin heavy chains (MHC) are used for characterization either with immunohistochemistry or via in situ hybridization. Actin filaments are thinner than myosin and constructed of actin monomers arranged in an a-helix. Because of this arrangement, a longitudinal cleavage will occur in the filament, in which the regulating protein tropomyosin is located. In addition, the protein troponin is arranged along the actin filament and is responsible for the initiation of the contraction process. Actin and myosin work together during the contraction process, and the filaments are regularly arranged, allowing for some overlap between

 Chapter . Table .. Proteins, enzymes and growth/transcription factors in skeletal muscle with tonic stimulation or endurance training. Gene Sarcomeric contractile proteins Myosin heavy chains IIb to IIx to IIa to I I to IIa to IIx to IIb Myosin light chains Fast to slow isoforms Actin Troponin subunit TnT,TnI,TnC Fast to slow isoforms

Protein

mRNA

+ –

+ –

+ ?

+ ?

+

+

Sarcomeric contractile-associated proteins Myosin-associated (titin, myomesin, creatine kinase) Actin-associated (nebulin, tropomodulin, actinin) Z-line-associated (paranemin, synemin, plectin) Exosarcomeric cytoskeletal proteins Intermediate filaments (desmin, skelemin, vimentin) Cytoskeletal anchor proteins (ankyrin, desmin, dystrophin, integrins, syntrophin, talin, vinculin) Mitochondrial proteins and enzymes TCA cycle enzymes (CS, SDH, MDH) Respiratory chain nuclear-encoded (cyt-c, NADH/cyt-c) mitochondrial-encoded (cyt-ox III, cyt-b) Mitochondrial membrane phospholipid (cardiolipin)

+

+

+

+ +

+/–

Cytosolic proteins and enzymes Glycolytic enzymes (HKII, PFK, LDH) Glycogen metabolism (phosphorylase, GS) Fatty acid metabolism (HAD, CAT) Amino acid metabolism (aminotransferase) Myoglobin Fatty acid binding protein Parvalalbumin Sarcoplasmic reticulum Ca2+-ATPase (fast to slow isoform)

+/– –? + + + + + +/–

Surface receptors, enzymes and transporters N-cadherin Acetylcholine receptor Ciliary neurotrophic factor receptor Beta-adrenergic receptor Adenylate cyclase Insulin-sensitive glucose transporter (GLUT-4)

–/+ + + + + +

Transcription factors and peptide growth factors Early response genes (c-fos, c-jun, egr-1) Myogenic growth factors (MyoD, myogenin) Fibroblast growth factors

+ + +

+/–

+ + + + +/–

+ + + + +

cyt-ox III, cytochrome oxidase III; CAT, carnitine acyltransferase; CS, citrate synthase; cyt-b, cytochrome-b; cyt-c, cytochrome-c; GS, glycogen synthase; HAD, b-hydroxyacyl coA dehydrogenase; HKII, hexokinase II; LDH, lactate dehydrogenase; MDH, malate dehydrogenase; NADH/cyt-c, nicotinamide adenine dinucleotide (reduced)/cytochrome-c ratio; PFK, phosphofructokinase; SDH, succinate dehydrogenase.

Skeletal Muscle structures, in order for actin and myosin to form crossbridges and create a contraction [–]. A short contraction — a twitch — is initiated via stimuli from motoric centers via myelinated amotoneurons to the motoric endplate, which ultimately leads to muscle contraction — altogether called exitation–contraction coupling []. When the action potential reaches the neuromuscular junction, local calcium channels are opened, enabling potassiumassociated initiation of fusion of acetylcholine-filled vesicles with the presynaptic junction cleft, triggering release of transmitter molecules. Other membranerelated proteins such as synapsin and synaptophysin also stimulate vesicle transport and transmitter release. When acetylcholine binds to the receptor on the sarcoplasmic reticulum, several processes are initiated, that all lead to a release of calcium from the sarcoplasmic reticulum, which binds to troponin and results in a cyclic interaction between actin and myosin leading to muscle contraction. The degree of muscle contraction is controlled by the number of motor units activated, and in addition to this the stimulation frequency is modulated and afferent signals from tendon and muscle modify the motoric activity, so that the desired amount of force is achieved []. The activation of a muscle fiber via propagation of the action potential does not occur exclusively on the fiber surface, but also across the fiber due to the t-tubuli system. Subsequent activation occurs via recently identified dehydropyridine receptors, which upon activation produce a transmitter substance which enables the sarcoplasmic reticulum system to release Ca2+. In addition to the contractile myofibrillar proteins, sarcomeric and exosarcomeric muscle proteins exist, including cytoskeletal proteins either as intermediate filaments or as cytoskeletal anchor proteins, which are believed to play an important role in force transmission. Models in which gene expression for some of these proteins is missing will often display decreased muscle function. Eccentric movements exert high loading forces on the muscle tissue compared with concentric contractions and it is generally accepted that this leads to muscle injury, soreness and elevated serum enzyme levels. Using eccentric exercise on a motor-driven ergometer in humans or eccentric exercise models in animals, it was demonstrated that ultrastructural abnormalities within



the myofibrils occurred. These included broadening, smearing or even total disruption of Z-discs, and disorganization of the adjacent A-bands [] (Fig. ..). There is growing evidence that the cytoskeletal protein titin is involved in these ultrastructural changes. Titin is a long elastic molecule which connects M-bands to Z-bands and plays an important stabilizing role for the contractile machinery of skeletal muscle as it is responsible for returning extended sarcomeres to their original length. Another cytoskeletal protein which is damaged by eccentric exercise is desmin, which is responsible for keeping myofibrils in register by connecting neighboring myofibrils at their Z-bands. It has been shown that after only a few minutes of loading desmin immunolabeling is lost in many muscle fibers — preferentially type II fibers. The relative role of cytoskeletal proteins in force transmission during muscle contraction is still debated but dystrophin, titin and desmin are three major proteins that have all been shown to be important (Fig. ..). The time pattern of morphological changes following eccentric exercise showed that in addition to the loss of desmin staining, fibronectin positive cells (indicative of sarcolemmal disruption) were demonstrated after a few hours. After  days some fibers had developed extreme sizes and abnormal shapes and were often invaded by inflammatory cells. In some cases also fibers expressing fetal myosin were found as a sign of regeneration, i.e. the injury had activated satellite cells and these had produced ‘new sarcoplasm’ where embryonic myosin isoforms were expressed [,]. Eccentric loading leads to a reduced capacity of the muscle to perform tetanic contraction, and the muscle strength can be reduced by more than % after damaging exercise. The lowest value is obtained either immediately or – days after exercise, and the muscle gradually recovers strength over – days []. Interestingly, this decrease in force is not related to pain as electrically stimulated contraction is also reduced. Furthermore it has been demonstrated that initial force reduction and especially recovery time is markedly reduced after training or even a few accustomizing bouts of exercise. The fact that some studies demonstrate a further loss in force for up to  days after exercise indicates that contraction triggers events that further decrease muscle performance. Muscle

 Chapter . shortening and thus reduction in the range of motion can also accompany eccentric exercise, most likely related to abnormally high levels of Ca2+ in the sarcoplasma, and may be complicated by increased water content. In addition to this, the eccentric exercise results in delayed-onset muscle soreness (DOMS) which reaches a maximum – days after exercise, and is described as a dull, aching pain combined with tenderness and stiffness. The tenderness is frequently localized in the region of the distal myotendinous junction, but can also be generalized throughout the muscle. Although there is an inflammatory response with macrophage accumulation and prostaglandin release, and thus sensitizing type III and IV pain afferents, the true explanation for DOMS remains undiscovered. Mitochondrial proteins are crucial for oxidative capacity of the muscle (see Chapter .) and whereas in endurance training gene expression and protein formation for the different enzymes roughly corresponds to the number of mitochondria, during muscle hypertrophy in response to resistance training the relative content of mitochondrial enzymes either remains constant or decreases. Studies have indicated that tonic contractile activity stimulates expression of protein-coding genes, and interestingly, several mitochondrial complexes require a coordinated expression of genes within both the nuclear and mitochondrial compartments. Cytosolic proteins are important not only for anaerobic fuel combustion but also for transportation of oxygen and the contraction process. Physical activity is shown to increase gene expression for enzymes involved in both lipid and amino acid metabolism. Glycolytic enzyme gene expression is shown to decrease in animal models, whereas enzyme activity can be shown to increase in human models. GLUT- exists both in the cytosol and located in the surface membrane and rises with contraction, and likewise gene expression for several surface receptors increases with activity. Myogenic transcription factors that are important during development and regeneration have also been shown to be activated in relation to mechanical loading of muscle. Using gene expression and protein formation as markers for adaptive responses to loading, it is important to note that transcription and translational

processes are influenced by several factors (Fig. ..). Firstly, an increase in protein synthesis may be due to and preceded by an increase in mRNA levels. However, it has to be noted that mRNA is subject to degradation as well as processing. Secondly, if the translational efficiency increases, protein formation can increase disproportionately to changes in mRNA. Whereas the levels of mRNA and protein can be determined for several of the factors discussed, the detailed transcriptional processes prior to mRNA formation, and especially the translational steps involved, have only been described to a minor degree for enzymes, proteins and other factors involved in adaptive responses to exercise. The messengers and signal transduction pathways involved in exercise are complex. Changes in intracellular Ca2+ concentration activate or repress signaling pathways for a variety of cellular responses. Changes in energy charges or phosphorylation potential may initiate changes in gene expression, and — though less well investigated — the redox state may also prove important in this process. Mechanical stretch is well known to cause a hypertrophic response in cardiac muscle, mediated via autocrine and paracrine effects of peptide hormones. In myotubes stretch is found to change Na+/K+-ATPase

DNA Transcription RNA processing

mRNA

Degradation

RNA stability

Translation Protein processing, transport, stability

PROTEIN

Degradation

Fig. .. Schematic representation of protein synthesis to illustrate events occurring in skeletal muscle and steps at which gene expression can be controlled.

Skeletal Muscle and phospholipase activity and activate growth factors, but MHC slow isoforms have also been shown to be induced by stretching. During force development under isometric conditions, the maximal force is dependent upon the sarcomere length, so that optimal force is achieved when optimal contact and thus overlap between actin and myosin is reached (length–tension relationship) []. In addition, a relationship between magnitude of force and contraction speed exists (force–velocity relationship) (Fig. ..). When the muscle is activated to overcome a resistance smaller that its maximal tetanic force, the muscle will shorten under the occurrence of a concentric contraction. The relationship between force and velocity follows a steep rectangular hyperbolic curve, indicat-

% of maximal force

(a)

100

Plateau

75 Descending limb

50 25 1.0

Ascending

1.5

2.0 2.5 3.0 Sarcomere length (mm)

3.5

(b) % of maximal isometric force

200 160

Lengthening

120 80

Shortening

40 0 –0.8



ing that force decreases markedly with increasing velocity []. This is related to the force by which cross-bridges between actin and myosin can be coupled and uncoupled. The higher the velocity in a contraction, the more myosin heads are in a state in which they are not tightly bound to actin, and thus cannot contribute to the development of large muscle force. The speed in which a certain force can be developed is trainable, and this may have great importance in rehabilitation and in patients with reduced muscle force, since it is not only the maximal force that an individual can produce which is crucial, but also the speed at which a certain force can be achieved. The higher the contraction speed, the more myosin heads will not reach an actin and thus will not develop the required force. Muscle contractions that result in shortening of the muscle are concentric, whereas contractions of muscle accompanied by lengthening are eccentric in nature. The magnitude of external resistance to movement vs. the development of torque produced by a muscle will determine whether there is a change in velocity during the movement and thus whether there is going to be a positive acceleration (speed increase) or a negative acceleration (deceleration or braking of the movement) independently of whether the contraction is concentric or eccentric. Interestingly, it can be debated whether isometric muscle contraction in fact is in accordance with the definition that no change in muscle length has occurred. As isometric or static contraction is normally defined by lack of change in external movement (e.g. over a joint), the fact that connective tissue of tendons is elastic will allow for a shortening of the muscle, and thus a concentric contraction, in the absence of any detectable external movement. Eccentric exercise is not only an important part of normal locomotion, but attracts special attention as this work mode results in the most dramatic changes in muscle with regard to factors such as absorption of power, both in relation to training and with injury.

Fiber types –0.4 0.0 0.4 Relative shortening velocity

0.8

Fig. .. Relationship between (a) sarcomere length and contraction force and (b) force–velocity relationship during different types of muscular contractions.

Within the individual motor units muscle fibers with specific characteristics exist with regard to contractile, histochemical and metabolic activity. Furthermore, muscle fibers from a given motor unit are known to be located over a relatively large area of the cross-

 Chapter . sectional area of the muscle (up to %), indicating that within a given small muscle region all fibers represented in the muscle will be present. Two main categories of motor unit exist, one of which possesses a relatively slow timewise development of maximal force (slow twitch) and the other a fast development of maximal force (fast twitch) [a, ,] (Fig. ..). With the use of histochemical characterization of skeletal musculature, determining myofibrillar ATPase activity and incubating at varying pH levels, three main fiber types were originally described: type I, type IIa and type IIb (now known to be identical to myosin heavy chain classification IIx, which will be used in the rest of this chapter). These are distinctly different from each other with regard to contractility, morphology and metabolic characteristics. Type I fibers are slow contracting, are more red in appearance, and are well equipped for oxidative metabolism, with regard to both enzyme and substrate content. In contrast type II fibers are fast contracting and more white in colour and contain more glycolytic enzymes and fewer oxidative enzymes than type I fibers [–]. Motor unit type FF Histochemical profile FG

More recent techniques have allowed refinement of our characterization of muscle fibers and determination of the myosin heavy chain (MHC) isoforms has allowed the demonstration of type I b-slow, type IIa and type IIx as well as several muscle fibers coexpressing two or all three of these isoforms []. The MHCIIb isoform has been demonstrated in species other than humans, and for practical purposes the MHC type IIx is equivalent to the ATPase-stained type IIb fiber (Fig. ..). During physical activity, activation of the different muscle fibers is known to depend on the intensity and duration of the work. Intense short-lasting activities involve mainly the type IIx fibers, whereas lowintensity prolonged exercise primarily activates type I fibers and type II fibers are first involved at a later time point when type I fibers have depleted their carbohydrate stores. The distribution of fiber types varies between individual muscles in both the upper and lower extremities, and some muscles are dominated by slowtwitch type I fibers (e.g. the soleus) whereas others possess up to % fast-twitch type II fibers (e.g. the

FR

S

FOG

SO

la afferents

IA EPSP Motoneuron

AcATPase

Ox

50

gm

40 30 Twitch response

20 10 0 0 100% 0 0

100ms Fatigue curves 2

4

6

0 100% 0 0

100ms

2

4

6 60

Time (min)

0 100% 0 0

100

2

4

200ms

6 60

Fig. .. Three types of muscle fibers representative of separate motor units in the cat. The different motor units are characterized by recruitment pattern, metabolism, twitch characteristics and fatiguability. FF, fast-fatiguable; FR, fast-resistible; S, slow, FG, fastglycolytic; FOG, fast-oxidativeglycolytic; SO, slow-oxidative.

Skeletal Muscle

Table .. Contraction speed (in sarcomere length units per second) of single fibers from human muscle with varying degrees of slow vs. fast fibers (Harridge, personal communication).

I/IIa IIa/IIx IIa

I

MHC

Histochemistry

I

20

IIa

40

60



IIx

IIb

80

100

Type I Type I/IIa Type IIa Type IIa/IIx Type IIx

Soleus

Vastus lateralis

Triceps brachii

0.27 – 1.25 – –

0.29 0.67 1.10 1.83 2.24

0.27 0.64 1.20 1.73 2.31

% Fig. .. Comparison of the fiber type composition in sedentary individuals determined by single-fiber analysis of myosin heavy chain (MHC) composition and myofibrillar ATPase histochemistry in biceps brachii muscle.

triceps brachii). Within a single muscle the relative distribution of the fiber types can vary, but probably not by more than –% between regions. The interindividual variation in muscle fiber type distribution is primarily genetically determined, and studies of monoand dizygotic twins have shown a close to similar fiber type distribution in monozygotic (r2 around .), but not in dizygotic twins. Furthermore, a certain fiber type (e.g. type I) from human musculature displays similar contractile patterns independent of the anatomic position (Table ..). This indicates that the characteristics of a human muscle are dependent on the relative contribution of the different fiber types rather than on variations in characteristics within a certain muscle fiber type. Although this thight correlation exists for isolated muscle fibers it cannot be extrapolated to whole muscle. However, use of the muscle plays a major role. It has been shown that the specific tension of the muscle fiber is reduced after, say,  days of bedrest. Surprisingly, a reduction in specific tension has also been demonstrated after monotonous use of the muscle at a low intensity, as occurs in extreme endurance training.

Muscle fiber plasticity The plasticity of muscle can in general be classified according to the ability to change either (i) the quantity (i.e. hypertrophy) or (ii) the type of protein (i.e. isoform or phenotype) of the different cellular compo-

nents of the muscle cell. The muscle cell may respond to loading by increasing the cross-sectional area with no change in the proportion of the different muscle proteins and their expression, and will in this case increase its maximal force but maintain its other inherent functional properties such as contractile speed or endurance []. If on the other hand the training results in altered expression in the type of protein (e.g. altered expression of MHC isoforms of the myofibrils) the muscle may also change its intrinsic contractile properties. In real life, responses to training may often be a combination of a change in the amount of protein and the type of protein isoform it expresses. A change in isoforms of proteins means in this situation a slight variation in the amino acid composition, whereby structure, function or enzymatic properties are influenced [,,]. To allow for muscle plasticity to occur, both the protein turnover and the protein synthesis rate have to be taken into account, and the protein half-life will be the important determinant of the time needed to achieve an alteration in muscle plasticity. Whereas some proteins have a relatively long half-life and therefore turnover time, others have a short half-life and thus allow a more rapid adaptation in response to training (e.g. days for glycolytic enzymes). Evidently, a rapid adaptation requires not only a short half-life for the protein but also a high protein synthesis rate in order to allow for synthesis to match or even surpass protein degradation. Furthermore, the time frame for muscle adaptation to training will be fully dependent on the different steps of gene expression, and pretranslational, translational and post-translational regulation often occurs at different time intervals dependent

 Chapter . Table .. Muscle fiber characteristics into functional units (based on myosin heavy chain isoforms). Properties

I

IIa

IIx

Myofibrillar ATPase SR Ca2+-ATPase Glycolytic enzymes ATP buffering enzymes High-energy phosphate levels Oxidative enzymes Blood flow Fatiguability Contractile speed

Low Low Moderately high Moderately high High High High Low Slow

Moderately high Moderately high Moderately high Moderately high High High High Moderate Moderately fast

High High High Moderately high Very high Moderately high Moderately high Moderate Fast

on the stimulus and the protein involved (Table ..). The mechanisms behind mechanical loading resulting in altered gene expression and thus altered protein content are not clear. Several potential messengers generated within contracting skeletal myofibers are illustrated in Table ... The acetylcholine released from the motor nerve binding to its receptor, and the subsequent release of Ca2+ from the SR and resulting myofiber contraction can either itself or by generating other intracellular messengers activate signals for altered gene expression in response to mechanical loading. These additional messengers can either be linked to receptor-linked pathways or stretch-dependent pathways, or be a part of the metabolic changes associated with the contraction. What has been shown so far is that resistance training decreases the Ca2+ concentration needed to elicit % of maximal tension, decreases MHC IIx gene expression, and increases contractile proteins in parallel, all of which together allows greater absolute workloads to be moved [,]. Furthermore, serum response element  of the skeletal a-actin promoter has been identified as part of the mechanotransduction pathway involved in enhancing actin gene transcription, which results in muscle enlargement (Table ..). Endurance training, on the other hand, increases and decreases the maximal shortening velocity of individual slow and fast fibers, respectively, both changes contributing to improved endurance performance. Expression of several genes is increased with training, and a complex interaction with and between modulators such as nerves,

cytokines, autocrine/paracrine substances, hormones, temperature, circulatory changes and fluid shifts within muscle takes place and is far from understood in relation to training of skeletal muscle [,]. With the use of immunohistochemical and molecular biological techniques for determination of MHC isoforms and thus characterization of fiber types, it has been demonstrated that endurance training can cause a fiber type shift from type IIx to IIa. Although animal studies using long-term low-frequency electrical stimulation of muscle have been able to demonstrate a fiber type shift from II to I, it is more questionable to what degree such a shift can occur in human skeletal musculature in relation to training. It is most likely that such a transformation can occur in humans, as is indicated by findings from long-term electrical stimulation of paralyzed muscle and observations on translocated muscle used for cardiomyoplasty, but obviously extremely long-term loading is required. Thus, it must still be concluded that a high relative content of type I fibers in an endurance athlete is due to genetic rather than training-induced factors. Termination of training or inactivity rapidly reverses the described training-induced changes in skeletal muscle. Loss of enzymes occurs most rapidly, followed by loss in muscle mass and finally a shift in muscle fiber type towards IIx. At extreme degrees of long-term inactivation (e.g. in spinal cord patients) a complete fiber type shift occurs from type I and IIa to type IIx. Inactivity leads to a loss in muscle mass initially due to both increased degradation and decreased synthesis of myofibrillar protein, followed by a period dominated by increased degradation, and only after  days of

Skeletal Muscle inactivity is a new and lower steady-state level for protein turnover reached. The degree of muscle atrophy with inactivity depends upon the relative reduction in activity []. Thus, antigravity muscles undergo a more pronounced degree of atrophy than other muscles. If muscle is rehabilitated after inactivity the morphology and characteristics of the muscle can be restored relatively fast in comparison with other structures like tendon and bone []. Endurance training markedly improves oxidative mitochondrial enzyme content and activity, which is important for both fatty acid oxidation, the TCA cycle and the respiratory chain. Values for oxidative enzyme content of – times normal as well as reticulumformed mitochondria can be obtained in elite endurance athletes [,–]. Whereas maximal training effects of type I fibers can be obtained with low and moderate workloads, a somewhat higher training intensity is required to obtain training adaptation of type II fibers (e.g. interval training). Whereas oxidative enzyme level can alter with training independent of fiber type specific myofibrillar isoforms, the fiber type composition in the individual muscle is of major importance for the content of glycolytic enzymes. The time course for adaptation of metabolic enzymes is shorter than for phenotypic changes of skeletal muscle [,]. Physical loading of muscle can be achieved either by passive stretching or by development of voluntary or electrically induced muscle force. Depending upon which loading the muscle is subjected to, an adaptation will occur in the form of either increased muscle mass, increased metabolic capacity or alteration in fiber types. In order to differentiate between different types of training they are mainly categorized into either endurance (low resistance, many repetitions) or resistance (high load, few repetitions) training or combinations of the two, which is typically what is seen within different sports events. Changes in muscle force are in general achieved with workloads that exceed –% of the maximal strength expressed either as maximal voluntary contraction (MVC) in isometric exercise or the performance of one maximal bout of dynamic contraction ( RM = repetition of maximum). In addition, the determination of maximal force developed at a certain angle-speed is used during isokinetic exercise. Although this latter form of contraction does not



fully reproduce the force produced during normal movements, it often correlates with maximal movement performed during functional activities and sports. The connection between the number of repetitions (in dynamic work) or holding time (in static work) and the relative workload varies extensively from muscle to muscle dependent upon the fiber type composition, in that a larger number of type I fibers will shift the curve to the right. For more practical reasons the curve can be used to conclude that a resistance that can be performed dynamically – times before fatigue develops or a static resistance that can be maintained for less than a minute corresponds to around % relative workload. Whereas changes in the nervous activation of the musculature can improve the performance of the muscle, changes in the muscle tissue force are primarily due to a muscle fiberhypertrophy. Although occasional reports have suggested that strength training can cause hyperplasia, the increase in muscle force is due to an increased muscle cross-sectional area (Fig. ..). In addition to this it has to be acknowledged that determination of anatomical cross-sectional area in many muscles may underestimate the increase in physiologic cross-sectional area due to the altered pennation angle of the muscle fibers after a training period (see Chapter . for details). Furthermore, it has been demonstrated that contractile proteins (e.g. myosin light chains) may also alter composition and thus contribute to the fact that training can result in increased contractility force of single muscle fibers in excess of what can be explained by fiberhypertrophy. By determination of maximal muscle force and electromyography the relative contribution in general of fiber hypertrophy and increased neural activation of the muscle can be determined. This principle is used for estimation of maximal contraction force in patients who cannot develop maximal voluntary force due to fatigue or pain. Short-lasting electrical contractions (twitches) on top of voluntary activation can be used for estimation of the true maximal muscle force in an individual. By stimulation at different degrees of voluntary contraction it is possible to estimate the maximal muscle strength, and, for example in elderly individuals, a marked portion of the interindividual variability in maximal voluntary strength can in fact be ascribed to variation in ability to contract the muscle voluntarily.

 Chapter . (a) Progress Most training studies

Most serious strength trainers

(Steroids)

Strength

Neural adaptation Hypertrophy

Activation

Time

(b) Neural factors A IEMG

At the onset of strength training, the dominant factor in strength improvement is an increased neural activation, which causes activation of more motor units and thereby recruitment of more muscle fibers. In addition to this, a more synchronized recruitment of motor units occurs. The neural improvement with training is most pronounced in the first – weeks of a training period, and interestingly, this effect is evident also in the contralateral extremity, whereas no crossover effect is observed with regard to structural muscle tissue adaptation []. Muscle fiber hypertrophy is first evident and measurable after – weeks, but data indicate that rates of transcription and formation of contractile proteins begin increasing within days into a training period. Muscle strength can be improved markedly over a short period of time (around % per day within the first – weeks). With static training the development of maximal force seems to play a more important role than the number of repetitions for the training effect achieved. Similarly, in dynamic exercise the most pronounced effects are evident with resistance training programs containing six or fewer repetitions per training series prior to fatigue (Table ..). These findings obviously have to be matched to the initial capacity of the individual prior to training, and thus the realistic possibilities of carrying out high-intensity training. Interestingly, muscle strength training can be carried out even at an advanced age, and it is quantitative rather than qualitative differences that are characteristic of the training responses seen in elderly as compared to young individuals. In general it is believed that the cross-sectional area of type I muscles can improve ~% with training whereas type II fibers enlarge by % of their initial area. More and more evidence points towards the satellite cells being involved in providing genetic material for myofibrillar protein formation and thus the development of hypertrophy. If training is carried out with low resistance but with a high number of repetitions, no marked strength improvement will be found, whereas muscle endurance will be improved markedly. Muscle strength training decreases mitochondrial and capillary density in the muscle due to a marked increase in the amount of contractile proteins. Furthermore, whereas strength training will not influence concentrations of glycolytic

Hypertrophy B

No change in activation

Increased

Force

Force

Before training After training Fig. .. (a) Response of muscle force to intensive training. (b) The difference in neural improvement or muscle hypertrophy.

enzymes and only slightly increases the amount of enzymes catalysing energy-rich phosphate compounds, muscle endurance training will markedly increase the capillary density, the number of mitochondria and the amount of glycolytic enzymes. The training effects are specific, and depend on the type of training program, and the transfer value is limited. This concept is important in rehabilitation, where movement patterns and contraction types should be tailored specifically to the functional aim.

Skeletal Muscle



Table .. Improvements in performance following  weeks of dynamic or isometric training in humans. Muscle endurance training (% improvement) Testing Static (60%, 5 s, 10–150/day, 35 days)

Dynamic (60%, 10–150/day, 35 days)

Static force Static endurance Dynamic force Dynamic endurance

0 0 29 630–5040

4–11 84–122 2–6 41–92

Strength training (% improvement) Type of training Program

Static force

Dynamic force

Static Dynamic

100%, 5 s,¥ 20, 45 days 50–80%, 6 ¥ 10, 30 days

35 0

0 370

Skeletal muscle injuries can be divided into two basic types.  In a less severe in situ necrosis type of injury only the myofibers are damaged, whereas the basal lamina and the mysial sheaths are not breached. In its mildest form such an injury occurs in eccentric exercise and more extensive in situ necrosis can be caused for example by ischemia as seen in compartment syndrome or after injection of local anesthetic (e.g. bupivacaine). Repair after in situ necrosis can be virtually complete.  In a shearing type of injury not only are the myofibers breached but their connective tissue sheaths and intramuscular blood vessels are also torn to a variable extent. Healing after a shearing injury is complicated by the scar formation and complete restoration of the muscle is usually not possible [,]. Following muscle damage several proteins are released into serum. One of the most commonly used markers of muscle injury is creatine kinase (CK) which is generally detectable – days post injury and can remain elevated for – days after prolonged strenuous exercise. Most of the measured CK is caused by the muscle-specific isoenzyme CK-MM. Carbonic anhydrase III (CA-III) and myoglobin (Mb) are more specific to muscle than total CK is, and the profile differs. CA-III is present in type I fibers only and Mb peaks immediately after long-distance running, making them suitable for markers of acute events. It must be acknowledged that a large variability exists with regard to interindividual differences in responses of

100 Maximum tetanic tension (% control)

Injury and repair

80 60 40

Sham operated Lengthening Isometric Shortening

20 0 0

5

10

15

20

25

30

35

Time after stimulation (days) Fig. .. Decline in performance in the recovery phase after isometric, dynamic contraction and lengthening contraction.

these muscle damage markers, and that only an indicative relationship between degree of muscle damage and serum markers can be demonstrated. The exact mechanism behind the cascade of changes associated with eccentric exercise is not clear, but free oxygen radicals and inflammatory processes are suggested to play a role. Two major hypotheses have been proposed to explain damage to skeletal muscle associated especially with eccentric exercise. The first emphasizes metabolic overload, where the ATP demand surpasses the production, leading to a vicious cycle of Ca2+ overloading of the cell and further

 Chapter . decrease in ATP production. Intracellular calcium activates phospholipase which in turn is involved in a subsequent breakdown of the cell membrane — explaining the fiber necrosis occurring days later — and causes an activation of the arachidonic acid cascade and the production of prostaglandins. The other hypothesis stresses mechanical factors as a cause of exercise-induced muscle damage, pointing out the relatively low metabolic cost but the high mechanical strain per muscle fiber during eccentric exercise. In support of the latter, mechanical disruption of the sarcolemma has been demonstrated immediately after exercise. It has been found that training of a specific muscle group diminishes the structural changes, strength reduction and clinical manifestations associated with eccentric exercise (Fig. ..). With regard to the cause of muscle injury in eccentric exercise, more recent data have suggested that the decline in force after eccentric contraction is related more to the magnitude of muscle strain than to the stress imposed upon the fibers. Putting this finding into perspective, it is likely that strain results in muscle fiber membrane disruption and subsequent proteolysis or conformational changes of the cytoskeletal network. A candidate could be the calcium-activated protease calpain which uses desmin as a substrate, and is activated by increased intracellular Ca2+ concentration. It can be hypothesized that muscle fiber strain increases calcium influx and intracellular Ca2+ via stretch-activated channels or disruption of t-tubuli or sarcoplasmic reticulum. In more extensive in situ necrosis type of injuries, as in the compartment syndrome, the myofibers become necrotized within their intact basal lamina over a variable length, in the most severe cases the entire length of the myofiber. Both the basal lamina and the connective tissue framework of different mysial sheath remain intact. The satellite cells are remarkably resistant to different types of injury, including ischemia, and they become activated after the insult has subsided and the regeneration process has been initiated. The basal lamina provides the scaffold within which the regeneration can proceed without major disturbing effects. The production of new myofiber to replace the necrotized part follows in general the same sequence as the formation of skeletal muscle during development (see above). The myoblasts fuse into myotubes which are also able to fuse with the surviving parts of the injured

myofiber and thereby restitution of the entire myofibers and bridging over the entire necrotized segment may occur [,,]. A shearing type of muscle injury may be caused by a strain, contusion, laceration or incision, in which myofibers together with their basal membrane, and their mysial sheaths are ruptured to a variable degree, and thus the functional continuity of the tendon– muscle–tendon complexes is disrupted. In these injuries the spontaneous contraction of the transected myofibers results in the formation of a gap between the stumps of the ruptured fibers, which forms the central zone (CZ) of the injury (Fig. ..). Due to the rich vascularization of skeletal muscle, hemorrhage from the torn vessels fills up the gap and this hematoma is later replaced by a connective tissue scar. The injury breaches the plasma membrane of the myofibers and thus exposes sarcoplasm to the extracellular space, initiating necrosis in the injured myofibers inside the preserved though ruptured original basal lamina. The extension of the necrosis along the ruptured myofiber must be halted to prevent destruction of the entire fiber. This is implemented by condensation of cytoskeletal material, which forms a so-called contraction band at a distance of approximately – mm from the rupture. This band acts as a barrier in the protection of which a demarcation membrane, i.e. a new plasma membrane, is formed and thereby the integrity of the myofiber, though divided into two parts, is restored. The necrotized part will be regenerated, i.e. it forms the regeneration zone (RZ) of the injury, which is delineated from the survival zone (SZ), where myofibers survive with certain reactive changes [,]. Blood-derived inflammatory cells gain immediate access to the injury site and substances released from the necrotized area serve as chemoattractants for further extravasation of inflammatory cells. Polymorphonuclear leukocytes of the acute phase are soon followed by monocytes, which are transformed into macrophages and begin to phagocytose the necrotic debris both in the RZ within the original basal lamina cylinders and in the CZ. The regeneration pattern after shearing muscle injury follows a remarkably uniform scheme. Satellite cells become activated by mitogenic factors derived from the necrotic tissue and by growth factors secreted

Skeletal Muscle



(1)

Rupture + necrosis + phagocytes

(2)

Proliferation of myoblasts

(3)

Late attachment to the scar Fig. .. Responses to a laceration trauma in rat muscle. See text for further explanation.

by macrophages. Experimental studies have suggested that sarcolemmal contact exerts a preventive effect upon satellite cell proliferation. This could explain why only the damaged parts of a fiber with injured sarcolemma respond with regeneration. On the other hand, it has been suggested that satellite cells from the surviving part are also recruited to the RZ. Several growth factors, including insulin-like growth factor I (IGF-I), transforming growth factor b (TGF-b) and basic fibroblast growth factor (bFGF), affect regeneration by either stimulation or inhibition of proliferation, and differentiation of satellite cells depending on the stage of regeneration. For example, bFGF response is coupled to plasma membrane wounding and occurs early in the regeneration, whereas IGF-

released from the satellite cell itself is thought to stimulate differentiation, which is followed by TGF-b-mediated inhibition of the differentiation process. However, it has to be acknowledged that most data on the involvement of growth factors in the regeneration process after muscle injury, derive from in vitro experiments, while results in humans are still almost non-existent. The activated satellite cells begin to proliferate at about  h post injury within the preserved basal lamina in the RZ. The satellite cells differentiate into myoblasts. This is associated — in not only developing but also regenerating muscle — with expression of myogenic transcription factors of the myoD gene family (MyoD, myogenin, Myf, Myf), which determine

 Chapter . the differentiation of the precursor cells along the myogenic lineage by inducing the production of muscle-specific proteins. Myoblasts fuse with each other into multinucleated myotubes. The regenerated muscle cells fill the original basal lamina cylinder of the RZ by approximately day , whereafter they extend out of the opening of this basal lamina into the connective tissue of CZ (see below). Proximally the myotubes fuse with the preserved myofibers of the SZ. The regenerating myofibers gradually acquire their mature form with bundles of myofilaments which become organized into regular sarcomeres thereby giving the myofiber its cross-striated appearance. Furthermore, myonuclei assume their normal subsarcolemmal localization [,]. The early phase of the regeneration process after shearing injury up until about day  is almost identical to that seen after in situ necrosis, because it occurs within the basal lamina scaffold. Thereafter, the ends of the regenerating fibers need to enter the connective tissue scar of CZ. This creates a situation in which regeneration of the injured myofibers and formation of the connective scar tissue between the stumps are two simultaneous processes which are at the same time dependent upon but also at odds with each other. On the one hand, the scar is needed to keep the stumps together and it provides the connective tissue with which the ends of the regenerating myofibers can reestablish the firm myofiber to extracellular matrix (ECM) attachment. On the other hand, if the connective tissue scar formation between the stumps is excessive it may impede regeneration of myofibers and reinnervation of the so-called abjunctional stumps (see below). Within the first day after muscle injury the hematoma between the ruptured myofibers is invaded by inflammatory cells including phagocytes which begin disposal of the blood clot. Blood-derived fibrin and fibronectin cross link to form a primary matrix, which acts as a scaffold and anchorage site for the invading fibroblasts and gives the initial strength to the scar to withstand the forces applied on it. Fibroblasts begin to synthesize both proteins and proteoglycans of the ECM. Fibronectin, collagen type III and tenascin are among the first ECM proteins to be expressed, followed later by production of type I collagen which remains elevated for several weeks. Parallel to the

deposition of ECM proteins, the tensile strength of the scar increases. Biomechanical tests have shown that upon pulling, regenerating muscle ruptures at the scar between the stumps until day . Thereafter the scar is stronger than the muscle tissue and the rupture occurs within myofibers close to their ends, at the site where the rupture most often occurs also in healthy muscle. The ends of the regenerating fibers attempt to pierce through the scar tissue from day  onwards and maintain a growth cone appearance until about day –. During this active growth period the regenerating fibers reinforce their integrin-mediated adhesion to the ECM (Fig. ..) on their lateral surfaces in both the intact (SZ) and the regenerating (RZ) parts of the myofibers. This lateral adhesion reduces movements of the stumps and the pull on the still fragile scar, and thus apparently reduces the risk of rerupture. Furthermore, lateral adhesion allows for the use of the injured muscle before complete healing has been achieved. Interestingly, reinforcement of lateral adhesion does not occur if muscle is immobilized after injury, indicating that signals of mechanical stress must be transduced from the surrounding ECM to induce this reinforcement. On the other hand, integrins appear to transduce signals of mechanical stress, which affect the synthesis of ECM proteins in the connective tissue cells, thereby regulating the composition of the surrounding ECM. It is likely that integrintransduced signals are essential also in regulating various cellular functions in regenerating myofibers. Thus, the increased expression of integrins is more important for enhanced signal transduction in the drastically altered mechanical stress situation in ruptured myofibers than for adhesion as such. These molecular findings support the importance of early mobilization during rehabilitation after muscle injuries. Around day  new myotendinous junctions are formed at the end of regenerating myofibers with clustering of integrin- and dystrophin-associated molecules. Having re-established firm terminal adhesion, myofibers no longer require reinforced lateral adhesion, and integrin and vinculin on the lateral sarcolemma decrease whereas immunoreactivity for dystrophin-associated molecules increases. Thus, these two complexes of adhesion molecules seem to have complementary roles in myofiber–ECM

Skeletal Muscle adhesion. Gradually the imposed scar diminishes in size, bringing the stumps closer to each other, and finally myofibers become interlaced. However, full fusion of the stumps does not occur, as indicated from high levels of integrins, for up to  months after the injury. Thus it appears that injuries resulting in the division of a muscle into two halves will result in persisting interposed scar tissue in the muscle. The volume of the interposed scar also appears to have significance for reinnervation, and the myogenically denervated abjunctional stumps are reinnervated by axons sprouting from nerves in the adjunctional stumps on the contralateral side of the scar. These thin axons are able to pierce through the scar and induce formation of new neuromuscular junctions on the abjunctional stumps. If the interposed scar is too dense or voluminous the sprouts may be unable to penetrate through it and the abjunctional stumps remain denervated, undergo neurogenic atrophy and are replaced by connective tissue. The processes occurring during regeneration are influenced by mobilization. As an example, adhesion protein complexes have been shown to respond after just a single bout of exercise with regard to transcription and mRNA formation, whereas the protein synthesis rate increases after repetitive exercise bouts only [,,]. Muscle ruptures due to a sports injury can also be complicated by rupture of intramuscular nerve branches, which leaves parts of the muscle denervated. Because in such an injury the nerve itself is damaged, the denervation and consequent atrophy of myofibers is neurogenic. In shearing injury parts of the ruptured myofibers may also become myogenically denervated. This occurs because each myofiber is innervated at a single neuromuscular junction located within the middle third of the myofiber, and the transection of the fiber often leaves the neuromuscular junction on one of the muscle fiber stumps. Finally, it has been shown that myoblasts grown in a non-moving culture system proliferated with random orientation, whereas cells which were cyclically lengthened and shortened became aligned and synthesized more protein []. This indicates that mechanical stress or at least strain has a pronounced effect on the myoblast maturation process, and demonstrates the importance of lengthening–shortening activity in rehabilitation after injury.



Summary Skeletal muscle represents a unique tissue with multinuclear cells and a variety of proteins responsible for mechanical function and energy supply, allowing stability and active movement. Muscle possesses an enormous ability to adapt to various types of mechanical loading and training. Increased loading results in enhanced protein turnover and in a higher net synthesis of both myofibrillar and mitochondrial components, and hypertrophy of the individual muscle cell occurs. Furthermore, muscle fiber types can alter with mechanical loading, favoring a more oxidative fiber type. Conversely, inactivity causes rapid loss of muscle tissue and oxidative capacity in a reversible fashion. Muscle fibers depend on cytoskeletal and extracellular matrix proteins present within and around muscle fibers in order to optimally transmit force, and overloading can result in both cytoskeletal damage and muscle cell rupture damage. Satellite cells play an important role in regeneration of muscle tissue, under the influence of mechanical stretching and active loading. Complex cellular and molecular regulation lies behind the response of muscle proteins to changes in contractile activity, and responses are modulated by factors as nerves, growth factors, hormones, temperature, circulation and fluid shifts. Such signaling pathways are just beginning to be identified.

Multiple choice questions  Prolonged endurance training results in increased oxidative capacity of the muscle and in: a a fiber type shift from type I to type II b no shift at all c a fiber type shift from type IIb/IIx to type IIa d a fiber type shift from type II to type I.  The primary function of the satellite cells involves: a synthesis of oxidative enzymes b connection of motor nerves to the sarcolemma c acting as a reservoir for formation of myoblasts and myofibrillar structure in injury and supplying genetic material for myofibrillar protein formation in strength training d formation of extracellular matrix proteins.  Tropomyosin is important for: a enabling motoneuron excitation b blocking of calcium uptake by the mitochondria

 Chapter . c inhibition of actin and myosin interaction d stimulation of cross-bridge shortening.  Resistance training results in the following adaptation(s) in skeletal muscle: a hyperplasia and hypertrophy b increased levels of oxidative enzymes and hypertrophy c hypertrophy d fiber type I formation and hypertrophy.

References  Lieber RL, Leonard ME, Brown-Maupin CG. Effects of muscle contraction on the load-strain properties of frog aponeurosis and tendon. Cell Tissues Organs ; : –.  Trestik CL, Lieber RL. Relationship between Achilles tendon mechanical properties and gastrocnemius muscle function. J Biomechan Eng ; : –.  Saltin B, Gollnick PD. Skeletal muscle adaptability. significance for metabolism and performance. In: Peachey LD, ed. Handbook of Physiology. Bethesda: American Physiological Society, : –.  Jansen JKS, Fladby T. The perinatal reorganization of the innervation of skeletal muscle in mammals. Prog Neurobiol ; : –.  Bischoff R. Interaction between satellite cells and skeletal muscle fibers. Development ; : –.  Milner-Brown HS, Stein RB, Yemm R. The contractile properties of human motor units during voluntary isometric contractions. J Physiol ; : –.  Miller JB, Stockdale FE. Developmental origins of skeletal muscle fibers; clonal analysis of myogenic cell lineages based on expression of fast and slow myosin heavy chains. Proc Natl Acad Sci ; : –.  Kirkwood SP, Munn EA, Brooks GA. Mitochondrial reticulum in limb skeletal muscle. Am J Physiol ; : C–C.  Hultman E. Physiological role of muscle glycogen in man, with special reference to exercise. Circulation Res ; : –.  Huxley AF, Niedergerke R. Structural changes in muscle during contraction. Interference microscopy of living muscle fibers. Nature ; : –. a Edgerton VR, Smith JL, Simpson DR. Muscle fibre type populations of human leg muscles. Histochem J ; : –.  Huxley HE, Hanson J. Changes in the cross-striations of muscle during contraction and stretch, and their structural interpretation. Nature ; : –. a Eftimie E, Brenner HR, Buonanno A. Myogenin and MyoD join a family of skeletal muscle genes regulated by electrical activity. Proc Natl Acad Sci ; : –.

 Dominguez R, Freyson Y, Trybus KM, Cohen C. Evidence that myosin neck bending is taking place during muscular contraction. Cell ; : –.  Hill AV. The heat of shortening and the dynamic constants of muscle. Proc Royal Soc London ; : –.  Friden J, Sjöström M, Ekblom B. Myofibrillar changes following intense eccentric exercise in man. Int J Sports Med ; : –.  Kääriäinen M, Kääriäinen J, Järvinen TLN, Sievänen H, Kalimo H, Järvinen M. Correlation between biomechanical and structural changes during the regeneration after laceration injury of skeletal muscle. J Orth Res ; : – .  Kääriäinen M, Kääriäinen J, Järvinen TLN, Nissinen L, Heino J, Järvinen M, Kalimo H. Integrin and dystrophin associated adhesion protein complexes during regeneration of shearing type muscle injury. Neuromusc Disord ; : –.  McCully KK, Faulkner JA. Injury to skeletal muscle fibers of mice following lengthening contractions. J Appl Physiol ; : –.  Gordon AM, Huxley AF, Julian FJ. The variation in isometric tension with sarcomere length in vertebrate muscle fibers. J Physiol ; : –.  Katz B. The relation between force and speed in muscular contractions. J Physiol ; : –.  Bodine SC, Roy RR, Eldred E, Edgerton VR. Maximal force as a function of anatomical features of motor units in the cat tibialis anterior. J Neurophysiol ; : –.  Burke RE. Motor unit types of cat triceps surae muscle. J Physiol ; : –.  Buchthal F, Schmalbruch H. Spectrum of contraction times of different fibre bundles in the brachial biceps and triceps muscle of man. Nature ; : –.  Peter JB, Barnard RJ, Edgerton VR, Gillespie CA, Stempel KE. Metabolic profiles on three fiber types of skeletal muscle in guinea pigs and rabbits. Biochemistry ; : –.  Thompson WJ, Sutton LA, Riley DA. Fibre type composition of single motor units during synapse elimination in neonatal rat soleus muscle. Nature ; : –.  Schiaffino S, Gorza L, Sartore S, Saggin L, Ausoni S, Vianello M, Gundersen K, Lomö T. Three myosin heavy chains isoforms in type  skeletal muscle fibres. J Musc Res Cell Motil ; : –.  Chahine KG, Baracchini E, Goldman D. Coupling muscle electrical activity to gene expression via cAMP-dependent second messenger system. J Biol Chem ; : – .  Baldwin KM, Klinkerfuss GH, Terjung RL, Mole PA, Holloszy JO. Respiratory capacity of white, red and intermediate muscle, adaptive response to exercise. Am J Physiol ; : –.  Salmons S, Henriksson J. The adaptive response of skeletal muscle to increased use. Muscle Nerve ; : –.

Skeletal Muscle  Booth FW, Baldwin KM. Muscle plasticity: energy demand and supply processes. In: Rowell LB, Shepherd JT, eds. Handbook of Physiology, Section . Oxford: American Physiological Society, : –.  Williams RS, Neufer PD. Regulation of gene expression in skeletal muscle by contractile activity. In: Rowell LB, Shepherd JT, eds. Handbook of Physiology, Section . Oxford: American Physiological Society, : –.  Williams P, Goldspink G. Change in sarcomere length and physiological properties in immobilized muscle. J Anat ; : –.  Thomason DB, Herrick RE, Surdyka D, Baldwin KM. Time course of soleus muscle myosin expression during hindlimb suspension and recovery. J Appl Physiol ; : –.  Gollnick PD, Armstrong R, Saubert C, Piehl K, Saltin B. Enzyme activity and fiber composition in skeletal muscle of untrained and trained men. J Appl Physiol ; : –.  Gollnick PD, Armstrong RB, Saltin B, Saubert CW, Sembrowich WL, Shepherd RE. Effect of training on enzyme activity and fiber composition of human skeletal muscle. J Appl Physiol ; : –.

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 Henriksson J, Reitman J. Time course of changes in human skeletal muscle succinate dehydrogenase and cytochrome oxidase activities and maximal oxygen uptake with physical activity and inactivity. Acta Physiol Scand ; : –.  Henriksson J. Training induced adaptation of skeletal muscle and metabolism during submaximal exercise. J Physiol ; : –.  Moritani T, Devries HA. Neural factors versus hypertrophy in the time course of muscle strength gain. Am J Phys Med ; : –.  Hurme T, Kalimo H, Sandberg M, Lehto M, Vuorio E. Localization of type I and III collagen and fibronectin production in injured gastrocnemius muscle. Lab Invest ; : –.  Hurme T, Kalimo H. Adhesion in skeletal muscle during regeneration. Muscle Nerve ; : –.  Henry MD, Campbell KP. A role for dystroglycan in basem*nt membrane assembly. Cell ; : –.  Vandenburg HH. Dynamic mechanical orientation of skeletal myofibers in vitro. Dev Biol ; : –.

Chapter 1.4 Neuromuscular Aspects of Exercise — Adaptive Responses Evoked by Strength Training PER AAGAA RD & A LF THORSTE NSSON

Ikai M, Steinhaus AH. Some factors modifying the expression of human strength. J Appl Physiol ; : –. Heavy-resistance strength training generally results in both neural and muscular adaptations. Muscle hypertrophy was already recognized in the late s and has since then been extensively documented at wholemuscle, muscle-fiber and muscle subcellular levels. About the same time it was observed that substantial gains in muscle strength could occur without any detectable changes in the muscle itself, particularly in the early stages of the training regime. (Recent methodologic developments have, however, demonstrated early changes to occur in RNA translation and transcription.) The logical conclusion was that the improvements in strength had to be accounted for by neural adaptations. This assumption required there to be a margin, or force reserve, in the muscle that would not be accessible with a normal maximal voluntary effort due to neural inhibitory mechanisms. Another assumption would be that these mechanisms could be overcome, disinhibited, by adaptations in the nervous system occurring as a result of strength training. Ikai and Steinhaus reported one of the first convincing demonstrations of the existence of such a muscular reserve of force inherent to the muscle, and thus the presence of inhibitory mechanisms. They showed that the static strength of the arm flexor muscles could be substantially increased above that voluntarily achiev-



able ‘by a loud noise, by the subject’s own outcry, by certain pharmacologic agents, and by hypnosis’. In Fig. .. (original figure) the strength output during repeated maximal voluntary efforts, is shown with and without a preceding gunshot or shout. Similar effects on strength were seen with the other interventions. The authors conclude that all their observations ‘support the thesis that the expression of human strength is generally limited by psychologically induced inhibitions’ and that the interventions decreased these inhibitions. They also emphasize the large variation between subjects in response to the interventions. They particularly point out one subject who showed no increase in strength under hypnosis. This subject was an ‘experienced weight-lifter’ and the interpretaBlank Shot Shout Blank control

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Time (min) Fig. .. Strength output, expressed in pounds (LBS), measured by Ikai & Steinhaus during repeated static contractions of the arm flexors [].

Neuromuscular Aspects of Exercise tion was that ‘he was able, probably because of long training, to approximate his physiological limit in the waking state’, thus suggesting a trainability of this neural phenomenon. The existence of a margin for improvement in strength by neural adaptations has since been convincingly demonstrated by other methods, such as electrical stimulation applied directly onto the muscle or to the nerve supplying it. By similar means, a smaller margin has been noted in trained athletes. In addition to the accumulation of indirect evidence for neural adaptations, particularly in the initial phase of a training program, more direct evidence for such adaptations has also emerged. Perhaps the most thoughtprovoking evidence has been obtained in experiments where the contractions have been only intended, and no activation of the muscles has actually occurred, as verified by electromyographic recordings[a]. Still, significant improvements in strength were seen (the hypothenar muscles of the hand were investigated) of a magnitude similar to that obtained with conventional ‘effortful’ contractions. The authors conclude: ‘These force gains appear to result from practice effects on central motor programming or planning’. Strength gains were also detected for the corresponding muscles of the opposite hand. Such transfer of training effects, presumably of neural origin, has been frequently documented in the literature. Obviously, these findings have interesting implications for rehabilitative training of unilateral neuromuscular injuries.

Introduction The assessment of maximal muscle strength For more than seven decades the contractile strength of human skeletal muscle in vivo has been evaluated by use of various types of dynamometers. Early mechanical devices allowed muscle contraction strength to be determined during isometric (static) contraction conditions. In addition, in vivo mechanical muscle performance was assessed in dynamic contractions using sophisticated flywheel methodology [,]. With the evolution of motor-driven dynamometers it became possible to obtain maximal muscle strength during concentric (shortening) and eccentric (lengthening) muscle contractions. Both isokinetic and non-



isokinetic dynamometers have been used to evaluate the dynamic strength properties of human muscle in vivo. While the isokinetic dynamometer is designed to keep joint angular velocity constant, non-isokinetic dynamometers allow acceleration and speed to vary freely throughout the movement. Non-isokinetic dynamometers have been used mainly to examine the strength capacity of the elbow flexors [,] and knee extensors [–]. These muscles have also been extensively investigated by use of isokinetic dynamometry [–] in addition to a large number of other human skeletal muscles [,]. The descriptive and clinical relevance of assessing maximal muscle strength by use of isokinetic dynamometry may not seem obvious at first hand. Even though the term ‘isokinetic’ denotes that joint angular velocity is kept constant (which may itself not always be true) [], this does not imply that any constancy should exist for the linear velocity of muscle shortening or lengthening. Furthermore, due to the variation in muscle lever arm length(s) throughout the range of joint movement, the recorded moment may not resemble the actual contractile force generated by the muscle []. In addition, neuromuscular activation may be reduced under certain loading conditions (e.g. eccentric contractions) and a coactivation of antagonist muscles can also occur. This applies to isokinetic dynamometry as well as to all other types of strength measurements. In result, inconsistent and conflicting moment– velocity relationships may be found in the literature with marked differences observed between studies and muscles examined [] as well as between subject groups of different training status []. Nevertheless, isokinetic dynamometry does appear useful for evaluating the expression of maximal voluntary muscle strength in vivo. Firstly, joint angular velocity and movement range can be reproduced with reasonable accuracy. In the experimental set-up this means that multiple trials can be performed and compared successively until reaching a given selection criterion. Secondly, the fact that joint movements are accurately reproduced ensures that the change in muscle strength induced by specific interventions (training, detraining) can be evaluated in a reliable way. Thus, it is important to recognize that a change in maximal isokinetic strength may be a valid indication of the underlying change in maximal muscle force, as for a given

 Chapter . subject the relation between joint angular velocity and muscle contraction velocity or between the measured muscle moment and the underlying muscle force is not likely to change. Thirdly, and perhaps most importantly, modern isokinetic dynamometers allow for a standardized and well-controlled evaluation of maximal eccentric muscle strength. This aspect of in vivo muscle function deserves special attention as it not only appears to comprise unique mechanisms of neuromuscular activation and inhibition but also involves factors of importance for dynamic joint stability and stiffness. A hyperbolic relationship exists between the contractile force and velocity of shortening of isolated muscle in vitro [,] (Fig. ..). Similar hyperbolic force–velocity relationships may be observed during in vivo contraction of human skeletal muscle [,,]. However, force–velocity relations that were clearly non-hyperbolic have been reported as well [,,]. Beyond any doubt the quadriceps femoris has been most extensively used to investigate the maximal contractile strength (moment of force) generated by human skeletal muscle, in vivo. The appearance of isokinetic (i.e. constant velocity) dynamometers has allowed maximal dynamic muscle strength to be obtained during standardized and easily reproducible experimental conditions (see above). While some studies obtained the peak moment of force (‘torque’) exerted within the total range of movement [–] others have recorded the moment of force at a specific knee joint angle [,,] or performed both types

of measurements [,–]. Concentric isokinetic quadriceps peak moment occurs at gradually more extended knee joint positions with increasing joint angular velocity [,,]. Accordingly, the corresponding moment–velocity relationship consists of moment values obtained at different parts of the quadriceps length–tension curve. Nevertheless, the moment– velocity pattern based on angle-specific moment appears to deviate most markedly from a hyperbolic curvature at least when obtained in untrained subjects, as reflected by a levelling-off (‘plateauing’) of moment at low angular velocities [,,,,,,–] (see Fig. ..). A similar plateauing of moment of force during slow concentric contraction has been reported for other muscle groups than the quadriceps, e.g. the arm flexors [,]. Interestingly, maximal arm flexor and extensor moments plateaued in subjects of low maximal muscle strength, whereas no plateauing could be demonstrated in subjects of high strength [] suggesting that this phenomenon can be modulated by strength training. This plateauing in slow concentric muscle strength has previously been hypothesized to arise from a force inhibiting neural mechanism, reducing the level of neural efferent motor drive [,]. Maximal eccentric contraction strength is equal to or up to about % higher than maximal isometric strength when recorded in the human quadriceps muscle, in vivo [,,–]. In contrast, maximal eccentric contraction force is –% greater than

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Fig. .. Contractile force — velocity relationships obtained for shortening (concentric) and lengthening (eccentric) contractions in isolated in vitro preparations of whole muscle [] and single muscle fibers [] obtained from the frog. Superimposed curves show muscle strength measured in vivo during maximal voluntary activation and/or when percutaneous electrical stimulation was applied to the quadriceps femoris muscle [].

Neuromuscular Aspects of Exercise

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Fig. .. Maximal concentric and eccentric quadriceps muscle strength obtained as isokinetic peak moment (triangles) and angle-specifc moment generated at ° knee joint angle (squares) before and after  weeks of (a) heavy resisitance strength training; and (b) low-resistance, high-velocity strength training using concentric contraction alone. Closed and open symbols denote pre- and post-training values, respectively. Adapted from [].

isometric or slow concentric force when obtained in isolated muscle preparations [,] (see Fig. ..). Reduced levels of neuromuscular activation are one likely reason for this apparent deficit in maximal eccentric muscle strength, in vivo. Consistent findings of a marked increase in maximal eccentric muscle strength following heavy-resistance strength training strongly suggest this mechanism of suppressed neural activation to be modifiable with training.

Changes in maximal muscle strength in response to strength training The influence of strength training on the maximal contraction strength of human muscle in vivo has been extensively investigated for the concentric part of the moment–velocity curve [,,,,,,]. Also, data exist for the training-induced change in maximal eccentric muscle strength [,–]. Following concentric strength training, maximal muscle strength and power have been reported to increase at the specific velocity employed during training



[,,,,]. These and similar observations have been taken to indicate a specificity of training velocity and training load. However, it is questionable whether a generalized concept of training specificity should exist, since muscle strength has been reported to increase also at velocities lower than the actual velocity of training [,,,] as well as at higher velocity [,,]. The conflicting findings of specific as well as non-specific training adaptations probably arise, at least partly, due to a varying influence of learning []. While training and data collection have often been performed on the same dynamometer, other studies have emphasized the use of different training and measuring devices. The latter approach is intended to reduce the influence of learning, in order to obtain a more valid measure of the neuromuscular adaptations induced by strength training. The levelling-off (plateauing) in muscle strength observed during slow concentric contraction has been reported to disappear in response to heavy-resistance strength training [,] (see Fig. ..). These findings point to the existence of a neural force-inhibiting mechanism, which can be modulated by training. Interestingly, strength training using lower loads and higher speeds appears to have no effect [] (see Fig. ..), suggesting that heavy training loads should be employed when intending to remove this forceinhibiting mechanism. Marked increases in maximal eccentric muscle strength have been observed following heavyresistance strength training [,–,–]. Eccentric or coupled concentric–eccentric training seems to evoke greater strength gains than concentric training alone [,–,]. Importantly, maximal eccentric strength appears to remain unchanged after lowresistance strength training [,] (see Fig. ..). Thus, the exertion of very large muscle forces during training is probably a major prerequisite for any change in maximal eccentric muscle strength to take place.

Neuromuscular adaptations evoked by strength training The adaptive changes observed in the neuromuscular system in response to specific types of strength training may be differentiated into neural and muscular factors. Thus, it is well known that changes in contractile properties, i.e. increases in maximal contraction force

 Chapter . and power as well as in the maximal rate of force development, can occur not only due to alterations in muscle morphology [] but also as a result of changes in the nervous system [,]. Neural adaptation mechanisms may involve changes in motoneuron recruitment and/or rate coding, more synchronized motoneuron firing patterns within the muscle itself as well as between muscle synergists, changes in spinal motoneuron excitability, and altered coactivation of antagonist muscles [–]. Early evidence, indicating neural mechanisms to play a significant role, was based on the findings that muscle strength increased more than could be accounted for by increases in muscle size alone [] and that strength gains were observed with no detectable muscle hypertrophy [,–]. More direct evidence has been provided with the use of electromyography (EMG), although inherent methodologic limitations may exist with the recording of surface EMG during voluntary muscle contraction. To overcome these problems, measurements of evoked spinal responses (H-reflex, V-wave) can be used to examine various aspects of neural adaptation evoked by strength training. In terms of muscle morphology, single muscle fiber area and whole-muscle area and volume have been demonstrated to increase following prolonged regimes of strength training []. In addition, based on the refinement of various in vivo muscle imaging techniques (MRI, ultrasonography), recent evidence suggests that muscle architecture in terms of muscle fiber pennation angle may also be altered, in turn contributing to the increase in physiologic muscle fiber area and contractile force generation with strength training []. The evaluation of muscle myosin heavy chain (MHC) content by use of electrophoretic analysis or immunochemical methods has provided a sensitive measure of the change in myosin isoform composition evoked by strength training. The emergence and evolvement of these methods have allowed an intensified focus on the change in muscle fiber composition induced by strength training and its impact on mechanical muscle performance. During static as well as dynamic contraction conditions, active muscle stiffness is determined by the total number of attached acto-myosin cross-bridges [] while also being strongly influenced by the pattern of neural activation []. Thus, the increase in muscle

size and/or neural innervation observed following strength training, in turn causing more cross-bridges to be attached during contraction, will have a strong positive effect on the ability to achieve high levels of muscle stiffness. In functional terms this effect would be beneficial over the whole movement spectrum, from athletes performing rapid and forceful movements to elderly individuals compensating for unexpected postural perturbations. The present chapter presents the involvement of various mechanisms and aspects of importance for the neuromuscular adaptation to strength training.

Adaptive changes in neural drive evaluated by electromyography EMG signal amplitude The electromyography (EMG) signal is constituted by the composite sum of all the muscle fiber action potentials present within the pick-up volume of the recording electrode(s). At the same time, this overall interference signal is modified by a multitude of intracellular and extracellular factors, which all exert a significant influence on the pattern of spatial and temporal summation of the single action potentials [,]. Acceptable test–retest reliability has been demonstrated for the EMG amplitude and power frequency obtained by use of surface electrodes []. Data based on intraclass correlation (ICC) analysis indicate that most of the variance in assessing reliability is among subjects rather than between days or trials []. For the human quadriceps femoris muscle, acceptable reproducibility was observed for the EMG recorded during static as well as dynamic contraction, including isokinetic knee extension [,,,]. Thus, with proper recording conditions and validated signal processing techniques, the surface electromyogram appears to be a useful tool for both clinical evaluation and research []. From a physiologic perspective the EMG signal can be seen as a complex combination of (i) motor unit recruitment, (ii) variation in firing frequency (rate coding), and (iii) synchronization between firing patterns of individual motoneurons []. EMG recording (Figs .. and ..) has been widely used to quantify the neural changes evoked by strength training. A majority of studies has demonstrated increased EMG

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signal amplitude after strength training, indicating a rise in the neural efferent drive to the muscle fibers [,,,,–,,,]. Importantly, neural drive has been found to increase not only in previously untrained subjects but also in highly trained strength athletes []. Thus, EMG increased when strength athletes used heavy training loads (above % of maximum), but decreased when training was performed at lower loads (–% of maximum) []. These findings suggest that heavy training loads should be used when seeking optimal neural enhancement. It is important to notice that the increase in surface EMG amplitude observed following strength training does not provide any conclusive evidence per se of the differential change in motoneuron recruitment, firing frequency or synchronization. In addition, it has not always been possible to demonstrate increases in EMG with strength training [–]. It should be recognized

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Fig. .. (a) Raw tracings of isokinetic knee joint moment and electromyography (EMG) signals obtained in an untrained male subject during maximal concentric (left) and eccentric (right) contraction of the quadriceps femoris muscle. (b) Maximal concentric and eccentric quadriceps muscle strength (left) and vastus lateralis EMG (right) measured in  untrained male subjects and displayed as a function of knee joint angle and joint angular velocity. Negative and positive velocities denote eccentric and concentric muscle contraction, respectively [].

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therefore that electrode positions as well as skin and muscle tissue properties (i.e. subcutaneous fat layer, muscle fiber pennation angle, etc.) may vary from one recording session to another despite careful measuring procedures. Moreover, the compound surface EMG signal can constitute a summation of several thousand action potentials, causing a significant portion of the signal to be inherently stochastic []. Consequently, the sensitivity of the EMG signal as a measure of training effects depends highly on the EMG processing routines used, i.e. sampling rate, filtering algorithms, cut-off frequencies, etc. However, many of the problems inherent with surface EMG can be reduced or even eliminated by use of more sophisticated EMG techniques (recording of intramuscular EMG using indwelling needle or wire electrodes, H-reflex and Vwave measurements, evoked cortical potentials, etc.) as described elsewhere in this chapter.

 Chapter . Motoneuron firing frequency

10 Force (N ¥ 1000–3)

Two basic questions can be raised: is motoneuron firing frequency influenced by strength training; and if that is the case, what is the functional significance? To address the latter question first, motor unit discharge rates have been recorded at much higher frequencies than needed to achieve full tetanic fusion in force. Thus, transient firing frequencies of – Hz were reported in brief bursts of activity during maximal voluntary contraction of human muscles in vivo [–]. Muscle innervation frequency influences not only the magnitude of contractile tension but also the rate of tension rise (i.e. rate of force development: RFD = Dforce/Dtime), as observed for whole muscle in situ [], single muscle fibers [,] and human muscle in vivo [–]. When individual motor units were examined in the neonatal rat [] it was noticed that RFD continued to increase at stimulation rates higher than the stimulation rate at which maximum tetanic tension was achieved [] (Fig...). Similar findings have been reported for whole-muscle preparations []. Corresponding results have been obtained for human musculature in vivo, as stimulation rates of  Hz were able to produce greater RFD, but not a greater peak isometric force, than  Hz stimulation rates []. Thus, the appearance of very high (i.e. supramaximal) firing frequencies likely serves to increase maximal RFD rather than increasing maximal contraction force per se [,] thereby causing a significant rise in contractile force in the initial phase of contraction (– ms). Importantly, at the onset of contraction the occurrence of discharge doublets in the firing pattern of single motoneurons (interspike interval < – ms, firing frequency >– Hz) cause a marked increase in contractile force and/or RFD [,,]. Thus, muscle force was markedly increased by addition of an extra discharge pulse (‘doublet’) as demonstrated during constant frequency stimulation of single motor units and whole isolated muscle [,] as well as in intact human muscle []. This phenomenon has been referred to as the catchlike property of skeletal muscle [–]. Interestingly, the occurrence of discharge doublets in the firing pattern of individual motor units was found to increase six-fold (from .% to .%) following ballistic resistance training [] (see Training for ‘explosive’ muscle strength, Fig. .. below).

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Time (ms) Fig. .. Single force–time curves recorded in isolated motor units in the rat soleus muscle using an innervation frequency that elicited maximal tetanic fusion and maximal contraction force (PO) compared to when even greater (i.e. supramaximal) innervation frequencies were used (RG) which also elicited maximal tetanic fusion, however at an elevated rate of force development. Adapted from [].

The maximal firing frequency of human muscle in vivo has been examined by use of intramuscular EMG recording techniques, which allow the firing pattern of single motor units to be identified. Based on such techniques, the maximal firing frequency obtained in the rectus femoris muscle during maximal voluntary contraction (MVC) was % greater in trained elderly weight lifters compared to agematched untrained individuals []. Furthermore, using a longitudinal study design maximal firing frequency has been found to increase after strength training of selected hand muscles [] and leg muscles (vastus lateralis [], tibialis anterior []). Following  weeks of ballistic-type resistance training Van Cutsem and coworkers reported a dramatic rise in the firing frequency of single motor units recorded in the tibialis muscle at the onset of maximal, forceful contraction. Mean firing frequencies of ., . and . Hz were observed in the first three interspike intervals, respectively, which increased to ., . and . Hz following the period of training [] (Fig. ..). Interestingly, training-induced increases in maximal motoneuron firing frequency appear to occur in both young and elderly individuals. Although elderly subjects initially demonstrated a lower maximal discharge rate than young subjects, no difference could be observed after strength training [,]. These data

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Interspike period Fig. .. Motoneuron firing frequency at the onset of contraction, obtained in the tibialis anterior muscle before and after a period of strength training. A marked increase in instantaneous firing frequency was observed following training, as all post-training values were greater than pre-training values (P < .). Data adapted from [].

show that maximal motoneuron firing frequency can be increased in response to strength training, and that this adaptation may overrule the age-related decline in maximal discharge rate. As depicted from the S-shaped relationship between firing frequency and contraction force [], an increase in maximal firing frequency can result in a relatively greater increase in surface EMG amplitude compared to the corresponding increase in maximal contractile force []. In consequence, traininginduced increases in EMG may exceed the increase in maximal muscle strength [,], although this is not always a consistent finding [,]. Obviously, such disproportionate changes in EMG and force with training do not provide any conclusive evidence for an increase in motoneuron firing frequency, as similar effects would be caused by more synchronized patterns of motoneuron firing (see below).

Motoneuron synchronization Synchronization in the firing patterns of different motoneurons has been examined by use of EMG crosscorrelation analysis techniques, to quantify the degree of temporal association between the discharge signals []. Based on such techniques, studies have shown



that the synchronization of motoneuron firing can be altered by learning [], which suggests that changes in synchronization may also occur as an adaptive response to strength training. Even though an increased incidence of synchronization between the firing patterns of different motor units within the muscle may occur with strength training [], the advantage of such intramuscular synchronization, if any, remains unsolved []. Studies using artificial nerve stimulation have shown that at submaximal contraction intensity, muscle force is greater with asynchronous than synchronous stimulation [,]. In addition, RFD in brief maximal contractions was higher during voluntary (i.e. asynchronous) contractions as compared to evoked tetanic (i.e. synchronous) contractions []. However, synchronous stimulation may not adequately mimic in vivo muscle contraction, where the occurrence of discharge doublets at the onset of contraction may yield a marked increase in RFD (see above). Milner-Brown and coworkers [] found that the discharge patterns of single motor units were more synchronized to the overall interference signal recorded by surface EMG following  weeks of strength training. As derived from single motor unit recording, observations of more synchronized firing patterns in weight lifters compared to skill-trained and untrained individuals [] support the notion that motor unit synchronization can be altered by strength training. Moreover, a longitudinal increase in synchronization between synergistic muscle pairs has been observed following ballistic strength training [], suggesting that intermuscular synchronization may also change as an adaptive response to strength training. An increase in motor unit synchronization induced by training is likely to result in a disproportionate increase in EMG amplitude, due to increased superposition of action potentials whose amplitudes are in phase and reduced summation of out-of-phase action potentials. Consequently, the peak-to-peak amplitude of the compound EMG signal is increased along with a decrease in median power frequency (MPF) [,a].

Motoneuron properties, evoked reflex responses Only a few studies have employed measurements of evoked spinal motoneuron responses to examine

 Chapter . STIM SPINAL CORD Sensory 1a Muscle spindle Presynaptic Motor INHIBITION a MUSCLE Postsynaptic H

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spinal and supraspinal mechanisms of importance for the training-induced change in maximal muscle strength. The Hoffmann (H) reflex [,] may be useful for the assessment of motoneuron excitability in vivo, although also reflecting the degree of presynaptic inhibition present for the Ia afferent synapses [,]. When the peripheral nerve is electrically stimulated, the H-reflex amplitude is seen to increase and then gradually decrease with rise in stimulation intensity, to become completely suppressed at stimulation intensities, which elicit a maximal M-response (Fig. ..). This suppression in H-reflex amplitude at maximum stimulation intensity occurs due to an increased collision between (i) antidromic nerve impulses in the motor axon (i.e. action potentials propagating backwards towards the spinal cord) and (ii) ortodromic nerve impulses caused by the Ia afferent reflex volley (i.e. action potentials propagating from the spinal cord to the muscle fibers). When the peripheral nerve is maximally stimulated during ongoing voluntary muscle contraction, the H-reflex response reappears (now denoted a V-wave) since the antidromic impulses are removed (‘cleared’) as a result of collision with efferent nerve impulses generated by the voluntary effort [,] (Fig. ..a). Thus, an increased descending motor drive causes more motoneuron axons to be cleared for passage of the evoked reflex response, which is directly reflected by an increase in V-wave amplitude []. At the same time, any increase in spinal motoneuron excitability and/or enhanced Ia synaptic

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Fig. .. (a) Raw EMG signal (sampling frequency  kHz) showing maximal M-wave and V-wave responses evoked in the soleus muscle by supramaximal stimulation of the tibial nerve during maximal isometric muscle contraction. (b) Mean V-wave and H-reflex amplitudes, obtained pre- and post- weeks of heavy-resistance strength training. The increases observed in Vwave and H-reflex amplitudes suggest an enhanced descending motor drive and/or increased excitability of spinal motoneurons and/or decreased Ia afferent presynaptic inhibition following the period of strength training [].

Neuromuscular Aspects of Exercise transmission efficiency would contribute to the increase in V-wave amplitude as well. Thus, V-wave and H-reflex measurements may be used to quantify the overall change in central descending motor drive, spinal motoneuron excitability and/or presynaptic inhibition induced by strength training [,–, ]. It is noticeable that the potential problem of invariant recording conditions with repeated measurements of surface EMG is eliminated with this particular type of evoked EMG recording, as the H-reflex and V-wave amplitude are both expressed relative to the peak-to-peak amplitude of the maximal Mresponse (Mmax) recorded during supramaximal stimulation of the motor nerve. Somewhat surprisingly, the H-reflex amplitude recorded in the soleus muscle during resting conditions (determined as Hmax/Mmax) was higher in endurance athletes than in power and sprint athletes [,a,b]. However, it could not be excluded that this finding occurred as a result of differences in muscle fiber composition between the two subject groups, since at low stimulation intensities the Ia afferent volley mainly excites the smaller motoneurons in the spinal cord which typically innervate the population of slow-twitch type I muscle fibers. In addition, it may be difficult to interpret differences in Hmax/Mmax between subject groups unless the shape of the H–M recruitment curve is identical in the groups examined. Otherwise the H-reflex would be elicited at different relative stimulation intensities, thereby evoking different amounts of antidromic clearing which would cause the H-reflex amplitude to differ. Although more time consuming, the H-reflex can alternatively be recorded using a stimulation intensity that evokes an M-response of a fixed percentage of the maximal direct M-response (e.g. % Mmax) [,,]. Ballet dancers demonstrate lower H-reflex amplitudes in the soleus muscle than physical education students, presumably due to increased presynaptic inhibition in the dancers []. In contrast, Mynark and Koceja [] observed no difference in soleus Hreflex amplitude between trained dancers and controls during standing or prone rest. However, H-reflex gain (ratio of H-reflex to background EMG) was lower in the dancers during isometric contractions at ,  and % MVC performed in a standing position, suggesting that the gating of spinal excitatory and in-



hibitory pathways can be modulated to adapt to the contraction-related demands placed upon the system during standing posture []. As previously described, the V-wave can be evoked when supramaximal H-reflex stimulation is superimposed onto maximal voluntary muscle contraction. Due to the supramaximal level of nerve stimulation, which excites all Ia afferent axons in the peripheral nerve, the V-wave response comprises all the spinal motoneurons, including the largest type II motor units. V-wave amplitudes recorded in the hand and lower limb muscles of sprinters and weight lifters were elevated relative to untrained control subjects [,,]. Using a longitudinal study design an ~% increase in V-wave amplitude was observed (recorded as V1/Mmax) following – weeks of strength training [], indicating an enhanced neural drive in descending corticospinal pathways, elevated motoneuron excitability and/or alterations in presynaptic inhibition. Recent results have verified these findings, demonstrating a % increase in V-wave amplitude (V1/Mmax) in response to  weeks of heavyresistance strength training [] (Fig. ..). Likewise, the H-reflex amplitude recorded during maximal contraction was found to increase after the period of training []. Interestingly, it appears difficult to elicit adaptive V-wave changes in certain hand muscles []. This finding suggests that the range of neural adaptation may differ between muscles involved in grasping tasks and muscles responsible for propulsive force generation, respectively. Collectively, the data based on measurement of evoked V-wave and H-reflex responses strongly support the notion that neural adaptation can occur both at spinal and supraspinal levels, involving increased motoneuron excitability (and/or changes in presynaptic Ia afferent inhibition) and enhanced central descending motor drive.

Eccentric muscle contraction It has been suggested that eccentric muscle contractions require unique activation strategies by the nervous system []. Indications of a preferential activation of high-threshold motor units have been demonstrated during eccentric muscle contraction of submaximal intensity [,], which was suggested to originate from an increased presynaptic inhibition

 Chapter . of Ia afferents synapsing onto the low-threshold motoneurons [,]. Measurements based on the H-reflex technique (see above) have shown that the modulation of spinal motoneuron excitability and/or presynaptic inhibition may differ between eccentric and concentric contractions of submaximal intensity []. Unique and distinct motor patterns could also exist during maximal eccentric contraction. Thus, raw EMG tracings obtained in the quadriceps femoris muscle demonstrate large EMG spikes dispersed by short interspike periods of low or absent EMG activity (Fig. ..). However, EMG mean or median power frequency (MPF) does not seem to differ between maximal concentric and eccentric quadriceps contractions [,,]. More than anything, these contrasting findings probably reflect the insensitivity of surface EMG spectral analysis for detection of subtle changes in motoneuron recruitment. Thus, the possibility exists that even if type II motor units were selectively activated during eccentric contraction, the corresponding increase in MPF due to their high firing frequency could be masked by a relative increase in synchronization as the result of their large unit size (i.e. many muscle fibers being innervated by the same motoneuron) and the appearance of temporal ‘on–off ’ activation patterns, both causing MPF to decrease. In consequence, recording of muscle EMG by use of intramuscular wire or needle electrodes could perhaps clarify this point, as it may allow the recruitment and firing pattern of single motor units to be identified. However, even when employing intramuscular techniques, it is difficult to discriminate signals from individual motor units during contractions of high intensity. Another experimental approach has been taken by use of muscle biopsy sampling, which demonstrated a clear pattern of selective glycogen depletion for histochemically stained type IIb fibers obtained in the vastus lateralis muscle acutely following bouts of maximal eccentric cycle sprint []. Although this finding suggests the presence of selective type II muscle fiber recruitment, it could also, at least in part, be explained by a greater glycogen breakdown rate in the type II fibers compared to type I fibers. Electrical transcutaneous stimulation of passive vs. active muscles has also been used to address the issue of neural activation during eccentric muscle contraction. For the quadriceps femoris and triceps surae muscles

eccentric contraction strength was higher than isometric strength during contractions evoked by electrical stimulation, but not during maximal voluntary muscle contractions [,,,] (Fig. ..). Moreover, with artificial activation the normalized moment– velocity relationship of human muscle in situ appears to have a more similar shape to that of isolated muscle in vitro, during both eccentric and concentric contractions [,,] (Fig. ..). Quadriceps muscle strength is elevated during eccentric but not concentric contractions when electrical transcutaneous stimulation is superimposed onto maximal voluntary contractions [,] (see Fig. ..). Interestingly, this evoked increase in eccentric contraction strength is seen only in sedentary subjects and not in strengthtrained athletes [], suggesting that the apparent deficit in eccentric muscle strength disappears as an adaptive response to strength training. More direct evidence exists to suggest that neuromuscular activation is in fact suppressed during eccentric contraction, as the EMG recorded in the quadriceps femoris muscle during maximal eccentric contraction was markedly less than that of maximal concentric contraction, particularly at high speeds [,,,,–] (Fig. ..). Hence, a neural regulatory mechanism that limits the recruitment and/or discharge rate of motor units during maximal voluntary eccentric muscle contraction has been proposed [,,,]. The precise mechanisms responsible for such an inhibition in motoneuron activation during eccentric contraction are not known. Although evidence of a preferential recruitment of type II motor units and derecruitment of type I units has been reported for submaximal eccentric muscle contraction in vivo [,], this could not be verified for maximal eccentric contraction as examined by surface EMG spectral analysis (MPF) [,–]. Unfortunately, no data are available on the recruitment and firing pattern of single motor units during maximal eccentric contraction. Recent results suggest that the apparent suppression in motoneuron activation during maximal eccentric contraction may be partly or fully removed following intense regimes of heavy-resistance strength training []. Thus, maximal eccentric muscle strength was seen to increase in parallel with a partial (lateral and medial vastii) or complete (rectus femoris)

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Fig. .. Maximal muscle strength (isokinetic moment of force) and EMG-velocity relationships determined during maximal voluntary eccentric and concentric contraction of the quadriceps femoris muscle. A significant suppression in quadriceps EMG was observed during slow concentric as well as in slow and fast eccentric contraction compared to fast concentric contraction. Data from [].

removal of suppressed EMG signal amplitudes following  weeks of strength training, which involved multiple exercise types (squat and leg press and knee extension) using heavy external loads (– RM) [] (Fig. ..). On the other hand, quadriceps EMG remained suppressed during maximal eccentric contraction, with no signs of a partial removal, when strength training was performed using a single type of exercise (i.e. maximal isokinetic knee extension) for a moderate period of time ( weeks) []. Based on these findings, the possibility exists that the removal of neural inhibition during maximal eccentric muscle contraction requires heavy-resistance strength training



regimes of long duration and/or a large total work load (number of exercises · number of sets · kg or Nm lifted or exerted in each set). The finding of a rapid and selective decrease in eccentric but not concentric muscle strength following  days of detraining in highly trained strength athletes [] further emphasizes the important effect of strength training not only for achieving but also for retaining optimal neural activation patterns during maximal eccentric muscle contraction. The specific mechanisms responsible for the adaptation in motoneuron activation during eccentric contraction are so far unidentified. During maximal voluntary muscle contraction afferent motor output is regulated not only via central descending pathways but also through sensory reflex pathways, including group Ib afferents from Golgi organs and group Ia and group II afferents from muscle spindles. Thus, the apparent suppression in motoneuron activation during maximal eccentric muscle contraction may be caused by inhibitory feedback from sensory group I and II afferents. Sensory Ib afferents from Golgi organs located in the muscle–tendon unit converge onto the entire motoneuron pool together with Ia and group II afferents from muscle spindles []. The Golgi Ib afferents excite inhibitory interneurons in the spinal cord, which in turn are influenced by higher central nervous system (CNS) centers through descending corticospinal pathways [,] (see Fig. .. below). It is possible that the removal of motoneuron inhibition, and the resulting increase in maximal eccentric muscle strength observed following heavy-resistance strength training, appears as a result of reduced inhibitory interneuron activity mediated via central descending pathways. Alternatively, reduced presynaptic inhibition of the Ia afferent inflow from muscle spindles would be expected to augment the excitatory spinal inflow during eccentric contraction as well. Significant increases in maximal eccentric muscle strength have been reported following heavyresistance strength training [,,–,–], whereas training using low resistance and faster speeds does not seem to have any effect [,] (Fig. ..). Generally, greater gains in eccentric strength have been observed following eccentric or coupled eccentric–concentric training as compared to concentric training [,–,] although not always a

 Chapter . Maximal contractile muscle strength

(a)

Strength

After strength training

Quadriceps Moment of force

Before strength training

Eccentric Fast

Concentric Slow

Neuromuscular activation

(b)

Knee angular velocity

Fast

Slow

EMG

After strength training RF

Quadriceps EMG

VL, VM

Before strength training Eccentric Fast

Concentric Slow

Slow

Fast

consistent finding [,]. Also, it should be recognized that concentric heavy-resistance strength training might elicit substantial gains in maximal eccentric [,,,] and coupled eccentric–concentric [] muscle strength. Eccentric strength training may evoke specific adaptive changes in the nervous system. Thus, recordings of surface EMG have demonstrated neural activation to dominantly increase in eccentric contraction conditions following eccentric training, while neural activation during concentric contraction mainly increased following concentric training [–]. These findings of training-specific neural adaptations are not surprising, given the fact that all training and strength evaluation tests were carried out in the same dynamometer [–]. Nonetheless, neural activation during maximal eccentric contraction also increased when different test and training devices were used [] (Fig. ..). In addition, neural contralateral effects, so-called crosseducation [], may be more pronounced with eccentric training, as indicated by a greater relative increase in strength reported for the non-trained limb following eccentric compared to concentric single-limb training []. A similar trend was reported by Seger & Thorstensson [] who also found contraction type

Knee angular velocity

Fig. .. (a) Heavy resistance strength training has consistently been shown to result in a significant increase in maximal eccentric and slow concentric strength of the quadriceps femoris muscle (VL, VM, RF). (b) Following  months of heavy resistance training the suppression of motoneuron activation was fully (RF) or partially (VL, VM) removed, in parallel with a marked increase in maximal eccentric muscle strength. Data from [].

and speed specificity in the transfer of strength gain from the trained to the contralateral, untrained, leg after both eccentric and concentric training.

Bilateral strength deficit Motoneuron activation and force generation may be significantly reduced in maximal bilateral compared to unilateral muscle contraction. Thus, less EMG and strength have been recorded from each limb during simultaneous contraction of the muscles in both limbs than measured during single limb contractions [–] although not present in all studies []. Interestingly, strength training involving bilateral muscle contractions appears to reduce or fully abolish the bilateral strength deficit []. Since the bilateral deficit in EMG and force can be observed in both maximal isometric and rapid dynamic contractions [], it has been suggested that the mechanism may act at higher centers involved in programming of the movement []. During volitional muscle contraction EEG potentials, defined as movement-related cortical potentials (MRCPs), generated by neural circuits involved in motor preparation and initiation can be obtained from the left (C) and right (C) motor cortex areas []. In

Neuromuscular Aspects of Exercise

0.15 EMG 0.075 (mV) 0 –500 Force 350 175 (N) 0 –500

Fig. .. Averaged movementrelated cortical potentials recorded from the left and right motor cortex area (C and C) and rectified EMG and isometric handgrip force obtained during maximal unilateral (UL) and bilateral (BL) contractions of right and left hand muscles in right-handed subjects. Data from [].

L C3 C4 0

250

Force 350 175 (N) 0 –500

maximal unilateral muscle contraction, MRCP amplitudes were significantly greater on the contralateral hemisphere [,] (Fig. ..). This contralateral asymmetry of large cortical MRCPs disappeared during maximal bilateral contractions, in which symmetric and MRCPs were observed at both hemispheres (Fig. ..). The bilateral deficit in force and EMG associated with reduced MRCPs suggests the involvement of an interhemispheric inhibition mediated by commissural nerve fibers in the corpus callosum []. Thus, the removal of the bilateral strength deficit, as observed following bilateral strength training, could be the result of adaptive changes in interhemispheric inhibition.

Antagonist muscle coactivation Coactivation of antagonist muscles is involved in many types of joint movements [,]. Antagonist muscle coactivation could be important for several reasons: to protect ligaments at the end-range of joint motion [,], to ensure a hom*ogeneous distribution of compression forces over the articular surfaces of the joint [], and to increase joint stiffness thereby providing protection against external impact forces as well as enhancing the stiffness of the entire limb []. In addition, maximal antagonist muscle strength may play an important role in the execution of fast, ballistic

500 UL R

R

C3

–10 (µV)

C4 0 250 Time (ms) UL

0.15 EMG 0.075 (mV) 0 –500



500 UL L

R

L

C4 C3

BL 0

250 BL

500 BL

UL

0 250 Time (ms)

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limb movements. Thus, high eccentric antagonist strength allows for a shortened phase of limb deceleration, thereby increasing the time available for limb acceleration, with a resulting rise in maximal movement velocity []. Coactivation is elevated during either of two states: when uncertainty exists in the required task, or during anticipation of compensatory muscle forces []. During maximal coactivation, the monosynaptic excitatory pathway (Ia) as well as the disynaptic reciprocal inhibitory pathway (Ib) are exposed to spinal inhibition via descending supraspinal pathways [,]. The increase in muscle and joint stiffness mainly results from a direct activation from the CNS with the cerebellum playing an important role in switching from reciprocal activation to coactivation [,]. It is not well known whether strength training per se may induce altered patterns of antagonist coactivation. Intuitively, a decrease in antagonist coactivation would seem desirable, as this would cause net joint moment (agonist joint moment minus antagonist joint moment) to increase. However, as implied above a decrease antagonist muscle coactivation may not be optimal for the integrity of the joint. Antagonist coactivation has been reported to decrease [a,], increase [] or remain unchanged [,,a,a,,,,

 Chapter . ] in response to strength training. Häkkinen and coworkers [a] found that coactivation of the lateral hamstring muscle during maximal isometric contraction of the quadriceps femoris was elevated in old subjects ( years) compared to middle-aged subjects ( years). However, after  months of heavy resistance-training coactivation decreased in the old subjects to reach a level similar to that recorded for the middle-aged subjects, which in turn did not change during the course of training [a]. Given that antagonist coactivation is markedly elevated when uncertainty exists in the motor task, subjects may occasionally demonstrate very high levels of coactivation during the initial round of experiments. This may, at least in part, explain the decrease in antagonist coactivation that has been observed with training. To minimize this potential problem, conditioning tests could be conducted prior to the round of actual pretraining testing. Interestingly, a differential change in antagonist motor pattern in terms of a selective decrease in medial (semitendinosus) but unchanged lateral (biceps femoris) hamstring EMG activity was observed in maximal isolated knee extension in response to  weeks of heavy-resistance training, involving isolated knee extension and squat exercises []. This adaptation indicates an important aspect of motor reprogramming, as it potentially counteracts excessive internal tibia rotation which otherwise may give rise to elevated stress forces in the anterior cruciate ligament (ACL) during active knee extension [,]. To obtain a valid measure of antagonist muscle coactivation it is crucial to ensure that the antagonist EMG signal is not contaminated by the EMG activity of adjacent agonist muscles, as a result of EMG crosstalk between electrode pairs [,]. The amount of cross-talk between two given EMG signals can be quantified by use of cross-correlation analysis [,]. Using a wide range of time phase shifts (i.e. from t =  to t = ±  ms) and long record lengths (>  data points), the peak cross-correlation coefficient raised to the second power, Rxy(t)2, may be taken to represent the percentage cross-talk between electrode sites []. Based on this methodology low levels of EMG cross-talk (–%) were demonstrated between adjacent quadriceps (agonist) and hamstring (antagonist) muscles in maximal isolated knee extension [], although substantially higher values have

also been reported []. Importantly, the level of cross-talk will depend strictly on the specific measuring set-up used, with electrode size and distance between electrodes being the most critical factors. The above findings therefore indicate that it may be possible, with careful experimental procedures, to minimize the magnitude of EMG cross-talk between antagonist and agonist muscles.

Neural inhibitory mechanisms Numerous pathways in the nervous system could be responsible for exerting an inhibitory synaptic drive onto the spinal pool of a-motoneurons. As an important feature, these pathways allow for an integration of spinal and supraspinal inputs. It appears therefore that changes in the spinal neural circuitry induced by training, including alterations in synaptic gating, may emerge as a result of adaptive changes at both spinal and supraspinal levels. Consequently, considerable plasticity can be expected for the neural adaptation to specific types of activity and training. For example, inhibition of various inhibitory pathways as a result of strength training would yield an increase in the net excitatory drive to the motoneuron pool.

Ib afferent inflow from Golgi organs Negative feedback via force-sensing afferents from the Golgi organs arises through the action of inhibitory Ib interneurons, which project to the motoneurons that control the muscle fibers affecting the Golgi organ (Fig. ..). Golgi organs are primarily located within the muscle, at the site of muscle fiber attachment to the aponeurosis or other tendinous structures (> %), rather than at the actual tendon (< %) []. Golgi organs respond not only to large but also to small increments in force and the widespread distribution of Golgi organs allows each motor unit to be monitored by at least one to three Golgi organs []. Consequently, active and passive muscle forces can be accurately monitored in every portion of the muscle []. Importantly, the Ib inhibitory interneurons are influenced by descending corticospinal pathways (i.e. rubrospinal and reticulospinal tracts) [,] (see Fig. ..). Conversely, information from Golgi organs reaches the cerebellum and cerebral sensory cortex through dorsal spinocerebral tracts, suggesting that Ib afferent feedback contributes to conscious

Neuromuscular Aspects of Exercise (a)

Corticospinal

Joint



(b) Input

Skin

Rubrospinal Reticulospinal

Ia Fig. .. (a) Negative feedback via force-sensing neural Ib afferents from Golgi organs arises through the action of inhibitory neurons (Ib In) which project to a-motoneurons that, in turn, control the muscle fibres that affect the Golgi organs. (b) Ib interneurons not only inhibit motoneurons that innervate their parent muscles, but also motoneurons controlling many other muscles (Het a).From [].

Ib In Ib In

Ib

sensations of contractile and passive muscle stress []. It is also noticeable that various sensory cutaneous afferents and joint afferents converge onto the pool of inhibitory Ib interneurons, in turn facilitating Ib inhibitory effects (Fig. ..). Interestingly, this includes the posterior articular nerve (PAN) of the knee joint, which contains sensory axons from the ACL, posterior cruciate ligament (PCL) and joint capsule [,]. The facilitary inflow to the Ib inhibitory interneurons from skin and joint sensory afferents not only constitutes a safety mechanism, causing muscle force to be suppressed during joint injury; it probably also contributes to the (re)programming of motor patterns when adapting to specific types of training or when rehabilitating from joint or ligament injury. It should be noted, however, that recent experimental evidence obtained in animal preparations suggest that in certain situations (e.g. quiet standing, specific phases of locomotion) the Golgi organs may exert a common excitatory feedback drive onto the motoneurons of antigravity muscles crossing the same joint []. Thus, the Ib afferent pathway appears to be highly complex, and also in humans the possibility exists that reflex reversal mechanisms are functioning at different levels of the CNS to facilitate motor function during standing and locomotion. It is plausible that the removal of motoneuron suppression and the resulting increase in maximal eccentric muscle strength observed following heavy-

a

Ib In

Het a

a

Excitatory synapses (EPSPs) Inhibitory synapses (IPSPs)

resistance strength training (Fig. ..) is the result of a down-regulation in spinal Ib inhibitory interneuron activity (i.e. ‘disinhibition’) mediated via central descending pathways.

Renshaw inhibition In the spinal cord Renshaw cells may serve as a variable gain regulator at the motoneuronal level, controlling the relationship between synaptic input and efferent axonal output. Recurrent inhibition, by which the motoneuron exerts an autoinhibitory influence on itself, is mediated via Renshaw cells (Fig. ..). Recurrent Renshaw inhibition has been considered as a factor limiting motoneuron discharge frequency, and also to have a regulating influence on the reciprocal Ia inhibitory pathway [,]. Animal experiments have shown that Renshaw cells are submitted to several types of supraspinal control that can enhance as well as depress the recurrent pathway [,]. Thus, with facilitation of Renshaw cells the input–output relationship of the motoneuron becomes impaired, whereas inhibition of the Renshaw cells causes the input–output relationship to be enhanced (Fig. ..). As compared to tonic contractions, Renshaw cell activity appears to be more inhibited in maximal phasic contractions, resulting in a reduced level of recurrent inhibition []. This could indicate that ‘explosive’ types of heavy-resistance strength training, aimed at maximizing the contractile rate of force

 Chapter . – +

(b)

Activity in descending fibers (n× f)in = input α Output = activity in motoneuronal pool (n× f)out ≈ force

Excitatory synapses (EPSPs) Inhibitory synapses (IPSPs)

(c) Output from motoneurons (n×f)out

(a)

Ia IN

(ii)

α

α

Inhibited Renshaw cells (i) Facilitated Renshaw cells

γ

RC Ia

Input to motoneurons (n× f)in

Fig. .. (a) Input and output connections of a-motoneurons and Renshaw cells, a specialized type of spinal interneuron. Excitatory and inhibitory synapses are shown. Note that the Renshaw cells themselves receive both excitatory and inhibitory synaptic inputs, from spinal as well as higher centers in the CNS. (b) Simplified diagram of input–output relations of a motoneuron pool involving two different situations: (i) with a facilitation of Renshaw cells, the efferent motoneuron output is diminished for a given neuronal input; (ii) conversely, the inhibition of Renshaw cells causes an overall disinhibition of the a-motoneuron pool, with a resulting rise in efferent motor output for a given synaptic input. The presence of recurrent inhibition provides a basis which allows the input–output relationship of the motoneuron pool to be dynamically modulated. (c) Concept of the motoneuron stage. Neurons constituting the efferent output are indicated by thick lines. RC, Renshaw cell; Ia IN, Ia inhibitory neuron. From [].

development, should be superior in evoking neural changes as compared to other types of strength training (i.e. low-resistance training, body building).

Adaptive changes in muscle morphology MHC isoform composition, fiber type conversion When a nerve impulse reaches the muscle fiber, the muscle membrane is depolarized and calcium is released to the interior of the cell from specialized intracellular organelles (sarcoplasmatic reticulum), in turn triggering a transient process of cyclic attachment and detachment of cross-bridges between actin and myosin molecules within the muscle fiber. As a result of this cross-bridge cycling, the actin and myosin filaments perform a sliding movement relative to each other while generating contractile force. In human skeletal muscle, the myosin molecule is constituted of three major types of polypeptide chains: the myosin heavy chain (MHC, molecular weight approx.  kDa) and two distinct types of light myosin chains

(alkali, regulatory chain and DTBN chain, each approx.  kDa) [,,]. Recent techniques, such as sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), have identified distinctly different myosin isoforms within the single muscle fiber as well as in muscle hom*ogenate samples. Using SDS-PAGE three different MHC bands have been separated in adult human skeletal muscle, reflecting differences in molecular density. These bands correspond to the MHC-I, MHC-IIa and MHC-IIx isoforms [] (Fig. ..). The fiber type distribution determined by conventional myosin ATPase histochemistry relates closely to the MHC isoform content [–]. Although –% of the variance was accounted for (r2, r-values of .–. observed), the remaining –% reflects that the SDS-PAGE analysis provides a more sensitive and consistent picture of MHC coexpression, i.e. the presence of two or more MHC isoforms within the muscle fiber [,]. The term MHC-IIx has found increasing use to denote the fastest contracting MHC isoform found in human skeletal muscle, due to a consistent hom*ology

Neuromuscular Aspects of Exercise



MHC IIX MHC IIA MHC I

MHC IIX MHC IIA MHC I Fig. .. SDS-PAGE gel separations showing MHC bands from two subjects before and after  days of heavy-resistance strength training followed by  days of detraining. Densitometric scans are shown above each of the lanes. Data from [].

in genome expression between this fast human isoform and the MHC-IIx isoform in the rat [,]. Although the MHC-IIb encoding gene has been found in the human genome [,], evidence for its expression at the protein level is lacking []. It appears, however, that the MHC-IIb isoform is dominantly expressed in certain specialized muscles of the larynx and the eye [a]. The distribution into various distinct MHC isoforms, as well as its responsiveness to change with training, has significant implications for in vivo mechanical muscle function and the adaptation to given physiologic demands [,]. For example, a positive relationship has been found between the percentage of fast MHC-II isoforms determined by gel electrophoresis and the ability to produce high muscle force during fast concentric contraction [,]. Similar findings have been reported when assessing myosin composition by use of conventional myosin ATPase histochemistry [,,,]. In human skeletal muscle shifts in fast myosin iso-

form composition, i.e. MHC-IIa Æ IIx or MHC-IIx Æ IIa, appear to be readily evoked by training or detraining, respectively [,,,,–]. However, it remains a matter of controversy whether training within a realistic physiologic range can induce transformation between slow and fast myosin isoforms, i.e. MHC-I Æ II or MHC-II Æ I [,,]. The finding of an extremely large proportion of IIa and IIx fibers in the quadriceps muscle of long-term spinal cord-injured subjects (> % vs. % in agematched healthy subjects) led Andersen and coworkers to suggest that the expression of the MHC-IIx isoform represents a default setting, which is overruled with any chronic increase in muscle activity []. Interestingly, a marked decrease in MHC-IIx and corresponding increases in type IIa and type I MHC were observed in spinal cord-injured subjects after  months of cycle training using functional electrical stimulation (FES) []. Not only endurance training but also resistance training appears to effectively suppress the expression

 Chapter . of MHC-IIx. Thus, few muscle contractions performed against heavy external loads two or three times per week can reduce MHC-IIx almost completely, with a corresponding increase in MHC-IIa [,,–,,,]. This indicates that the total number of contractions or nerve impulses is not the only factor which influences the down-regulation of MHC-IIx with resistance training, as otherwise suggested with prolonged endurance training []. Rather, the magnitude of contractile force exerted by the muscle fibers appears to be a governing factor as well. Intense muscle contractions may lead to structural deformation of the sarcolemma and the cytoskeleton, thereby activating mechanosensitive or stretchsensitive signaling pathways affecting gene regulation of the nucleus []. Furthermore, exercise-induced changes in gene expression are accelerated by activation of gene-encoding transcription factors such as the myogenic regulatory factor family (MyoD, myogenin, Myf, MRF) []. The mechanical stress load exerted on the muscle fiber probably acts through similar intracellular pathways to switch off or down-regulate the MHC-IIx gene, while up-regulating the MHC-IIa gene. Also, exercise-induced activation of specific intracellular kinases, which controls the rate of RNA transcription/translation, thereby regulating protein synthesis rate, appears to be involved in the hypertrophic response to resistance training. For example, a strong positive relationship between the activation (i.e. phosphorylation) of pS6k, a -kDa S protein kinase, and the long-term increase in muscle mass with resistance training was recently reported in the rat, suggesting that this protein kinase plays an important role in the intracellular signaling cascade related to training-induced growth of skeletal muscle []. Data obtained in humans suggest that in the initial phase of resistance training (– weeks), the increased rate of myofibrillar protein synthesis is mediated mainly by a more efficient translation of mRNA []. On the other hand, the finding that intense bouts of resistance exercise can induce rapid changes in mRNA (– h) which precede changes in MHC content (– weeks) [a], indicate that resistance training may exert a strong and immediate modulatory effect on gene encoding as well. Similar findings have been reported following high-intensity endurance exercise []. In addition, the mismatch between the

expression of specific MHC isoforms and their respective mRNA isoforms observed with resistance training (and detraining) suggests that differentiated adaptive responses may exist for the pre- and posttranslational mechanisms related to gene expression [].

Muscle fiber size As a result of differences in spinal a-motoneuron cell soma size, the small low-threshold motor units are preferentially recruited in low-level isometric muscle contraction, whereas with increase in muscle force there is an additional and progressive recruitment of large high-threshold motor units, cf. ‘Henneman’s size principle’ []. Thus, heavy-resistance strength training will activate both low-threshold and highthreshold motor units, thereby involving slow type I as well as fast type II muscle fibers. Consequently, heavy-resistance strength training can induce significant alterations in muscle fiber morphology as manifested by an increase in type I and type II muscle fiber cross-sectional area [,,,] (Fig. ..). A majority of studies, however, have found a preferential or more pronounced hypertrophy of the type II muscle fibers [,,,,,–] (Fig. ..). Altogether these findings suggest that type II muscle fibers possess a greater adaptive capacity for hypertrophy compared to type I fibers. Muscle fiber hypertrophy occurs primarily due to an accumulation of contractile proteins (i.e. myosin and actin) as reflected by an increase in the size and number of myofibrils within the muscle cell, leaving the total number of muscle fibers basically unaltered []. Seen in this perspective, individuals genetically predisposed to have a large number of muscle fibers in a given muscle would appear to have the greatest potential for overall muscle hypertrophy in response to training. There is a possibility that neoformation of muscle fibers (hyperplasia) may occur as an effect of intensive resistance training, although for human skeletal muscle its existence remains questionable []. The muscle fiber hypertrophy induced by resistance training is often accompanied by an increase in the cross-sectional area or total volume of the muscle obtained by magnetic resonance imaging (MRI) or computed tomography (CT) scanning. Although at first hand a conflicting finding, disproportionate changes in

(a)

2

Muscle fiber CSA (mm )

(b)

2

Muscle fiber CSA (mm )

(c)

Fig. .. Muscle fiber cross-section from muscle biopsy samples obtained in the vastus lateralis and stained for myofibrillar ATPase after pre-incubation at pH . (a). (b-c) Muscle fiber cross-sectional area (CSA) with fiber types IIA and IIX collapsed, before and after  weeks of heavy resistance strength training (n = ). Note the increase in type II muscle fiber with training. A trend towards increased type I fiber area was also observed with training [].

 Chapter . MRI muscle cross-sectional area (CSA) and single muscle fiber CSA may occur with resistance training. Thus, mid-thigh quadriceps CSA as well as total quadriceps volume increased ~ %, whereas singlefiber CSA increased ~ % following  weeks of resistance training [,,]. In studies using combined muscle biopsy sampling and muscle imaging (MRI, CT) the increase in muscle fiber CSA induced by resistance training generally appeared to exceed the increase in whole-muscle CSA [,–]. These findings are not explainable by an altered ratio of non-contractile to contractile tissue, which appears to remain unchanged with resistance training in animal models [] as well as in humans [,]. Rather, the disproportionate alteration in fiber CSA and whole-muscle CSA appears to be caused by training-induced alterations in muscle architecture. Thus, muscle fiber pennation angle may increase in response to prolonged heavy-resistance strength training, a change that allows physiologic muscle CSA (muscle fiber CSA) to increase more than anatomic muscle CSA (see ‘Changes in muscle architecture’, below). An upper limit seems to exist to the increase in muscle fiber size induced by resistance training []. Most likely this limit is closely linked to the genetic endowment of the individual. Because the myonuclei of adult muscle fibers are not capable of mitosis and therefore unable to divide, the nuclear/cytoplasmic ratio would approach zero with unlimited increase in muscle fiber size. Obviously, this would dilute the amount of mRNA in the cell, at some point causing net protein synthesis to cease. Interestingly, satellite cells may play an important role for the maintenance of a constant nuclear/cytoplasmic ratio during cellular hypertrophy. Satellite cells are located dormant under the muscle cell basal membrane. During normal muscle growth, satellite cells contribute nuclei to the muscle cell by proliferating, differentiating and fusing to existing myofibers [,]. The satellite cellderived myonuclei are no longer capable of dividing, but begin to produce muscle-specific proteins that add to the increase in myofiber size [,]. The proliferation and differentiation of satellite cells are stimulated by endogenous growth factors such as testosterone, insulin-like growth factor I (IGF-I),

growth hormone, insulin and interleukin- []. In addition, data exist which suggest that satellite cell activation may be enhanced by anabolic steroid use. Thus, high-level power lifters reporting several years of high-dose anabolic steroid usage (average  years) demonstrated ~ % and ~ % elevated myonuclei number in their type IIa and I muscle fibers, respectively, together with a ~ % larger mean muscle fiber area compared to age-matched power lifters that did not use steroids []. Interestingly, type I muscle fibers have a lower nucleus/cytoplasm ratio than type II fibers []. Thus, the type I fibers would be expected to respond most markedly to anabolic steroid usage, as in fact supported by recent experimental evidence []. Opposite to that observed with resistance training, a reduction in muscle fiber CSA (atrophy) may be seen following intensive endurance training [,–]. From a muscle perfusion perspective this adaptation is very important, since it results in an elevated capillary to muscle fiber CSA ratio, which in turn facilitates O2 delivery and free fatty acid (FFA) uptake into the muscle cell due to the reduced diffusion distance. The elevated FFA uptake results in a reduced rate of glycogen breakdown to yield an enhanced endurance performance (prolonged time to exhaustion). Thus, regimes of concurrent strength and endurance training appear to involve stimuli for cellular hypertrophy as well as atrophy. As a functional consequence, no (or only minor) muscle fiber hypertrophy and no signs of a reduction in capillary density have been observed when strength and endurance training are combined [–]. With regard to muscle metabolism and endurance, it is noteworthy that the number of capillaries per fiber appears to either increase [,,] or remain unchanged [,] following prolonged (months) resistance training. Likewise, capillary density (cap/mm2) seems to remain unchanged [,,]. Thus, the capacity for capillary perfusion does not seem markedly impaired by resistance training, at least when performed for – weeks. On the other hand, previous findings of a reduced capillary density in experienced weight lifters and power lifters [] but not in body builders [] suggest that the specific type of resistance exercise could play an important role for this parameter.

Neuromuscular Aspects of Exercise Muscle cross-sectional area and volume

raphy to address the alteration in macroscopic muscle dimensions evoked by resistance training (Fig. ..). An accurate estimate of the total volume of a given muscle can be provided by the recording of successive axial MR images along the entire length of the limb.

During recent years there has been a progressively growing interest in the use of non-invasive imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT) and ultrasonog(b) (Lfemur3)

(a)



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Fig. .. (a) Coronal MRI scan of m. quadriceps femoris. (b) The relationship between quadriceps muscle CSA and total quadriceps volume. Pre- and post-training values are shown by closed and open symbols, respectively. (c) Axial MRI images of the thigh obtained at % femur length (proximal site) and % femur length (distal site) before and after  weeks of heavy-resistance strength training. Data adapted from [ and ].

 Chapter . The determination of muscle volume can be quite time consuming and costly in terms of time spent in the MR scanner. It is therefore interesting to note that in the quadriceps femoris muscle, which is the muscle that has been most frequently used to examine the effects of resistance training, a strong relationship can be found between muscle CSA obtained at % segment length and total muscle volume determined by recording of multiple axial images [] (Fig. ..b). Thus, training-induced changes in muscle volume may be well represented by changes in single-site CSA, at least when evaluating large subject groups. Anatomic muscle CSA obtained by use of MRI or CT has been reported to increase –% in response to prolonged heavy-resistance strength training [,,,a,,–,]. Corresponding increases have been found for total quadriceps volume [,,]. Using MRI some researchers have been able to identify the perimeter of the different quadriceps femoris muscles in successive axial images obtained along the length of the femur, to report differentiated hypertrophic response of each muscle compartment (i.e. vastus lateralis, medialis, intermedius and rectus femoris) following resistance training [,]. However, such differentiation is not always possible, since substantial fusion may exist between adjacent vastii. Based on cadaver data,  of  dissected quadriceps muscles showed fusion between the lateral and deep vastii at more than % of the entire length of the muscle []. In addition, axial MR scans typically show a lack of distinct fascial boundaries between the lateral and deep vastii (posterolaterally) and between the medial and deep vastii (anteromedially) when obtained proximally [] (Fig. ..c). Obviously, such fusion of adjacent muscle compartments will have important implications for the interpretation of MRI-based muscle CSA data. Resistance training involving eccentric alone or coupled eccentric–concentric muscle contractions seems to result in more pronounced morphologic changes than concentric training alone. Accelerated muscle hypertrophy was found after eccentric or coupled eccentric–concentric training compared to concentric training alone, as reflected by a greater increase in single muscle fiber CSA obtained by biopsy sampling [,,] although not confirmed by all studies [,]. Likewise, a greater increase in

anatomic muscle CSA obtained by use of MRI or anthropometric measures has been observed following eccentric strength training in most [,,] but not all studies []. Furthermore, muscle fiber area remained above pretraining values following detraining from eccentric but not concentric resistance training [], indicating that the hypertrophic response to eccentric training is more long lasting. The above disparities are likely to be related to differences in training duration between studies. With sufficient duration therefore, eccentric resistance training appears to be more effective for inducing muscle fiber hypertrophy and overall muscle growth than concentric training alone.

Muscle architecture Many, if not most, skeletal muscles are characterized by a pennate arrangement of the muscle fibers relative to their insertion at the aponeurosis or tendon. This allows physiologic muscle cross-sectional area (equivalent to the muscle fiber area perpendicular to the longitudinal axis of the individual muscle fibers) to greatly exceed the anatomic muscle cross-sectional area measured in a plane perpendicular to the longitudinal axis of the whole muscle. The maximal forcegenerating capacity of a given muscle is determined by its physiologic CSA, as this represents the maximal number of acto-myosin crossbridges that can be activated during contraction. For a given volume of muscle, physiologic CSA and thereby maximal contractile muscle force is progressively increased at more steep muscle fiber pennation angles, to reach an upper limit at a pennation angle of ° [,]. Consequently, pennate muscles are able to exert very large contractile force compared to non-pennate muscles. Muscle fiber pennation angle was previously estimated from dissection of cadaver specimens. However, more adequate and accurate measuring techniques have emerged, based on the appearance of highresolution ultrasonography techniques (Fig...). This has allowed fiber pennation angle to be measured at specific muscle lengths (joint angles) and at specific levels of muscle tension. Ultrasound imaging has been increasingly used to investigate the strain and stress forces generated in human tendon and aponeurosis in vivo [–]. In addition, ultrasonography

Neuromuscular Aspects of Exercise



Fig. .. Sagittal plane ultrasound image obtained in the relaxed quadriceps femoris muscle at % femur length. Muscle fiber pennation angle (qp) in vastus lateralis was measured as the angle between VL muscle fibre fascicles and the deep aponeurosis.

has been used to address the more chronic change in muscle fiber pennation angle induced by resistance training. Findings of steeper muscle fiber pennation angles and greater anatomic muscle CSA in the triceps brachii muscle of body builders compared to untrained subjects [] suggest that the muscle hypertrophy induced by resistance training could be associated with an increase in fiber pennation angle. This notion was confirmed by longitudinal data demonstrating a significant increase in muscle fiber pennation angle from .° to .° in the triceps brachii muscle following  weeks of resistance training []. Likewise, an increase in fiber pennation angle from . to .° was reported for the vastus lateralis muscle after  weeks of intense heavyresistance strength training []. In contrast, Rutherford and Jones found an unchanged fiber pennation angle in the lateral and medial vastii after  weeks of resistance training, despite a % and % increase in anatomic CSA and maximal isometric strength, respectively []. These conflicting results were probably caused by differences in total training load, which differed by a factor of three. Thus, a change in muscle

architecture evoked by resistance training appears to require considerable effort and time. The training-induced increase in muscle fiber pennation angle was suggested to allow muscle fiber CSA and thereby maximal force-generating capacity to increase significantly more (%) than whole-muscle CSA and volume (%) []. Thus, the disproportionate change in macroscopic versus microscopic morphometry observed with strength training [,–] implies that muscle CSA or volume obtained by MRI or CT (i.e. reflecting changes in anatomic CSA) cannot replace the information obtained by measurements of single muscle fiber area in biopsy samples (i.e. reflecting changes in physiologic CSA), or vice versa. Clearly, the adaptation in muscle fiber pennation angle should be taken into account when examining training-induced changes in maximal muscle strength, in vivo.

Functional aspects Training for ‘explosive’ muscle strength ‘Explosive’ muscle strength can be defined as the rate of force development (RFD = Dforce/Dtime) exerted

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within the very initial phase of contraction (– ms) (Fig. ..). The ability to generate very steep increases in muscle force at the onset of contraction has important functional significance for the force and power generated during rapid, forceful movements. Thus, contraction times of – ms can be observed in many types of fast movement (e.g. sprint running, long jump take-off, karate, boxing). In contrast, it takes about – ms to reach maximal force in the human quadriceps femoris muscle [,] (Fig. ..). Consequently, contractile RFD is a major determinant of the maximal force and velocity that can be achieved in very fast movements. In isometric contraction conditions, RFD is determined by the level of neural activation (efferent motor drive), muscle size (muscle CSA and volume) and fiber type composition (MHC isoforms) while also influenced by the length–tension characteristics of the muscle. During dynamic contraction, the RFD will

also be influenced by the force–velocity characteristics of the muscle. Acutely, a rise in RFD is seen with increasing motoneuron firing frequency [] and overall neural drive. In terms of muscle morphology, a large CSA will also result in a large absolute RFD. Maximal cross-bridge cycle transition rate appears to be the major limiting factor for the maximal intrinsic RFD of mammalian muscle fiber []. Thus, a predominance of type II MHC isoforms results in a high RFD [], due to their elevated rate of cross-bridge cycling []. In consequence, the maximal muscle force that can be reached in situations of short contraction times (i.e. <  ms) is positively related to the proportion of type II MHC []. Based on electromyography (EMG) recordings (Figs .. and ..a), efferent neural drive to the muscle fibers has been found to increase in response to strength training [,,,,a,–,a,,, ]. Because a ‘parallelism’ of the rate of EMG and force development may exist [], concurrent adaptations in neural drive and contractile RFD can be expected following resistance training. In line with these expectations, RFD and neural efferent drive have both been reported to increase in response to strength training [,,,a,,,] (Fig. ..). Interestingly, Schmidtbleicher and Buerhle [] found that ‘power training’ at lower loads and fast contraction velocities had no strong effect on these parameters. Duchateau and Hainaut [] used electrically evoked tetanic contractions to address changes in intrinsic muscle properties, and found that peak RFD was augmented to a greater extent by fast ballistic training than isometric training (% vs. %) in the adductor pollicis muscle. This latter finding suggests that not only heavy-resistance strength training but also maximal ballistic training using lower loads could have an important effect on the increase in RFD. Comparing dynamic and isometric ballistic training (i.e. at high RFD), Behm and Sale observed the increase in RFD to be similar with both these types of training regimes, during evoked as well as voluntary contraction conditions []. Thus, the involvement of an intended ballistic effort may be more important for inducing increases in RFD than the type of contraction actually performed. The marked increase observed in neural drive suggests that the increase in contractile RFD is mainly caused by neural adaptation. In particular the finding

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Fig. .. Changes in RFD and neural drive pre- and post- weeks heavy resistance training. Error bars denote SEM. (a) Rate of force moment of development during maximal isometric contraction of the quadriceps femoris muscle calculated in time intervals from the onset of contraction. (b) Neural drive calculated as the mean integrated EMG divided by integration time. (c) Neural drive quantified as the rate of EMG rise [].

of disproportionately large increases in EMG amplitude (–%) and rate of EMG rise (–%) compared to RFD (–%) and maximal muscle strength (%) (Fig. ..) suggests that an increase in motoneuron firing frequency may be responsible for the training-induced rise in contractile RFD []. This notion was further supported by the finding that RFD normalized to MVC, i.e. expressed as % MVC/s, increased in the initial phase of contraction (–/ MVC, corresponding to the initial – ms)



[]. Muscle fiber hypertrophy could also have contributed to the increase in RFD, as evidenced by an increase in type II muscle fiber CSA following training (%) []. Recently, Duchateau and colleagues reported increased contractile RFD together with an increase in firing frequency as well as a six-fold increased occurrence of ‘discharge doublets’ in the firing pattern of single motor units following ballistic-type resistance training [] (Fig. ..). This increased incidence of ‘discharge doublets’ may be particularly important for the training-induced increase in RFD, by taking increasing advantage of the catch-like property of skeletal muscle (See Adaptive changes in neural drive: motoneuron firing frequency). Collectively, the above findings suggest that the (see Adaptive changes in neural drive: motoneuron firing frequency) major stimulus for training-induced increases in RFD may reside in the high-frequency motor unit firing pattern associated with an intended ballistic movement []. For this purpose training probably should involve heavy-resistance strength training combined with a more ballistic type of training using somewhat lower loads. Based on the training experience accumulated in top-level track and field athletics and power lifting, the most optimal training stimulus perhaps can be achieved when heavy-resistance strength exercises executed in an ‘explosive’ manner (i.e. emphasis on acceleration of the load) are combined with specific ballistic-type exercises using lower loads. There is no doubt that the increase seen in contractile RFD is one of the single most important functional benefits associated with resistance training. Very fast movements are characterized by muscle contraction times of – ms, which is considerably less than the time it takes to reach maximal force (Fig. ..). Consequently, increases in RFD evoked by resistance training may greatly enhance the maximal force and velocity that can be achieved during very fast movements. In support of this notion, maximal muscle force and power were markedly elevated during very fast movement speeds following heavy-resistance strength training []. Likewise, the increase in contractile RFD likely is responsible for the increase in maximal unloaded movement speed reported following heavyresistance strength training []. It is important to notice that training-induced changes in contractile RFD will have important functional consequences,

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not only in athletes, but also in non-athletic subjects. For example, in the elderly individual, high muscular RFD may play an important role for the ability to rapidly regain postural balance and thereby avoid falls.

Training for optimal neural and morphologic adaptation From the findings presented in this chapter strength training appears effective for evoking significant adap-

tive changes within the nervous system as well as in the muscle itself (Fig. ..). Training with heavy loads (– RM) seems to emphasize various aspects of neural adaptation, in turn causing significant increases in contractile RFD [] and maximal eccentric strength []. The use of moderate to heavy training loads (– RM) may be more optimal for the development of muscle hypertrophy [] and may also prove more effective for inducing alterations in muscle

Neuromuscular Aspects of Exercise 6–12-RM loads ‘muscle volume training’

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

Maximal muscle strength ‘Explosive’ muscle strength (rate of force development)

1– 8-RM loads ‘explosive type training’

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Eccentric muscle strength

Fig. .. Diagram summarizing neural and morphological effects evoked by resistance training. *≠ Muscle cross-sectional area (CSA); ≠ CSA type II muscle fibers (type II MHC isoforms). Changes in muscle architecture (≠ fiber pennation angle). ** ≠ Neural drive to muscle fibers (≠ iEMG); ≠ motoneuron excitability; Ø motoneuron inhibition.

architecture. It should be noted, however, that the adaptation evoked by resistance training involves a mixture of neural and morphologic mechanisms that often cannot be separated from each other. As described above, the increase in maximal muscle strength can be the result of changes in muscle size or muscle architecture (angle of fiber pennation), and/or of neural changes, i.e. enhanced efferent motor outflow to the muscle fibers. The increase in contractile RFD is caused by an increased neural drive, especially within the initial – ms of contraction. In addition, there may be a significant contribution from muscle fiber hypertrophy. The functional outcome is that movements can be performed more rapidly and that muscle force and power generated during fast movements will be enhanced. Eccentric muscle strength is increased mainly due to neural adaptation mechanisms, which likely include a reduced inhibition of the motoneurons during maximal eccentric contraction. However, muscle fiber hypertrophy will contribute as well. These adaptations cause muscle force and power to be enhanced in functional situations, such as during rapid limb acceleration and deceleration, and in forceful stretch–shortening cycle activities, e.g. jumping and sprinting. Moreover, an increase in the maximal eccentric strength of antagonist muscles has been suggested to be of importance for the magnitude of dynamic joint stabilization provided by antagonist coactivation [,,]. In consequence, the increase in eccentric antagonist muscle strength may be expected to result in a reduced incidence of joint injury. Another important aspect that is often overlooked, is that regular resistance training may allow the individual to tolerate better a higher intensity of training which, in turn, will improve performance.

Summary Strength training induces marked increases in maximal concentric, eccentric and isometric muscle strength as well as in the contractile rate of muscle force development. Adaptive changes occur both in the nervous system and within the muscle itself. Experimental data obtained by electromyography have indicated several mechanisms for neural adaptation, including increase in efferent motor drive, increased motor unit firing frequency, enhanced intramuscular and intermuscular motor unit synchronization, increased motoneuron excitability and decreased presynaptic inhibition of spinal a-motoneurons. Down-regulation of inhibitory pathways, at either the supraspinal or spinal level, e.g. of Ib Golgi afferents and Renshaw recurrent inhibition, may contribute to the increase in maximal muscle strength in response to heavy-resistance strength training, particularly during eccentric muscle contractions. Adaptations in muscle morphology include increase in muscle fiber crosssectional area (CSA), whole-muscle CSA and volume, and changes in muscle architecture in terms of an increased angle of muscle fiber pennation, as demonstrated by histochemical, magnetic resonance and ultrasonographic techniques, respectively. Using modern gel electrophoresis and antibody classification methods, effects of strength training have also been demonstrated at the subcellular level, e.g. as shifts in myosin heavy chain isoforms, mainly between MHC-IIa and IIx. The enhancement of neuromuscular function induced by strength training will have significant benefits for the performance and ability to endure intense training in most sports as well as for carrying out many activities in everyday life, not least in the elderly. Training with moderate to heavy loads

 Chapter . and eccentric, concentric and isometric contractions, should be integral parts of preventive and rehabilitative training for muskuloskeletal injuries.

Multiple choice questions  Which of the following statements about isokinetic strength measurements is correct? a ‘Isokinetic’ implies that the muscle contraction velocity is kept constant over the whole range of motion. b Under true isokinetic conditions the measured moment of force equals the net muscle strength produced around the joint investigated. c Since the muscle lever arm changes with joint angle over the range of motion, the muscle force has to change accordingly to keep the torque constant. d Under eccentric isokinetic measurements the dynamometer has to produce a torque that is lower than the net torque produced by the muscles. e During isokinetic strength measurement the joint angular velocity is constant over the entire range of motion.  Which of the following neural adaptations is least likely to occur after heavy-resistance strength training? a Increased efferent drive from higher neural centers to the agonist motoneuron pool. b Increased firing frequency of agonist a-motoneurons. c Decreased presynaptic inhibition of Ia afferents onto hom*onymous motoneurons. d Increased activation from supraspinal centers onto the Renshaw cells innervating the agonist motoneurons. e Decreased inhibition from Ib afferents on agonist motoneurons.  Which of the following muscular adaptations is the least likely to occur after heavy-resistance strength training? a A shift from myosin isoform MHC-IIx to MHCIIa. b A larger relative area of type II as compared to type I muscle fibers. c A higher number of capillaries per muscle fiber. d A larger angle of pennation. e An increased number of type IIb muscle fibers.

 Which of the following statements about eccentric (lengthening) muscle contractions is false? a In eccentric muscle contractions the force produced per unit of muscle activation is larger than in concentric muscle contractions. b In eccentric muscle contractions the EMG required to produce a certain muscle force is lower than in concentric muscle contractions. c The effect of slow vs. fast movement velocity on maximal voluntary muscle strength is smaller in eccentric than in concentric muscle contractions. d Combining eccentric and concentric contractions in strength training gives a larger strength gain than concentric training alone. e The potential gain in maximal voluntary strength by disinhibition of inhibitory pathways is smaller in eccentric than in concentric muscle contractions.  Which of the following statements about neural adaptations to strength training is false? a Training of each limb separately will decrease the difference in strength between summed unilateral and bilateral contractions, respectively (the so-called bilateral strength deficit). b Training of one limb can increase the strength of the other, so called cross-education. c Training with ballistic movements can lead to an increased occurrence of so-called discharge doublets, which, in turn, may lead to a higher rate of force development (RFD). d The intention and effort to develop force quickly during heavy-resistance strength training can lead to an increased ability to produce force at high speeds. e Strength training of agonist muscles does not necessarily result in a decreased coactivation of antagonist muscles.

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elicited by quadriceps contraction. Am J Sports Med ; : –. Koh TJ, Grabiner MD. Cross talk in surface electromyograms of human hamstring muscles. J Orth Res ; : –. Koh TJ, Grabiner MD. Evaluation of methods to minimize crosstalk in surface electromyography. J Biomech ;  (Suppl. ): –. Aagaard P, Simonsen EB, Andersen JL, Magnusson P, Bojsen-Møller F, Dyhre-Poulsen P. Antagonist muscle coactivation during isokinetic knee extension. Scand J Med Sci Sports ; : –. Lundberg A, Malmgren K, Schomburg ED. Convergence from Ib, cutanous and joint afferents in reflex pathways to motoneurons. Brain Res ; : –. Lundberg A, Malmgren K, Schomburg ED. Role of joint afferents in motor control exemplified by effects on reflex pathways from Ib afferents. J Physiol ; : –. Pearson KG. Proprioceptive regulation of locomotion. Curr Opin Neurobiol ; : –. Pierrot-Deseilligny E, Morin C. Evidence for supraspinal influences on Renshaw inhibition during motor activity in man. In: Desmedt JE, ed. Spinal and Supraspinal Mechanisms of Voluntary Motor Control and Locomotion. Prog. Clin. Neurophysiol, Vol. . Basel: Karger, : –. Hultborn H, Lindström S, Wigström H. On the function of recurrent inhibition in the spinal cord. Exp Brain Res ; : –. Schiaffino S, Reggiani C. Molecular diversity of myofibrillar proteins: gene regulation and functional significance. Physiol Rev ; : –. Staron RS, Johnson P. Myosin polymorphism and differential expression in adult human skeletal muscle. Comp Biochem Physiol ; B: –. Adams GR, Hather BM, Baldwin KM, Dudley GA. Skeletal muscle myosin heavy chain composition and resistance training. J Appl Physiol ; : –. Andersen JL, Aagaard P. Myosin heavy chain IIX overshooting in human skeletal muscle. Muscle Nerve ; : –. Fry AC, Allemeier CA, Staron RS. Correlation between percentage fiber type area and myosin heavy chain content in human skeletal muscle. Eur J Appl Physiol ; : –. Staron RS, Karapondo DL, Kraemer WJ, Fry AC, Gordon SE, Falkel JE, Hagerman FC, Hikida RS. Skeletal muscle adaptations during early phase of heavy-resistance training in men and women. J Appl Physiol ; : –. Staron RS, Leonardi MJ, Karapondo DL, Malicky ES, Falkel JE, Hagerman FC, Hikida RS. Strength and skeletal muscle adaptations in heavy-resistance trained women after detraining and retraining. J Appl Physiol ; : –. Andersen JL, Klitgaard K, Saltin B. Myosin heavy chain isoforms in single fibres from m. vastus lateralis of sprint-

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ers: influence of training. Acta Physiol Scand ; : –. Ennion S, Sant’ana Pereira JAAA, Sargeant AJ, Young A, Goldspink G. Characterization of human skeletal muscle fibres according to the myosin heavy chains they express. J Musc Res Cell Motil ; : –. Smerdu V, Karsch-Mizrachi I, Campione M, Leinwand LA, Schiaffino S. Type IIx myosin heavy chain transcripts are expressed in type IIb fibers of human skeletal muscle. Am J Physiol ; : C–C. Weiss A, McDonough D, Wertman B, Acakpo-Satchivi L, Montgomery K, Kucherlapati R, Leinwand L, Krauter K. Organization of human and mouse skeletal myosin heavy chain gene clusters is highly conserved. Proc Natl Acad Sci USA ; : –. Weiss A, Schiaffino S, Leinwand L. Comparative sequence analysis of the complete human sarcomeric myosin heavy chain family: implications for functional diversity. J Mol Biol ; : –. Baldwin KM, Haddad F. Invited review. Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle. J Appl Physiol ; : –. Andersen JC, Weiss A, Sandri C, Schjerling P, Thornell LE, Pedrosa-Domellof F, Leinwand L, Schiaffino S. The B myosin heavy chain gene is expressed in human skeletal muscle. J Physiol ; : –. Pette D, Staron RS. Cellular and molecular diversities of mammalian skeletal muscle fibers. Rev Physiol Biochem Pharmacol ; : –. Aagaard P, Andersen JL. Correlation between contractile strength and myosin heavy chain isoform composition in human skeletal muscle. Med Sci Sports Exerc ; : –. Harridge SDR, White MJ, Carrington CA, Goodman M, Cummings P. Electrically evoked torque-velocity characteristics and isomyosin composition of the triceps surae in young and elderly men. Acta Physiol Scand ; : –. Gregor RJ, Edgerton VR, Perrine JJ, Campion DS, DeBus C. Torque-velocity relationships and muscle fiber composition in elite female athletes. J Appl Physiol ; : –. Johansson C, Lorentzon R, Sjöström M, fa*gerlund M, Fugl-Meyer AR. Sprinters and marathon runners. Does isokinetic knee extensor performance reflect muscle size and structure? Acta Physiol Scand ; : –. Andersen JL, Mohr T, Biering-Sørensen F, Galbo H, Kjaer M. Myosin heavy chain isoform transformation in single fibers from m. vastus lateralis in spinal cord injured individuals: effects of long term functional electrical stimulation (FES). Pflügers Arch ; : –. Hather BM, Tesch P, Buchanan P, Dudley GA. Influence of eccentric actions on skeletal muscle adaptations to resistance training. Acta Physiol Scand ; : –. Staron RS, Malicky ES, Leonardi MJ, Falkel JE,

Neuromuscular Aspects of Exercise

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Hagerman FC, Dudley GD. Muscle hypertrophy and fast fiber type conversion in heavy resistance-trained women. Eur J Appl Physiol ; : –. Fitts RH, Widrick JJ. Muscle mechanics: adaptations with exercise-training. Exerc Sports Sci Rev ; : –. Harridge SDR. The muscle contractile system and its adaptation to training. In: Marconnet P, Saltin B, Komi PV, Poortmans J, eds. Human Muscular Function During Dynamic Exercise. Basel: Karger, : –. Kraemer WJ, Patton JF, Gordon SE, Harman EA, Deschenes MR, Reynolds K, Newton RU, Triplet NT, Dziados JE. Compatibility of high-intensity strength and endurance training on hormonal and skeletal muscle adaptations. J Appl Physiol ; : –. Howald H, Hoppeler H, Claasen H, Mathieu O, Staub R. Influences of endurance training on the ultrastructural composition of different muscle fiber types in humans. Pflügers Arch ; : –. Williams RS, Neufer PD. Regulation of gene expression in skeletal muscle by contractile activity. In: Rowell LB, Shephard JT, eds. Handbook of Physiology, Exercise: Regulation and Integration of Multiple Systems. New York: Oxford University Press, : –. Cox DM, Quinn ZA, McDermott JC. Cell signaling and the regulation of muscle-specific gene expression by myocyte enhancer-binding factor . Exerc Sports Sci Rev ; : –. Barr K, Esser K. Phosphorylation of pS6k correlates with increased skeletal muscle mass following resistance training. Am J Physiol ; : C–C. Welle S, Bhatt K, Thornton CA. Stimulation of myofibrillar synthesis by exercise is mediated by more efficient translation of mRNA. J Appl Physiol ; : –. Caiozzo VJ, Haddad F, Baker MJ, Baldwin KM. Influence of mechanical loading on myosin heavy-chain protein and mRNA isoform expression. J Appl Physiol ; : –. O’Neill DS, Zheng DA, Anderson WK, Dohm GL, Houmard JA. Effect of endurance exercise on myosin heavy chain gene regulation in human skeletal muscle. Am J Physiol ; : R–R. Andersen JL, Schiaffino S. Mismatch between myosin heavy chain mRNA and protein distribution in human skeletal muscle fibers. Am J Physiol ; : C–. Henneman E. Relation between size of neurons and their susceptibility to discharge. Science ; : –. McCall GE, Byrnes WC, Dickinson A, Pattany PM, Fleck SJ. Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training. J Appl Physiol ; : –. MacDougall JD, Ward GR, Sale DG, Sutton JR. Biochemical adaptation of human skeletal muscle to heavyresistance training and immobilization. J Appl Physiol ; : –. Roman WJ, Fleckenstein J, Stray-Gundersen J, Alway SE, Pesock R, Gonyea WJ. Adaptations in the elbow flexors of

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elderly males after heavy-resistance training. J Appl Physiol ; : –. Thorstensson A, Hultén B, v Döbeln W, Karlsson J. Effect of strength training on enzyme activities and fiber characteristics in human skeletal muscle. Acta Physiol Scand ; : –. Goldspink DF. Cellular and molecular aspects of adaptation in skeletal muscle. In: Komi PV, ed. Strength and Power in Sports. The IOC Encyclopaedia of Sports Medicine, Vol. III. Oxford: Blackwell Scientific Publications, : –. Aagaard P, Andersen JL, Leffers AM, Wagner Å, Magnusson SP, Halkjær-Kristensen J, Dyhre-Poulsen P, Simonsen EB. A mechanism for increased contractile strength of human pennate muscle in response to strength training: changes in muscle architecture. J Physiol ; : –. Esmarck B, Andersen JL, Olsen S, Mizuno M, Kjaer M. Timing of protein intake after resistance exercise bouts is paramount for muscle hypertrophy over a -week training period in elderly humans. J Physiol  (abstract). Frontera WR, Meredith CN, O’Reilly KP, Knuttgen HG, Evans WJ. Strength conditioning in older men: skeletal muscle hypertrophy and improved function. J Appl Physiol ; : –. Mikesky AE, Giddings CJ, Matthews W, Gonyea WJ. Changes in muscle fiber size and composition in response to heavy-resistance exercise. Med Sci Sports Exerc ; : –. Wang N, Hikida RS, Straon RS, Simoneau JA. Muscle fiber types of women after resistance training — quantitative ultrastructure and enzyme activity. Pflügers Arch ; : –. Alway SE, Grumbt WH, Stray-Gundersen J, Gonyea WJ. Effects of resistance training on elbow flexors of highly competitive bodybuilders. J Appl Physiol ; : –. Vierck J, O’Reilly B, Hossner K, Antonio J, Byrne K, Bucci L, Dodson M. Satellite cell regulation following myotrauma caused by resistance exercise. Cell Biol Int ; : –. Stein RB, Capaday C. The modulation of human reflexes during functional motor tasks. Trends Neurosci ; : –. Yan Z. Skeletal muscle adaptation and cell cycle regulation. Exerc Sports Sci Rev ; (): –. Kadi F, Eriksson A, Holmner S, Thornell LE. Effects of anabolic steroids on the muscle cells of strength trained athletes. Med Sci Sports Exerc ; : –. Tseng BS, Kasper CE, Edgerton VR. Cytoplasmto-myonucleus ratios and succinate dehydrogenase activities in adult rat slow and fast muscle fibers. Cell Tissue Res ; : –. Kadi F. Adaptation of human skeletal muscle to training and anabolic steroids. Acta Physiol Scand Suppl ; : –. Klausen K, Anderson LB, Pelle I. Adaptive changes in

 Chapter .

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work capacity, skeletal muscle capillarization and enzyme levels during training and detraining. Acta Physiol Scand ; : –. Ratzin Jackson C, Dickinson AL, Ringel SP. Skeletal muscle fiber area alterations in two opposing modes of resistance-exercise training in the same individual. Eur J Appl Physiol ; : –. Terados N, Melichna J, Sylven C, Jansson E. Decrease in skeletal muscle myoglobin with intensive training in man. Acta Physiol Scand ; : –. Bell GJ, Syrotuik D, Martin TP, Burnham R, Quinney HA. Effect of concurrent strength and endurance training on skeletal muscle properties and hormone concentrations in humans. Eur J Appl Physiol ; : –. Hickson RC, Dvorak BA, Gorostiaga EM, Kurowski TT, Foster C. Potential for strength and endurance training to amplify endurance performance. J Appl Physiol ; : –. Tanaka H, Swensen T. Impact of resistance training on endurance performance. Sports Med ; : –. Green H, Goreham C, Ouyang J, Ball-Burnett M, Ranney D. Regulation of fiber size, oxidative potential, and capillarization in human muscle by resistance training. Am J Physiol ; : R–R. Luhti JM, Howald H, Claasen H, Rosler K, Vock P, Hoppeler H. Structural changes in skeletal muscle tissue with heavy-resistance exercise. Int J Sports Med ; : –. Tesch PA, Thorson A, Colliander EB. Effects of eccentric and concentric resistance training on skeletal muscle substrates, enzyme activities and capillary supply. Acta Physiol Scand ; : –. Tesch PA, Thorsson A, Kaiser P. Muscle capillary supply and fiber type characteristics in weight and power lifters. J Appl Physiol ; : –. Schantz P. Capillary supply in hypertrophied human skeletal muscle. Acta Physiol Scand ; : –. Aagaard P, Simonsen EBEB, Andersen JL, Leffers AM, Wagner Å, Magnusson SP, Halkjær-Kristensen J, DyhrePoulsen P. MRI assessment of quadriceps muscle size before and after resistance training. Determination of volume vs single-site CSA. Med Sci Sports Exerc ; (5) (Suppl.): . Rutherford OM, Jones DA. Measurement of fiber pennation using ultrasound in the human quadriceps in vivo. Eur J Appl Physiol ; : –. Willan PLT, Mahon M, Goland JA. Morphological variations of the human vastus lateralis muscle. J Morph ; : –. Walker PM, Brunotte F, Rouhier-Marcer I, Cottin Y, Casillas JM, Gras P, Didier JP. Nuclear magnetic resonance evidence of different muscular adaptations after resistance training. Arch Phys Med Rehab ; : –. Alexander RMcN, Vernon A. The dimensions of knee and ankle muscles and the forces they exert. J Hum Mov Stud ; : –.

 Herbert RD, Gandevia SC. Changes in pennation with joint angle and muscle torque: in vivo measurements in human brachialis muscle. J Physiol ; : –.  Magnusson SP, Aagaard P, Rosager S, Dyhre-Poulsen P, Kjaer M. Load-displacement properties of the human triceps surae aponeurosis in vivo. J Physiol ; : –.  Narici MV, Binzoni T, Hiltbrand E, Fasel J, Terrier F, Cerretelli P. In vivo human gastrocnemius architecture with changing joint angle at rest and during graded isometric contraction. J Physiol ; : –.  Kawakami Y, Abe T, f*ckunaga T. Muscle-fiber pennation angles are greater in hypertrophied than in normal muscles. J Appl Physiol ; : –.  Kawakami Y, Abe T, Kuno S, f*ckunaga T. Training induced changes in muscle architecture and specific tension. Eur J Appl Physiol ; : –.  Fitts RH, McDonald KS, Schluter JM. The determinants of skeletal muscle force and power: their adaptability with changes in activation pattern. J Biomech ;  (Suppl. ): –.  Harridge SDR, Bottinelli R, Canepari M, Pellegrino MA, Reggiani C, Esbjörnsson M, Saltin B. Whole-muscle and single-fiber contractile properties and myosin heavy chain isoforms in humans. Pflügers Arch ; : – .  Komi PV. Training of muscle strength and power: interaction of neuromotoric, hypertrophic and mechanical factors. Int J Sports Med ;  (Suppl.): –.  Aagaard P, Simonsen EB, Andersen JL, Magnusson SP, Halkjær-Kristensen J, Dyhre-Poulsen P. Increased contractile RFD and neuromuscular activation induced by heavy-resistance strength training. Med Sci Sports Exerc ; () (Suppl.): S (abstract).  Schmidtbleicher D, Buehrle M. Neuronal adaptation and increase of cross-sectional area studying different strength training methods. In: Johnson B, ed. Biomechanics X-B. Champaign, Illinois: Human Kinetics Publishers, : –.  Duchateau J, Hainaut K. Isometric or dynamic training: differential effects on mechanical properties of a human muscle. J Appl Physiol ; : –.  Behm DG, Sale DG. Intended rather than actual movement velocity determines velocity-specific training response. J Appl Physiol ; : –.  Schmidtbleicher D, Haralambie G. Changes in contractile properties of muscle after strength training in man. Eur J Appl Physiol ; : –.  Schmidtbleicher D. Training for power events. In: Komi PV, ed. Strength and Power in Sports. The IOC Encyclopaedia of Sports Medicine, Vol. III. Oxford: Blackwell Scientific Publications, : –.  Aagaard P, Simonsen EB, Magnusson P, Larsson B, Dyhre-Poulsen P. A new concept for isokinetic hamstring/quadriceps strength ratio. Am J Sports Med ; : –.

Chapter 1.5 Biomechanics of Locomotion ERIK B. SIMONSE N & PAAVO V. KOMI

Classical reference

Introduction

Muscle power – +

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Winter D. A. Biomechanics and Motor Control of Human Movement. New York: John Wiley & Sons, Inc., .

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Biomechanics is a scientific interdiscipline combining physics, anatomy and physiology. Within sports medicine biomechanics is useful for measuring loadings of anatomic structures in general and for evaluating function before and after some sort of intervention such as rehabilitation and/or surgery. In this chapter space does not permit a wide-ranging presentation of biomechanical analyses of a great number of sporting events. The purpose of the chapter is therefore to present the most commonly used methods of biomechanics to readers, who are assumed to be only remotely familiar with biomechanics. After the methodological part a few examples of biomechanical movement analysis are presented. It is hoped that by the end of the chapter the reader will appreciate the possibilities of biomechanics in relation to sports medicine.

Biomechanical equipment

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Fig. .. Kinetic analysis of a continuous flexion/extension of the elbow joint. The top panel shows the net joint moment calculated by inverse dynamics. Extensor dominance is here defined as positive values. The middle panel shows the angular velocity; extension is positive. The lower panel shows the muscle power obtained by multiplication of joint moment and angular velocity; positive power indicates concentric contraction and negative power eccentric contraction of the dominating muscle group at a given point during the movement. Adapted from Winter [].

A major part of all biomechanical research is concerned with movement analysis, which requires some sort of recording of the actual movements. In the early days of biomechanics and up until recently, -mm cine-film was widely used for this purpose. One advantage of film was that it could easily be recorded at various frequencies, up to several thousands of frames per second if necessary during very fast movements. The major disadvantages were that the media were expensive and the development process often took days. The use of video cameras provides instant recordings but normally at slow sampling frequencies like  or  Hz, which is sufficient for walking but not for faster move-

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 Chapter . ments. Also, the resolution of video recordings is much poorer than that of film and with high-speed video cameras poorer still. However, the technology is constantly improving and high-speed video has started to appear in less expensive versions with increasingly high resolution. A high-speed shutter is a common facility, which should not be confused with high-speed video recordings. Shutter refers to the duration of the exposure of each frame. During recordings of fast movements it is normally necessary to use a shuttertime of / or / of a second to ‘freeze’ the movement, otherwise fast-moving markers will appear blurred on the video recordings. When using several video cameras it is often convenient to ensure that they operate synchronously. This can easily be accomplished through a standard genlock facility, which allows one camera (master) to control exposure of the other cameras (slaves). Cameras with a built-in video recorder (camcorders) cannot be genlocked. Using several cameras will normally also require some sort of event synchronization, which means that one frame corresponding to a certain time position of a recording can be identified on all cameras. A simple way to perform event synchronization is to flash a light in the field of view from a position visible to all cameras.

Force platforms A force platform is a device designed to measure external reaction forces, which are often termed ground reaction forces. A force platform can normally measure forces in three orthogonal directions together with torsional moments about three orthogonal axes. The latter are used for calculations of center of pressure, which is the location on the force platform where the resultant force is applied. During dynamic movement the center of pressure changes location continuously (Fig. ..) and it may be used to find the point of application of force on the foot during e.g. running, which is required to calculate joint moments by inverse dynamics (see later). The center of pressure on a force platform may also be used as a biomechanical parameter itself representing projections of the whole-body center of mass (postural sway) during standing. A force platform needs to be of a particular size if it is to record reliable forces during human movement.

Fig. .. Top: the resulting vector of the ground reaction forces must be aligned to the foot to calculate joint moments by inverse dynamics. The point of force application called the center of pressure changes continuously during e.g. the stance phase of walking, as demonstrated in the lower panel.

Most platforms are about  ¥  ¥  cm, which gives the construction a resonance frequency of about  Hz. This is sufficient to ensure that vibrations are not created by forces originating from human movements. Hitting the platform with a hammer will start a vibration of the natural frequency. Biomechanical laboratories for the investigation of, for example, gait have been designed in various ways.

Biomechanics of Locomotion

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Fig. .. Schematic drawing of a gait lab with five cameras (C–), two force platforms (P and P) and photocells to record the gait velocity during experiments.

C3 Video recorders A/D converter

EMG receiver

One approach is to use a motor-driven treadmill with a number of cameras placed around it. The use of a treadmill has both advantages and disadvantages. The advantages are that it may reduce the space requirements considerably and that the gait velocity can be strictly controlled. The major disadvantage is that investigation of kinematics is limited. To calculate net joint moments by inverse dynamics in two dimensions both the vertical and the horizontal ground reaction force need to be measured and the center of pressure aligned to the spatial positions of the foot. Therefore, the majority of gaitlabs consist of some sort of walkway containing one or two force platforms (Fig. ..).

In vivo tendon and ligament force measurements in humans Information on the forces produced by individual skeletal muscles, tendons and ligaments is important to the understanding of muscle mechanics, muscle physiology, musculoskeletal mechanics, neurophysiology and motor control. The methods applied to produce these forces have been both direct and indirect. Indirect estimation can refer to such methods as the mathematical solution of the actual muscle force in the indeterminate musculoskeletal system. Electromyography (EMG) has been used as an

Trigger

Speed counter

indirect predictive measure of individual muscle torques. Both of these estimates are subject to error, the magnitude of which may vary considerably. For example, the main problem in the use of EMG is its sensitivity to varying conditions of muscle action types, velocity of shortening or lengthening, fatigue, training and detraining. Recent developments in technology and surgical implantation procedures have made it possible to measure forces of the muscle–tendon unit (and ligaments) quite successfully. Since Salmons [] introduced a version of the buckle transducer for recording tendon forces in animals, a number of experiments have been performed, especially investigating cat locomotion. These important developments then led to application of this direct in vivo technique in human locomotion [], primarily for studying the loading of the Achilles tendon (AT) during normal activities such as walking, running, hopping and jumping [–]. The buckle transducer in human experiments is shown schematically in Fig. ... The transducer consists of a main frame, two strain gauges, and a center bar placed across the frame. The size of the frame and bending of the cross-bar varies depending on the size of the AT in question. Final selection of the frame and cross-bar is done during surgical operation, which is performed under local anesthesia. To provide normal propriocep-

 Chapter . 38 mm

20mm

A

A

B

B V [2.5 V]

R1 A

R2

R1

R

120 Ω

R1 B

R1 R2

R

120 Ω –12 Bridge configuration

Fig. .. (a) Schematic presentation of the ‘buckle’-type transducer designed for experiments in which human subjects can perform even maximal activities, e.g. in running and jumping. A, Main buckle frame; B, cross-bar. R1 and R2 are resistors of the 1/2 Wheatstone bridge configuration. The lower part demonstrates schematically (and with slight exaggeration) the bending of the Achilles tendon when the transducer is in situ. (b) Schematic presentation of the buckle transducer implanted around the Achilles tendon [].

tion, lidocaine is not injected into the tendon or muscle tissues. The operation usually lasts – min while the subject is in a prone position on the operating table. The cable containing the wires from the strain gauges is threaded under the skin and brought to the exterior approximately  cm above the transducer. After the cut has been sutured and carefully covered with sterile tapes, the cable of the transducer is connected to an amplifying unit for immediate check-up. Calibration of the transducer is usually performed immediately before the experiments. In contrast to the animal experiments, a slightly more indirect approach must be used to calibrate the AT transducer in human subjects. Experiments can then be performed for approximately – h, depending on the quantity of local anesthesia applied, and measurements can vary from slow walking to maximal jumping. Use of the buckle transducer in the study of AT force measurements produces important parameters such as peak-to-peak force and rate of force development which can then be used to describe the loading characteristics of the tendon under normal locomotion. When these parameters are combined with other external measurements, such as cinematography for calculation of muscle–tendon complex length

changes, the important concepts of muscle mechanics, such as instantaneous length–tension and force– velocity relationships can be examined in natural situations such as stretch–shortening cycle (SSC) activities [,]. Simultaneous recording of EMG activity can add to the understanding of the force potentiation mechanism during SSC-type movement. The major advantage of direct in vivo measurement is that continuous recording of AT force is possible, which is immediately available for inspection. The second important feature of this measurement approach is the fact that several experiments can be performed in one session and the movements are truly natural. The section on p.  gives examples of the AT force recordings during different locomotion tasks performed with the buckle transducer. The buckle transducer method is naturally quite invasive, and may raise objections from the ethical committee in question. Due to the relatively large size of the buckle there are not many tendons which can be selected for measurements. The AT is, however, an ideal one due to large space between the tendon and bony structures within the Karger triangle. Other restrictions in the use of this method are difficulties in the calibration procedure, and problems in the applica-

Biomechanics of Locomotion



Compressive force Core n1

Fig. .. Basic demonstration of how compression on the optic fiber (left) causes microbending (right) and less light through the core–cladding interface. (From Alt et al. [].)

Bending θ′1

Bending

Cladding n2

tion of the technique when long-term and repeated implantation may be of interest. As is the case in animal experiments the buckle transducer method cannot isolate the forces of the contractile tissue from the tendon tissues. The method can therefore only be used to demonstrate the loading characteristics of the entire muscle–tendon complex.

F d

Fd =F′d′ Fd =F′d′ d

d′ F′

Optic fiber technique

PTF calibration Knee extension force (N)

In order to overcome some of the disadvantages of the buckle transducer technique, an alternative method has recently been developed. As was the case for the buckle method this new optic fiber technique was first applied to animal tendons []. However, it had already been successfully used as a pressure transducer in sensitive skin application [] and for measurement of foot pressure in different phases of cross-country skiing []. The measurement is based on light intensity modulation by mechanical modification of the geometric properties of the plastic fiber. The structure of optical fibers used in animal and human experiments [,–] consists of two-layered cylinders of polymers with small diameters. When the fiber is bent or compressed the light can be reduced linearly with pressure, and the sensitivity depends on fiber index, fiber stiffness and/or bending radius characteristics. Figure .. demonstrates the principle of the light modulation in the two-layer (cladding and core) fiber when the fiber diameter is compressed by external force. The core and cladding will be deformed and a certain amount of light is transferred through the core–cladding interface. In order to avoid the pure effect of bending of the fiber, when the fiber is inserted through the tendon (Fig. ..) it must have a loop large enough to exceed the so-called critical bending radius.

400 300 200

1 y=

100

41

.3 7

3 x–

6 .3

7

r =0.97 0.1

0.5

1.0

1.5

2.0

2.5

Optic fibre signal (V) Fig. .. Measured forces and moment arms for the calibration of patellar tendon force (PTF). The optic fiber output was related to the muscle force (F) that had been converted from the external force output (F¢) using equation Fd = Fd¢, where d is moment arm of tendon force and d¢ is moment arm of the foot or leg [].

Figure .. demonstrates how the optic fiber is inserted through the tendon. A hollow -gauge needle is first passed through the tendon (a). The sterile optic fiber is then passed through the needle; the needle is removed and the fiber remains in situ (b). Both ends of the fiber are then attached to the transmitter–receiver unit and the system is ready for measurement (c). The

 Chapter .

(a)

(b)

Transmitter–receiver unit

Optic fiber compression (c) Fig. .. Demonstration of the insertion of the optic fiber into the tendon. (a) After the -gauge needle has been inserted through the tendon, the . mm thick optic fiber is threaded through the needle. The needle is then removed and the optic fiber remains in situ inside the tendon (b), and both ends of the fiber are connected to the transmitter–receiver unit (c). In real measurement situations this unit is much smaller and can be fastened onto the skin of the calf muscles.

calibration procedure usually provides a good linear relationship between external force and optic fiber signal. Figure .. gives a representative example of such a relationship for the patella tendon measurements. Although the optic fiber method may not be more

accurate than the buckle transducer method, it has several unique advantages. First of all it is much less invasive and can be reapplied to the same tendon after a few days of rest. In addition, almost any tendon can be studied provided that the critical bending radius is not exceeded. The optic fiber technique can also be used to

Biomechanics of Locomotion  measure the loading of the various ligaments. In the hands of an experienced surgeon the optic fiber can be inserted through even deeper ligaments such as the anterior talofibular ligament []. In such a case, however, special care must be taken to ensure that the optic fiber is in contact with the ligament only and that contact with other soft tissue structures is prevented by catheters.

Foot pressure transducers Force platforms as described above can be used to measure both static and dynamic plantar forces provided that the platform is capable of producing independent measures of both vertical and shear forces. In many applications, both clinical and athletic, it is desirable to have a continuous recording of the pressure distribution under the foot. Forces acting under the foot in various foot pathologies such as diabetic neuropathy, leprosies, injury and deformation are naturally different from these measured in healthy athletes. Post-operative follow-up of corrective surgery such as free flap reconstruction of severe tibial factures can be performed by measuring plantar pressures under the foot []. The behavior of the foot–shoe interface cannot usually be detected with force plates or even with pedopadographs. For this reason discrete in-shoe transducers have been developed. In the basic design a number of pressure-sensitive transducers are implanted in the shoe insole. The sensors can be of different types, such as capacitive, conductive polymer, sensitive ink or various forms of piezoelectric resistors. For technical details the reader is referred to the thorough review article of Cabb and Claremont []. The number of sensors per insole varies depending on the manufacturer. In some cases there can be close to  discrete sensors or as few as  in one insole. The common rule is that the smaller the number of sensors, the more carefully the sensor locations must be planned in order to match the important anatomic loading sites of the foot. In athletic activities it is desirable to use devices which allow continuous recording for several minutes. In the author’s (Komi) laboratory considerable experience has been gained from the use of a portable, in-shoe pressure data acquisition system (Paromedsystem®, GmBH, Germany) (Fig. ..), which

Fig. .. In-shoe data acquisition system (Paromed-system“, GmBH, Germany) widely used in measurements of plantar pressures during different activities. Both insoles have  piezoelectric microsensors embedded into water-filled hydrocells.

measures simultaneously plantar pressure distribution and EMG activities. The system has in each insole  piezoelectric microsensors embedded into water-filled hydrocells. The insoles ( in total) and EMG cables (from muscles) are connected to the ‘Data Logger’ which is fixed by a belt to the subject’s back. The sampling frequency for the plantar pressures is  Hz. The analysis produces continuous records from each channel and the computer software produces (also continuous) contour curves during the entire contact phase on the ground. Figure .. gives an example of the pressure contours from a patient who had clear asymmetry due to femur length discrepancy. As with any biomechanical method, plantar pressures provide only partial information on locomotion and loading characteristics. For this reason it is very desirable to combine plantar pressure recordings with other parameters obtained from e.g. video cameras and EMG amplifiers. Figure .. is an example of such an arrangement, where ski-jumping take-off is studied using a variety of different measuring techniques []. In addition to plantar pressure measurements, the forces can also be recorded from a -m force plate placed under the take-off table [] or from the smaller force plates implanted into the ski bindings (Pelkonen et al. in progress).

 Chapter .

Longer leg

Shorter leg

Fig. .. Example of the plantar pressure contour curves during the contact phase of walking in a patient with considerable leg length discrepancy [].

Tape recorder Photocells

. . Remote control

Data logger

EMG

15 16 14 11

13 12

10

DC receiver

Camera Sync DC transmitter

16 15 14 13 11 10

12

9

9 7

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6 4 1

Goniometers and accelerometers An electrogoniometer is an analog device used to record joint angles. A simple type of goniometer consists of a potentiometer with two rods, which can be aligned and attached to, for example, the thigh and the shank to measure the knee-joint angle. The potentiometer type of goniometer has to be aligned so that the axis of rotation of the potentiometer is more or less identical to the joint’s axis of rotation. Another type of goniometer is based on strain gauge technology as it measures the bending of a spring. This type has the advantage that it does not need to be aligned to the

Fig. .. Schematic presentation of how plantar pressure measurements can be combined with other biomechanical parameters in the study of ski-jumping [].

joint’s axis of rotation and it is available for measurements in two perpendicular planes, e.g. for flexion/extension and abduction/adduction at the shoulder joint. Three-dimensional goniometers, which also include inward/outward rotation, exist but they are rare. A typical example of the use of goniometers is in the measurement of muscle strength parameters in isokinetic devices. Compression of soft tissues usually dislocates the joint’s axis of rotation with respect to the axis of rotation of the lever arm, resulting in inaccurate data on joint position (Fig. ..) []. Accelerometers are small lightweight transducers

Biomechanics of Locomotion 190

1000

180 160

Goniometer 800

Force

150

KinCom

600

140 400

130

Force (N)

Knee joint angle (%)

170

120 200

110 100

90 0

1000

2000

3000

4000

Time (ms)

Fig. .. Knee joint angle and force vs. time measured during a concentric contraction at °/s. The curves labeled ‘KinCom’ and ‘Goniometer’ are angle measurements from the KinCom machine and the knee-mounted goniometer, respectively (‘ deg.’ denotes full extension). The goniometer signal shows the correct knee joint angle because the center of the knee joint becomes misaligned with the machine’s axis of rotation during the maximal contraction [].

capable of measuring acceleration. Like force transducers they can be based on strain gauge or piezoelectric technology. The latter transducers can only measure dynamic events, while an accelerometer based on strain gauges is capable of measuring the gravitational acceleration, when for example lying on a table. Major problems with the use of accelerometers are that they are difficult to ‘mount’ on a human being and that they measure the acceleration in only one direction. One solution is to use three accelerometers mounted perpendicular to each other and then compute the ‘resulting’ acceleration. This gives an accurate value but the direction of the acceleration is largely unknown. The reader is referred to Winter et al. [] and Dyhre-Poulsen et al. [] for examples of the use of accelerometers.

Electromyography Electrical potentials from active muscle fibers may be recorded by intramuscular needle or wire electrodes or on the skin by surface electrodes. During dynamic movement needle electrodes are considered too inconvenient. Wire electrodes are useful for recording from



‘deep’ muscles as surface electrodes have a pick-up depth of only a few mm. Very thin wires (ª mm) are used to record from single motor units but wires of about  mm in diameter inserted a few cm apart largely resemble the EMG from surface electrodes. Wire electrodes are difficult to work with, but in some cases there are no alternatives as, for example, with the iliopsoas muscle [,]. To obtain high-quality EMG signals from the skin it is necessary to remove hair and dead cells to reduce skin resistance. Ag/AgCl adhesive electrodes with a lead-off area of ª mm2 with some sort of electrolytic gel are normally placed about  cm apart along the estimated muscle fiber direction. A bipolar set-up means that the two electrodes will measure the potentials relative to a reference electrode, preferably placed over bony tissue. The surface EMG is an AC signal, which oscillates between negative and positive values some – times per second. It is, however, a compound signal made of many interfering action potentials from single motor units. Therefore, the surface EMG contains frequency components from about  to  Hz. Normally, a sampling frequency of  Hz is sufficient to obtain an acceptable digital representation of a raw surface EMG. When used for biomechanical movement analysis EMG signals are often full wave rectified and lowpass filtered with a cut-off frequency of about – Hz (Fig. ..). This representation is called a ‘linear envelope’ and it is convenient for quantification in terms of amplitude, integrated EMG and duration. The integrated EMG is the area under the linear envelope. Recordings of EMG during dynamic movement are often contaminated by so-called movement artefacts, which are low-frequency components of the recordings originating from movements of the electrodes rather than being a part of the EMG. In the recording phase such artefacts can be more or less abolished by the use of preamplifiers positioned close to the recording electrodes, because these preamplifiers not only amplify the signal but also lower the impedance before ‘transportation’ through wires to the main amplifier. It is possible to remove movement artefacts further subsequently by application of a highpass filter with a cut-off frequency of – Hz. Electromyography is very useful when combined

 Chapter . Biomechanical analysis Offline/online digitization

Fig. .. (a) A so-called ‘raw’ EMG recording of the soleus muscle during walking. In (b) the signal is rectified and all negative values are made positive and in (c) the rectified signal has been lowpass filtered with a cut-off frequency of  Hz to form a linear envelope.

with biomechanical movement analysis. Calculation of net joint moments by inverse dynamics gives only the net result of the muscle contractions about the joint. Information about cocontraction cannot be provided without simultaneous EMG recordings.

Computer systems for biomechanical movement analysis can be divided into offline and online systems. The latter may use active or passive markers. Active markers emit light or sound or other signals which are registered by a receiver unit several times per second. Passive markers most often reflect infrared light, which is flashed by special video cameras. The video signal is looped through a special electronic device, which will extract only the light of infrared intensity. The center of each marker is then calculated and x,y-coordinates are transferred to a computer. This whole process runs on line, i.e. – times per second for up to six cameras. As a consequence the visible video pictures are lost and only the coordinates of the small markers placed at anatomic landmarks on the subject are left in a computer. If anything goes wrong, for example if markers passing close by each other get mixed or if a marker cannot be ‘seen’ by at least two cameras at any time, it is often difficult to correct the errors. However, when such systems work perfectly, they can provide almost instant results. Online systems are typically limited to permanent laboratories. Offline systems are based on video recordings. Normally, analog video signals are stored on tape and later sampled by a computer with a so-called frame-grabber. Video recordings from digital cameras can also be input to a computer by commercial interface devices. Once the video sequences exist in digital form in a computer, they can be processed frame by frame by specially dedicated software. Usually contrasting markers are placed at anatomic landmarks on the subject and these can then be digitized manually or semiautomatically to obtain x,y-coordinates from each frame. If the software can identify a large number of markers on most of the frames the process of offline digitization may be fairly fast, meaning for example – min for  frames corresponding to a gait cycle of  frames per camera and five cameras. A major advantage of offline video analysis is that field events can easily be recorded and analysed even from sports competitions without markers on the subjects.

Vertical displacement (m)

Biomechanics of Locomotion R. asis 7

0.30 0.28 0.26 0.24 0.22 0.20 0.18 0.16 0.14 0.12 0.10 0.08

R. trochanter

5 4

50

100 150 Frames

200

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Fig. .. Vertical displacement of an ankle joint marker during a normal walking cycle. The noisy curve is raw data from digitization while the smooth curve represents the same signal lowpass filtered with a cut-off frequency of  Hz (the film was recorded at  frames/s).



14 L. asis

6

R. tibial tubercle 3 R. malleolus

11 L. metatarsal head V L. metatarsal head V 9 8 L. heel X

Fig. .. Marker placement on a three-dimensional link segment model [].

Noise reduction/filtering In every process of digitization of markers placed on a subject small errors will be present. A marker placed on the skin will move with the skin, but most importantly it is impossible for either a computer or a human being to digitize exactly the center of a marker. These errors represent a kind of noise component superimposed on the pure movement signal (Fig. ..). It can be shown that the noise is of a random character but of an absolute amplitude []. This amplitude may be – mm on a scale of  m. The result of a digitization is so-called time–position data and the noisy component seems to affect the time–position data only to a certain degree. However, when the first derivative is taken (differentiation) to obtain velocity data, the noise becomes more evident, and with the second derivative it becomes clear that something has to be done to reduce the errors from digitization. Various types of digital smoothing or filtering can be applied to time–position data to reduce the noise, but most often a so-called th order lowpass Butterworth filter is used to remove frequency components above e.g.  Hz. However, this implies that both the noise and some fraction of the real movement signal are attenuated and it follows that movement data will never be accurate when originally obtained as time–position data. After filtering, velocity and acceleration can be calculated so that clear signals are obtained, and provided the same

cut-off frequency is used throughout an experiment the error component can be assumed to be of a constant and systematic nature (Fig. ..).

Link-segment models In a biomechanical analysis of movement the human body is normally converted into a model consisting of rigid body segments connected by hinge joints (two dimensional) or spherical joints (three dimensional) (Fig. ..). The segments are most often assumed to be rigid, each segment mass is set to a certain fraction of the whole body and the segment center of mass is assumed to be located at a certain proportional distance along. The anthropometric data used to establish a link-segment model are normally based on Dempster [] and the model is therefore confined to data from a limited number of Caucasian cadavers. Biomechanics worldwide is in great need of additional anthropometric data relating to ethnic differences. It is obvious that a link-segment model is basically inaccurate in many aspects. However, it is reasonable to assume that the inaccuracies of a model represent a systematic error, which allows the investigator to compare results on the same subject in various situations. Several mechanisms may be studied with link-segment models, while absolute values can never be accurate.

 Chapter . Kinematics A kinematic analysis of a movement usually includes calculation of joint angles. An anatomic joint angle is an angle between two segments while a so-called segment angle is between a segment and the vertical or the horizontal plane. Joint angular velocity obtained by time differentiation of angle data is also often considered part of a kinematic analysis, because this parameter can be expressed as, for example, flexion and extension indicated by positive and negative angular velocity, respectively (see Fig. .. above). All positions and velocities are in principle kinematic parameters. Segmental mechanical energy in terms of potential, kinetic and rotational energy also belongs to kinematics, because accelerations are not needed for these calculations.

Kinetics Kinetic parameters are acceleration, force and moment (torque). The most common kinetic parameter is so-called net joint moments calculated by inverse dynamics. These moments provide information as to which muscle group is exerting the strongest force on a joint and how strongly these muscles are pulling on the bones. When no external forces are acting on the body segments of interest, as occurs e.g. during kicking or throwing, the calculation of inverse dynamics is fairly simple. Continuous extension and flexion of the elbow joint represents a situation with no external forces. A calculation of joint moments by inverse dynamics shows that this movement is fairly complicated with regard to muscle action and contraction mode (see Fig. ..). It can be seen that a positive moment in this case indicates extensor muscle dominance while a negative moment indicates flexor dominance. A counterclockwise pulling direction is normally defined as positive. The term dominance refers to the fact that both flexors and extensors may be active simultaneously (cocontraction) and as a consequence a zero moment could theoretically be the result of intensive cocontraction. It is further seen from Fig. .. that flexion and extension are ‘out of phase’ with the joint moment in certain time periods. However, this could merely mean that, for example, the flexor muscles decelerate the last part of the extension and then turn the movement directly into flexion. Multiplication of angular

velocity and joint moment yields power and it is seen that negative power means eccentric muscle work and positive power concentric work (Fig. ..). It is considered an important feature of inverse dynamics that the method can provide information about the contraction mode of the muscles. During jumping, walking and running external reaction forces are applied to the most distal segment, the foot. These forces have to be measured by a force platform together with the center of pressure on the platform, so that the point of force application on the foot can be found on every frame. This method of inverse dynamics is also called the free body segment method, because the calculations are performed on one segment at a time. The calculation includes joint reaction forces acting on both ends of the segment, inertial properties and the influence of the moment from the previous segment (Fig. ..). The joints of the lower extremities are positioned so that a positive moment about the ankle joint is a dorsiflexor moment, a positive moment about the knee joint is an extensor moment and a positive moment about the hip joint a flexor moment. The example of walking shows that the ankle joint is plantar–flexor dominated during the stance phase, the knee joint shows short flexor, extensor, flexor and extensor dominance while the hip joint is extensor dominated in the first half of the stance phase and flexor dominated in the last part of the stance phase (Fig. ..). The reason why walking with flexor dominance about the knee joint is possible without collapsing is that the movement is dynamic and that the three joints of the leg operate together. The moments of the ankle, knee and hip joint are often added to form a so-called support moment representing the action of the whole leg. Doing so requires extensor moments to be considered as positive during the calculation (Fig. ..). If the support moment is positive, the leg will not collapse. Bone-on-bone forces can be calculated as the sum of all forces acting about a joint. After calculation of the net joint moment it is necessary to compute an estimated internal moment arm for the dominating muscle group to obtain the muscle force. Bone-on-bone forces are often confused with joint reaction forces, which are a part of the inverse dynamics calculation (see Fig. ..). Cocontraction about the actual joint will cause the bone-on-bone forces to be underesti-



Biomechanics of Locomotion Fyj θj

Fxj ms⋅ays

Mj

R1

CGs

R3

l⋅αs

ms⋅axs

EFy

Ws

R2

R4

EFx

Mp Fig. .. Free body diagram showing the calculation of inverse dynamics in two dimensions. M denotes a moment; F, joint reaction force; EF, external reaction force; I, moment of inertia; a, angular acceleration; m, segment mass; W, m ¥ g of a segment; R a, distance to segment mass center; a, linear acceleration of segment mass center; q, segment angle with respect to the horizontal plane. Suffix j denotes the joint of interest and the proximal end of the segment; p refers to parameters transferred from the previous segment and acting on the distal end of the segment; x, horizontal direction; y, vertical direction.

Fxp Fyp Mj

= + – – – + – +

Is R1 R1 R3 R4 R2 R2 Mp

• • • • • • •

α cosθj sinθj EFy EFx cosθj sinθj

• Fyj • Fxj

• Fyp • Fxp

(s1) (s2) (s3) (s4*) (s5*) (s4) (s5) (s6)

+

Fyj = ms • ays + Ws + Fyp – Efy*

Hip

Knee +

+ Ankle

Fxj = ms • axs + Fxp – Efx*

mated; it is therefore considered ideal to record an EMG simultaneously. The reader is referred to Scott and Winter [] and Simonsen et al. [] for examples of bone-on-bone forces during locomotion.

Muscle–tendon unit models As mentioned above it is possible to deduce from inverse dynamics whether the muscles contract eccentrically or concentrically. However, this applies to muscles spanning only one joint. Several muscles are bi-articular and their length changes depend on the motion of the two joints they cross. On the basis of cadaver studies [,] it is possible to model a number of muscles in the lower extremities all working in the sagittal plane with flexion or extension. Models of the soleus and the gastrocnemius muscles are seen in Fig. ... The length of a muscle–tendon unit is in this case calculated from origin to insertion. Since the muscle fibers are normally only a few cm long and connected in series with the aponeurosis and tendons it is not possible to separate the length changes of the muscle fibers and the tendinous structures, respectively.

Three-dimensional analysis Using only one camera for a movement analysis limits the calculations to two dimensions (D). This is not necessarily considered a disadvantage since many movements take place primarily in the sagittal plane and a D analysis is much easier to perform than a three-dimensional (D) one []. A D set-up requires that each marker of interest is visible to at least two cameras at any point during the movement. Most systems require some sort of calibration cube to be filmed by all cameras. Digitizing markers on the cube with known coordinates in D makes it possible to calculate the exact position of the cameras and to calculate further the third dimension of each marker by so-called direct linear transformation [].

Three-dimensional kinetics The complexity of calculating joint moments by inverse dynamics increases almost exponentially when advancing from D to D. In D it is necessary to compute joint centers, but the biomechanical commu-

 Chapter . MV

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900

1100

nity suffers from the lack of anthropometric data for this purpose. The formulas published by Vaughan et al. [] are often used, but these formulas are only based on X-ray data from one subject and alternative formulas are mostly substantiated. Another complication with D is that calculation of joint centers is closely related to specific marker set-ups. It is necessary to place three markers on each segment in order to calculate the segment’s attitude, which again allows for calculation of joint moments about anatomic axes. This means that, for example, a hip flexor moment can

Fig. .. A complete twodimensional analysis of one walking cycle consisting of recordings from film, force platform and EMG. From top to bottom: stick-diagram of the movement, ground reaction forces (the horizontal line represents body mass), net joint moments of ankle, knee and hip joint and the total support moment of the leg, rectified EMGs from the rectus femoris, semitendinosus, vastus lateralis, soleus and tibialis anterior muscles with changes in muscle–tendon lengths superimposed on the EMGs (inflection denotes lengthening of the muscle–tendon unit).

be recognized irrespective of how the subject turns in space during the recorded movement. A major drawback of the D approach is that only few joints are spherical joints. For example, it seems nonsensical to calculate abduction/adduction moments about the knee joint. Nevertheless relatively large moments of abduction/adduction about this joint appear from a D kinetic analysis of walking or running []. Moments of internal/external rotation must also be considered very uncertain due to small movements of segment rotation about a longitudinal axis.

Biomechanics of Locomotion  (a)

(b) K

o

l1

K

η2

o l2

A

l2

η3

n

i ζ F

A

η3

n

i ζ F

Fig. .. Trigonometric models of (a) the soleus and (b) gastrocnemius muscles (the two heads are lumped). K, knee joint; A, ankle joint; i, insertion; o, origin; h2, knee joint angle; h3, ankle joint angle; l2, length of the soleus muscle–tendon unit; l1 + l2, length of the gastrocnemius muscle–tendon unit; zF is an angle taken from Frigo and Pedotti [].

Fig. .. Illustration of a three-dimensional link-segment model consisting of pelvis, thigh, shank and foot segments connected by spherical joints. The markers used for digitization are shown; in this case the Helen Hays marker set-up was used, which includes some of the markers on wands sticking out from the segments. To calculate joint moments representing anatomic flexion/extension, abduction/adduction and inward/outward rotation no matter how the subject is oriented in space, it is necessary to define local segment coordinate systems, which are related to the global reference coordinate system of the laboratory. (Adopted from Arial Dynamics Inc.)

Inverse dynamics

Fig. .. The top flow diagram illustrates the process of inverse dynamics. However, the position data are not coordinates of markers but a joint angle calculated using marker coordinates. The lower panel shows the process of forward dynamics (simulation), where you start with muscle force and end with movement. q is a joint angle, w angular velocity, a angular acceleration, I moment of inertia, t muscle moment, l internal moment arm, F muscle force and Dt a time constant.

∆θ =ω ∆t

ω

∆ω =α ∆t

α

τ = ⋅α

τ

F=

τ l

θ

∆t

Simulation Calculation of net joint moments by inverse dynamics is called inverse because one actually works in the opposite direction to nature when measuring the movements and the external forces used to calculate the muscle forces that generated the movement. Using forward dynamics represents a method which simulates biology in the sense that you build a link-segment

F

θ =ω⋅∆t

ω

ω =α⋅∆t

α

α=

τ

τ

τ = F⋅l

Forward dynamics (simulation)

model in a computer with muscles attached to the segments (Figs ..–..). The muscles possess anatomic and physiologic properties like fiber length, tendon length, tendon compliance, internal moment arms of the muscles, force–velocity relationship and length–tension relationship. The computer is then programmed to activate the muscles in random order until the desired movement is accomplished, which

 Chapter . Gerritsen et al. [] found that a simulation model of human walking driven by simulated muscles could recover from a sudden perturbation while a model driven by ‘mechanical’ joint moments lost balance and fell to the floor.

Examples of biomechanical investigations Different movement strategies in vertical jumping Vertical jumping is often used as a standard test for dynamic strength in the lower extremities. Three types of vertical jumps prevail in the literature: (i) drop jump, in which the subject starts by jumping downward from a box onto the floor and performs a vertical jump immediately after the landing: this is a typical SSC (stretch–shortening cycle) type of exercise; (ii) countermovement jump, which is also an SSC exercise but with less eccentric loading; and (iii) squat jump (Figs .. and ..), where the subject starts from a static squatting position, i.e. a movement ideally consisting of pure concentric contractions. Fig. .. Illustration of a computer model for simulation of walking. (Adopted from Musculographics Inc.)

may take weeks or months. Optimization of a simulation model is accomplished with a so-called cost function, which signifies the target of the simulation or rather the criteria of success. Performance optimization is, for example, the length of a long jump calculated theoretically from the vertical and horizontal velocities of a long jump model at take-off, but the same movement may be optimized by tracking the joint displacements or the ground reaction forces produced by a real long-jumper. For a review see van den Bogert []. It is often necessary to perform experiments with inverse dynamics to verify the behavior of a model. However, once a simulation model moves realistically it is possible to ‘ask’ the model questions, which cannot easily be investigated experimentally with real subjects. Examples of such questions or rather manipulations are to make certain muscles stronger or weaker or to move the insertion point of a muscle. It is also possible to apply perturbations to a moving model.

Direct in vivo tendon forces during normal locomotion Normal locomotion and/or muscle function usually refers to stretch–shortening cycles [], where the active muscle is first stretched (eccentric action) prior to shortening (concentric action). The purpose of SSC is to make the performance more efficient as compared to isolated forms of either isometric or concentric actions. Figure .. is a typical example of how the buckle transducer technique, which can be used to characterize the loading of the triceps surae muscle– tendon complex, is combined with simultaneous EMG recordings. The figure shows several important features of the loading characteristics in this example of moderate-speed running. First, the changes in the muscle–tendon length (segment length) are very small (–%) during the stretching phase. This suggests that the conditions favor the potential utilization of short-range elastic stiffness (SRES) [] in the muscle. Various length changes are reported in the literature demonstrating that the effective range of SRES in in vitro preparations is –% [,]. In the intact muscle tendon, in vivo, this value is increased because series

Biomechanics of Locomotion 

Nm

TO

SJ

700 500 o/s 300 100 –100 500

Hip joint Knee joint Ankle joint Angular vel.

300 100

–100 3000 2000 w 1000 0 –1000 800

Net. moment

Power m. glut. max.

0 500

m. add. magn.

0 2500

Fig. .. A squat jump performed with a simultaneous strategy. From top to bottom: stick diagram showing a subset of the frames, which were recorded at  Hz; angular velocity of extension; net joint moments; net joint power; and rectified EMG from seven muscles. Extensor-dominated moments are all positive and positive power indicates concentric contractions. SJ is start of the jump and TO is toe-off.

µV

m. rect. fem.

0 1500

m. vast. lat.

0 800

m. semit.

0 2000

m. gastroc.

0 1500 m. soleus 0 –300

elasticity and fiber geometry must be taken into account. This could then increase the muscle–tendon lengthening to –%. When measurements are made at the muscle fiber level the values could be naturally smaller, as shown by Roberts et al. [] in turkeys running on level ground. Achilles tendon force (ATF) curves similar to the one shown in Fig. .. can then be used to plot both the peak-to-peak ATF and the rate of ATF development during ground contact against the running velocity. This presentation is from a subject who was

–200

–100 Time (ms)

100

able to run at different velocities (ranging from  to  m/s) with the buckle transducer around his AT. The figure shows that the maximum ATF seems to have reached its highest value by a speed of  m/s, in which case the value was  kN corresponding to . body weight (BW). As the cross-sectional area of the tendon was . cm2, the peak force for this subject was . kN/cm2, a value which is well above the range of the single load ultimate tensile strength []. The qualitative presentation shows that the maximum rates of ATF development, measured during the sharp

 Chapter .

SJ

700 500 o/s 300 100 –100 500 Nm

TO Hip joint Knee joint Ankle joint

300

Angular vel.

100 –100 3000 2000 w 1000 0 –1000 1500

Net. moment

Power m. glut. max.

0 800

m. add. magn.

0 2500

µV

m. rect. fem.

0 1500

m. vast. lat.

0 2000

m. semit.

0 2000 m. gastroc.

0 1500

m. soleus

0 –300

–200

–100 Time (ms)

rising phase after the contact, increased linearly with the increase in running velocity during contact. This information is important, because it suggests that the rate of force development rather than the peak-to-peak force may be more relevant for characterizing biological tissue loading during locomotion. It is well known from basic muscle physiology that the force–velocity (F–V) relationship [] describes the fundamental mechanical properties of human muscle. This Hill curve differs, however, in one fundamental respect from the natural situation: the forces

100

Fig. .. A squat jump performed with a sequential strategy. From top to bottom: stick diagram showing a subset of the frames, which were recorded at  Hz; angular velocity of extension; net joint moments; net joint power; and rectified EMG from seven muscles. Extensor-dominated moments are all positive and positive power indicates concentric contractions. SJ is start of the jump and TO is toe-off.

are measured during constant (maximal) activities. In natural and normal locomotion, such as SSC of Fig. .., the EMG activity is variable and not constant in any parts of the cycle. Thus the instantaneous force– velocity curves measured for the functional contact phase are consequently very different from the classical curve obtained for pure concentric actions with isolated preparations [] or with human forearm flexors [,]. Figure .. gives examples of the instantaneous F–V curves for running (a) and hopping (b). The

Biomechanics of Locomotion  B

C

10

1 mV

M. tibialis anterior

Tendon force (kN)

A

1 mV M. gastrocnemius

(a)

8 6 4

Heel running Ball running

2 0 3

4

5

6

7

8

9

8

9

M. soleus 0 %

Segment length (∆%)

10 500 N

Vertical force

Achilles tendon force

500 N

Horizontal force

100 N 100 ms

Fig. .. Demonstration of stretch–shortening cycle (SSC) for the triceps surae muscle during the (functional) ground contact phase of human running. Top: Schematic position representing the three phases of SSC (preactivation (A), eccentric (B) and concentric (C)). The rest of the curves represent parameters in the following order (from top to bottom): rectified surface EMG records of the tibialis anterior, gastrocnemius and soleus muscles; segmental length changes of the two plantar flexor muscles; vertical ground reaction force; directly recorded Achilles tendon force; and the horizontal ground reaction force. The vertical lines signify, respectively, the beginning of the foot (ball) contact on the force plate and the end of the eccentric phase. The subject was running at moderate speed [].

buckle experiments (left) did not include comparative records obtained in a classical way, but the form of the FV curves suggests considerable force potentiation in the concentric phase. Our recent experiments with the optic fiber technique, although not yet performed at high running speeds, suggest similar potentiation. The right side of Fig. .. shows simultaneous plots for both patella and AT forces during hopping. The

Tendon force development (kN/s)

1 mV 200 (b) Ball running

150 100

Heel running

50 0

3

4

5

6

7

Running velocity (m/s) Fig. .. Peak Achilles tendon forces (a) and peak rates of tendon force development (b) for one subject running at different velocities. The buckle transducer was implanted around the subject’s Achilles tendon [].

data signify that in short contact hopping the triceps surae muscle behaves in a bouncing ball-type fashion (see also [,]). When the hopping intensity is increased or changed to countermovement-type jumps, the patella tendon force increases and the AT force may decrease []. The classical type of curve obtained with constant maximal activation for an isolated concentric action is also superimposed with the AT force in the same graph (Fig. .., right). The shaded area between the two AT curves suggests a remarkable force potentiation for this submaximal effort. The direct in vivo technique reliably measures the forces in the tendon (and ligament), but the results and relationships obtained cannot, however, be used to generate simultaneous information about: (i) the change in length of the muscle fibers; (ii) the change in the fiber orientation with the line of force application; or (iii) the change in length of the tendinous compartment. Thus the force–velocity curves presented in Fig. .. must be interpreted more correctly as referring

 Chapter . (a)

F 10

4

(b) 5.78 m / s

3

8 6

F AT

2

9.02 m / s

4 1 2 –1.5

–1

–0.5

PT 0

0.5

1

1.5

2

Velocity

–0.4

–0.2

0.2

0.4

0.6

Velocity (m / s)

Fig. .. Examples of instantaneous force–velocity curves measured in (a) human running and (b) hopping. The records on the left were obtained with the buckle transducer [] and those on the right with the optic fiber []. Each record is for a functional (contact) phase on the ground. In each curve the upward deflection signifies stretching (eccentric actions) and the downward deflection shortening (concentric action) of the muscle tendon complex during ground contact. The velocity axis has been derived from segmental length changes according to Grieve et al. [].

to the function of the muscle–tendon as one entity. However, experiments are currently in progress to utilize a relatively high resolution and frame rate (>  Hz) ultrasound technique to capture the movements in the fascicle compartment during SSC actions in combination with the optic fiber and EMG recordings for both triceps surae and quadriceps femoris muscles.

Plantar pressures during sporting activities The basic methodology of plantar pressure recording was introduced above on p. . The experimental setup shown schematically in Fig. .. was successfully used in actual ski-jumping. Figure .. gives examples of how this methodology produced results from the various plantar pressure sensors and from the EMG activities recorded from selected muscles. It is clear from simple observation of Fig. .. that the jumper ML had a clearly unbalanced take-off as shown by dramatic bilateral differences in the pressure contours at the moment of take-off. These results also demonstrate that during the run-in and take-off, the locations which detect the pressures are primarily points  and  (heel area) and  and  (toe area). Figure .., on the other hand, gives a unique demonstration of the plantar pressures of selected insole points and EMG activities throughout the entire ski-jumping performance, including not only the takeoff but also the entire run-in, flight and landing. While ski-jumping take-off represents an explosive

type muscle action with relatively small impact loading, the triple jump is an activity where the impact loads on muscle, joint and bones are probably the highest of all sporting activities (Figs ..–..). Figure .. gives an example of the ground reaction forces and plantar pressures (one sensor only) during the contact phases of the hop, step and jump. In these situations the maximal vertical force (Fz) can exceed   kN in the braking phase, being slightly higher on the ‘step’ contact as compared to ‘hop’ or ‘jump’ of the triple jump. In relative units these values represent – times the body weight. When compared with normal walking, for example, the triple jump loading, as measured with Fz ground reaction forces, is almost  times greater.

Modeling anterior cruciate ligament loadings at the knee joint A side-cutting maneuver is an important and common movement in many sports events, especially ballgames. The purpose of the maneuver is to pass a defending player by faking the direction opposite to the intended movement. Normally, the player will approach the defending player head on, touch down on the left foot, brake the forward velocity and step to the right side. During the braking action, the quadriceps femoris muscle contracts eccentrically causing an anterior shear force on the tibia that stresses the anterior cruciate ligament (ACL) of the knee joint (Fig. ..). The peak knee joint moment ( Nm) calcu-

Biomechanics of Locomotion 

Take-off

Run-in

Jumper ML 82 m,22.4 m/s

Jumper APN 93 m,23.2 m/s

Fig. .. An example of the selected pressure, EMG (GL, gluteus; VL, vastus lateralis; GA, gastrocnemius) and sync pulse curves from one ski-jump with run-in speed of . m/s and length of jump  m [].

EMG (mV)

Plantar pressure (N/cm2)

Fig. .. Examples of the pressure contours from two different ski jumpers (ML and APN) during the run-in and take-off phases. Sensor locations of the pressure insoles are shown as well [].

Landing

Take-off 20

Run-in

Curve

Flight L #2

20 20 20 20

R #2 L #13 R #13 L #16

20

R #16

1 GL 1

VL

0.5

GA SYNC 1

2

3

4 Time (s)

5

6

7

 Chapter . lated by inverse dynamics was found to occur during the braking action at a knee joint angle of ° (average of six subjects). The model then showed an average shear force on the ACL of  N (range – N) (Fig. ..). The ACL has been shown to have a maximum strength of  N in young people []. Therefore, the side-cutting maneuver cannot directly cause a rupture of a normal ACL []. The hamstring muscles have frequently been sugHop

Step

Jump

Fz Fy

5000 N

P14

50 N cm2

GM

0.5 mV

2500 N

gested to be able to lower the loadings on the ACL. However, an EMG analysis showed that these muscles were only moderately activated during the braking action of the side-cutting maneuver. The peak amplitudes of the medial and lateral hamstrings were  and % of maximum EMG, respectively (Figs .. & ..). In comparison the vasti were activated close to %. Estimates of shortening and/or lengthening velocities were calculated by muscle models based on cadaver data from Frigo and Pedotti [] and expressed as percentage muscle fiber length per second using cadaver data from Wickiewicz et al. []. These calculations showed that the hamstring muscles shortened during the braking action and that the shortening velocity was up to about % fiber length per second, which strongly indicates that the muscles cannot produce force of any significance in this situation. Thus the hamstring muscles cannot reduce ACL loadings during a side-cutting maneuver [].

Summary 100 ms Fig. .. Example of the two-dimensional ground reaction forces, plantar pressure distribution of the forefoot sensor (P), and raw EMG signal of the gluteus maximus (GM) in the triple jump. The length of jump was . m [].

1000

15 16 14 11 10

13 12

16 15 14 13 11 10

9 7

6

750

4 1

Pressure (kPa)

Walking Hop of the triple jump Step of the triple jump Jump of the triple jump

12

9 8

8

5

5

3

3

2

2

7

Biomechanics is an interdiscipline mostly concerned with movement analysis. The laws of physics are used to calculate strain applied to anatomic structures during movement. Movements are recorded by video cameras, and small markers or sensors are placed on the subject at anatomic landmarks. The video signals

6 4 1

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10 11 12 13 14 15 16

Sensor numbers

Fig. .. Example of the peak pressures of the various sensors for one male jumper measured during the hop, step and jump phases of the triple jump and during walking. The missing standard deviation bars indicate that the signals exceeded the range of sensors [].

Biomechanics of Locomotion  Hop

Step

Jump

Touchdown

Midstance

Fig. .. The contour curves of the plantar pressures measured  ms after touchdown, in the middle of the stance phase and the toe-off. The arrows indicate jumping direction [].

Toe-off

700

Pressure (kPa)

P6

600

r = 0.96 P < 0.01 n = 10

P9 r = 0.92 P < 0.01 n = 10

P12 r = 0.88 P < 0.01 n = 10

Q

500

b H

400

β F 10

11

12 13 Length (m)

14

15

a

C

P

Hs Fig... Relationship between the length of the triple jump and the peak plantar pressures of the lateral forefoot (sensors ,  and ) of one experienced male jumper measured during the hop, step and jump.

are analysed by computer in real time or off line depending on the specific equipment. The coordinates of the markers are used to calculate velocities and accelerations and joint angles, and when combined with measurements of external forces acting on the body, net joint moments or muscle forces can be calculated by a method called inverse dynamics. Movement analysis in three dimensions requires the use of several video cameras recording from different views. The third dimension is then calculated by direct linear transfor-

T

Qs Fig. .. A biomechanical model of the knee joint intended to evaluate stress applied to the anterior cruciate ligament during movement. Abbreviations: F, femur; T, tibia; P, patella; C, force acting on the anterior cruciate ligament; Q , quadriceps femoris muscle; H, hamstring muscles; Qs, quadriceps shear force; Hs, hamstring shear force; and b, the angle between a and b signifying the angle of the patellar ligament relative to tibia, which changes with the position of the knee joint.

 Chapter .

2000 Fy

1500 1000 N

500 0 Fx

–500 200

Nm 100

Knee joint moment

0 %

100 VM 0 100 VL 0 100 Gmax 0 100 SMT 0 100 BFcl 0

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150

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450

mation. External reaction forces are most often measured by force platforms, but a detailed pressure distribution of the plantar surface of the foot can also be measured using special devices mounted inside a shoe. Power generated by the muscles during movement

550

Fig. .. One subject performing a side-cutting maneuver. From top: stick diagram of the left leg during a sidecutting maneuver; the vertical (Fy) and the horizontal (Fx) ground reaction force; the net knee joint moment; EMG from five leg muscles. The EMGs are linear envelopes and expressed relative to a maximum EMG measured during isometric conditions. The curves superimposed on the EMGs are estimates of muscle–tendon unit length changes. Inflection indicates lengthening. Abbreviations: VM, vastus medialis; VL, vastus lateralis; Gmax, gluteus maximus; SMT, semitendinosus and semimembranosus muscles, BFcl, biceps femoris caput longum muscle.

may be calculated using net joint moments and angular velocity. Muscle power then provides detailed information about the muscle activity with regard to eccentric and concentric contractions.

Biomechanics of Locomotion



100 m. tlb. ant. 0 100 m. soleus 0 100 m. gas. lat. 0 100 m. gas. med. 0 100

% maximal EMG

m. biceps fem. 0 100 m. semitend. 0 100

m. glut. max.

0 100

m. vastus lat. 0 100 m. vastus med. Fig. .. Linear envelope EMGs from seven leg muscles recorded during a side-cutting maneuver. The bottom panel is the vertical ground reaction force. The data represent an average of  trials across six subjects and are expressed relative to maximum EMG. Error bars are standard error of the mean.

0 1800

N Ground reaction

0 100

300 Time (ms)

500

 Chapter . Multiple choice questions  a b c  a b c  a b c  a b c  a b c

Noisy movement data are filtered with a: highpass filter bandpass filter lowpass filter. Inverse dynamics is a method used to calculate: joint moments joint angles angular acceleration. A goniometer measures: acceleration velocity angles. Center of pressure is measured on: a force platform the floor the foot. Tendon forces may be measured using: a force platform optic fibers EMG.

References  Salmons S. The th International Conference on Medical and Biomechanical Engineering — meeting report. Bio Med Eng ; : –.  Komi PV. Physiological and biomechanical correlates of muscle function: Effects of muscle structure and stretchshortening cycle on force and speed. Exerc Sport Sci Rev/ACSM ; : –.  Komi PV, Salonen M, Järvinen M, Kokko O. In vivo registration of Achilles tendon forces in man. I. Methodological development. Int J Sports Med ; : –.  Komi PV. Relevance of in vivo force measurements to human biomechanics. J Biomech ;  (Suppl. ): –.  Gregor RJ, Komi PV, Browing RC, Järvinen M. A comparison of the triceps surae and residual muscle moments at the ankle during cycling. J Biomech ; : –.  f*ckashiro S, Komi PV, Järvinen M, Miyash*ta M. Comparison between the directly measured Achilles tendon force and the tendon force calculated from the ankle joint moment during vertical jumps. Clin Biomech ; : –.  Voigt M, Dyhre-Poulsen P, Simonsen EB. Stretch-reflex control during human hopping. Acta Physiol Scand ; (): –.  Komi PV. Stretch-shortening cycle: a powerful model to study normal and fatigued muscle. J Biomech ; : –.  Komi PV, Belli A, Huttunen V, Bonnefoy R, Geyssant A, Lacour JR. Optic fiber as a transducer of tendomuscular forces. Eur J Appl Physiol ; : –.

 Bocquet J-C, Noel J. Sensitive skin-pressure and strain sensor with optical fibres. In: Proceedings of nd Congress on Structural Mechanics of Optical Systems, – January , Los Angeles, California, USA.  Candau R, Belli A, Chatard JC, Carrez J-P, Lacour J-R. Stretch shortening cycle in the skating technique of cross country skiing. Sci Motricité ; : –.  Arndt AN, Komi PV, Brüggemann G-P, Lukkariniemi J. Individual muscle contributions to the in vivo Achilles tendon force. Clin Biomech ; : –.  Finni T, Komi PV, Lepola V. In vivo muscle dynamics during jumping. In: Third Annual Congress of the European College of Sport Science, – July , Manchester, UK.  Finni T, Komi PV, Lepola V. In vivo human triceps surae and quadriceps femoris muscle function in a squat jump and counter movement jump. Eur J Appl Physiol ; : –.  Alt W, Lohrer H, Gollhofer A, Komi P. Estimation of ankle ligament load using a fiber optic transducer in vivo. ; in press.  Perttunen JR, Nieminen H, Tukiainen E, Kuokkanen H, Asko-Seljavaara S, Komi PV. Asymmetry of gait after free flap reconstruction of severe tibial fractures with extensive soft-tissue damage. Scand J Plastic Reconst Surg Hand Surg ; (): –.  Cabb J, Claremont DJ. Transducers for foot pressure measurement: survey of recent developments. Med Biol Eng Computing ; : –.  Komi PV, Virmavirta M. Ski jumping take-off performance: determining factors and methodological advances. In: Müller E, ed. Science and Skiing. Cambridge: Chapman & Hall, Cambridge University Press, : –.  Virmavirta M, Avela J, Komi PV. A comparison of different methods to determine the take-off velocity in vertical jumps. In: Häkkinen K, Keskinen KL, Komi PV, Mero A, eds. Book of Abstracts. XVth International Congress of Biomechanics, : –.  Sørensen H, Zacho M, Simonsen EB, Dyhre-Poulsen P, Klausen K. Joint angle errors in the use of isokinetic dynamometers. Isokinetics Exerc Sci ; : –.  Winter DA, Wells RP, Orr GW. Errors in the use of isokinetic dynamometer. Eur J Appl Physiol Occup Physiol ; : –.  Dyhre-Poulsen P, Laursen AM. Programmed electromyographic activity and negative incremental muscle stiffness in monkeys jumping down. J Physiol ; : –.  Dorge HC, Andersen TB, Sørensen H, Simonsen EB, Aagaard H, Dyhre-Poulsen P, Klausen K. EMG activity of the iliopsoas muscle and leg kinetics during the soccer place kick. Scand J Med Sci Sports ; (): –.  Andersson EA, Nilsson J, Thorstensson A. Intramuscular EMG from the hip flexor muscles during human locomotion. Acta Physiol Scand ; (): –.  Winter DA. Biomechanics and Motor Control of Human Movement. New York: John Wiley & Sons, Inc., .  Dempster WT. Space Requirements of the Seated Operator.

Biomechanics of Locomotion

  



 

  

  

WADC Technical Report. Ohio: Wright Patterson Airforce Base, : –. Scott SH, Winter DA. Internal forces at chronic running injury sites. Med Sci Sports Exerc ; (): –. Simonsen EB, Dyhre-Poulsen P, Voigt M, Aagaard P, Sjøgaard G, Bojsen-Møller F. Bone-on-bone forces during loaded and unloaded walking. Acta Anat ; : –. Frigo C, Pedotti A. Determination of muscle length during locomotion. In: Asmussen E, Jørgensen K, eds. International Series of Biomechanics VI-A : –. University Park Press, Baltimore. Grieve DW, Pheasant S, Cavanagh PR. Predictions of gastrocnemius length from knee and ankle joint posture. In: Asmussen E, Jorgensen K, eds. Biomechanics VI-A. Baltimore: University Park Press, : –. Alkjær T, Simonsen EB, Dyhre-Poulsen P. Comparison of inverse dynamics calculated by two- and three-dimensional models during walking. Gait Posture ; in press. Miller NR, Shapiro R, McLaughlin TM. A technique for obtaining spatial kinematic parameters of segments of biomechanical systems from cinematographical data. J Biomech ; : –. Vaughan CL, Davis BL, O’Connor JC. Dynamics of Human Gait. Leeds, UK: Human Kinetic Publishers, : –. van den Bogert AJ. Analysis and simulation of mechanical loads on the human musculoskeletal system: a methodological overview. Exerc Sports Sci Rev ; : –. Gerritsen KG, van den Bogert AJ, Hulliger M, Zernicke RF. Intrinsic muscle properties facilitate locomotor control — a computer simulation study. Motor Control ; : –. Rack PMH, Westbury DR. The short range stiffness of active mammalian muscle and its effect on mechanical properties. J Physiol ; : –. Ford LE, Huxley AF, Simmons RM. Tension responses to sudden length change in stimulated frog muscle fibres near slack length. J Physiol ; : –. Huxley AF, Simmons RM. Proposed mechanism of force generation in striated muscle. Nature ; : –.

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 Roberts TJ, Marsch RL, Weyand PG, Taylor CR. Muscular force in running turkeys. the economy of minimizing work. Science ; : –.  Butler DL, Grood ES, Noyes FR. et al. Effects of structure and strain measurement technique on the material properties of young human tendons and fascia. J Biomech ; : –.  Hill AV. The heat and shortening of the dynamic constant of muscle. Proc Royal Soc London, B ; : –.  Wilkie DR. The relation between force and velocity in human muscle. J Physiol ; : .  Komi PV. Measurement of the force–velocity relationship in human muscle under concentric and eccentric contraction. In: Jokl E, ed. Medicine and Sport, Biomechanics III, Vol. . Basel: Karger, : –.  f*ckashiro S, Komi PV. Joint moment and mechanical power flow of the lower limb during vertical jump. Int J Sports Med ; : –.  Woo SL, Hollis JM, Adams DJ, Lyon RM, Takai S. Tensile properties of the human femur–anterior cruciate ligament–tibia complex. The effects of specimen age and orientation. Am J Sports Med ; : –.  Simonsen EB, Magnusson SP, Bencke J, Næsborg H, Havkrog M, Ebstrup JF, Sørensen H. Can the hamstring muscles protect the anterior cruciate ligament during a side-cutting maneuver. Scand J Med Sci Sports ; : –.  Wickiewicz TL, Roy RR, Powell PL, Edgerton VR. Muscle architecture of the human lower limb. Clin Orth Rel Res ; : –.  Perttunen JR, Kyröläinen H, Komi PV, Heinonen A. Biomechanical loading in the triple jump. J Sports Sci ; : –.  Komi PV. Stretch–shortening cycle. In: Komi PV, ed. Strength and Power in Sport. The IOC Encyclopaedia of Sports Medicine, Vol. III. Oxford: Blackwell Scientific Publications : –.  Virmavirta M, Komi PV. Plantar pressures during ski jumping take-off. J Appl Biomechan ; (): –.

Chapter 1.6 Connective Tissue in Ligaments, Tendon and Muscle: Physiology and Repair, and Musculoskeletal Flexibility PETER MAGNUS S ON, TI MO TA KA LA , STEVEN D. AB RA MOWI TCH, JOHN C. LOH & SAVI O L - Y. WOO

Classical reference Woo S.L-Y. et al. Mechanical properties of tendons and ligaments II. The relationships of immobilization and exercise on tissue remodeling. Biorheology ; : –. Considering the enormity of problems related to injuries to tendons and ligaments, relatively little used to be known about the stress-related remodeling of these soft tissues. Tipton, Akeson, Noyes and Woo are credited with demonstrating the deleterious effects of immobilization on tendons and ligaments around the knee, including joint stiffness and significant weakening of the biomechanical properties of ligaments. On the other hand, studies were also performed to reveal the positive, but limited, effects of exercise on the properties of tendons and ligaments. It was then possible to establish a non-linear relationship between increased or decreased stress and motion, and the homeostasis of soft tissues. Whether these processes cause changes in the mechanical properties or changes in the mass of these tissues, or both, was the subject addressed in the paper by Woo and coworkers. Using a rabbit model, femur–medial collateral ligament–tibia complexes (FMTC) were tensile tested after  and  weeks of immobilization, and after  weeks of immobilization followed by  weeks of



remobilization. It was found that the - and -week immobilized groups had failure loads of only % and %, respectively, of the contralateral controls (P < .) with all specimens failing by tibial avulsion. In the remobilized groups, the mechanical properties of the FMTC remained inferior to the controls and the mode of failure was still tibial avulsion. The effects of short-term ( months) and long-term ( months) exercise in the swine digital extensor and flexor tendons were also compared. Animals were exercised by running at a speed of – km/h for a total of  km/week. In the extensor tendon of the forepaw, exercise had no significant effects on mechanical properties in the short term, but long-term increases in cross-sectional area and tensile strength over those of age-matched, non-exercised controls were observed. On the other hand, in the flexor tendon, there were no significant effects on mechanical properties nor cross-sectional area of the tissue substance, but there was a % increase in ultimate load which could be attributed to an increase in strength of the tendon–bone junction. As a result of the data obtained in this study, together with those published by Noyes, Tipton and Laros, a hypothetical curve was drawn to represent the homeostatic response of soft tissues in response to stresses and motion, depicting a highly non-linear relationship (Fig. ..). Immobilization can significantly compro-

Connective Tissue in Ligaments, Tendon and Muscle Decrease stress

Tissue mass, tissue stiffness, and strength

Immobilization

Increase stress Normal activity

Exercise

In-vivo loads and activity levels Fig. .. Hypothetical response of ligaments to levels of stress.

mise both the structural properties of the bone– ligament–bone complex and the mechanical properties of the ligament, with weakening more pronounced at the insertion sites. The effects of exercise or increased tension are much less pronounced, as the gains are minimal even with a substantial duration of exercise.

Biochemical composition of muscle extracellular matrix: the effect of loading Extracellular matrix Multicellular organisms are formed of specialized cells that are assembled in tissues. The extracellular matrix (ECM) outside the cells is a complex and dynamic meshwork that contains collagens, noncollagenous glycoproteins, proteoglycans and elastin. The extracellular matrix supports the cellular elements and maintains the structural integrity of multicellular organisms. Further, it helps cells to bind together and regulates various cellular processes, such as cell growth, proliferation, differentiation, migration and adhesion.

Skeletal muscle collagen Collagen is the most abundant protein of the ECM and constitutes about –% of all protein in the body []. To date  distinct collagen types have



been identified in vertebrates []. They are usually divided into two subgroups on the basis of their supramolecular structures: fibrillar-forming and nonfibrillar-forming collagens. In skeletal muscle, collagen is mainly present in three fibrillar-forming forms, collagen types I, III and V, and one non-fibrillarforming collagen, type IV of basem*nt membranes [,]. Of these, types I and III are the most abundant. In addition, collagen types II, XI, XIII, XIV, XV and XVIII have been found in skeletal muscle and type VI in cardiac muscle [–]. In epimysium and perimysium collagen type I and III are present, with the former dominating, while all major collagen types have been observed in the endomysium [,]. It has been shown that slow-twitch muscles contain more collagen than fast-twitch muscles [–], and that the concentration of endomysial collagen is higher around slow than fast skeletal muscle fibers in rats [].

Post-translational processing of collagen In skeletal muscle collagen is produced principally by fibroblasts on the membrane-bound ribosomes of the rough endoplasmic reticulum. Collagen biosynthesis is characterized by the presence of an extensive number of co- and post-translational modifications of the polypeptide chains, which contribute to the quality and stability of the collagen molecule [] (Fig. ..a). The polypeptide chains form triple-helical procollagen molecules that are secreted into the extracellular space by exocytosis. Procollagens contain aminoterminal and carboxy-terminal extension peptides at the respective ends of the collagen molecule, and after secretion, the amino-propeptides are cleaved by specific proteinases and the collagens self-assemble into fibrils or other supramolecular structures. The three polypeptide chains, which form the triple-helical structure, are called a-chains. The molecular organization of the different collagen types differs so that type I collagen is a heterotrimer of two identical a(I) chains and one a(I) chain, type III collagen is a hom*otrimer with a(III) chains. The most common form of type IV collagen consists of two a(IV) chains and one a(IV) chain, although other forms also exist. The a-chains are composed of repeating amino acid sequences Gly-X-Y, where the glycine residue in every third position enables the three a-chains to coil around one another. Proline and

 Chapter . (a)

DNA

DNA

DNA

Collagen type 1 mRNA

P4H mRNA

LO mRNA

Peptide chains

P4H

LO

Nucleus

Transcription Endoplasmatic reticulum

Translation

Post-translational modifications Cell membrane

Secretion

Post-translational modifications

Extracellular space

Collagen LO

Stable collagen

(b)

DNA

DNA

MMP mRNA

TIMP mRNA

MMP proenzyme

TIMP

n

io bit

i

Inh Active MMP COLLAGEN

DEGRADED COLLAGEN

Fig. .. (a) Collagen expression. Scheme of pre- and post-translational events in collagen expression (PH, prolyly -hydroxylase; LO, lysyl oxidase). PH activity correlates with collagen synthesis. LO activity is required for formation of pyridinoline cross-linked stable collagen. (b) Collagen degradation. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) regulate the degradation of collagen.

-hydroxyproline residues appear frequently at the Xand Y-positions, respectively, and promote the formation of intermolecular cross-links []. The stability and quality of the collagen molecule are largely based on the intra- and intermolecular cross-links. The hydroxyproline as a part of the polypeptide chain is an almost unique feature of collagen, and its assay is therefore suitable for evaluating collagen content []. The formation of -hydroxyproline is catalyzed by

prolyl -hydroxylase (PH). The levels of PH activity generally increase and decrease with the rates of collagen biosynthesis, and assays of the enzyme activity have been used for estimating changes in the rate of collagen biosynthesis in many experimental and physiologic conditions [,–]. The activity of galactosylhydroxylysyl glucosyltransferase (GGT), another post-translational enzyme of collagen synthesis, also reflects the rate of collagen biosynthesis, although the changes in GGT activity are usually less pronounced and occur more slowly than in the case of PH [,,,–].Total collagen concentration is –% higher in slow-twitch than in fast-twitch muscle []. The concentration is higher both around individual type I fibers than type II fibers, and in the endomysium and perimysium of slow-twitch muscle than fast-twitch muscle []. Muscle is attached to its tendon at the end of the fibers, where the collagen fibrils of muscle fuse or interdigitate with the collagen fibrils of the tendon []. Collagen degradation is initiated by matrix metalloproteinases (MMPs), which are present in tissues mostly as latent proMMPs. Tissue inhibitors of MMPs (TIMPs) inhibit their activation. The scheme of collagen degradation is presented in Fig. ..(b).

Functions of collagen in skeletal muscle The connective tissue network of skeletal muscle has a dynamic role during muscle differentiation and normal muscle growth and it serves as a supportive structure in skeletal muscle and tendon [,,,]. Collagen forms the linkages between the muscle and its associated collagenous tissues such as tendon or fascia, and is also the fibrillar component of the cell-tocell connections both between individual muscle cells and between the muscle cells and neighboring small blood vessels and nerves. It gives coherence and mechanical strength and also functions as an elastic, stress-tolerant system as well as distributing the forces of muscular contractions in both muscle and tendon. The tensile strength is based on intra- and intermolecular cross-links, and the orientation and density of the fibrils and fibers. In addition, collagen like the other ECM compounds conforms to the microenvironment around single muscle fibers and participates in the growth of cells and tissue regeneration after damage [].



Connective Tissue in Ligaments, Tendon and Muscle (a) Relative to the control

Effects of immobilization on collagen in skeletal muscle synthesis and degradation

Control Immobilized

The metabolism of muscular and tendinous collagen and the connective tissue network is known to respond to altered levels of physical activity. Cast immobilization of rat hind limb leads to a decrease in the enzyme activities of collagen biosynthesis in both skeletal muscle and tendon [,], which suggests that the biosynthesis of the collagen network decreases as a result of reduced muscular and tendinous activity. The rate of total collagen synthesis depends mostly on the overall protein balance of the tissue [], but it seems to be positively affected by stretch in both muscle and tendon [,]. Changes in the total collagen content of muscle, measured as hydroxyproline content, are usually small or absent during immobilization lasting for a few weeks, which probably reflects the slow turnover of collagen [], but increased collagen contents have also been observed []. Collagen expression during immobilization has been shown to be at least partially down-regulated at the pretranslational level []. The mRNA for the a-subunit of PH had already decreased after  day of immobilization. The mRNAs for type I (Fig. ..a) and III collagens were also decreased after  days of immobilization. Stretch seems to counteract this decrease []. Breakdown of ECM compounds like collagens is initiated by MMPs. Immobilization leads to an increase in proMMP- expression at both pre- and post-translational levels suggesting accelerated collagen breakdown. It is of interest that stretch partially prevents this phenomenon also [].

GGT enzyme activities and the hydroxyproline (Hyp) concentration decreased to the control level in spite of accelerated muscular growth [].

Effects of denervation and reinnervation on collagen in skeletal muscle

Effects of increased physical activity on collagen in skeletal muscle

The responses in muscular collagen biosynthesis differ between denervation and disuse atrophies []. Denervation atrophy is associated with an increase in the activities of PH and GGT and muscular collagen concentration suggesting development of fibrosis of the muscle tissue. Thus denervation seems to ‘uncouple’ the regulation of the adaptive responses of muscular collagen biosynthesis from the atrophy process of the whole muscle []. Perimysial collagen accumulation occurs also in muscle of spinal cord-injured individuals []. During reinnervation both the PH and

The specific activities of PH and GGT, as well as Hyp concentration, are known to be greater in the antigravity soleus muscle than in the dorsiflexor tibialis anterior which is not tonically active [,]. Skeletal muscle is known to respond to increased loading caused by endurance training [,,], acute exercise [] (Fig. ..b) or experimental compensatory hypertrophy [,] by increased collagen synthesis and/or accumulation in the muscle. Strenuous exercise, especially acute weight-bearing exercise that contains eccentric components, is known to cause muscle dam-

1 ***

1

3

(b) 2

7

**

**

Relative to the control

**

1

Control

1

2

4

7

14

Time after running (days) Fig. .. (a) Type I collagen mRNA level in cast-immobilized soleus muscle. The results indicate a rapid pretranslational down-regulation of type I collagen expression during immobilization. (b) Prolyl -hydroxylase (PH) after a single bout of prolonged exercise in rat quadriceps femoris muscle (MQF). The results suggest accelerated collagen synthesis.

 Chapter . age []. Up-regulation of collagen synthesis may be a part of the repair process but may also occur without any evidence of muscle damage []. Acceleration of collagen biosynthesis after exercise may thus reflect both physiologic adaptation and repair of the damage. Exercise training before exhaustive running has been shown to partially prevent the increase in collagensynthesizing enzymes []. (Pro)MMP- is upregulated at both pre- and post-translational levels after a single bout of exercise, suggesting an increase in the capacity of collagen degradation.

Tendon injury Tendons serve to transmit force from the contractile unit to the bone in order to produce movement. In contrast to the muscle, the cross-sectional area of the tendon is relatively small, and thus, the stress (force/area) imposed on the tendon is substantial during physical activities. However, tendons are remarkably strong and can withstand stresses that far exceed those transmitted during daily activities, including sports. Nevertheless, tendon injuries as a result of physical activity remain a substantial clinical problem, and the reasons for these injuries remain an enigma. Moreover, it is particularly puzzling that these patients are often relatively well-trained individuals. Consequently, appropriate and effective treatments, and possible preventive efforts, based on scientific evidence are currently lacking. Many tendon injuries are thought to be caused by ‘overloading’ of the tendon with a gradual onset of symptoms and a presumed associated inflammatory response and structural changes. However, a large portion of the existing knowledge on connective tissue properties and metabolism has been limited to animal models and some cadaver studies with respect to tendon mechanical properties. While such studies have contributed important information to our understanding of connective tissue they also draw attention to the limited conclusive evidence available on in vivo changes in the physically active human body. One problem with animal studies has been the difficulty in establishing a model that could reproducibly mimic an ‘overload’ time course of events. Moreover, there has been a lack of techniques that allow for the continuous sampling of tissue variables during exercise, which may prove useful in studying potential contributory factors for ‘overload’ reactions. However, some recent

in vivo human models have been developed that can monitor metabolism, blood flow and inflammatory activity and collagen turnover during exercise. These methods, together with the recently developed method of ultrasound determination of the mechanical properties of human tendon during muscular contraction, may prove valuable in future research efforts to understand tendon adaptation to physical activity.

Collagen metabolism and tendon loading It is commonly believed that, if not inert, tendon is metabolically relatively inactive. However, animal studies suggest that tensile strength, stiffness, crosssectional area and collagen content are augmented with increases in physical activity, which suggests that the tendon is metabolically active. In contrast, decreased physical activity and immobilization down-regulate collagen biosynthesis [,]. Collagen synthesis depends on overall protein synthesis, but appears to also be affected by tensile loading [,]. Interestingly, in an animal model it has been demonstrated that cell metabolism and matrix turnover is not necessarily uniform throughout the whole tendon tissue (deep vs. superficial) []. Therefore, the possibility cannot be excluded that intratendinous connective tissue turnover is multicompartmental, with ‘rapid’ and slow turnover compartments, rather than involving just a single compartment. Ultimately, such intratendinous differences may have a profound effect on the corresponding mechanical properties. Recently the microdialysis technique was used for in vivo determination of indirect markers of collagen turnover in the peritendinous tissue about the Achilles tendon [,]. It was shown that both a single bout of exercise and chronic ( weeks’) exercise appear to stimulate human type I collagen synthesis [,] (Fig. ..). Furthermore, collagen degradation seems to be transiently elevated initially, but with time a net synthesis takes place []. Whether the synthesis results in macroscopically increased tendon mass, and thereby increased strength and stiffness, remains unknown. However, it was recently shown that well-trained runners had a markedly greater Achilles tendon cross-sectional area than age-matched sedentary controls (Magnusson et al., unpublished) (Fig. ..). These data suggest that the human tendon is metabolically active and that it is affected by physical activity. How-

Connective Tissue in Ligaments, Tendon and Muscle

12

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Fig. .. Carboxy-terminal propeptides of type I collagen (PICP) measured as a marker for collagen synthesis during rest, immediately after (recovery) and  h after a -km run.

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Fig. .. Mean blood flow values as determined with the Xe washout technique in the peritendinous space  cm proximal to the insertion of the human Achilles tendon, in vivo. Note that blood flow increases –-fold with intermittent static exercise.

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Fig. .. The cross-sectional area of the Achilles tendon in well-trained runners (> km/week) and controls (Magnusson et al., unpublished).

ever, it remains unknown exactly how degradation and synthesis are affected by the time course of events (loading/restitution) and to what extent various forms of loading affect their interrelationship.

Blood supply and inflammatory reaction It is widely believed that the Achilles tendon is injury prone secondary to a compromised blood supply – cm proximal to the insertion onto the calcaneus. Using a xenon washout technique it was recently shown that blood flow in the peritendinous region of the human Achilles tendon rose up to – times during resisted plantar flexion, which parallels the augmented flow to the muscle [,] (Fig. ..). Further, the

simultaneous use of near-infrared spectroscopy indicates that vasodilatation and tissue oxygenation are coupled during exercise []. These data suggest that blood flow is not necessarily compromised in the region of the Achilles tendon, although its role in tendon pathology remains unknown. Moreover, exactly how and what factors contribute to the regulation of blood flow in the tendon region remains to be addressed. Bradykinin plays a role in both vasodilatation and nociception, and is therefore particularly interesting as a potentially important regulator in tendon tissue. For human mesenchymal tendon cells in cultures, it has been demonstrated that repeated stretches lead to an increase in prostaglandin production that can be blocked by endomethacin []. A system has recently been developed that allows cells to be grown in microgrooves instead of substrates with smooth culture surfaces []. In this new culture system, tendon fibroblasts were found to become elongated in shape and aligned in the direction of microgrooves with and without stretching, and therefore the shape and alignment of the tendon fibroblasts and their loading conditions are similar to those in vivo (Fig. ..). Furthermore, preliminary data revealed

 Chapter .

Fig. .. Fibroblasts grown in silicon microgrooves and aligned along the direction of stretch.

that cyclic stretching of the tendon fibroblasts induced the production of PGE in a stretchingmagnitude-dependent manner. Specifically, at % stretching the PGE production was not increased; however, at % and % the PGE levels were increased about .- and .-fold, respectively, compared with the unstretched cells. Since PGE is a known inflammatory mediator, the results of this study suggest that tendon overuse injury may involve the release of PGE from overstretching of tendon fibroblasts in vivo, and this may subsequently result in the tendon inflammation and pain often seen in the clinical setting. Moreover, in a human model it has also been shown that exercise is associated with peritendinous release of prostaglandin [,]. That is, inflammatory mediators are released in response to tensile loading of the human tendon, but to what extent this response is related to collagen synthesis/degradation and hence tissue strength and quality, and thus ability to withstand repetitive tensile loading remains unknown. While it is generally believed that repetitive loading leads to microscopic failure of collagen structures and an inflammatory process followed by symptomatic pain, the exact etiology remains to be established. Animal models have been developed in an effort to examine the initiating factors of tendon overuse injuries. One such representative model of tendon injury was created by injection of bacterial collagenase into Achilles tendons of horses and rabbits [,]. Microscopic examination revealed degenerative

changes in the tendons and increased numbers of capillaries. However, according to current standards for evaluating tendon disorders, these models appear to represent tendinosis rather than tendon overuse injury, which is associated with tendon inflammation. Recently, our research center developed an animal model of tendon overuse injury [] by means of the use of cell activating factors (a combination of various cytokines). When injected into rabbit patellar tendons, the cytokines produced biologic and biomechanical changes in the tendons. These include increased cellularity at and around the injection site (Fig. ..), and decreased failure load of the tendon (Fig. ..). Thus, this model offers an opportunity to study tendinitis, but whether this model represents tendon overuse injury induced by repetitive loading remains to be verified.

Tendon strain and regional differences The tendon stress during muscular contraction is associated with a given tendon strain (% elongation). Although unsubstantiated, it is commonly believed that the magnitude of tendon strain may be associated with microtears of the tendon and subsequent clinical symptoms. Investigations of human tendon behavior have largely been limited to biomechanical testing of isolated cadaver tissue specimens. However, the recent advance of using real-time ultrasonography has provided a useful method for studying human aponeurosis and tendon tissue behavior during contraction, in vivo. Using such a method it was recently shown that the mechanical properties of the human Achilles tendon and aponeurosis, in vivo, exceeded those mechanical properties previously reported for the human tibialis anterior tendon, in vivo, but were similar to those obtained for various human and mammalian tendons during isolated biomechanical testing procedures [] (Fig. ..). It remains unexplored whether the mechanical properties of the tendon are altered in response to various types of exercise. The tendon has a complex anatomic hierarchy and whether there are regional differences in the stress– strain distribution throughout the tendon is also unknown at present. It has been shown that strain of the collagen fibril is less than that of the whole tendon []. Such a discrepancy in fibril and tendon strain suggests that some structural gliding may develop

Connective Tissue in Ligaments, Tendon and Muscle

Fig. .. Saline solution injection causes minimal cellularity at the injection site (a). In contrast, cytokine injection increases cellularity at  weeks (b). The matrix appears unchanged.

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Fig. .. Cytokine-injected tendons in rabbits had significantly lower ultimate load (*P < .) at  weeks after injection compared with the control group injected with saline. Data are adapted from Stone et al.  [].

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within the tendon. Whether such an intratendon differential strain (shear) plays a role in mechanical signaling for tendon metabolism, or if it is a potential mechanism for ‘microtear’ and subsequent inflammatory reactions and clinical symptoms is unresearched. Further, intra- and intermolecular cross-links are formed that promote stability of the collagen molecule and collagen fibril, respectively. Pyridinoline is an important component of cross-links of the mature collagen fiber, and it has been shown that the ratio of pyridinoline to collagen is particularly high in tendon and ligament compared to bone []. Therefore, crosslink formation probably plays an integral role in tissues that are subjected to tensile stress. Nevertheless, it re-

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Fig. .. The estimated stress–strain for the proximal and distal human Achilles tendon and aponeurosis after correction for small amounts of ankle joint rotation and antagonist coactivation.

mains unknown whether various aspects of physical activity (contraction mode, intensity, duration and restitution time) have any effect on these cross-link formations and subsequent tendon properties. Animal models have shown that there is an inverse relationship between type III and type I collagen fibril diameter during development: type III collagen fibril

 Chapter . number declines with maturation and larger type I fibrils increase [], which may reflect a change to a larger and more stress-resistant fibril. However, regionspecific observations of fibril morphology have not been made in a human tendon model, nor has it been investigated whether the different regions within a tendon vary in their mechanical properties.

Biomechanics of human skeletal muscle–tendon flexibility Physical activity is important to maintain good health, and human movement is not possible without some degree of the fitness component commonly called musculoskeletal flexibility. Flexibility training is thought to be an important and effective training stimulus for maintenance and augmentation of flexibility. Clearly the demands of participation in sports require a certain sport-specific musculoskeletal flexibility. In sports such as gymnastics the necessity for immense flexibility is obvious; however, reaching for a ball in soccer, clearing a hurdle or performing a tennis serve may also require a certain sport-specific flexibility, which may be achieved by specifically designed flexibility training programs. However, it should also be kept in mind that an individual’s existing flexibility may be an inherent characteristic or a sport-specific adaptation, and not just the result of flexibility training []. Although there is presently no universally accepted definition of flexibility it is most commonly defined as maximal joint range of motion across a joint or series of joints. Flexibility has also been defined as the length–tension relationship of the muscle–tendon unit. However, the former appears to be a more clinically useful definition since it can easily be measured with a goniometer. It should be noted that a goniometer endpoint measurement is subjective in nature and therefore provides no information about the resistance the muscle provides throughout the range of motion; thus the ‘stiffness’ or ‘compliance’ of the muscle cannot be evaluated. The following section will consider the biomechanics of stretching of the muscle–tendon unit, and it should be kept in mind that it does not cover stretching of the injured or immobilized muscle–tendon unit, complex issues like flexibility and injury risk.

Mechanisms for flexibility improvement It is indisputable that increases in musculoskeletal

flexibility can be achieved by flexibility training. However, the mechanisms for both the short- and longterm changes in flexibility as a result of flexibility training have until recently been largely unclear. The immediate or short-term response to stretching has previously been attributed to either neurophysiologic [] or mechanical factors []. The neurophysiologic explanation suggests that the limiting factor during stretching is muscular resistance attributed to reflex activity, as measured by electromyography (EMG). Thus, the aim of stretching would be to inhibit the reflex activity, which in turn would reduce resistance and thereby allow for further increases in joint range of motion []. Paradoxically, the particular stretching techniques most effective in increasing joint range of motion have been associated with an elevated EMG response []. At the same time, it has been shown that during a -s static stretch resistance declines by ~ % in the absence of any measurable EMG response []. Therefore, contractile reflex activity does not appear to significantly contribute to resistance to stretch. The other common explanation for the effects of stretching includes an altered mechanical property of the muscle []. Yet a third mechanism was recently suggested, where improvement in joint range of motion was attributed to an amplified stretch tolerance, rather than a change in EMG activity or mechanical properties [,].

Biomechanical response to stretch The relationship between the force and the deformation (expressed as the slope of the line, DF/DL) is the stiffness of the structure []. That is, the increase in deformation is proportional to the applied force (Hooke’s law), such that a stiffer structure will deform less for a given applied external load. The reciprocal of stiffness (DL/DF) is termed compliance. The area under the curve is the energy absorbed by the structure that can potentially be returned when the load is removed. The application of an external applied tensile force will be opposed by the internal bonds of the structure. This tensile stress can be defined as the internal force divided by the cross-sectional area of the material (F/area). The stress will cause the structure to change in shape, or deform, which is called tensile strain. Tensile strain can be defined as the change in length divided by the original length ((DL/Lo), which

Connective Tissue in Ligaments, Tendon and Muscle

A single static stretch In the animal models it is known that materials respond in a non-linear fashion during the dynamic and static loading phase of a stretch, indicating viscoelastic behavior [,,]. Recently it was also shown in a human model that the muscle–tendon unit behaves in a similar fashion during stretching [–,–]. That is, the muscle displays viscoelastic properties in the absence of any measurable EMG response from the target muscle being stretched (Fig. ..). During the dynamic loading phase there is a non-linear increase in resistance to stretch, and during the static loading phase there is a non-linear decline in resistance to stretch, a viscoelastic stress relaxation response. The viscoelastic stress relaxation response is most pronounced in the initial – s, but continues to significantly abate for approximately  s. During a -s static stretch resistance declines by about % altogether. Although there is significant viscoelastic stress relaxation during a -s static stretch there is no measurable effect on the subsequent immediate stretch []. This means that resistance to stretch diminishes during the static phase of a stretch, but has no lasting effect on the viscoelastic properties.

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is a dimensionless unit, but often expressed as a percentage of the original length. The relationship between stress and strain (Dstress/Dstrain) is the elastic modulus of the material, sometimes referred to as Young’s modulus. Biological materials are viscoelastic and do not respond to external loading in a way that can be described in simple linear mechanical terms. Viscoelastic behavior has been described in rheological models where the relationship between force and deformation is dependent on time. Linear elasticity is a load-dependent response and linear viscosity is a rate-dependent response []. Typically tissues will respond in a non-linear fashion with an initial ‘toe-region’ followed by an approximately linear region during dynamic loading on account of its viscoelastic properties. If the tissue is held fixed at some new length, static loading, the tension will decline in a non-linear fashion with time, which is termed viscoelastic stress relaxation (Fig. ..). These are the two phases that a muscle–tendon undergoes during a static stretch.

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Fig. .. A static stretch of the hamstring muscle group for one individual. (a) The passive torque about the knee joint that corresponds to the tension in the hamstring muscles during the passive static stretch procedure is shown. A maximal voluntary contraction (MVC) is performed at the end of the stretch. (b) The corresponding EMG amplitudes. Note the absence of EMG activity in the hamstring muscles despite the increase in torque in the dynamic loading phase, and the decline in torque in the static loading phase (viscoelastic stress relaxation). (c) The angle (negative value indicates greater angle of stretch) of the mechanical lever arm that passively stretches the hamstring muscles at . rad/s (∞/s) during the dynamic loading phase. During the static loading phase the lever arm remains stationary.

Repeated stretches — short-term effect Animal data demonstrate that if the target tissue is stretched repeatedly, resistance to stretch, in both the dynamic and the static portion, will decline with each subsequent stretch []. Therefore, stretching of a muscle group in the sports arena or rehabilitation setting is typically not performed once as described above, but is repeated several times. In the human muscle–tendon complex the effect of five consecutive

 Chapter .

Repeated stretches — long-term effect While earlier literature attributed short-term changes in flexibility to neurophysiologic events, it commonly ascribed long-term improvements in flexibility to changes in the passive properties []. In a recent study static stretching exercises for the human hamstring muscle group were performed in the morning ( ¥  s) and in the afternoon ( ¥  s) on one leg while the opposite side served as control []. After  weeks the resistance to stretch for a given angle was unchanged on both sides (Fig. ..). However, when stretched to a maximal tolerated joint angle the stretch side could be extended further after training, i.e. the subjects became more flexible. This increase in angle was accompanied by a comparable increase in peak torque and energy (without any change in EMG activity). Therefore, increases in flexibility, i.e. maximal range of motion, can be achieved from stretch training as a consequence of increased tolerance to tensile load, rather than through a change in the viscoelastic properties of the muscle. On the basis of these results, and since the change in the viscoelastic behav-

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-s static stretches has been examined []. To see if any effect was lasting in nature the resistance to stretch was re-examined  h later. In the last of the five stretches both passive energy (the area under the curve of the dynamic loading phase) (%) and stiffness (%) declined. However, surprisingly, the observed decline in the viscoelastic properties was transient since they had returned to baseline values when measured  h later. In contrast to a single -s stretch, the -s stretch had an effect on the subsequent stretch; however, again the effect on the viscoelastic properties was transient (> h). Although stretching procedures places tensile load on several structures it remains unknown what their relative contributions are to the stress relaxation response. The transmission of tension in passively stretched muscle is complex and may engage several structures, including titin, intramuscular connective tissue and tendon. Passive stretch in a physiologic range results in % strain of tendon, but % strain of the muscle–tendon junction [], demonstrating differential viscoelastic properties in various regions of the muscle–tendon unit, and that tendon is less likely to deform during loading.

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Angle (rad) Fig. .. Maximal torque-angle data for one subject in the dynamic loading phase of a static stretch before and after  weeks of flexibility training twice a day. (a) The training side. Note that after training the subject reached a greater knee joint angle prior to the onset of discomfort with an accompanying increase in torque. It should also be noted that the pre- and posttraining slope is similar. That is, the muscle–tendon unit did not change its passive properties (slope), but the subject’s tolerance to stretch was enhanced after training. (b) The control side: The slope and the endpoint do not differ over the training period.

ior is transient in nature and reverses within  h (see above), it is questionable if stretching, as it is commonly performed by athletes, can permanently change the passive properties of a muscle. The mechanism for an altered stretch tolerance is presently unknown. However, the increased tolerance on the training side and lack thereof on the control side suggests that peripheral mechanisms, such as afferent information from muscle, tendon and joint receptors,

Connective Tissue in Ligaments, Tendon and Muscle 40

Stiffness (D Nm / D rad)

may play a role. However, the possibility cannot be excluded that central factors may be involved as well. Finally, from a clinical standpoint it is important to point out that although the passive properties do not appear to be altered as a result of flexibility training it does lead to improvements in joint range of motion. Therefore, to meet sport-specific flexibility demands it may be desirable to perform flexibility training. Finally, the possibility cannot at present be ruled out that stretching in a skeletally immature person may have a long-lasting effect on the viscoelastic properties of the muscle–tendon unit, nor is it known whether such changes are advantageous or not.

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Unquestionably people exhibit differences in musculoskeletal flexibility. A component of a person’s existing flexibility may be inherited, a sport-specific adaptation (loading history) or achieved by flexibility training. Previous investigations on human flexibility have measured maximal joint range of motion, but not the passive properties of the muscle–tendon unit. At the same time, it has been shown that tolerance to tensile load plays an important role in short-term and long-term gains in flexibility (see above) rather than the passive properties of the muscle. To address whether tolerance also contributed to differences in flexibility endurance athletes were classified as tight (inflexible) and normal based on a simple toe-touch test. It was observed that both passive properties (stiffness) of the hamstring muscle group and stretch tolerance explained the difference in flexibility []. That is, ‘tight’ athletes had a muscle–tendon unit with greater stiffness than athletes with normal flexibility for a given common angle (Fig. ..a). However, the athletes with normal flexibility achieved a greater maximal joint angle (muscle length) and accompanying maximal tensile stress, and thus had a greater tolerance to tensile loading. When the tensions in the individual muscles were analysed it was observed that a combination of a more extended knee joint angle, i.e. a reduced moment arm, and a greater external moment explained the substantial differences in stress between the tight and flexible subjects at a maximal joint angle (Fig. ..b). Towards the extremes of motion, as in hurdling, considerable passive tension is probably generated and may therefore play a role in the deceleration

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Fig. .. (a) Absolute biceps femoris moment stiffness data (mean ± s.e.m.) for angles common to all subjects in the flexible and tight groups (*P < .). The moment stiffness followed an exponential curve and elevated earlier during knee extension in the tight than in the flexible subjects. Thus, after . rad the stiffness reached  and  DNm/Drad for the respective groups. However, the flexible subjects reached a greater maximal angle of stretch, and had at that angle a greater stiffness than the flexible subjects (tolerance). (b) Muscle stiffness (Dstress/Dlength) for the biceps femoris muscle as a function of normalized length change. Significantly different from inflexible, *P < ., **P < ..

of the leg in the terminal swing phase. The material properties of skeletal muscle are thought to be related to the amount of collagen [], and perhaps collagen content or the number of cross-links contributed to the observed difference in stiffness. It is well known that stiffness of connective tissue increases with aging, in part due to an increase in cross-

 Chapter . links. Interestingly, when we examined the musculoskeletal passive properties on a cross-sectional basis in a very narrow age range, younger athletes (– years) had a muscle–tendon unit with greater stiffness than slightly ‘older’ athletes (– years) for a given common angle. Such differences may be related to agerelated changes in connective tissue []. However, the younger athletes also achieved a greater maximal joint angle (muscle length) and accompanying maximal tensile stress, and thus had a greater tolerance. Therefore, it appears that material properties and tolerance to tensile load play a role both in determining differences in flexibility and in age-related changes in flexibility.

Warm-up and stretching Warming up prior to participation in sport is commonly believed to aid performance and reduce injury risk, and because the muscle–tendon unit is thought to exhibit temperature-dependent viscoelastic behavior, it is recommended that warm-up precedes stretching exercises []. Although there is limited scientific evidence in a human model for such a tenet it was recently investigated whether the passive energy absorption of the human muscle–tendon unit would decrease after a brief (-min) warm-up exercise bout, and sustained (-min) exercise []. It was clearly demonstrated that a -min warm-up procedure and  min of continuous running elevated intramuscular temperature significantly (from . °C to . °C), but did not affect the passive energy absorption of the hamstring muscle–tendon unit. When static stretching exercises were added to the regimen after the min warm-up period the passive energy absorption declined immediately; however, this reduction in passive energy absorption was not sustained after an additional  min of continuous running. It is well known that continuous exercise rapidly results in an equilibrium between heat production and heat dissipation. In the above experiment about % of the temperature increase occurred in the initial  min of work, which confirms that increased tissue temperature can be achieved relatively soon after initiation of exercise, and that  min of warm-up exercise may be sufficient preparation for muscle performance []. Temperature-dependent viscoelastic behavior of biological tissue has previously been shown in temperature ranges

that far exceed those achieved during a warm-up procedure in human skeletal muscle []. However, it appears that despite the repeated mechanical loading during  min of running, and its associated increase in intramuscular temperature, the passive energy absorption of the muscle–tendon unit remains unchanged. It has been suggested that elastic recoil may play a role in energy expenditure during locomotion [,], and although this is speculative, the temperature and repetitive load insensitive passive energy behavior may serve to maintain passive elastic energy return during locomotion.

Ligaments: physiology and repair Athletic activities can result in a wide variety of joint injuries through either direct trauma or repetitive stress []. Although the predilection for specific injuries varies with the sport (e.g. elbow instability in baseball players, shoulder dislocations in football players and wrestlers, knee injuries in basketball players), all injuries can be debilitating and often involve ligamentous structures. Ligaments are structures that are known to play an important role in mediating normal joint mechanics. These parallelfibered, dense connective tissues share the transmission of forces with other periarticular tissues to provide joint stability []. In the knee, a common injury site is the medial collateral ligament (MCL). Injuries to this structure may be isolated to the superficial MCL or extend to include the deep capsular and posterior oblique ligaments [–]. Laboratory studies using animal models have shown that a ruptured MCL can heal spontaneously without surgical intervention. However, the healed tissue remains mechanically, structurally and materially inferior to normal ligaments [–]. Nevertheless, the ability of the MCL to heal offers an opportunity for the examination of the mechanism of ligament healing. In addition, anatomically, the MCL is a broad, flat ligament with a good aspect ratio (length to width) and relatively uniform cross-sectional area making it well suited for biomechanical studies. Understanding healing in the MCL provides a good foundation for understanding the healing processes of other ligaments. In this section ligament healing and repair using the MCL as a model will be presented. Also, current and future approaches towards enhanc-

Connective Tissue in Ligaments, Tendon and Muscle ing the quality of the healed ligament, namely functional tissue engineering that includes the use of growth factors, gene transfer technology, cell therapy, tissue scaffolding and other mechanical factors, will be examined.

Natural history of MCL injury Healing of the MCL has been found to be a long and complex process that is subject to local and external influences. Generally, the process involves several discrete but overlapping phases: the acute inflammatory or reactive response phase, the repair phase, and finally the tissue remodeling phase. In the acute inflammatory phase, the cellular and tissue responses to injury occur within approximately the first  h following a given insult. Capillary damage results in enhanced permeability of local blood vessels, allowing inflammatory cells to migrate into the tissue defect. Fibroblastic proliferation and the formation of scar matrix consisting of randomly aligned collagen and amorphous ground substance occurs simultaneously []. The repair phase encompasses those cellular and tissue processes occurring from – h until roughly  weeks post injury. This time period marks the gradual subsiding of inflammation together with the active commencement of the healing process. Grossly, highly vascular granulation tissue fills the tissue defect, covering the free ends of torn or ruptured tissue [,]. Fibroblasts become the predominant cell type and continue to actively synthesize extracellular matrix. This matrix becomes progressively more organized with time, yet collagen fibrils remain relatively disorganized. The remodeling phase is also marked by tissue remodeling, lasting months and years after the initial injury. It should be noted that an injured MCL never regains the properties of the normal MCL [–]. The healed ligaments have elevated numbers of vessels, fat cells and voids and increased water content. The diameter of collagen fibers is smaller with fewer numbers of stable collagen cross-links. The healing MCL also contains elevated type III and V collagens, along with an elevated number of proteoglycans (PG).

Biomechanical properties Biomechanical characterization of the MCL can be done via (i) functional testing, which involves deter-



mining its contribution to knee kinematics as well as the in situ forces in the MCL in response to an external load, and (ii) uniaxial tensile testing, which provides an assessment of the structural properties of the femur–MCL–tibia complex (FMTC) and mechanical properties of the ligament substance. Readers are encouraged to study Chapter  of The Orthopedic Basic Science Book (published by the American Academy of Orthopedic Surgery) for details []. Functional testing provides insight into the kinematics or motion of the knee joint which is governed by a combination of joint geometry and tensile properties of ligaments. Each joint has six degrees of freedom (DOF): three translations and three rotations. For the knee joint, there are three axes that can be defined: the femoral shaft axis, the epicondylar axis, and a floating anterior–posterior axis perpendicular to these two axes. Translation along these three axes will lead to distraction/compression, medial–lateral translation, and anterior–posterior translation, respectively. Rotations about these three axes will lead to internal–external rotation, flexion–extension, and varus–valgus rotation, respectively. Structural properties of the FMTC are extrinsic measures of performance of the overall structure in response to a uniaxial tensile test. These properties are obtained from the resulting load–elongation curve (Fig. ..a). The stiffness, in N/mm, is the slope of the curve between two defined limits of elongation. The ultimate load, in N, is the highest load placed on the complex before failure and the ultimate elongation, in mm, is the maximum elongation of the complex. Finally, the energy absorbed at failure, in N-mm, is the area under the entire load–elongation curve. These data are a reflection of the overall properties of the complex spanning from insertion to insertion. Mechanical properties of the ligament’s midsubstance are intrinsic measures of the local tensile properties as represented by a stress–strain curve (Fig. ..b). Stress is defined as force per unit crosssectional area, while strain in the MCL is typically defined as the ratio of the difference between the initial length and current length to the initial length. The modulus, in MPa, is obtained from the linear slope of the stress–strain curve between two limits of strain. The tensile strength, in MPa, is the maximum stress achieved; while the ultimate strain (percentage) is the

 Chapter . the modulus and tensile strength of the healing MCLs at all time periods, remained significantly inferior, in spite of increased cross-sectional area. Thus, the healing process involves a larger quantity of poorer quality ligamentous tissue.

Ultimate load

(a) 800

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200 0 0

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There are numerous factors that contribute to the healing response of an injured ligament. Known factors include the site and severity of the injury. In addition to intrinsic factors such as circulation and infection, studies have also shown that treatments such as repair vs. non-repair, rehabilitation and exercise can have significant impact on the process of ligament healing.

Intrinsic factors Ultimate strain

0 0

Factors influencing ligament healing

8

Fig. .. (a) Typical load–elongation curve of a bone–ligament–bone complex. (b) Typical stress–strain curve describing the mechanical properties of the ligament substance.

strain at failure. Finally, the strain energy density, in MPa, is the area under the stress–strain curve. A system for tracking markers that strategically delineates the midsubstance is necessary to measure local strain. Video analysis techniques have assisted the tracking of stain markers deployed in one- or two-dimensional patterns on the ligament’s surface. In addition, stress is determined from the gross load-cell readings normalized by the specimen’s cross-sectional area. Using the skeletally mature New Zealand white rabbit as a model, the structural properties of the healing FMTC and the mechanical properties of the healing MCL have been demonstrated to remain inferior to those of the intact ligament up to  year after injury []. Structural properties of the FMTC, including stiffness and ultimate load to failure improved during the early stages of healing (i.e. from  to  weeks), but remained inferior to controls. After  weeks of healing, only the stiffness of the FMTC returned to near normal levels, while the ultimate load was still significantly lower than the controls. Further,

There exist a number of intrinsic factors that may contribute to the healing response of the injured ligament. In a study on the healing MCL of hypophysectomized rats, interstitial cell-stimulating hormone (ICSH) and testosterone replacement significantly affected the ultimate load of the repaired ligament, as well as the collagen and glycosaminoglycan synthesis or degradation rates []. Any disease that affects endocrine or metabolic homeostasis may also affect ligament healing. For example, diabetes mellitus can result in circulatory abnormalities that may negatively affect ligament healing as insulin deficiency has been shown to alter collagen synthesis and cross-linking [,]. Ligament healing can also be affected by local conditions such as poor circulation or infection which hinders the proliferation of cells, thereby prolonging the inflammatory phase of healing.

Surgical repair vs. non-repair For an isolated MCL injury, animal studies have shown better results with non-operative treatment than surgical repair followed by immobilization []. Earlier studies in the canine model and more recent studies using a rabbit model examined the effects of suture repair of the injured MCL [,,]. At  weeks, no statistically significant differences could be demonstrated between surgically repaired and non-repaired groups for any biomechanical property, including varus–valgus knee rotation, and structural properties

Connective Tissue in Ligaments, Tendon and Muscle of the FMTC. However, the mechanical properties of the MCL midsubstance, i.e. the quality of the healed tissue, were significantly different from intact MCLs. These findings are in agreement with clinical reports which have reported positive outcomes with nonoperative treatment followed by early motion and functional rehabilitation []. As a result of scientific studies and clinical experience, it is now generally agreed that the preferred method of treatment for isolated grade III injuries of the MCL [] is nonoperative (conservative).

Immobilization vs. controlled motion and exercise In the past, immobilization following ligament injury was believed to protect the healing ligament from stress []. However, it has been shown in the laboratory that immobilization can result in disorganization of collagen fibrils, decreases in the structural properties of the FMTC, resorption of bone at the ligament insertion sites, and many detrimental effects on the knee joint []. Conversely, controlled motion has been shown to be beneficial to the healing ligament []. Intermittent passive motion has been reported to improve the longitudinal alignment of cells and collagen at  weeks. Improved matrix organization and collagen concentration, together with an increase of up to four times in the ultimate load of the FMTC were demonstrated []. Some clinical data exist on the advantages of motion following ligament injury showing that clinical results are better with early motion and functional rehabilitation following isolated MCL injuries at -year follow-up []. Current clinical recommendations after MCL injuries include an early controlled range of motion exercises as soon as pain subsides [,]. However, in an unstable joint, i.e. cases involving multiple ligamentous injuries, motion too early or applied too aggressively may be detrimental to the healing process.

Combined MCL and ACL injuries Severe knee injuries can involve multiple ligaments, and the prognosis for these combined ligamentous injuries is generally worse regardless of which treatment is selected. For a combined ACL + MCL injury, multiple treatment modalities have been studied clinically,



including combined MCL repair and ACL reconstruction, ACL reconstruction only, or non-operative treatment of both ligaments []. No differences in valgus instability or knee function during activities were observed between the three groups studied. The effects of ACL deficiency on the healing of the injured MCL have been studied in our research center using rabbit and canine models []. Biomechanical evaluation indicated that following an untreated ACL + MCL injury, there was a significant increase in varus–valgus laxity, a reduction in tissue quality of the healed MCL, and considerable degeneration of the joint. Other animal studies suggest that MCL repair with ACL reconstruction reduces varus–valgus laxity and improves structural properties of the FMTC in the short term (i.e.  weeks). After  weeks, however, no differences in biomechanical or biochemical properties were observed. Further studies in our research center revealed that non-operative treatment with full weight bearing and mobilization of the MCL injury with reconstruction of the ACL can result in successful MCL healing []. This approach also appears to be the preferred method of treatment for many clinicians [].

Future directions Functional tissue engineering is a multidisciplinary field that has gained major interest in the scientific community. The ability to produce tissue that replicates or enhances normal functioning tissue is of obvious practical benefit. There are several methods of approach to tissue engineering for ligament healing on the horizon. The use of growth factors, gene transfer technology, cell therapy tissue scaffolding and mechanical factors are all being studied. These new approaches are promising and a brief discussion of each will be presented.

Growth factors Growth factors are small polypeptides synthesized by a variety of cells that function by binding to specific cell surface receptors which activate complex intracellular signal transduction pathways. Growth factors regulate cell migration, proliferation, differentiation and matrix synthesis and aid in repairing a damaged ligament by regulating cellular behavior and modulating the wound environment [–]. At our research center, platelet-derived growth factor-BB (PDGF-

 Chapter . BB), basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) have been found to have a stimulatory effect on cell proliferation, while transforming growth factor-b (TGF-b) promoted matrix synthesis of MCL fibroblasts in a rabbit model suggesting that ligament healing may be promoted with a combination of these factors []. A follow-up in vivo study demonstrated that high-dose PDGF-BB in vivo resulted in an FMTC with higher ultimate load, energy absorbed to failure and ultimate elongation than controls []. Additionally, an ongoing in vitro study (unpublished) in our laboratory suggests a timespecific response to the addition of TGF-b. Preliminary data suggest collagen synthesis to injured rabbit MCL fibroblasts increases with the addition of TGFb at day , but not at days  or . To date, only a few growth factors have been studied (TGF-b, PDGF, EGF, etc.); however, much research is required to identify and delineate the effects of yet undiscovered and unstudied growth factors.

Gene transfer technology The application of gene transfer technology to ligament healing was examined recently []. Both retroviral in vitro transfection of the desired genes into the cells followed by the transplantation of genetically modified cells into the host tissue and adenoviral direct delivery of genes into host cells were used in the MCL of rabbit knees [,]. Both techniques resulted in expression of the lacZ marker gene by fibroblasts. Gene expression lasted for up to  days in the retroviral technique and up to  weeks in the adenoviral technique []. Therapeutic methods for ligament repair using non-viral gene transfer have also been investigated []. In one experiment, the HVJ–liposome complex containing an antisense nucleotide for decorin (a proteoglycan) was injected into the healing sites of injured MCLs. Mechanical properties, including ultimate stress, were shown to be significantly improved. Despite these promising results, major obstacles impede practical implementation of gene transfer as a biological intervention in ligament healing []. These obstacles include immune response of the viral proteins and transgene-encoded proteins [], viability of transfected cells in vivo after retransplantation, and loss of gene expression of the retrovirus by promoter methylation []. Fortunately, it is believed

that ligament healing requires gene expression of the order of weeks, so this strategy is considered very promising.

Stem cell therapy The principle of stem cell therapy is to provide a source of cells for ligaments or a mechanism to introduce genes for gene transfer []. The success of cell therapy for ligament repair relies on the viability of the transplanted cells and the affinity of the cells for the host tissue. Mesenchymal stem cells (MSCs) are considered a candidate for cell therapy. MSCs have been demonstrated to differentiate into various cells that form mesenchymal tissues under different culture conditions in vitro [–]. Multipotent differentiation of these cells into mesenchymal tissues has also been demonstrated in vivo [,]. In our research center, nucleated cells obtained from centrifuged bone marrow were used as transplantation donor cells [–]. Female transgenic rats were used as donors and recipients, with transgenes introduced into chromosome . The nucleated cells were injected into a pocket made around the transected MCL of recipient rats. Preliminary results revealed the survival of donor cells at the healing site of the MCL  and  days postoperatively. Transplanted donor cells could also be identified in the midsubstance of ligaments at  days. This is significant in that the migratory potential of transplanted cells may have been demonstrated. Migration of transplanted cells is an attractive attribute for ligament healing. These early results are encouraging [].

Tissue scaffolds Tissue scaffolds are extracellular matrix materials that serve as the structural framework upon which tissue regeneration can occur. A variety of biological and non-biological scaffolding materials have been used [,]. The application of small intestinal submucosa (SIS) scaffolding techniques to ligament healing has been investigated in our research center. When a mop-end tear of a rabbit MCL was approximated and covered with SIS, the healed ligament was found to have a larger cross-sectional area with increased stiffness. A number of issues including possible host immunological response, ascertaining the strength properties of scaffold-derived grafts, the degree of in-

Connective Tissue in Ligaments, Tendon and Muscle corporation into host tissue, and the long-term viability of tissue remain to be addressed.

Mechanical factors The effects of mechanical factors on ligament fibroblasts have been studied with a new apparatus developed in our research center. Previous studies have shown that cells grown and stretched on culture dishes with smooth surfaces realign nearly perpendicular to the direction of stretch. This orientation is in contrast with the in vivo model where cells align along the collagen fiber direction []. Using a cell stretching apparatus whereby cells are grown in an oriented fashion on silicon dishes that contain parallel microgrooves, we are able to align fibroblasts to grow along the direction of stretch (see Fig. ..). As this model better mimics the in vivo environment, future experiments exploring the effects of ligament fibroblasts will be closer to those in the in vivo situation.

Discussion Ligamentous healing is a complicated process that involves multiple factors including extent of injury, vascular supply, time of medical intervention, and the effects of biomechanical and biochemical environments. New technologies like the Robotic/UFS testing system have opened the door to a better understanding of the effects on joint motion on ligament healing []. Animal and clinical research at different levels of the healing cascade from growth factors to tissue scaffolds has increased understanding of the healing process. Clearly, advances in the ability to heal ligaments will require future investigators that come from multiple fields including biology, biochemistry, bioengineering, medicine, surgery, and others. It is only with this collaborative approach that valuable information may be derived, such that the successful management of the debilitating effects of ligamentous injuries can become more achievable.

Summary The extracellular matrix outside the cells is a complex and dynamic meshwork of collagens, non-collagenous glycoproteins, proteoglycans and elastin. The matrix supports the cellular elements and maintains the structural integrity of multicellular organisms. It also binds cells together and regulates various cellular processes,



including cell growth, proliferation, differentiation, migration and adhesion. The tensile strength of the matrix is based on intra- and intermolecular crosslinks, and the orientation and the density of the fibrils and fibers. The metabolism of collagen and the connective tissue network is known to respond to altered levels of physical activity. Biosynthesis decreases with reduced activity, and changes associated with immobilization can in part be counteracted by stretch. Exercise accelerates biosynthesis, and may reflect both physiologic adaptation and repair of the damage. Tendon injuries as a result of altered and/or increased physical activity are a considerable clinical problem. What constitutes the most effective treatment and possible preventive efforts is currently unknown. Many tendon injuries are thought to be due to ‘overloading’ of the tendon with a gradual onset of symptoms and a presumed associated inflammatory response and structural changes. However, a large proportion of the existing knowledge on connective tissue properties and metabolism has been limited to animal models. Nevertheless, some recent in vivo human models have been developed that can monitor metabolism, blood flow and inflammatory activity and collagen turnover during exercise. These methods, together with the recently developed method of ultrasound determination of the mechanical properties of human tendon during muscular contraction, may prove valuable in the future research efforts to understand tendon adaptation to physical activity. Physical activity can result in a wide variety of joint injuries, and often includes the MCL. Although the MCL can heal spontaneously without surgical intervention it remains mechanically, structurally and materially inferior to normal ligaments. Ligamentous healing is a process that involves multiple factors including extent of injury, vascular supply, time of medical intervention, and the effects of biomechanical and biochemical environments. The healing response may be influenced by intrinsic factors, including endocrine and metabolic homeostasis. The current recommended method of treatment for isolated grade III injuries of the MCL is non-operative, including early controlled range of motion exercises. However, functional tissue engineering, including growth factors, gene transfer technology, cell therapy and tissue scaffolding are being studied with respect to ligament heal-

 Chapter . ing. Early data show that some growth factors have stimulatory effects on cell proliferation and the mechanical properties of ligaments. Gene transfer as a biological intervention in ligament healing is also a potentially promising treatment strategy. Stretching is often performed to improve musculoskeletal flexibility, and muscle displays viscoelastic properties in the absence of muscle activity. Resistance to stretch diminishes during a stretch, but has no lasting effect on the viscoelastic properties. Flexibility improvements can be achieved with stretch training due to altered tolerance to tensile load, rather than a change in the viscoelastic properties of the muscle. Physical activity elevates intramuscular temperature, but does not affect the passive properties of the hamstring muscle–tendon unit.

Multiple choice questions  Which of the following is a unit of stiffness: a N-mm b N/mm c MPa d mm.  Which phase of ligament healing is marked by inflammation, blood vessel permeability, and early fibroblast proliferation: a reactive phase b repair phase c remodeling phase d none of the above.  Which of the following influences a person’s musculoskeletal flexibility: a tolerance to tensile load b age c stiffness d all of the above e a and c.  Which of the following statements are true? a All major collagen types have been observed in the endomysium. b The concentration of endomysial collagen is higher around slow than fast skeletal muscle fibers. c Proline and -hydroxyproline promote the formation of intermolecular cross-links. d All of the above.  The human Achilles tendon responds to acute tensile loading by:

a b c d

an increased blood flow an increased collagen metabolism a but not b a and b.

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 Chapter .  Watanabe N, Woo SL-Y, Papageorgiou C, Wang JH. Potential use of bone marrow cells for medial collateral ligament healing. Trans Tissue Engineering Workshop : .  Awad HA, Butler DL, Boivin GP, Smith FN, Malaviya P, Huibregtse B, Caplan AI. Autologous mesenchymal stem cell-mediated repair of tendon. Tissue Engineering ; (): –.  Kim SS, Vacanti JP. The current status of tissue engineering as potential therapy. Semin Pediatric Surg ; (): –.  Zimmerman SD, McCormick RJ, Vadlamudi RK, Thomas DP. Age and training alter collagen characteristics in fastand slow-twitch rat limb muscle. J Appl Physiol ; : –.  Wang JH. Substrate deformation determines actin cytoskeleton reorganization: a mathematical modeling and experimental study. J Theoret Biol ; (): –.  Rudy TW, Livesay GA, Woo SL, Fu FH. A combined robotic/universal force sensor approach to determine in situ forces of knee ligaments. J Biomech ; (): –.  Magnusson SP, Gleim GW, Nicholas JA. Shoulder weakness in professional baseball pitchers. Med Sci Sports Exerc ; : –.  Hutton RS. Neuromuscular basis of stretching exercise. In: Komi PV, ed. Strength and Power in Sports. The IOC Encyclopaedia of Sports Medicine, Vol. III. Oxford: Blackwell Scientific Publications. : –.  Taylor DC, Dalton JD Jr, Seaber AV, Garrett WEJ. Viscoelastic properties of muscle–tendon units. The biomechanical effects of stretching. Am J Sports Med ; : –.  Moore MA, Hutton RS. Electromyographic investigation of muscle stretching techniques. Med Sci Sports Exerc ; : –.  Magnusson SP, Simonsen EB, Dyhre-Poulsen P, Aagaard P, Mohr T, Kjaer M. Viscoelastic stress relaxation during static stretch in human skeletal muscle in the absence of EMG activity. Scand J Med Sci Sports ; : –.  Magnusson SP, Simonsen EB, Aagaard P, Dyhre-Poulsen P, McHugh MP, Kjaer M. Mechanical and physiological responses to stretching with and without preisometric contraction in human skeletal muscle. Arch Phys Med Rehab ; : –.

 Magnusson SP, Simonsen EB, Aagaard P, Sorensen H, Kjaer M. A mechansim for altered flexibility in human skeletal muscle. J Physiol ; : –.  Butler DL, Grood ES, Noyes FR. Biomechanics of ligaments and tendons. In: Hutton RS, ed. Exercise and Sports Sciences Reviews. Philadelphia: Franklin Institute, : –.  Viidik A. Functional properties of collagenous tissues. Int Rev Connective Tissue Res ; : –.  Kovanen V, Suominen H. Effects of age and life-long endurance training on the passive mechanical properties of rat skeletal muscle. Comp Gerontol ; : –.  Magnusson SP, Simonsen EB, Aagaard P, Boesen J, Kjaer M. Determinants of musculoskeletal flexibility: Viscoelastic properties, cross-sectional area, EMG and stretch tolerance. Scand J Med Sci Sports ; : –.  Magnusson SP, Simonsen EB, Aagaard P, Kjaer M. Biomechanical responses to repeated stretches in human hamstring muscle in vivo. Am J Sports Med ; : –.  Magnusson SP, Aaagaard P, Larsson B, Kjaer M. Passive energy absorption by human muscle–tendon unit is unaffected by increase in intramuscular temperature. J Appl Physiol ; : –.  Magnusson SP, Aagaard P, Nielson JJ. Passive energy return after repeated stretches of the hamstring muscle– tendon unit. Med Sci Sports Exerc ; : –.  Lieber RL, Leonard ME, Brown CG, Trestik CL. Frog semitendinosis tendon load-strain and stress-strain properties during passive loading. Am J Physiol ; : C–C.  Gajdosik RL. Effects of static stretching on the maximal length and resistance to passive stretch of short hamstring muscles. J Orth Sports Phys Ther ; : –.  Garrett WE. Muscle strain injuries: clinical and basic aspects. Med Sci Sports Exerc ; : –.  Astrand PO, Rodahl K. Textbook of Work Physiology. New York: McGraw-Hill Co., .  Saltin B, Hermansen L. Esophageal, rectal, and muscle temperature during exercise. J Appl Physiol ; : –.  Alexander RM. Energy-saving mechanisms in walking and running. J Exp Biol ; : –.  Gleim GW, Stachenfeld NS, Nicholas JA. The influence of flexibility on the economy of walking and jogging. J Orth Res ; : –.

Chapter 1.7 Cartilage Tissue — Loading and Overloading KAROLA ME SSNE R, JACK LEWIS, TE D OE GE MA & HEIKKI J. HE L MI NE N

Classical reference Swanepoel MW, Adams LM. The stiffness of human apophyseal articular cartilage as an indicator of joint loading. Proc Inst Mech Eng ; : –. Despite the fact that osteoarthrosis is a considerable problem, relatively little is known about the mechanical properties of joints under mechanical loads.The apophyseal joints are of interest because their primary function is to restrict motion and they are subjected to prolonged loading. It has been hypothesized that articular cartilage is mechanically conditioned by the daily amount of stress imposed on it, such that ‘soft’ cartilage conditioned by low magnitudes of stress is more susceptible to injury by infrequent high magnitudes of stress. Swanepoel and Adams measured the mean thickness and stiffness of the human lumbar apophyseal cartilage in the upper lumbar segments (see Tables .. and ..). The data indicated that there were region-specific differences within the joint. Moreover, compared to previous data in the literature, the data of Swanepoel and Adams suggest that the articular cartilage of human apophyseal joints is softer than the articular cartilage of the ankle, knee and hip joint. Together the results suggest that low daily load conditioning has influenced the mechanical properties of the joint.

ical integrity and biological stability for a lifetime. However, loads that are outside of this range and are too high or too low can stimulate cartilage to remodel, compromising its functional capacity. Also, loads occurring during trauma can lead to cartilage damage and subsequent degeneration. Understanding the response of cartilage to underloading, overloading, impact loading and altered loading is essential in guiding injury prevention and treatment. The mechanical properties of adult articular cartilage depend on the content of the different extracellular matrix proteins (proteoglycans, collagens, etc.), and their three-dimensional structure and interactions. Table .. Thickness distribution of the cartilage of the superior concave apophyseal surface (mm ± % CI). From Table  in Swanepoel & Adams. Area

Anterior

Center

Posterior

Superior Center Inferior

1.20 ± 0.23 1.13 ± 0.10 0.91 ± 0.12

1.07 ± 0.18 1.21 ± 0.10 1.14 ± 0.12

0.79 ± 0.17 1.03 ± 0.13 1.09 ± 0.12

Table .. Stiffness distribution of the cartilage of the superior concave apophyseal surface (MPa ± % CI). From Table  in Swanepoel & Adams. Area

Anterior

Center

Posterior

Superior Center Inferior

2.84 ± 0.64 2.79 ± 0.30 2.77 ± 0.39

2.23 ± 0.46 3.01 ± 0.35 2.92 ± 0.42

2.21 ± 0.45 2.51 ± 0.48 2.57 ± 0.63

Background Loading is essential for cartilage health and function. Cartilage can sustain loads over a large range of load magnitudes and frequencies and maintain its mechan-



 Chapter . Cartilage with a high content of glycosaminoglycans (GAGs), attached to the core protein of aggrecan, the main cartilage proteoglycan (PG), is stiffer during compressive tests than cartilage with a lower GAG content []. Thus, physiologically high-loaded cartilage regions appear to be stiffer than low-loaded areas within the same joint []. Chondrocytes harvested from various regions of adult sheep knees maintain in culture their location-specific production of PGs []. Since chondrocytes from newborn lambs do not show similar location-specific variations in matrix production, it is reasonable to suggest that the loading conditions during postnatal development determine this change in chondrocyte phenotype. Thus, each part of a particular joint is optimally adapted to the physiologic loading conditions in adulthood by the characteristics of its cells and the construction of the extracellular matrix. Since cartilage is a tissue with low turnover, it should be noted that this adaptation takes approximately  years in humans.

Responses of articular cartilage to cyclic, static and impact loading Loading models Two tools that have been used to study cartilage response to load are in vitro models of cartilage explant loading and in vivo models of cartilage impact loading. In this section, work in these two areas will be reviewed. These two tools address several issues related to cartilage function. First is the question of what loads are required for healthy cartilage. Too small a load can lead to atrophy, an excessive load can lead to cartilage damage and future degeneration. Second is the question of cartilage response to excessive functional loading, such as might occur during aggressive activity with repetitive loading. Under what loads and conditions might cartilage be damaged, what actually occurs in the cartilage during this injurious loading, how might this be prevented, and how might it be treated if damage does occur? Finally, there is the question of the response of cartilage to traumatic impact loading. Under what conditions is cartilage and the cartilage/bone interface damaged, what is the nature of this damage, and how might it be treated? Before examining these questions, it is useful to de-

scribe what is known of the load environment of articular cartilage. In moderate activities, such as walking, maximum surface pressures in the hip joint have been measured to be of the order of – MPa []. During lifting, pressures rose to nearly  MPa []. The time history of this loading would be of the order of /s for walking, with load rise times of the order of  ms []. This rise time reduces to approximately  ms in jogging []. Surface pressures in trauma can rise to and above the failure level of cartilage. These values for joints are not well known, but from in vitro tests are estimated to be in the range of  MPa [,] to  MPa, with rise time of a few ms. The in vivo environment of cartilage is thus quite dynamic.

Loading of cartilage explants In vitro models of cartilage response to moderate load have consisted of cartilage explants, subjected to a variety of controlled load environments []. These models usually consist of cartilage removed from an animal at slaughter, maintaining the cells in the living state. Cartilage pieces, with or without the bone, are prepared and loaded in a culture environment. The time history of loading is varied, with load frequency, duration and magnitude as variables. Outcome variables have included synthesis rates of PGs and matrix proteins, gene regulation, tissue swelling as a measure of matrix damage, cell viability and mechanical properties of the explant. The numerous studies all differ in test conditions and outcome variables, making precise comparison difficult. However, several general conclusions have emerged from this work. Static compression of unconfined cartilage explants causes a dose-dependent inhibition of PG synthesis []. Compressive stress of  MPa for  h in cow cartilage reduced PG synthesis rates by % []. Increased stress or duration further depresses synthesis. Ragan et al. [] further found that  h of static compression depressed mRNA levels for both aggrecan and the normal type IIa collagen.

Cyclic and static loading Cyclic or intermittent compression has various effects on cartilage explants, depending on the loading conditions, such as frequency, time between loads and test duration. Cyclic compression generally increases PG synthesis in the short term [] and alters expression of

Cartilage Tissue other matrix proteins []. Unconfined compression of cartilage disks at  Hz produced an increase of % in PG synthesis rate []. However increasing both the load magnitude and the duration of loading can reduce PG synthesis [], and increase release from the matrix and cell death []. Cyclic loading also alters the synthesis and retention of fibronectin, with either increases [] or decreases [], depending on the loading conditions. Fibronectin is an important molecule in matrix assembly, which increases during remodeling, but is also rapidly up-regulated in response to matrix damage. The studies discussed so far have focused on cartilage function as influenced by loads within a relatively normal range. Other investigators have specifically explored the upper limits of normal loading and how cartilage explants respond to loads above this limit. Quinn et al. [,] studied the effect of injurious static compression on cartilage explants. They imposed strains over % on bovine cartilage discs  mm in diameter by  mm thick, leading to grossly visible cracks. They found decrease in tensile strength, increased cell apoptosis and elevated PG turnover, including increased synthesis and loss of the small PGs. Cells also appeared to be slower in response to cell stimulatory factors, such as interleukin  (IL-). How much of this change is due to loss of cells and alteration of remaining viable cells is unknown. Chen et al. [] applied cyclic loads of increasing magnitude and loading rate to cartilage explants. They found that damage to the cartilage required repeated impacts with a peak stress of at least . MPa and a stress rate of at least  MPa/s for  min or longer, suggesting that impact damage is cumulative and stress-rate dependent. Explants loaded repetitively at  MPa at . Hz for ,  and  min showed increased water content, increased fibronectin synthesis and increased collagen breakdown. The latter observation supported the assumption that increased water content was due to collagen damage in the matrix. Tests of static and cyclic compression on cartilage explants have shown that load affects chondrocyte metabolism, but it is difficult to understand the relevance of specific values to in vivo conditions. At what point will change in chondrocyte biology lead to cartilage damage in vivo and how is this damage defined? How are the explant loading and stress conditions related to



in vivo conditions? While it is clear that increasingly severe loading leads to a progressive process of matrix damage, reduced synthesis of matrix structural molecules, increased lytic enzymes and cell death, the load conditions in vivo for this process are still poorly defined. These experimental models can be considered useful in the study of cartilage response to loading and damage, but not for simulations of in vivo function. This is still an area of active research that must progress further before clinical relevance can be defined.

Impact loading Impact loading of cartilage explants provides a closer simulation of in vivo injurious load conditions than static and cyclic loading conditions. Joint trauma, and cartilage load during that trauma, are due to a single high-magnitude load, that occurs in the order of milliseconds. Although the specific time/load history will not be known, the approximate histories can be reasonably estimated. The outcome variables are also better defined. Immediate and future cell and matrix damage are the main concerns. Several investigators have studied cartilage explants under impact loading. The classic study was performed by Repo and Finlay [], who loaded cartilage explants with a thin subchondral bone plate with a falling plate, with a displacement stop. They measured cell viability by autoradiography of incorporated radioactive proline, and found that cell death began at about  MPa, with fracturing and fissuring occurring simultaneously with cell death. Jeffrey et al. [,] used a different drop weight system to load cartilage explants with no bone with up to  MPa surface stress. They found increased mass due to swelling and decreased cell viability with severity of impact. They also found increased loss of newly synthesized protein and GAG when impacted explants were cultured up to  days after impact. Torzilli et al. [] and Borelli et al. [] used a similar impact system to impact -mm thick strips of cartilage with stresses ranging from . MPa to  MPa. These authors used a conventional materials test machine to load the tissue at a constant stress rate of  MPa/s. They measured PG synthesis by sulfate incorporation, cell viability and death with the fluorescing dyes fluoresceine diacetate and ethidium bromide, and water content. They found stimulated PG synthesis at the

 Chapter . lower stress levels ( ° following ACL reconstruction is thought to be associated with patellofemoral pain []. It is desirable to have a detection threshold that is less than the clinically relevant measure. This approach to measurement error is much more useful than citing a unitless measurement of reliability such as a test–retest correlation or even a specific error in degrees as described by other researchers for a given test. For many motions, error in goniometric assessment of ROM is primarily due to the subjective nature of assessing the limits of motion. For example, maximum straight leg raise ROM is a standard assessment of hamstring flexibility. Determination of maximum passive ROM is a function of the force applied by the tester and the subject’s perception of the discomfort of the stretch. An increase in ROM may be attributed to a change in muscle tension due to a stretching intervention. However, the increased ROM may simply be due to increased force applied by the tester and increased tolerance of the stretch by the subject []. However, this issue may be less important in the rehabilitation setting where ROM is often limited by pain and the intervention is geared towards limiting the pain restriction rather than altering the mechanical properties of the tissues surrounding the joint. For example, shoulder flexion ROM may be limited by pain in patients with subacromial impingement. Rehabilitation is aimed at reducing the inflammation causing this pain thereby allowing a greater ROM. In this situation an alteration in tolerance of the stretch is the goal, not a source of measurement error.

 Chapter . Goniometric and alternative measurement techniques Physical therapists routinely differentiate between passive and active ROM measurements. There are no specific criteria for when to perform one vs. the other, or which is more clinically important. For some motions active ROM may be more accurate because the tester can use both hands to orient the goniometer. For some passive measurements the tester must hold the limb in position while trying to orient the goniometer and this can lead to error. However, active ROM may sometimes be limited by agonist muscle weakness rather than by a restriction of joint motion. Active ROM can also be documented using electrogoniometers. However, these have not gained wide clinical use possibly due to issues of cost. They are most applicable to evaluating functional ROM with specific tasks but measurement error issues remain unresolved []. Fluid-based goniometers, working on the principle of a carpenter’s level, have also been used to measure joint ROM []. While these have not gained popular use, the advent of digital levels in carpentry may provide a new perspective on their use in assessing joint angles. Some alternative techniques negate the use of a goniometer. For example, internal rotation of the shoulder is frequently measured by noting the maximal vertebral level reached by the patient’s thumb []. This may be an easier test for the orthopedist to perform than a goniometric measurement. The question of which is more clinically useful remains open to debate and may depend on the specific pathology. Subacromial impingement is associated with a loss of internal rotation and part of the rehabilitation process involves restoring this motion. The loss of internal rotation ROM is thought to be due to tightness in the posterior capsule. In accordance with this assumption, Tyler et al. [] developed a specific measurement of posterior capsule tightness. This measurement involves measuring the height at which the elbow hangs when the arm is held in an abducted position in sidelying. Intratester reliability was good (intraclass correlation coefficient (ICC) = .–.). Patients with impingement had posterior capsule tightness that was related to the loss of internal rotation ROM []. It has yet to be determined if the posterior capsule measurement is more clinically relevant than internal rotation ROM.

Summary For most orthopedic conditions accurate measurement of joint ROM during rehabilitation is essential for evaluating progress. Standard goniometry is the most accepted and practiced clinical method of assessing ROM. It is important to understand what represents a clinically relevant loss or change in ROM for a given motion and whether the measurement technique can actually detect such a change. To this end the clinician should determine their own threshold of detection for common goniometric assessments.

Evaluation of joint stability Static joint stability Most clinical assessments of joint stability involve manual tests that, for the most part, require a high degree of expertise. Furthermore these manual tests are graded according to a subjective assessment of joint motion. The Lachman test for anterior knee instability and the anterior drawer tests for ankle and anterior shoulder instability are common clinical tests. In general the clinician attempts to assess the magnitude of translation and the quality of the ultimate restraint to translation, i.e. ‘end feel’ or ‘endpoint’. These tests are used initially to diagnose injuries and subsequently to assess the quality of repair. The improvement in joint stability with surgical repairs and reconstructions is usually so dramatic that clinical tests are often adequate for demonstrating improvements despite their subjective nature. However, clinicians often have difficulty in discriminating subtle but clinically important changes in joint stability that may occur during rehabilitation in non-surgical or postsurgical patients. One of the largest postoperative patient populations in sports medicine is the ACL reconstruction patient. The Lachman and pivot shift tests are performed routinely following surgery but it is unclear if these tests are sensitive to changes in graft integrity. For example, a change in Lachman grade from grade  (– mm) to grade  (– mm) may be difficult to detect in a large number of patients. Various techniques have been developed to increase the sensitivity of clinical tests of joint stability. For example, stress radiography has been used to compare different ankle ligamentous reconstruction procedures []. More applicable to the rehabilitation set-

Principles of Rehabilitation and Sport-Specific Training ting is the use of knee arthrometers to assess graft integrity following ACL reconstruction. The KT is the most widely used arthrometer. It was initially developed to aid in the diagnosis of ACL injuries [] and was also used to document improvements with surgery []. Serial KT- testing is now practiced to assess changes in graft integrity during rehabilitation [,]. While this is definitely a useful adjunct to evaluation in rehabilitation there are several issues that must be taken into account when interpreting the results.  As with any test it is necessary to establish the measurement error. Robnett et al. [] estimated that the KT- may only be able to detect a -mm change from a previous measurement in anterior tibial displacement. While this is probably more sensitive than a manual Lachman test a more sensitive measure is probably needed to detect changes in graft integrity on a case-by-case basis. As previously mentioned with respect to goniometric measurements, it is beneficial for the clinician to get an estimate of their own detection threshold, which is about a -mm error for most experienced testers. This detection threshold will allow for detection of clinically relevant changes in graft integrity.  The original criteria for interpreting KT- results were based on the ability to detect ACL disruption. A -mm or more side-to-side difference in anterior tibial displacement was established as a valid criterion for identifying ACL disruption []. However, this criterion clearly does not apply to patients who have had ACL reconstructions. As many as onethird of patients can be expected to have a difference of  mm or more following ACL reconstruction with a positive endpoint on Lachman tests and no associated symptoms [,]. Postoperatively a difference of less than  mm has been categorized as normal, – mm as loose, and greater than  mm as a failure []. However, this grading system has not been validated, since the clinical significance of a – mm difference or greater than  mm difference postoperatively has yet to be established. The value of postoperative KT- measures has been questioned [].  Little is known about what factors affect postoperative KT- results. The tension at which the graft is set intraoperatively will impact on arthrometric stability measurements [,]. If the graft is set at a tension



of  N or less patients will have greater postoperative laxity. A tension of – N results in greater stability. It is of note that preoperative KT- measurements are related to postoperative KT- results (r = ., P < .) []. Patients with greater preoperative side-to-side difference in anterior tibial displacement had greater postoperative laxity. About % of our patients have greater than  mm side-to-side difference following ACL reconstruction and three-quarters of these patients had greater than  mm difference preoperatively. It may not be possible to assess KT- results following surgery without knowing a patient’s preoperative scores. Evaluation criteria for following ACL reconstruction should include the side-to-side difference and the improvement from the preoperative measure. A side-to-side difference of greater than  mm with an improvement in anterior displacement of  mm or more should be regarded as a good surgical result. The use of arthrometers to evaluate joint stability has been primarily limited to the knee joint. However, some attempts have been made to use a similar approach in documenting anterior shoulder instability [,]. The KT- arthrometer has actually been used for this purpose with promising preliminary results []. However, the development of a jointspecific arthrometer is required. An ankle arthrometer has been developed for measuring anterior–posterior and inversion–eversion laxity []. Preliminary results in subjects without pathology showed good reliability but validity in a patient population has yet to be tested.

Dynamic joint stability Although many surgical and non-surgical treatments are aimed at improving dynamic joint stability true objective tests of dynamic stability are lacking. Eastlack et al. [] have developed a battery of dynamic hopping tests for ACL-deficient patients in an attempt to identify individuals who will not develop functional instability. These tests are an important adjunct to rehabilitation for the ACL-deficient patient. While the long-term prognosis for the patients identified as ‘copers’ remains unknown these tests may be useful in identifying patients for whom surgery can be delayed until the end of a season. This provides an opportunity to rehabilitate the patient to return to play within the

 Chapter . season of injury, perform postseason surgery and return to play the following season again. Balance training is an integral part of rehabilitation for ankle instability [,]. Surprisingly, a standardized clinical test has not been developed to assess balance in the athletic ankle instability population. Indices of postural sway based on center of pressure distribution on a force plate have been used to assess balance in patients with a history of ankle sprains, but these tests do not lend themselves to wide clinical use [,,]. Proprioception training (often including balance exercises) is also an integral part of most upper and lower extremity rehabilitation programs. Proprioception refers to the combination of sensation of joint movement and sensation of joint position []. Ligamentous injuries are thought to result in a loss of proprioception while certain rehabilitation techniques are aimed at restoring proprioception (see [] for review). The actual measurement of proprioceptive deficits usually involves testing the ability to detect the initiation of passive joint motion (kinesthesia) or the ability to detect when the joint has returned to a previous position (joint position sense). One of the advantages of these tests is that the movement velocities are extremely slow, thereby reducing measurement error. Information with respect to clinical significance of these proprioception deficits and functional carryover of training effects is lacking. A disadvantage of the measurement technique is that neuromuscular proprioceptive feedback is removed by the passive nature of the test movement. Given the potential for neuromuscular input and adaptation during dynamic motions [] a more integrated approach to the measurement of proprioception may be needed.

Evaluation of muscle function In sports medicine the restoration of muscle function is by far the largest component of most rehabilitation protocols. It follows that most standard evaluations of progress in rehabilitation primarily involve an assessment of muscle function. This assessment is usually based on some measurement of force-generating capacity. A multitude of factors must be considered when choosing a particular test of muscle function. Typical considerations include:  What are the specific muscle groups of interest?

 Will voluntary or artificially stimulated contractions be evaluated?  Is the goal to assess strength, endurance or power?  Should the assessment involve concentric, eccentric or isometric contractions?  Will the test instrument be an isokinetic dynamometer, a free weight isotonic system, a hand-held dynamometer or some other device?  Will measurements be made throughout the range of motion? The answer to each of these questions will vary depending on such factors as the specific injury, the patient’s symptoms, the time post injury or surgery, the functional demands of the particular muscle group to be tested and accessibility of the instrumentation.

Affected muscle groups — linkage It is often a mistake in rehabilitation to concentrate on the muscle groups surrounding the injured joints and ignore potential deficits in muscle groups along the kinetic chain. The concept of linkage describes how impairments in one area can impact other areas in the musculoskeletal system. This has been best illustrated in ankle pathology where proximal muscle groups may be more affected than the muscles surrounding the injured joint []. There is an association between ankle sprains and hip abduction weakness but it is unclear if it is a cause or effect. Furthermore, following ankle injury there is increased reliance on the hip musculature in response to ankle perturbations [].

The role of neuromuscular stimulation techniques For the most part muscle function testing will involve voluntary contractions. However, it is often difficult for clinicians to determine the extent to which muscle weakness is due to incomplete activation as opposed to atrophy. This is an important issue since the optimal treatment for reversing atrophy usually involves resistance exercises aimed at overloading the muscle. By contrast, the optimal treatment for improving muscle activation often involves modalities that reduce pain and/or joint effusion or stimulation protocols aimed at ‘muscle re-education’. Specific stimulation protocols have been developed to identify the contribution of inhibition to muscle weakness []. Stimulation training protocols may be beneficial in conditions where inhibi-

Principles of Rehabilitation and Sport-Specific Training tion limits training effects with voluntary contractions. For example, Snyder-Mackler et al. [] demonstrated that electrical stimulation enhanced recovery of quadriceps strength following ACL reconstruction. However, strength recovery was highly dependent on the training contraction intensity which was limited by the patient tolerance of the associated discomfort. The electrically stimulated training intensity ranged from < % of the contralateral maximal voluntary contraction (MVC) to % of the contralateral MVC. The training dosage involved  stimulated contractions three times per week, from the second to the sixth postoperative week. Quadriceps strength was approximately % of the uninvolved side following  weeks of stimulation compared with approximately % in the comparison group. While these results are very encouraging, the question of patient comfort remains a confounding factor. In a similar study Lieber et al. [] found that patients could only tolerate electrical stimulation intensities sufficient to elicit contractions from % to % of MVC from  to  weeks following ACL reconstruction. Not surprisingly, electrical stimulation did not prove better than voluntary contractions. In contrast to electrical stimulation, magnetic stimulation of peripheral nerves represents a relatively painless alternative to electrical stimulation which has a wide application in musculoskeletal rehabilitation. Polkey et al. [] demonstrated that single magnetic pulses to the femoral nerve could be used to objectively assess muscle strength and fatigue in both normal subjects and patients with known muscle weakness. However, they did not quantify contraction intensities elicited from stimulation trains resulting in tetanic contractions. The technology is now available to deliver trains of pulses to peripheral nerves to elicit tetanic contractions for as long as  s. This offers the potential to deliver supramaximal contractions to assess strength independently of neural inhibition and to train muscles which cannot be fully activated voluntarily. This technology was recently applied in a group of subjects without pathology []. Magnetic stimulation of the femoral nerve elicited torques of % MVC with minimal discomfort. The magnitude of torque response was inversely related to the subject’s percentage body fat. The primary limitation to eliciting greater torques was related to specifications of the unit



rather than to subject tolerance. With the addition of more booster units, higher frequencies and intensities could be used and should produce even higher torque levels. However, at present this technology is too expensive for wide clinical use and the software applications are not conducive for training protocols.

Strength, endurance and power A common misconception is that decreased muscle strength (weakness) and decreased muscle endurance (increased fatigability) occur concomitantly following injury and associated disuse. However, muscle strength and endurance are at best unrelated and may in fact be inversely related. Snyder-Mackler et al. [] found that quadriceps weakness following ACL reconstruction was inversely related to reduced fatigue. The rate of torque decline (fatigue) during sustained electrically stimulated submaximal knee extension contractions was markedly less on the involved side compared to the non-involved side  weeks following surgery. The results were recently confirmed in the same patient population using voluntary contraction and electromyographic indices of fatigue []. Both studies point to the possibility of selective fast-twitch fiber atrophy as a mechanism for the observed effects. The clinical relevance of these findings is that quadriceps endurance exercises are not indicated following ACL reconstruction. The fact that a weak muscle may be less fatigable can be seen as a functional adaptation to counteract the increased demands placed on it. During repetitive activity a weak muscle will be working at a higher relative intensity than a contralateral normal muscle for a given absolute load. Thus the weak muscle can be expected to fatigue more rapidly because it is working at a higher relative intensity. The fatigue resistance (apparent in the weak muscle when tested at similar relative loads) may help to offset the fatigue induced by working at a higher relative intensity. Muscle endurance exercise are often used in rehabilitation to prepare patients for the specific demands of their sports. These exercises are an important part of the sport-specific phase of rehabilitation. It is important that the chosen exercises are as sport specific as possible since endurance exercises have been shown to be very task specific with minimal carryover to related tasks []. Task specificity [] and poor measurement

 Chapter . reliability (compared with strength tests) [] may limit the efficacy of standardized endurance tests in rehabilitation. The disassociation between strength and endurance, apparent in patients following ACL reconstruction, is also apparent in patients with low back pain. In this condition patients present with normal strength but decreased endurance []. Thus endurance-type training is indicated for this patient population. Muscle power is frequently overlooked in rehabilitation. Many dynamic sports require the ability to produce high muscle forces in a minimal amount of time. For these activities performance is dependent on muscle power rather than muscle strength. While high load is optimal for strength training the optimal load for power training is dependent on the force–velocity relationship of the muscles involved. For isolated muscles the relationship of muscle force to the velocity of contractile shortening is an inverse hyperbolic curve. Muscle force is highest during low-velocity movements and lowest during high-velocity movements. In contrast the relationship of muscle force to muscle power is parabolic. Maximum muscle power occurs in the midportion of the force–velocity curve at muscle forces of –% of maximum. Training studies have demonstrated that high-velocity training with loads equal to –% MVC result in the greatest gains in power. Clinically, the force–velocity relationships for single joint movements can be estimated according to the relationship of torque to angular velocity. Based on this relationship a power curve can be calculated from which an optimal training intensity can be set for power training.

Contraction type The contraction type to be tested is to some extent dependent on the test instrument used. For the most part clinicians can decide between purely concentric, eccentric or isometric tests or reciprocal concentric/ eccentric tests. Isokinetic dynamometers provide the greatest freedom of choice in this regard. Measurement error is an important consideration in choosing the appropriate contraction type. However, a definitive statement cannot be made regarding differences in measurement error between each of the three contraction types. Error will be affected by the joint being

tested, the muscle group and the chosen contraction velocity. Generally slow-speed concentric and isometric contractions are thought to be the most reproducible []. Clinical factors may dictate the choice of contraction type. For example, isometric strength at ° was used to quantify quadriceps weakness in the early postoperative phase following ACL reconstruction []. The potential for pain during testing was reduced by testing in a position of minimal patellofemoral compression. This could have also been achieved by testing concentrically at high speed, but this may be a less reproducible test. High-speed eccentric testing may be more informative in assessing recovery from a muscle strain [] but may also have increased risk of re-injury. Often concentric testing is preferred because of the low muscle forces relative to eccentric and isometric contractions. There is also less post-test muscle damage with concentric testing. If the goal of a test is to assess fatigability eccentric contractions are not appropriate since eccentric contractions are much more fatigue resistant than concentric and isometric contractions [,].

Test instrument Typically strength can be measured on an isokinetic dynamometer, a free weight isotonic system or a handheld dynamometer or manually using a clinical grading system. While the latter method is common in physicians’ offices or on the sidelines of sports events the other more objective measures are usually available in the rehabilitation setting. The primary disadvantage of isotonic testing using a free weight apparatus is that repeated trials are required to establish a onerepetition maximum. However, this type of testing replicates the training situation for many patients. Although isokinetic dynamometry is regarded as the gold standard for strength assessment, hand-held dynamometers offer a much less expensive, portable alternative. The reliance on tester strength limits the number of motions that can be tested, but hand-held dynamometry has been used effectively to test shoulder abduction [], shoulder internal–external rotation and scapular-plane elevation [,], and hip flexion, abduction and adduction []. In fact measurement error was shown to be better for hand-held dynamometry than for isokinetic testing of shoulder abduction strength [].

Principles of Rehabilitation and Sport-Specific Training Functional range of motion One of the advantages of isokinetic testing is that it allows maximal force to be generated throughout the full range of motion unlike isotonic or single-angle isometric testing. However, only rarely do clinicians take advantage of this and actually examine strength through the functional range. For example strength loss with aging is associated with a loss of functional range of the muscles []. The shape of the length–tension curve (i.e. the ROM–torque curve) may be revealing of functional capacity following injury but has not been studied specifically. A decreased slope on the descending limb of the length–tension curve (i.e. increased force-generating capacity at increased muscle lengths) is thought to protect muscle from exercise-induced damage []. It may be useful to examine the ability to generate muscle force at increased muscle lengths in patients recovering from muscle strains.

Summary Specific tests for assessing joint ROM, joint stability and muscle function encompass most of the types of evaluations performed in rehabilitation. Functional tests, such as the single-limb hop test used in ACL reconstruction rehabilitation, provide an additional picture of general musculoskeletal performance. When such tests are applied they should involve a combination of a sport-specific demand and an injuryspecific demand. Using the same example of the single-limb hop test for the ACL reconstruction patient this involves a sport-specific demand for high friction sports such as basketball and soccer but is an inappropriate test for a low friction sport such as ice hockey []. Certain general principles apply to evaluations regardless of whether they involve testing ROM, stability or muscle function. The measurement error should be sufficiently low to enable the detection of clinically relevant effects. Clinicians should establish their own detection thresholds for commonly used clinical tests. Interpretations of test results must be based on established criteria validated for the specific patient population. As new tests and new testing equipment are developed to provide more accurate or less expensive assessments, these tests should be validated with the appropriate patient populations.



Fitness training and performance testing Introduction In order to understand how to perform fitness training and how to evaluate performance in a sport the physical requirements of the sport have to be understood. Performance in any sport is determined by the athlete’s technical, tactical, physiological and psychosocial characteristics (Fig. ..). These elements are closely linked to each other, e.g. the full technical quality of an athlete may not be exploited if the athlete’s physical capacity is low. The physical demands in a sport are very much related to the activities of the athlete. In some sports continuous exercise is performed with either a very high or moderate intensity during the entire event, such as a -m and a marathon run, respectively (Fig. ..). In other sports like soccer and basketball athletes perform different types of exercise ranging from standing still to maximal running, and the intensity can vary at any time. Under optimal conditions the physical demands of the sport are closely related to the athlete’s physical capacity, which can be divided into the following categories: (i) the ability to perform prolonged exercise (endurance); (ii) the ability to exercise at high intensity; (iii) the ability to sprint; and (iv) the ability to develop a high power output (force) in single actions during competition such as kicking in soccer and jumping in basketball (Fig. ..). The basis for performance within these categories is the characteristics of the cardiovascular system and the muscles, combined with the interplay of the nervous system. These characteristics are to a great extent determined by genetic factors but they can also be developed by training. A number of environmental factors such as temperature and for outdoor sports the weather and the surface of the competition ground also influence the demands on the athletes. In some sports it is important that the athlete has a very high capacity within at least one of the categories of physical capacity to perform at a top level; for example, a marathon runner needs a high endurance capacity, but not a well-developed ability to produce a high power output. In other sports, such as team sports, an athlete may need an all-round fitness level. In such sports an athlete with a moderate en-

 Chapter .

Psychological/social Tactical

Performance

Technical

Physiological

Coordination Flexibility Sensorimotor

External factors temperature attitude field condition nutrition (diet/fluid)

Endurance performance

High-intensity exercise performance

Aerobic performance aerobic power aerobic capacity

Intrinsic factors age/maturation sex anthropometry

Sprint performance

Anaerobic performance anaerobic power anaerobic capacity

Cardiovascular system

Force development

Muscle strength low-speed force high-speed force

Muscle characteristics

Fig. .. Physiologic factors within a holistic model of performance in a sport. Performance is determined by an athlete’s tactical, psychological/social, technical and physiologic capacity. These areas overlap and influence each other. The physiologic factors can be divided into several performance abilities (upper part). These are dependent on variables, which in part can be evaluated separately (middle part). Cardiovascular capacity, neural factors and muscle characteristics comprise basic components of physiologic performance that are determined by both intrinsic biologic make-up and training status (lower part). Performance in a sport can also be influenced by various external factors, including environment and nutrition.

durance capacity may to some extent compensate for this weakness by having good capabilities in other areas relevant to the sport, e.g. a high technical standard or good sprinting ability. In the remainder of this chapter the general principles of training to improve specific aspects of physical performance will be described and the use of tests to evaluate performance of athletes will be discussed.

Physiology of training Fitness training in any sport has to be focused on the demands of the sport, and in many sports it has to be multifactorial in order to cover the different aspects of

physical performance in the sport. To be able to fulfil these requirements, it is useful to divide fitness training into a number of components related to the purpose of the training (Fig. ..). The terms aerobic and anaerobic training are based on the energy pathway that dominates during the activity periods of the training session (Fig. ..). Aerobic and anaerobic training represent exercise intensities below and above the maximum oxygen uptake, respectively. However, in some sports like ball games, in which the ball is used in the fitness training, the exercise intensity for an athlete varies continuously, and some overlap exists between the two categories of training.

Principles of Rehabilitation and Sport-Specific Training 100

100 m

90 800 m

Intensity (% of maximum)

80 70 60 50 40

. V O2max Marathon

30 20 10

Cycling

Soccer Time

Fig. .. Examples of exercise intensities in various sports. Note that the intensity corresponding to the maximum oxygen · uptake (V 2 max) is around % of maximal intensity, but there are large individual differences.

The separate components within fitness training are briefly described below. They include aerobic, anaerobic and specific muscle training.

Aerobic training Aerobic training causes changes in central factors such as the heart and blood volume, which result in a higher maximum oxygen uptake []. A significant number of peripheral adaptations also occur with this type of training []. The training leads to a proliferation of capillaries and an elevation of the content of mitochondrial enzymes, as well as the activity of lactate dehydrogenase – isozymes (LDH1–2). Furthermore, the mitochondrial volume and the capacity of one of the shuttle systems for NADH are elevated []. These changes cause marked alterations in muscle metabolism. The overall effects are an enhanced oxidation of lipids and sparing of glycogen, as well as a lowered lactate production, both at a given and at the same relative work-rate []. The optimal way to train central and peripheral factors is not the same. Maximum oxygen uptake is most effectively elevated by exercise intensities of –% of V˙2 max (–% of maximal intensity; Fig. ..). For a muscle adaptation to occur, an extended period of training appears to be essential, and therefore, the mean intensity needs occasionally to be below % of V˙2 max. This does not imply that high-intensity train-



ing does not elevate the number of capillaries and mitochondrial volume in the muscles engaged in the training, but that the duration of this type of training is often too short to obtain optimal adaptations at a local level. The dissociation between changes in V˙2 max and muscle adaptation by means of training and detraining is illustrated by results from two studies. In one study long-distance runners were kept inactive for  weeks (first week with the leg in a cast) which did not result in a change in V˙2 max []. On the other hand, the detraining period led to a % decrease in performance in an exhaustive run (from about –. min) which was associated with a % lowering of the activity of the oxidative enzyme succinate dehydrogenase (SDH). During the following  weeks of retraining V˙2 max did not change, whereas performance and SDH were still lowered by  and %, respectively. The level of inactivity does not have to be as extreme as in this study to have a marked effect on performance and muscle respiratory capacity. In another study topclass soccer players abstained from training for  weeks []. It was found that V˙2 max was unaltered, whereas performance in a field test was lowered by %, and there was a reduction in oxidative enzymes of –% (Fig. ..). The recovery processes from intense exercise are related both to the oxidative potential and to the number of capillaries in the muscles []. Thus, aerobic training not only improves endurance performance of an athlete, but also appears to influence an athlete’s ability to repeatedly perform maximal efforts. The overall aim of aerobic training is to increase the work-rate during competition, and also in ball games to minimize a decrease in technical performance as well as lapses in concentration induced by fatigue towards the end of a game. The specific aims of aerobic training are as follows. • To improve the capacity of the cardiovascular system to transport oxygen. Thus, a larger percentage of the energy required for intense exercise can be supplied aerobically, allowing an athlete to work at higher exercise intensity for prolonged periods of time. • To improve the capacity of muscles specifically used in the sport to utilize oxygen and to oxidize fat during prolonged periods of exercise. Thereby, the limited store of muscle glycogen is spared and an athlete can

 Chapter .

FITNESS TRAINING Low-intensity training AEROBIC TRAINING

Moderate intensity training Highintensity training Production training Speed endurance training

ANAEROBIC TRAINING

Maintenance training Speed training

Muscle strength training SPECIFIC MUSCLE TRAINING

Functional training

Low-speed training Concentric training

Basic training

High-speed training

Isometric training

Muscle speed endurance training Flexibility training

CS

11.5

4.0

11.0

3.5

10.5

3.0

10.0

50 40 30 20

Season

After de-training

HAD mmol/min g d.w.

4.5

mmol/min g d.w.

Time to finish

min

L/min

Maximum oxygen uptake

Fig. .. Components of fitness training.

50 40 30 20

Fig. .. Maximum oxygen uptake, performance in a field test, activities of oxidative enzymes citrate synthase (CS) and b-hydroxy-CoA-dehydrogenase (HAD; involved in fat oxidation) of Danish top-class soccer players during the season and after  weeks of holiday.

Principles of Rehabilitation and Sport-Specific Training exercise at a higher intensity towards the end of a game. • In some sports, like team sports, to improve the ability to recover after a period of high-intensity exercise. As a result, an athlete requires less time to recover before being able to perform in a subsequent period of high-intensity exercise.

Components of aerobic training Aerobic training can be divided into three overlapping components: aerobic low-intensity training (aerobicLI), aerobic moderate-intensity training (aerobicMO) and aerobic high-intensity training (aerobicHI) (Fig. ..). Table .. illustrates the principles behind the various categories of aerobic training, which take into account the fact that in some sports the training may be performed as a game, and thus the heart rate of the athlete may frequently alternate during the training. During aerobicLI athletes perform light physical activities, such as jogging and low-intensity games. This type of training may be carried out the day after a competition or the day after a hard training session to help the athlete to return to a normal physical state. AerobicLI may also be used to avoid athletes getting into a condition known as ‘overtraining’ in periods involving frequent training sessions (maybe even twice a day) and a busy competitive schedule. The purpose of aerobicMO is to elevate the capillarization and the oxidative potential in the muscle (peripheral factors). Thus, the functional significance is an optimization of substrate utilization and thereby an improvement in endurance capacity. One of the aims of aerobicHI is to improve central factors such as the



pumping capacity of the heart which is closely related to V˙2 max. These improvements increase an athlete’s capability to exercise repeatedly at high intensities for prolonged periods of time.

Anaerobic training In a number of sports an athlete performs activities that require rapid development of force, such as sprinting, quickly changing direction or jumping. Also, in many sports the lactate-producing energy system (glycolysis) is highly stimulated during periods of competition. Therefore, the capacity to perform highintensity exercise may specifically have to be trained. This can be achieved through anaerobic training. Anaerobic training results in an increase in the activity of creatine kinase (CK) and glycolytic enzymes; such an increase implies that a certain change in an activator results in a higher rate of energy production of the anaerobic pathways. Intense training does not appear to influence the total creatine phosphate (CP) pool, but it allows the muscle glycogen concentration to be elevated, which is of importance for performance during repeated high-intensity exercise []. The capacity of the muscles to release and neutralize H+ (buffer capacity) is also increased after a period of anaerobic training []. This will lead to a lower reduction in pH for a similar amount of lactate produced during high-intensity exercise. Therefore, the inhibitory effects of H+ within the muscle cell are smaller, which may be one of the reasons for a better performance in high-intensity tests after a period of anaerobic training. Another important effect of the anaerobic training is an increased activity of the muscle

Table .. Principles of aerobic training. Heart rate

Oxygen uptake

% of HRmax

Low-intensity training Moderate-intensity training High-intensity training *If HRmax is 200 beats/min.

% of V·O2 max

Beats/min

Mean

Range

Mean*

Range*

Mean

Range

65 80 90

50–80 65–90 80–100

130 160 180

80–160 130–180 160–200

55 70 85

20–70 55–85 70–100

 Chapter . Table .. Principles of anaerobic training. Duration

Speed training

Exercise

Rest

Intensity

Number of repetitions

2–10 s

> 10 times the exercise duration

Maximal

2–10

> 5 times the exercise duration 1–3 times the exercise duration

Almost maximal High

2–10 2–10

Speed endurance training Production 15–40 s Maintenance 20–90 s

Na+/K+ pumps resulting in a reduced net loss of potassium from the contracting muscles during exercise, which may also lead to increased performance []. The overall aim of anaerobic training is to increase an athlete’s potential to perform high-intensity exercise. The specific aims of anaerobic training are summarized below. • To improve the ability to act quickly and to produce power rapidly. Thus, an athlete reduces the time required to react and elevates sprinting performance. • To improve the capacity to produce power and energy continuously via the anaerobic energyproducing pathways. Thereby, an athlete elevates the ability to perform high-intensity exercise for longer periods of time. • To improve the ability to recover after a period of high-intensity exercise, which is particularly important in ball games. As a result, an athlete requires less time before being able to perform maximally in a subsequent period of exercise, and in ball games the athlete will therefore be able to perform high-intensity exercise more frequently during a match.

Components of anaerobic training Anaerobic training can be divided into speed training and speed endurance training (Fig. ..). The aim of speed training is to improve an athlete’s ability to act quickly in situations where speed is essential. Speed endurance training can be further separated into two subcategories: production training and maintenance training. The purpose of production training is to improve the ability to perform maximally for a relatively short period of time, whereas the aim of maintenance training is to increase the ability to sustain exercise at a

high intensity. Table .. illustrates the principles of the various categories of anaerobic training. Anaerobic training must be performed according to an interval principle. During speed training the athletes should perform maximally for a short period of time (<  s). The periods between the exercise bouts should be long enough for the muscles to recover to near-resting conditions, so as to enable an athlete to perform maximally in a subsequent exercise bout. In many sports, speed is not merely dependent on physical factors. It also involves rapid decision-making which must then be translated into quick movements. Therefore, in ball games speed training should mainly be performed with a ball. Speed drills can be designed to promote an athlete’s ability to sense and predict situations, and the ability to decide on the opponents’ responses in advance. Through speed endurance training the creatine kinase and glycolytic pathways are highly stimulated. The exercise intensity should be high (> % of maximal intensity; Fig. ..), to elicit major adaptations in the enzymes associated with anaerobic metabolism. In production training the duration of the exercise bouts should be relatively short (– s), and the rest periods in between the exercise bouts should be comparatively long (– min) in order to maintain a very high intensity during the exercise periods throughout an interval training session. In maintenance training the exercise periods should be – s and the duration of the rest periods should be one to three times longer than the exercise periods, to allow athletes to become progressively fatigued. The adaptations caused by speed endurance training are mostly localized to the exercising muscles. Thus, it is important that an athlete performs move-

Principles of Rehabilitation and Sport-Specific Training



is to increase performance of a muscle to a higher level than can be attained just by participating in the sport. Specific muscle training can be divided into muscle strength, muscle speed endurance and flexibility training (Fig. ..). The effect of this form of training is specific to the muscle groups that are engaged, and the adaptation within the muscle is limited to the kind of training performed. A brief description of muscle strength training is given below. Further information about strength training can be obtained in Chapter .. (a)

18

180

16

160

14 12

140

10 120

8

100

6 4

80

2 E 0

(b)

Lactate concentration (mmol/L) ( )

Heart rate (beats/min) ( )

Strength training

E 1

2

E

3 4 5 6 Time (min)

E 7

8

Fig. .. Speed endurance soccer training game. Two against two with man-to-man marking and two goalkeepers. The players play for  min followed by  min of rest. Below is shown the heart rate and blood lactate response for a player. The high heart rate towards the end of the exercise periods and the high lactate levels show that the anaerobic system is heavily stimulated.

ments in a manner similar to those used during competition, e.g. an oarsman should train in the boat or on a rowing ergometer. In ball games this can be obtained by performing high-intensity games or drills with a ball. Figure .. illustrates a soccer game within the maintenance category of speed endurance training. It also shows heart rate and blood lactate values for a player during the game, illustrating that the game fulfils the criteria for speed endurance training.

Specific muscle training Specific muscle training involved training of muscles in isolated movements. The aim of this type of training

In many sports there are activities which are forceful and explosive, e.g. high jumping, hiding in boxing and turning in ice hockey. The power output during such activities is related to the strength of the muscles involved in the movements. Thus, it is beneficial for an athlete in such sports to have a high level of muscular strength, which can be obtained by strength training. Strength training can result in hypertrophy of the muscle, partly through an enlargement of muscle fibers. In addition, training with high resistance can alter the fiber type distribution in favor of fast-twitch fibers []. There is also a neuromotor effect of strength training and part of the increase in muscle strength can be attributed to changes in the nervous system. Improvements in muscular strength during isolated movements seem closely related to training speeds. However, significant increases in force development at very high speeds (– rad/s) have also been observed with slow-speed high-resistance training []. One essential function of the muscles is to protect and stabilize joints of the skeletal system. Hence, strength training is also of importance in preventing both injuries and reoccurrence of injuries. A prolonged period of inactivity, e.g. during recovery from an injury, will considerably weaken the muscle. Thus, before an athlete returns to training after an injury, a period of strength training is needed. The length of time required to regain strength depends on the duration of the inactivity period but generally several months are needed. In a group of soccer players observed for  years after a knee operation, it was found that the average strength of the quadriceps muscle of

 Chapter . the injured leg was only % of the strength in the other leg []. The overall aim of muscle strength training is to develop an athlete’s muscular make-up. The specific aims of muscle strength training are: • to increase muscle power output during explosive activities such as jumping and accelerating; • to prevent injuries; and • to regain strength after an injury. Components of strength training Strength training can be divided into functional strength training and basic strength training (Fig. ..). In functional strength training, movements related to the sport are used. The training can consist of activities in which typical movements are performed under conditions that are physically more stressful that normal. During basic strength training muscle groups are trained in isolated movements. For this training different types of conventional strength training machines and free weights can be used, but the body weight may also be used as resistance. Strength training should be carried out in a manner that resembles activities and movements specific to the sport. Based on the separate muscle actions the basic strength training can be divided into isometric, concentric and eccentric muscle strength training (Fig. ..). Several principles can be used in concentric strength training. Table .. illustrates a principle which is based on determinations of five-repetition maximum ( RM) and which allows for muscle groups to be trained at both slow and fast speeds.

Common to the two types of strength training is that the exercise should be performed with a maximum effort. After each repetition an athlete should rest a few seconds to allow for a higher force production in the subsequent muscle contraction. The number of repetitions in a set should not exceed . During each training session two to four sets should be performed with each muscle group, and rest periods between sets should be longer than  minutes. During this time the athletes can exercise with other muscle groups.

Training methods A major part of fitness training in any sport should be performed in a manner closely related to the activities specific to that sport, e.g. with a ball in basketball, since this ensures that the specific muscle groups used in the sport are trained. In addition, in some sports the athletes will thus develop technical and tactical skills under conditions similar to those encountered during a match. Thirdly, this form of training usually provides greater motivation for the athletes compared to training not focused on the sport. Individual physical demands must be considered when planning fitness training and a part of the fitness training may, even in team sport, be performed on an individual basis. The training should be focused on improving both the strong and weak abilities of an athlete. It is important to be aware of the fact that, due to hereditary differences, there will always be differences in the physical capacity of athletes, irrespective of training programs.

Table .. Principles of muscle strength training.

Concentric Low-speed High-speed

Workload

Number of repetitions

Rest between repetitions (s)

Number of sets

5RM* 50% of 5RM

5 15

2–5 1–3

2–4 2–4

5–15

2–4

Isometric 85–100% of max maintained for 5–15 s *RM, repetition maximum.

5–10

Principles of Rehabilitation and Sport-Specific Training Evaluation of physical performance

180 170 160 Nm

This section will deal with various aspects of evaluation of physical performance and give a number of examples of tests that are relevant and easy to use.

150

Reasons for testing

140

Competition naturally provides the best test for an athlete but it is difficult to isolate the various components within the sport and get objective measures of performance. Fitness testing can provide relevant information about specific parts of a sport. Before selecting a test, clear objectives should be defined. There may be a number of reasons for testing an athlete: • To study the effect of a training program. • To motivate an athlete to train more. • To give an athlete objective feedback. • To make an athlete aware of the aims of the training. • To evaluate whether an athlete is ready to compete. • To determine the performance level of an athlete during a rehabilitation period. • To plan short- and long-term training programs. • To identify the weaknesses of an athlete.

130

Choosing a test To obtain useful information from a test, it is important that the test to be performed is relevant and resembles the conditions of the sport in question. For example, a cycle test is of minor relevance for a swimmer. There are a number of laboratory tests which evaluate various aspects of performance (Fig. ..) and are commonly used. These include determination of maximum aerobic power (maximum oxygen uptake) to evaluate the athlete’s ability to take up and utilize oxygen as described in Chapter .. A Wingate test consists of  s of maximal cycle exercise aiming at determining the maximum anaerobic power and ability to maintain a high power output. Strength measurements in which strength or power of an isolated muscle group is measured during either isometric, concentric or eccentric contractions are other laboratory tests often used. Such tests provide general information about the capacity of an athlete and may separate different performance levels of athletes within a sport. For example, for soccer players the



*

*

120 0 GoalCentral Fullbacks Midfield Forwards keepers defenders players

Fig. .. Maximum knee extensor torque (Nm) under isokinetic loading at a velocity of °/s for Danish top-class soccer players in various positions. Means + SE are given. * Significantly different from goalkeepers, central defenders and forwards.

strength produced by the knee extensors during an isokinetic movement at a velocity of °/s was significantly higher for goalkeepers, defenders and full-backs than for midfield players and forwards (Fig. ..). In some sport such general tests can provide information as to sport-specific requirements; e.g. to be a top-class cross-country skier a maximum oxygen uptake of higher than  mL/min/kg is needed. Such classical laboratory tests may also be useful for comparisons of performance between various sports. However, they may only to a limited extent express the performance of the athlete during competition. For example, Fig. .. shows that for  top-class soccer players there was no relationship between peak knee extensor power output and kick performance, suggesting that the strength of the knee extensors alone does not determine the final impact on the ball in a kick. Strength of other muscle groups, such as the hip muscles, may be important and technical skill is also a predominant factor in the soccer kick, which incorporates a complex series of synergistic muscle movements, involving the antagonistic muscles as well. Being more specific to the sport will increase the validity of a test, i.e. the test result better reflects the performance of the athlete. Below are provided a number of examples of sport-specific tests that are simple to organize; some require special equipment in order to

 Chapter .

Moment, 30°/s (Nm)

450 400 350 300 250 200 150 0

r = 0.28 0

95

100

105

110

115

Peak ball velocity (km/h) Fig. .. Individual relationship between kick performance (peak ball velocity) and maximum knee extensor torque (Nm) under isokinetic loading at a velocity of °/s for Danish top-class soccer players.

simulate the activities in the sport and others require only simple materials.

Rowing performance Rowing is characterized by a certain movement involving muscles of the whole body. A rowing ergometer has been developed in which it is possible to simulate the movement in the boat. Performance can be evaluated by measuring the total work performed within a given time, e.g.  min as in some races, or the time to exhaustion at a given external work rate []. To obtain further information about the oarsman a number of physiological measurements can be added to the test such as pulmonary oxygen uptake in which the rate of rise of oxygen uptake in the initial phase of exercise and the peak oxygen uptake during the rowing are determined. It is of no doubt that such a test has a high validity for rowing performance on water.

Running tests One of the most widely used field tests is the Cooper test. In the Cooper test the participants run the furthest possible distance in  min. It is simple to perform, but it has the disadvantage that the athletes need to know how to tactically perform the test in order to obtain the best test result. It also requires a course with a distance of at least  m. Its popularity probably re-

sults from the fact that it is simple and a correlation between performance and V˙2 max has been observed. However, the type of running in the test may only be relevant for track runners and they have the most simple test in any case, namely the competition. Furthermore, the relationship between the test and V˙2 max may not be very useful, since in many sports, such as ball games, V˙2 max is a poor marker of physical performance during competition. The ‘yo-yo’ tests are a series of tests that evaluate various aspects of performance in an easy way []. The tests contain running activities that are relevant for many sports. With the tests the physical capacity is evaluated in a fast and simple manner. Two markers are positioned  m apart. A CD is placed in a CD player and the test can be performed. The participant runs like a yo-yo back and forth between the markers at given speeds that are controlled by the CD. The speed is regularly increased, and when the individual no longer can maintain the speed, the test is ended. The test result is determined as the distance covered during the test. It is also possible to perform the tests without exhausting the participants. In this case the test is stopped after a given time and the heart rate is measured to evaluate the development of the cardiovascular system. The lower the heart rate the higher is the capacity of the individual. This type of test is especially useful for athletes that are in a rehabilitation period. The tests can be used by anyone, irrespective of training status, since each of the three tests has two levels. There is a test for untrained and less trained individuals, and one test for well-trained athletes. There are three yo-yo tests. In one test the participants perform continuous exercise, called the yo-yo endurance test, and in two tests the participants carry out intermittent exercise, namely the yo-yo intermittent endurance test and the yo-yo intermittent recovery test. The principles of the yo-yo intermittent tests are similar to the continuous yo-yo test, except that in the intermittent tests the athletes have a period of active rest between each of the  ¥ -m shuttles. The tests are briefly described below and examples given of sports where each of the tests is relevant. Also provided are examples of how the tests have been used to determine the performance of athletes.

Principles of Rehabilitation and Sport-Specific Training PreDuring preparation period

1800 1200

*

1600

*

*

*

1100

1400 1300 1200

Distance (m)

Distance (m)



900

*

1000 900

*

800 700

Guard

Forward

Center

Fig. .. Yo-yo intermittent endurance test performance of male top-class basketball players in different positions. * Significantly different from center players.

Yo-Yo endurance test The yo-yo endurance test lasts for – min and is used for the evaluation of the ability to work continuously for a longer period of time. This test is especially useful for individuals that participate in endurance exercise, such as distance running. Yo-Yo intermittent endurance test The yo-yo intermittent endurance test lasts – min and consists of –-s intervals of running interspersed with regular -s rest periods. The test evaluates an individual’s ability to repeatedly perform intervals over a prolonged period of time. The test is especially useful for the athlete that performs interval sports, such as tennis, team handball, basketball and soccer. Figure .. shows the performance of topclass basketball players in different positions. Yo-Yo intermittent recovery test The yo-yo intermittent recovery test lasts – min and focuses on the ability to recover after intense exercise. Between each exercise period (– s) there is a -s pause. The test is particularly suitable for sports in which the ability to perform intensive exercise after short recovery periods can be decisive for the outcome of a competition, such as badminton, soccer, basketball, ice hockey and football. The test is able to pick up changes in performance illustrated in Fig. .., which shows the performance level of professional

0 Fullbacks Central Midfield Forwards defenders players Fig. .. Yo-yo intermittent recovery test performance of professional male soccer players in different positions of a team at the start (open bars) and at the end (solid bars) of a -week preparation period prior to the season. Means are given. * Significantly different from the start of the preparation period.

soccer players before and after a preparation period before a new season. All player groups had marked improvements, showing that the test is able to detect significant changes in physical capacity in soccer. Repeated sprint test The ability to be able to run fast and to perform repeated sprints can be tested easily by having the athlete sprint a given distance a number of times separated by a period of recovery that allows a decrease in performance. In relation to the latter aspect Balsom et al. [] observed that performance in a -m sprint could be maintained when subjects have a recovery period between each sprint of  s, but a marked decrease was found when the recovery time was  s. This means that in order to evaluate an athlete’s ability to recover from intense exercise the rest period between -m sprints should be less than  s and preferably  s. In a test to measure the ability to sprint and at the same time change direction, athletes perform seven sprints each lasting about  s, separated by -s rest periods. Figure .. shows how the performance of  professional soccer players changed during a preparation period. The significant decrease in the sprint time shows that the test can be used to detect changes in performance.

 Chapter . Preparation period Start of season

7

Time (s)

6

*

*

*

*

5

4 0 Fullbacks

Central defenders

Midfield players

Forwards

Fig. .. Mean time of repeated sprints for professional male soccer players in different positions of a team at the start (open bars) and at the end (solid bars) of a -week preparation period prior to the season. Means are given. * Significantly different from the start of the preparation period.

Summary The performance potential of an athlete can be improved by fitness training, which can be divided into aerobic training, anaerobic training, and specific muscle training. Common to all types of fitness training is the fact that the exercise performed during the training should be as similar as possible to the sport. There are a number of reasons to use tests to evaluate performance of an individual. It is, however, important that the test chosen is relevant for the activity of the individual, e.g. a cycling test for a cyclist and an intermittent running test for a basketball player. Laboratory tests can provide general information about the fitness level of an individual, but they rarely give an exact measure of performance in a sport. By using a field test a more precise measure of performance will often be obtained.

Multiple choice questions  Standard goniometric measurements: a can detect changes in joint range of motion of ∞ b have associated errors that are objective in nature c have associated errors that are related to the patient’s perception of tension d measure joint range of motion, but not muscle– tendon stiffness e all of the above.

 Immobilization: a causes muscle atrophy b results in a disproportionate loss of muscle endurance and strength c in the early phase of rehabilitation should focus on local muscle endurance training d all of the above e a and b, but not c.  In speed endurance training: a changes mainly of central factors are induced b performance intensities should be –% of V·2 max c the duration of exercise bouts should be relatively short (– s) d the specific aim is to oxidize fat during prolonged exercise periods e all of the above.  Strength training: a Strength training results in hypertrophy of the muscle fibers and changes in the nervous system. b In basic strength training muscle groups are not trained in isolated movements. c High-resistance training can change the fiber type distribution towards fast-twitch fibers. d The number of repetitions in a set should exceed . e a and c. f All of the above.  Relevant for a soccer player: a isokinetic strength of the knee extensors b yo-yo intermittent endurance test c yo-yo intermittent recovery test d repeated sprint test e all of the above.

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Principles of Rehabilitation and Sport-Specific Training

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measurement error (reliability) in variables relevant to sports medicine. Sports Med ; : –. Cosgarea AJ, Sebastianelli WJ, DeHaven KE. Prevention of arthrofibrosis after anterior cruciate ligament reconstruction using the central third patellar tendon autograft. Am J Sports Med ; : –. McHugh MP, Tyler TF, Gleim GW, Nicholas SJ. Preoperative indicators of motion loss and weakness following anterior cruciate ligament reconstruction. J Orth Sports Phys Ther ; : –. Sachs RA, Daniel DM, Stone ML, Garfein RF. Patellofemoral problems after anterior cruciate ligament reconstruction. Am J Sports Med ; : –. Magnusson SP, Simonsen EB, Aagaard P, Dyhre-Poulson P, McHugh MP, Kjaer M. Mechanical and physiological responses to stretching with and without pre-isometric contraction in human skeletal muscle. Arch Phys Med Rehab ; : –. Christensen HW. Precision and accuracy of an electrogoniometer. J Manipul Phys Ther ; : – . Rheault W, Miller M, Nothnagel P, Straessle J, Urban D. Intertester reliability and concurrent validity of fluid-based and universal goniometers for active knee flexion. Phys Ther ; : – . Mallon WJ, Herring CL, Sallay PI, Moorman CT, Crim JR. Use of vertebral levels to measure presumed internal rotation at the shoulder: a radiographic analysis. J Shoulder Elbow Surg ; : –. Tyler TF, McHugh MP, Gleim GW, Nicholas SJ. Association of KT- measurements with clinical tests of knee stability one year following anterior cruciate ligament reconstruction. J Orth Sports Phys Ther ; (): –. Tyler TF, McHugh MP, Gleim GW, Nicholas SJ. The effect of immediate weight bearing after anterior cruciate ligament reconstruction. Clin Orth Rel Res ; : –. Liu SH, Baker CL. Comparison of lateral ankle ligamentous reconstruction procedures. Am J Sports Med ; : – . Daniel DM, Stone ML, Sachs R, Malcom L. Instrumented measurement of anterior laxity in patients with acute anterior cruciate ligament disruption. Am J Sports Med ; : –. Malcom LL, Daniel DM, Stone ML, Sachs R. The measurement of anterior knee laxity after ACL reconstructive surgery. Clin Orth ; : –. Barber-Westin SD, Noyes FR, Heckmann TP, Shaffer BL. The effect of exercise and rehabilitation on anterior– posterior knee displacements after anterior cruciate ligament autograft reconstruction. Am J Sports Med ; : –. Robnett NJ, Riddle DL, Kues JM. Intertester reliability of measurements obtained with the KT- on patients with reconstructed anterior cruciate ligaments. J Orth Sports Phys Ther ; : –.

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 Aglietti P, Buzzi R, Menchetti PM, Giron F. Arthroscopically assisted semitendinosus and gracilis tendon graft in reconstruction for acute anterior cruciate ligament injuries in athletes. Am J Sports Med ; (): –.  Passler JM, Babinski K, Schippinger G. Failure of clinical methods in assessing graft integrity after anterior cruciate ligament reconstruction: an arthroscopic evaluation. Arthroscopy ; : –.  Nicholas SJ, D’Amato MJ, Hershman EB, McHugh MP, Tyler TF, Gleim GW, Kolstad K. Does initial graft tension during acl reconstruction affect the restoration of static knee stability. In: Proceedings of the American Orthopaedic Society for Sports Medicine. Specialty Day. Orlando FL: The American Orthopaedic Society for Sports Medicine,  March : –.  Yasuda K, Tsujino J, Tanabe Y, Kaneda K. Effects of initial graft tension on clinical outcome after anterior cruciate ligament reconstruction. Am J Sports Med ; : – .  Pizzari T, Kolt GS, Remedios L. Measurement of anteriorto-posterior translation of the glenohumeral joint using the KT-. J Orth Sports Phys Ther ; : –.  Sauers EL, Borsa PA, Herling DE, Stanley RD. Instrumental measurement of glenohumeral joint laxity and its relationship to passive range of motion and generalized joint laxity. Am J Sports Med , : –.  Kovaleski JE, Gurchiek LR, Heitman RJ, Hollis JM, Pearsall AW. Instrumented measurement of anteroposterior and inversion–eversion laxity of the normal ankle joint complex. Foot Ankle Int ; : –.  Eastlack ME, Axe MJ, Snyder-Mackler L. Laxity, instability, and functional outcome after ACL injury: copers versus non-copers. Med Sci Sports Exerc ; : –.  Holme E, Magnusson SP, Becher K, Bieler T, Aagaard P, Kjaer M. The effect of supervised rehabilitation on strength, postural sway, position sense and re-injury risk after acute ankle ligament sprain. Scand J Med Sci Sports ; : –.  Rozzi SL, Lephart SM, Sterner R, Kuligowski L. Balance training for persons with functionally unstable ankles. J Orth Sports Phys Ther ; : –.  Gauffin H, Tropp H, Odenrick P. Effect of ankle disk training on postural control in patients with functional instability of the ankle joint. Int J Sports Med ; : –.  Leanderson J, Eriksson E, Nilsson C, Wykman A. Proprioception in classical ballet dancers. A prospective study of the influence of an ankle sprain on proprioception in the ankle joint. Am J Sports Med ; : –.  Lephart SM, Pincivero DM, Giraldo JL, Fu FH. The role of proprioception in the management and rehabilitation of athletic injuries. Am J Sports Med ; : –.  Hutton RS, Atwater SW. Acute and chronic adaptations of muscle proprioceptors in response to increased use. Sports Med ; : –.  Nicholas JA, Strizak AM, Veras G. A study of thigh muscle

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weakness in different pathological states of the lower extremity. Am J Sports Med ; : –. Beckman SM, Buchanan TS. Ankle inversion injury and hypermobility: effect on hip and ankle muscle electromyography onset latency. Arch Phys Med Rehab ; : –. Manal TJ, Snyder-Mackler L. Failure of voluntary activation of the quadriceps femoris muscle after patellar contusion. J Orth Sports Phys Ther ; : – . Snyder-Mackler L, Delitto A, Stralka SW, Bailey SL. Use of electrical stimulation to enhance recovery of quadriceps femoris muscle force production in patients following anterior cruciate ligament reconstruction. Phys Ther ; : –. Lieber RL, Silva PD, Daniel DM. Equal effectiveness of electrical and volitional strength training for quadriceps femoris muscles after ACL surgery. J Orth Res ; : –. Polkey MI, Kyroussis D, Hamnegard CH, Mills GH, Green M, Moxham J. Quadriceps strength and fatigue assessed by magnetic stimulation of the femoral nerve in man. Muscle Nerve ; : –. Kremenic I, McHugh M, Ben-Avi S, Leonhardt D. Quadriceps activation via transcutaneous magnetic stimulation of the femoral nerve. In: Proceedings of the Orthopaedic Research Society th Annual Meeting. San Francisco, CA, – February . Snyder-Mackler L, Binder-Macleod SA, Williams PR. Fatigability of human quadriceps femoris muscle following ACL reconstruction. Med Sci Sports Exerc ; : – . McHugh MP, Tyler TF, Nicholas SJ, Browne MG, Gleim GW. Electromyographic analysis of quadriceps fatigue following anterior cruciate ligament reconstruction. J Sports Phys Ther ; : –. Enoka RM, Stuart DG. Neurobiology of muscle fatigue. J Appl Physiol ; : –. Pincivero DM, Lephart SM, Karunakara RA. Reliability and precision of isokinetic strength and muscular endurance for the quadriceps and hamstrings. Int J Sports Med ; : –. Suzuki N, Endo S. A quantitative study of trunk muscle strength and fatigability in the low back pain syndrome. Spine ; : –. Sapega AA. Muscle performance evaluation in orthopaedic practice. J Bone Joint Surg (Am) ; : –. Jonhagen S, Nemeth G, Eriksson E. Hamstring injuries in sprinters. The role of concentric and eccentric hamstring muscle strength and flexibility. Am J Sports Med ; : –. Hortobágyi T, Tracy J, Hamilton G, Lambert J. Fatigue effects on muscle excitability. Int J Sports Med ; : –. Tesch PA, Dudley DA, Duvoisin MR, Hather BM, Harris RT. Force and EMG signal patterns during repeated bouts

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of eccentric muscle actions. Acta Physiol Scand ; : –. Magnusson SP, Gleim GW, Nicholas JA. Subject variability of shoulder abduction strength testing. Am J Sports Med ; : –. Magnusson SP, Constantini NW, McHugh MP, Gleim GW. Strength profiles and performance in Masters’ level swimmers. Am J Sports Med ; : –. Magnusson SP, Gleim GW, Nicholas JA. Shoulder weakness in professional baseball pitchers. Med Sci Sports Exerc ; : –. McHugh MP, Spitz AL, Lorei MP, Nicholas SJ, Hershman EB, Gleim GW. Effect of anterior cruciate ligament deficiency on the economy of walking and jogging. J Orth Res ; : –. Brown M, Fisher JS, Salsich G. Stiffness and muscle function with age and reduced muscle use. J Orth Res ; : –. McHugh MP, Connolly DAJ, Eston RG, Kremenic IJ, Gleim GW. The role of passive muscle stiffness in symptoms of exercise-induced muscle damage. Am J Sports Med ; : –. Tyler TF, McHugh MP. Neuromuscular rehabilitation of a female olympic ice hockey player following ACL reconstruction. J Sport Phys Ther ; : –. Ekblom B. Effect of physical training on oxygen transport system in man. Acta Physiol Scand Suppl ; (): . Henriksson J, Hickner RC. Skeletal muscle adaptation to endurance training. In: Macleod DAD, Maughan RJ, Williams C, Madely CR, Charp JCM, Nutton RW, eds. Intermittent High Intensity Exercise. London: E and FN Spon Publication, : –. Schantz P, Sjøberg B. Malate–aspartate and alphaglycerophosphate shuttle enzyme levels in untrained and endurance trained human skeletal muscle. Acta Physiol Scand ; : A. Houston ME, Bentzen H, Larsen H. Interrelationships between skeletal muscle adaptations and performance as studied by detraining and retraining. Acta Physiol Scand ; : –. Bangsbo J, Mizuno M. Morphological and metabolic alterations in soccer players with detraining and retraining and their relation to performance. In: Reilly T, Lees H, Murphy WJ, eds. Science and Football I. London: E & FN Spon Publication, : –. Tesch PA, Wright JE. Recovery from short-term intense exercise: its relation to capillary supply and blood lactate concentration. Eur J Appl Physiol ; : –. Reilly T, Bangsbo J. Anaerobic and aerobic training. In: Elliott B, ed. Applied Sport Science: Training in Sport. Australia, : –. Pilegaard H, Domino K, Noland T, Juel C, Hellsten Y, Halestrap AP, Bangsbo J. Effect of high intensity exercise training on lactate/H+ transport capacity in human skeletal muscle. Am J Physiol ; : E–E.

Principles of Rehabilitation and Sport-Specific Training  Bangsbo J. Physiology of muscle fatigue during intense exercise. Clin Pharm Sport Exerc ; –.  Andersen JL, Klitgaard H, Bangsbo J, Saltin B. Myosin heavy chain isoform in single fibres from m. vastus lateralis of soccer players: effects of strength-training. Acta Physiol Scand ; : –.  Aagaard P, Trolle M, Simonsen EB, Klausen K, Bangsbo J. Moment and power generation during maximal knee extension performed at low and high speed. Eur J Appl Physiol , ; : –.

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 Ekstrand J. Soccer injuries and their prevention. Thesis, Linköping University Medical Dissertation , .  Bangsbo J, Petersen A, Michalsik L. Accumulated O2 deficit during intense exercise and muscle characteristics of elite athletes. Int J Sports Med ; : –.  Bangsbo J. Fitness Training in Football — a Scientific Approach. Bagsvaerd: HO & Storm, .  Balsom PD, Seger JY, Sjödin B, Ekblom B. Physiological responses to maximal intensity intermittent exercise. Eur J Appl Physiol ; : –.

Chapter 2.3 Physical Activity and Environment PETER BÄRTSCH, BODIL NI E LSE N J OHA NNS E N & JUHANI L E PPÄLUOTO

Classical reference Nielsen M. Die Regulation der Körpertemperatur bei Muskelarbeit. Skand Arch Physiol ; : –. The thermal environment has profound effects on performance and health. The maintenance of core temperature at optimal level in a range of environmental temperatures is essential for performance. This is accomplished through the action of the autonomic control centers in the hypothalamus. The rise in body core temperature during exercise was considered to be the result of a failure in the ability of the organism to dissipate fully the increased heat produced during exercise. Marius Nielsen demonstrated that the rectal temperature increased and after – min reached a new, higher level, which was maintained until the exercise was stopped. (He had one subject work at constant intensity and rectal temperature for 1/2 h.) From his experiments it seemed that the rise in core temperature was only dependent on the exercise intensity. Thus, at ambient temperatures of between  and  °C, the core temperature level for a given intensity was the same, despite large variations in the contribution of evaporation, convection and radiation to the total heat loss. He concluded from the experiments that the rise in body temperature during exercise was a regulated rise, probably beneficial for performance. Discussions on the setting of body temperature during exercise have now gone on for more than  years. The knowledge of the anatomic organization and function of the temperature centers in the brain



inspired discussions as to the validity of rectal temperature as an index of the regulated temperature. Other candidates such as tympanic temperature, supposed to reflect brain temperature, or esophageal temperature, an index of the temperature of the blood leaving the heart were proposed. The latter is today preferred by exercise physiologists for reflecting fast changes in core temperature and signals to the brain centers. The concept of a setting of the temperature at higher levels during exercise has also changed. Now it seems that a mathematical/technical description of the resetting during exercise is rather a reduction in the set point, rendering the ‘human thermostat’ more sensitive to

Fig. ... Rectal temperature during exercise at different intensities. From [].

Physical Activity and Environment an absolute core temperature during work. How the setting of the core temperature during exercise relative to the V˙2 max is accomplished is still an open question. The beneficial effect of a high core temperature in endurance sport activities is now also questionable, as discussed in the section on exercise and temperature (p. ).

Introduction The first part of this chapter discusses the profound effects thermal environment has on performance and health. The maintenance of core temperature at optimal level for performance is accomplished through the action of the autonomic control centers in the hypothalamus. This is possible within a wide range of environmental temperature conditions, the prescriptive, or thermoneutral zone. The historical figure (Fig. ..) shows data from the work of M. Nielsen. This paper supports the notion of regulation of body core temperature at an optimal level for performance. The individual’s capacity for heat production by shivering and heat loss by sweat evaporation and vasodilatation determines the limits for performance. Proper clothing allows activity in even the coldest climates. However, cold exposure can result in injuries, local tissue damage and hypothermia. The cooling effect of the environmental temperature is strongly influenced by the wind speed. In hot environments the cardiovascular stress is increased, and sweating may result in dehydration. This combination markedly reduces performance, especially in endurance-type events and may lead to heat-related illness. These disorders, heat exhaustion and heat stroke can best be prevented by fluid replacement and by a prior acclimatization to heat. The second part of this chapter discusses the effects of altitude on physical performance. Reduced air pressure (and consequently reduced partial pressure of oxygen), reduced air density, lower temperature and a lower water content of air may all affect physical performance at high altitude in different ways and degrees depending on the type of exercise. Hypoxia is certainly the factor that has the biggest impact on life at high altitude. Immediate adjustments to maintain adequate oxygen supply to the tissue are an increase of ventilation and cardiac output for a given workload. The major long-term adjustments (acclimatization) con-

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sist of a further slow increase of ventilation, increased erythropoiesis and adaptations at the tissue level. Athletes try to profit from altitude acclimatization for sealevel performance by training at high altitude. Because the decrease of performance at altitude may offset benefits from acclimatization, many athletes prefer to ‘sleep high and train low’. Most issues regarding different modalities or concepts of high altitude are still rather controversial. Rapid adjustments to hypoxia may not always be very successful. A significant number of individuals develop acute mountain sickness and some even life-threatening illnesses such as high-altitude pulmonary or cerebral edema during the first few days after rapid ascent to altitudes above – m. The prevalence of these acute highaltitude illnesses increases with altitude and rate of ascent. Furthermore, there is a considerable interindividual difference in susceptibility to these illnesses.

Thermal environment Introduction Temperature regulation is a good example of a homeostatic mechanism. It keeps the (deep) body temperature within a very narrow range that allows maintenance of bodily functions in almost every climatic condition. Humans with their naked skin and numerous sweat glands are tropical animals, and the capacity of the thermoregulatory system is directed towards heat dissipation rather than heat conservation. Technical developments in clothing and housing have, however, allowed people to inhabit permanently all places on the earth and even in space at temperatures close to absolute zero.

Heat balance The metabolic processes liberate heat as a waste product. When substrates are metabolized in the human body most of the energy equivalent of the combusted substrate is converted into heat. During exercise some of the energy is transformed to external work, but the efficiency of these processes is usually less than –%. The efficiency, E, is defined as: E % = (external work ¥ 100%) metabolic energy cost

 Chapter .

M±W=±C±R±E±S (Heat liberation = heat loss) where M is metabolic energy liberation W is external work (positive when going downhill) C is heat exchange by convection R is heat exchange by radiation E is heat exchange by evaporation and S is heat storage. This last term becomes zero when the heat gains and losses are equal. Physical laws determine the direction and magnitude of the heat exchanges by convection and radiation, i.e. the temperature difference between the body surface and the air temperature, respectively, the mean radiant temperature of the environment. The heat loss by evaporation depends on the water vapor pressure difference between the skin surface and the air[]. However, physiologic mechanisms influence the skin surface temperature and vapor pressure through the control of skin blood flow and sweating. The skin surface temperature varies with the temperature in the environment. In cool conditions the difference to the environment is wide, so heat loss by C and R are the main routes for heat loss. The warmer the environmental conditions become, the more the skin surface temperature approaches the environmental temperature, and therefore, the need for evaporative heat loss increases. At an air temperature of about  °C skin temperature equals environmental temperature, and the total heat liberation must be dissipated by evaporation of sweat (Fig. ..). In the diagram the

700 I 500 Watts

Therefore, –% of the liberated energy appears as heat in the active muscle tissue. The amount of heat generated in the body must be dissipated to the environment, or else the heat content and the temperature of the body will increase and endanger the homeostatic milieu of the body. The autonomic temperature centers in the hypothalamus control the body core temperature by appropriate activation of, respectively, heat loss or heat conservation processes. In this way the body core temperature is maintained at a constant, regulated level in the face of varying environmental temperatures. This balance can be described by the heat balance equation:

III II

300

100 0 IV

–100 5

10

15

20

25

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35

Temperature (°C) Fig. .. Heat exchange during exercise at  W for  min at different room temperatures in a nude subject. I Total heat production, II heat loss, III evaporative heat loss, IV convective and radiative heat loss (after []).

heat lost by convection, radiation and evaporation in an exercising (cycling) person is illustrated for environmental temperatures between  °C and  °C. During exercise part of the heat production is stored in the body, causing the core temperature to increase.

Core temperature The core temperature of the body is measured in the deep esophagus or in the rectum. For clinical purposes a less reliable measurement can be obtained by measuring oral temperature or tympanic temperature, the latter by infrared radiation receivers. The body temperature during rest is maintained close to  °C, varying in a circadian rhythm. During exercise the body temperature increases to higher levels, proportional to the relative workload, i.e. to the percentage of the maximal aerobic capacity of the individual [] (Fig. ..). This higher temperature is maintained as long as the exercise is continued, and within the prescriptive zone, it is independent of the environmental temperature.

The prescriptive zone The body core temperature during exercise is uninfluenced by environmental temperature over a wide range of temperatures [,] due to the thermoregulatory control of the heat production and heat loss mecha-

Physical Activity and Environment C°

Male Female

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Tes (°C)

39.0

Fig. .. Esophageal temperature (Tes) at -min exercise in seven subjects with different maximal aerobic capacity. (a) Tes plotted against absolute oxygen uptake; (b) Tes plotted against relative oxygen · uptake, %V 2 max (after []).

38.0 37.0

1.0 2.0 3.0 O2 uptake (L/min)

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Physiologic responses to cold exposure

300 W 200 W 100 W Rest

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Ta (°C) Fig. .. Esophageal temperature in one subject after  h at rest and cycling at intensities between  and  W at environmental temperatures between – and  °C. The thermoneutral zone marked with arrows moves to the left with increasing work and heat production (adapted from Kitzing et al. Int Z Angew Physiol ; : –).

nisms, i.e. shivering, skin blood flow and sweating. The range of environmental conditions in which the body temperature is independent of these conditions is called the prescriptive zone []. Above the upper critical temperature, core temperature increases to a higher level than during exercise in thermoneutral conditions, while on the other hand, below the lower critical temperature the core temperature falls. The actual range of the prescriptive zone, also called the thermoneutral zone, depends on the rate of heat production and additionally, for the upper limit, on the physiologic capacity for heat dissipation, whereas for the lower critical temperature, on the maximal rate of heat production and vasoconstriction (Fig. ..).

Technical developments have changed the situations in which humans are exposed to cold. The number of people working outdoors in cold conditions is presently declining, while that of people participating in recreational activities, e.g. winter sports is evidently increasing. Physical fitness is important for the thermoregulatory responses to cold. Fit people have a higher metabolic response and a higher skin temperature at the onset of shivering. On the other hand, body fat provides protection against cooling []. Cold can be defined as conditions which activate heat conservation responses, and may be experienced in air or water, or in contact with solid materials. Unclothed or clothed parts of the body can be locally exposed to cold (hands, face and legs) or the whole body may be cooled. The duration of the cold exposure may last for seconds to several weeks, and can be recurrent. The effects of cold exposure will therefore depend on these factors. Many of the cold-induced physiologic responses attenuate physical performance. Low temperature of muscles causes poor efficiency and coordination, and risk of muscle and tendon tears. Shivering muscles make use of energy stores, and shivering may also cause clumsiness. Physiologic mechanisms activated by cold are presented in the box below. Cold-induced skin vasoconstriction leads to increased blood pressure, plasma extravasation (leakage of fluid from the plasma to the interstitium) and diuresis. Increased sympathetic activation and hemoconcentration reduce maximal physical performance. Finally bronchoconstriction in winter athletes is common and may lead to exercise-induced asthma (see Chapter .). A recent study showed that % of the Olympic winter

 Chapter . sport athletes in the US had exercise-induced bronchoconstriction [].

Physiologic mechanisms activated by cold Increased heat production: • cold sensations activate voluntary movements • sympathetic nerves become active • norepinephrine secreted, availability of thyroid hormones increased • all leading to increased expression of mitochondrial uncoupling proteins for heat production in muscle • muscle tension increases and shivering starts • food intake increases. Decreased heat loss: • skin blood flow decreases • horripilation • behavioral activity, curling up.

Heat production in the cold Voluntary activity (behavioral thermoregulation) Unpleasant cold sensations result in behavioral responses (increased motor activity, curling up and searching for warmer places and clothing). Shivering The hypothalamic temperature center receives inputs from skin cold receptors and projects them to the motor cortex and finally to the motor nerves. This leads to increased muscle tone and to oscillating contractions of muscles, shivering, that occurs mostly in trunk muscles. Shivering increases metabolic rates by – times the resting value. Due to the increased metabolic rate shivering should be avoided in winter sports.

Chemical or non-shivering thermogenesis Chemical thermogenesis is well established in rodents and newborn humans and closely related to uncoupling protein  (UCP ) in brown fat. Cold exposure elicits the release of norepinephrine and thyroid hormones and activates sympathetic nerves that stimulate the expression of UCP . It uncouples the normal oxidative phosphorylation in the mitochondria and the production of protons is decreased. Less ATP is formed and more heat is generated (Fig. ..). The role of UCP  in adults is not well established, but recent studies have shown the presence of hom*ologues of UCP . UCP  is widely expressed in fat, muscles and viscera and stimulated by starving and fatty acids. UCP  is abundantly expressed in skeletal muscles and is stimulated by cold. UCP  and  also regulate the production of ATP and their roles in heat production are under research []. Meals increase heat production by a mechanism formerly called specific dynamic action, now dietinduced thermogenesis (DIT). The resting metabolic rate is increased about % for – h after a meal.

Heat loss In cold environments radiation and convection are the main avenues for heat loss. In winter sports convection dominates the heat transfer, since warm layers of air around the body are rapidly conveyed away from the skin by the air movement produced by the ongoing activity. The so-called wind chill index (WCI) has been constructed in which the combined effects of environmental temperature and wind are converted to a hypothetical temperature in still air, which has the same cooling effect as the actual wind speed and temperature [,]. The values calculated are rates of heat loss per m2 (Fig. ..). For instance, – °C at a wind speed of  m/s corresponds to the temperature of – °C in still air. Climatic conditions with a WCI of between  and  W/m2 are very cold, between  and  W/m2 bitterly cold and between  and  W/m2 dangerous: exposed flesh will freeze in  min. Frostbite begins to occur when WCI is over  W/m2. The WCI concept was re-examined [], and the predictions compared with the incidences of finger frostbite. The conclusion was that there is little risk of finger frostbite at temperatures above – °C independent of wind velocity, while below – °C the

Physical Activity and Environment H+

Basal state

1200 1400 1600 W/m2

2

Cold

ot

on

se

ha

pu

m

UTP

4

t yn

-s

p

P AT

UCPs H+ H+

ATP

ADP

Wind speed (m/s)

Pr



Bitterly cold

Freezing cold

Flesh freezes Flesh freezes in 1 min in 1 h

6 8 10 12 14

Respiratory chain

Heat

After cold stimulation H+ NE cAMP Lipase FFA T3 UTP

16 10

p

m

n

pu

e

as

to

o Pr

th

P AT

H+ H

Respiratory chain

–5 –10 –15 –20 –25 –30 –35 –40 Air temperature (°C)

Fig. .. Diagram for estimating the combined cooling effect of temperature and wind speed (wind chill index, WCI). The index estimates the effect on exposed, unprotected skin areas (in W/m2) and the exposure time before freezing. The curves were constructed by using the formula WCI = ( · v2 + . – v) · ( – Ta), where v is wind velocity and Ta ambient temperature.

n -sy

UCPs +

5

ATP

ADP Heat

competitions, but wind speed has not been taken into account, which it ought to be. Physicians responsible for medical care in skiing competitions or mass events should be encouraged to use a WCI rather than the simple thermometer reading.

Clothing

Fig. .. Mitochondrial activity in basal state, and after cold stimulation. After cold stimulation the uncoupling protein (UCP) in brown fat allows a shortcut for protons through the mitochondrial membrane, releasing the energy bound in the H+ as heat. The stimulation is achieved by norepinephrine (NE) or thyroid hormone (T), which increase the formation of cAMP, lipase and free fatty acids (FFAs). FFA displaces uridine triphosphate (UTP) from the UCP channel (protein allowing protons to enter the mitochondria).

effect of wind speed is underestimated. Thus, in skiing competitions or other outdoor mass events special caution has to be paid to the WCI. If the weather conditions show a WCI of more than  W/m2, sports competitions should be cancelled, and expeditions require special clothing. In the Nordic countries the lower limit is set at – °C air temperature for skiing

In cold weather appropriate clothing is necessary to maintain the proper heat balance. In winter sports such as skiing, biathlon and orienteering heat production is high, and the main emphasis should be placed on the protection of fingers, feet, ears and nose against local cooling and frostbite. An additional problem due to the unavoidable sweating is the transport of the moisture away from the skin and through the clothing. New synthetic fibers allow sweat to pass through the textile, but they are not suitable in events in which heat production is smaller, such as mountaineering or trekking. In cross-country skiing competitions the metabolic rate exceeds  W; in this situation clothing with an insulation value of –. clo units is sufficient at the temperature of – °C. At the same temperature a resting subject needs an insulation of – clo units. (The clo unit is defined by the insulation value of traditional indoor clothing;  clo = . m2 · °C/W. See also [].) This great variation in required insulation between

 Chapter . rest and activity is a problem for people who have accidents or get tired during outdoor activities in cold climates. Furthermore, clothing soaked by rain loses its thermal insulation properties and presents a serious thermoregulatory problem in cold and windy conditions []. Enough (and dry) clothing must be brought along! The IREQ index [] makes it possible to calculate the cold protective clothing needed for any combination of activity level and climatic variables.

Acclimatization to cold Practically no studies exist in which the effects of cold acclimatization on physical performance have been studied. We know from some studies that the unpleasantness of cold sensations becomes reduced or habituated after – daily cold exposures, and that increased sympathetic activity and shivering is attenuated within a week [–]. True cold acclimatization is difficult to induce in humans. Three types of adaptation to cold are described: (i) metabolic, where a greater metabolic response to cold stress is developed [,]; (ii) hypothermic, where core temperature falls (e.g []); and (iii) insulative [] with a lowering of the skin to environment gradient and heat loss, and with little change in core temperature and metabolic rate during cold exposure. Immersion in cold water  days per week over  weeks has been found to induce the type of adaptation described as insulative []: a lowering of resting rectal temperature, a slower rise in metabolic rate (indicating a delay in onset of shivering) and a lower skin temperature. It appears that a repeated fall in core temperature is necessary to induce the sympathetic activation, while a cold skin alone is enough to stimulate the increased vasoconstrictor response obtained after  weeks’ daily cold water immersions []. However, when healthy men were exposed to cold air for  days, a hypothermic type of acclimatization was observed instead (i.e. reduced cold sensations, decreased core and increased skin temperature in some places, reduced norepinephrine response, and no changes in metabolic rate or heat debt responses) []. It is evident that acclimatization in cold water is different from that in cold air. Moreover, cold water acclimatization increases norepinephrine response and peripheral resistance, and decreases cardiac output [,], all of which are not beneficial for physical performance.

Therefore, cold air and not cold water acclimatization is perhaps the type of acclimatization that should be used if performance in cold air is to be improved. It is evident that unacclimatized subjects perform less well than acclimatized, and therefore some kind of cold acclimatization should be obtained before winter sports competitions. It is in the author’s knowledge that subjects who are about to participate in the demanding polar expeditions acclimatize by sleeping overnight outdoors for several weeks before their expeditions (see Case story ..).

Performance in cold conditions As mentioned in the introduction most of the energy liberated during physical exercise is converted to heat. Depending on the metabolic rate, the prescriptive zone and upper and lower critical temperature shifts (see Fig. ..) and the physiologic mechanisms for heat loss and heat conservation are taxed to varying degrees, depending on how the heat balance is attained. Therefore, some benefits for exercise and performance are obtained in cooler environments. In submaximal cycling at ambient temperatures of , ,  and  °C, the time to exhaustion was longest at  °C and shortest at  °C, demonstrating that the effect of ambient temperature on exercise capacity follows an inverted U-shaped relationship []. This study demonstrates that exercise capacity is greater in low suprazero ambient temperatures than at higher temperatures, where the physiologic load on the circulatory system is higher. The ambient temperatures in winter sports are usually below the freezing point and evidently the best conditions for prolonged high intensity physical activity prevail close to but above zero. Optimal performance must therefore be obtained by choosing the proper clothing. The deleterious effects of cold on performance are manifested on two levels. The more common is the effect of peripheral vasoconstriction and cooling, which lowers the temperature in the tissues, e.g. in hands and feet. The rate of the physiologic and chemical processes is then slowed down, including the rate of muscle contraction and nerve conductivity. Furthermore, stiffness in tendons and connective tissue is increased. This leads to clumsiness and increases the risk for injury (Fig. ..). Thus, for winter sports competitions warming up is of great importance.

Physical Activity and Environment

Case story 2.3.1 Instructions to participants in mass events in winter sports After mass sport events we often read in newspapers that a participant, usually an older man, has succumbed before the finishing line. Several studies on sport-related sudden deaths have been reported and recently reviewed []. The incidence of sudden deaths increases after – years of age and peaks at – years. Males clearly outnumber females. Deaths are often related to high dynamic loads (tennis, skiing, swimming, cycling). The incidence is higher in cross-country skiing than in jogging/running, indicating that skiing produces a higher cardiovascular load than running. Cold

Stimulation 35.8°C

19.7°C

General The harmful effects of cold on the human body may be a direct effect of the low temperature, e.g. frostbite, trenchfoot and hypothermia. Indirectly, cold environments may exert a stress on human health. Cold weather in winter is a challenge and a significant risk factor, especially in the elderly, causing an excess mortality from cardiovascular diseases. A short review of cold injuries and their treatment is presented in a recent paper []. Their occurrence in winter sports is fairly uncommon. The physicians of the Finnish elite skiing team and the mass skiing events report that during the last  years no cold injuries have been diagnosed (Dr P. Mäkelä, team physician, personal communication). An annual incidence of cold injuries in Finland is presently . cases per   inhabitants and they are mostly mild. The annual incidence of mild cold injuries varies from . to .% of the population exposed to winter conditions by their recreational or professional activities []. The inci-

12.9°C

20

30

40

The less common effect of cold is when the whole body is cooled, resulting in a fall in core temperature (hypothermia, see below).

Cold injuries

15.1°C

10

exposure also contributes an increased risk for cardiac deaths. In younger age groups infections or vaccinations are further risk factors. Based on these findings some suggestions for participants in winter sports can be made.  Long-term training and cold acclimatization is necessary before demanding mass events in cold climates.  Subjects over  years should have a cardiac check-up.  Ongoing infections and recent vaccinations are absolute risk factors for participation.  Finally, the organizers must arrange appropriate medical aid (resuscitation unit with defibrillator) at larger mass events and competitions.

22.1°C

17.3°C



ms

Fig. .. The effect of local tissue temperature on muscle action potential. Note the increased latency and the stretched duration of the potential with decreasing temperatures (after Vanggaard Aviat Space Environ Med ; : –).

 Chapter . dence of frostbite requiring hospitalization is far lower: .–.% []. On the other hand, fatal casualties have at all times occurred in conjunction with polar and high-altitude expeditions, and also in subjects using alcohol or drugs affecting the central nervous system in winter conditions. Direct cold injuries Frostbite and trenchfoot Skin begins to freeze at temperatures between  and – °C. Vascular endothelium is damaged by ice crystals. Edema, inflammation and blisters develop. At lower temperatures larger skin areas freeze and become marble-white and hard. Symptoms are numbness, pain and cold, and pale or bluish skin. In mild cold exposures a small white area on skin (frostnip) develops, which disappears rapidly when warmed. For clinical reasons frostbite is divided into superficial and deep injuries; the former is limited to skin only but the latter extends to subcutis and muscles. Trenchfoot or immersion foot develops usually when the feet are exposed for several hours (>  h) to wetness and temperatures between  and  °C (but not below zero). Trenchfoot is a vascular injury leading to edema. The foot is swollen, numb and often bluish. After some time there is a hyperemic phase with pain and ulcerations. Treatment of frostbite and immersion foot Local pain, frostnip and numbness in cold environment are warning signs of the development of frostbite. When frostbite has occurred, the following measures should be taken:  Prevent further heat loss, e.g. with warm clothing, drinks and shelter.  Immobilize the frostbite area and transfer the patient to first aid, or deep injuries to hospital.  If frostbite is deep, thawing during transport should be avoided if it is not absolutely certain that refreezing can be prevented. The following measures are strictly forbidden: thawing and refreezing, rubbing with snow or hand, ointments, alcohol, local warming by fire. First aid of superficial frostbite consists of thawing in a warm water bath, analgesic drugs, sterile bandages, immobilization and elevation of the frostbitten area.

Table .. Symptoms and signs at different levels of hypothermia (after []). Core temperature (°C) 36 35

34 33–31 30–28 27–25 24–20 17 9

Symptoms Increased metabolic rate Maximal shivering, hyperreflexia, speech disorders, delayed cerebration Responsive and compatible with exercise, blood pressure normal Amnesia, consciousness clouded, pupils dilated, blood pressure low Slow pulse and breathing, cardiac arrhythmia, muscular rigidity Unconscious, reflexes lost,‘cold and dead’, ventricular fibrillation Pulmonary edema, mortality high, cardiac arrest Isoelectric ECG Surgical hypothermia

Blisters should not be punctured. Deep injuries should always be treated in hospital. Recent information on the occurrence and modern treatment of frostbite is described by Paton []. Hypothermia (Table ..) Whole-body cooling may occur during winter sports activities due to fatigue or accidents. In such situations of decreased heat production the clothing is no longer sufficient to maintain heat balance; this may also occur if the insulation effect of the clothing has become reduced due to soaking with sweat. Hypothermia may also occur after accidents in water. In this case the cooling is very rapid, and the victim may lose consciousness within – min. The thermal conductivity and the specific heat capacity of water are, respectively,  and  times that of air. This means that the heat loss to the environment is much greater in water than in air at the same temperature. Furthermore, the skin temperature becomes almost equal to the water temperature. The heat loss to the water is determined by the heat transport from the core to the skin surface, that is the ‘conductance of the peripheral tissues’, which depends on the skin circulation and also on the amount of the insulating fat tissue

Physical Activity and Environment Tre Tes °C 38.0

Bicycle 140 W Ta 24°C subj.E.T.

Swim 0.5 m/s TH2O 16°C

Temperature (°C)

Vo2 L/min

Ts 30

3.0 36.0

28

2.5

37.0

36.0

26

2.0 35.0

Swim 0.5 m/s TH2O 16°C 38.0

37.0 Fig. .. Core temperature and oxygen uptake during swimming in water at  °C followed by cycling in  °C. Oxygen uptakes, V2, are shown as bars, the shaded areas being the V2 in thermoneutral condition, the light areas the extra V2 due to shivering. One subject (from B. Nielsen. Acta Physiol Scand ; : –).



10 20

in the skin. The range of the prescriptive zone in water is very narrow compared to air, only – °C. A resting lean subject in water cannot maintain thermal balance at water temperatures below – °C. At water temperatures of – °C the core temperature will fall about – °C in  min in a swimmer despite swimming activity and maximal shivering (Fig. ..). The fall in core temperature causes a reduction in muscle force and contraction velocity, a fall in V˙2 max and early fatigue []. Hypothermia is defined as a condition where deep body temperature is below  °C and actions have to be taken to restore the normal body temperature. In hostile mountain conditions four states of hypothermia have been recognized: (i) below  °C full consciousness but shivering; (ii) impaired consciousness but no shivering; (iii) below  °C unconsciousness; and (iv) below  °C cardiac and respiratory arrest. Treatment of hypothermia When respiratory movements and heart function stop death will occur within minutes to half an hour, depending on the cooling rate. Even in this state patients can be revived. The proper procedure is under discussion, and depends on whether it takes place under field conditions, or in a hospital ward. If the deep temperature is below  °C, the physician/hospital should always be consulted. Outside the hospital ward further heat loss should be prevented, e.g. by warm blankets

30 40

50 60 70

80 90

35.0 100 110 120

Time (min)

and the patient must be handled cautiously (e.g. no unclothing). The general principle is that rewarming should take place from the interior to avoid the ‘afterdrop’, the extra fall in core temperature, which takes place if the cold blood from the periphery is redistributed back into the core of the body. This may cause a sudden heart stop. Indirect cold injuries Cold climates also have indirect harmful effects on human health. Raynaud’s syndrome or white finger disease is mostly an idiopathic phenomenon, in which cold or even emotional exposure leads to cold, pale and numb fingers. Long-lasting vasospasms may lead to ulceration. Raynaud’s syndrome may also relate to smoking, previous frostbite, vascular diseases, abnormal plasma proteins or compression of thoracic nerves. The syndrome can be treated by vasodilating agents or by protecting hands from cold. Desensitization treatment (putting hands in cold water) is also often a good measure. Cold urticaria is a skin allergy caused by local or general cold. Usually a large wheal appears on skin exposed to cold. The wheal disappears after – h in a warm environment. In rare cases cold exposure causes angioedema (swelling of veins and tissues, which may be lifethreatening and calls for immediate treatment in hospital if the throat and respiratory pathways are affected). The main treatment includes avoiding

 Chapter .

Physiologic responses to hot (and humid) environments

Physiologic mechanisms activated by heat Increased heat loss: • Vasodilatation, increased skin blood flow • Sweat secretion (evaporation) Decreased heat production: • Inertia • Decreased food intake

Heat acclimation 41.0 12

34

5

6 7 8 910

40.0 Tes (°C)

exposure to cold (water, air) and use of antihistamine drugs. Daily cold showers may also help, but the possible development of angioedema should be taken into account. Cold-induced increases in blood pressure and hemoconcentration and increased sympathetic activity are well-known risk factors for heart diseases and may explain the high mortality from cardiovascular diseases in winter mentioned above.

Subj. JBO

39.0 38.0 37.0 0

10

20

30 40 Time (min)

50

60

70

Fig. .. Esophageal temperature during exercise in  °C dry heat till exhaustion for  consecutive days (one subject). The endurance time increased from  to  min with acclimatization (from []).

hyperthermia. Performance is markedly hampered under these adverse conditions, as athletes are forced to lower their exercise intensity (to reduce heat production) or they will attain critically high body temperatures of – °C, which per se will cause fatigue [,] (see Fig. ..).

Cardiovascular changes in hot conditions Sweating The physiologic capacity for heat dissipation is closely linked to the ability to sweat. This depends on the size of the individual, on the physical fitness, and on the state of heat acclimatization. Maximal sweating rates may vary between  and  mL/h for a sedentary person, to about  L/h in very well trained and heat-acclimatized individuals exercising in dry heat. The evaporation of  L sweat removes approximately  kJ ( kJ). However, in humid conditions the amount of sweat which can evaporate may be restricted (evaporation depends on the difference in water vapor pressure between skin and air). If the water vapor pressure difference is too small not all the sweat produced can evaporate; only the evaporated sweat removes heat, the rest drops off and is wasted []. Due to the physical limits for evaporation, heat loss is drastically impaired in hot humid environments, and exercise is often associated with advancing degrees of

The circulatory capacity also affects the ability to sustain exercise in the heat, and hence determines the upper critical temperature. The amount of blood needed for the transport of heat to the skin, Hskin, is expressed by the equation: Hskin = Q skin ◊ c ◊ (Tar - Tv ) where Q skin is blood flow to the skin in L/min, c the heat capacity of blood (approx.  kJ/kg) and Tar - Tv is the temperature of arterial and venous blood, respectively, reaching and leaving the skin. If we substitute Tar with Tre, rectal or esophageal temperature, and Tv with Tsk, and rearrange the equation, we obtain: Q sk = Hskin c(Tre - Tsk ). In warm conditions the difference (Tre – Tsk) becomes smaller, thus the skin blood flow necessary to carry the heat to the skin increases. At rest and during mild to moderate exercise this extra skin blood flow is adequately supplied by an increase in cardiac output and a

Physical Activity and Environment

Dehydration If no fluid is ingested during prolonged physical activity, sweating leads to dehydration, loss of water from the body water compartments. This is a problem, especially in warm environments. Sweat also contains electrolytes, but in lower concentration than the body fluids. So after sweating the body becomes hypohydrated and hyperosmotic. Both hypohydration and hyperosmolality impair performance by effects on cardiovascular function and sweating [,]. Thus, each % loss of body weight by dehydration increases heart rate by – beats/min, and core temperature by

24 Cardiac output (L/min)

(a)

22 20 *† *†

18

*†

16 17 Two-legged blood flow (L/min)

(b)

16 15 14 13

† *†

12 11 9

Blood flow non-exercising tissues (L/min)

(c)

8 7 6 5 *†

4

*

3 (d) Fore arm blood flow (ml/100 g/min)

redistribution of blood flow (diminished renal and splanchnic flow). However, during more intense exercise or when hyperthermia is combined with dehydration, cardiac output is limited and skin tissue and active muscles must compete for the available blood flow. A limit is reached for the ability of the heart to supply blood both to the exercising muscles and to cover the thermoregulatory demand for skin blood flow. Under this condition, the core temperature increases, and the skin blood flow may be reduced (see equation). This is when the upper critical temperature is surpassed. Hot environments represent an additional load on the circulatory system. The temperature-induced vasodilatation and increased skin circulation result in redistribution of blood volume to the periphery, and a fall in central blood volume and reduced filling of the heart. This becomes even worse in the case of dehydration (see below) where plasma volume is reduced. The stroke volume decreases and heart rate is increased to maintain blood pressure. Depending on the severity of the exercise, a compensatory increase in cardiac output may take place. The competition for blood flow between the thermoregulatory need for skin circulation, and the metabolic demand for blood flow to the exercising muscles results firstly in a reduction in skin circulation, and in increased heat storage as mentioned above. But ultimately, with advancing dehydration, blood pressure and cardiac output become reduced, and the blood flow to the exercising muscles also falls (Fig. ..). The performance/endurance for continued exercise declines, resulting in exhaustion, which is caused primarily not by metabolic alterations but by hyperthermia [,,].



18 16 14 12 10 8 6 4 2

20

40

60

80 100 120 140

Time (min) Fig. .. Cardiac output and blood flows during dehydration and control trials (from []).

. °C during exercise. Also the loss of sodium in the sweat (– g NaCl per L sweat) can be a problem in prolonged exercise. This has to be taken into consideration together with the rehydration and food intake after exercise (‘miner’s cramp’, see Chapters . and .). With increasing dehydration performance is

 Chapter . increasingly reduced, as a result of the reductions in the volume of circulating blood, and the rising core temperature. Severe dehydration during continued exercise leads to earlier fatigue due to hyperthermia; it may cause heat exhaustion or in extreme situations heat stroke (see below).

Heat injury When the body core temperature increases above the normal level, due to internal or environmental heat stress, clinical symptoms of heat illness may develop. These symptoms range from mild discomfort, swelling of the legs, dizziness or ortostatic syncope in the upright position, heat cramps and heat exhaustion, to the severest form of heat illness, heat stroke, which may be lethal. Heat exhaustion is usually the result of fluid loss from the vascular system with accompanying cardiovascular disturbances, such as reductions in skin and splanchnic blood flow and a tendency for a fall in blood pressure. Of note is the fact that the environmental temperature is not necessarily very high in conditions where an endurance athlete performing at high metabolic rates becomes heat exhausted. The upper critical temperature for a good marathon runner may be as low as  °C (see Fig. ..). The treatment for heat exhaustion is to put the patient in a supine position, cool him or her, and supply ample water to drink. The heat exhaustion may develop into heat stroke, a potentially fatal syndrome, involving high core temperature, often but not always ceased sweating, unconsciousness, neurologic disorders, metabolic disturbances, cardiovascular failure with low blood pressure and weak pulse. This condition calls for immediate hospitalization and treatment with intravenous infusion and control of acid–base balance. Causes for the development of the heat stroke syndrome are not fully understood (Fig. ..). It appears that endotoxins (lipopolysaccharides, LPS) from Gram-negative bacteria in the gastrointestinal tract are liberated, because the intestines become permeable to LPS due to the heat-induced reduction in splanchnic blood flow. This may add a fever to the already high core temperature. Furthermore, a multitude of cellular dysfunctions/damages due to high temperature may be involved in the clinical picture. Several factors such as age, state of training, exercise level, state of

Case story 2.3.2 Copenhagen Marathon, heat exhaustion in temperate climate conditions A young student of physical education had prepared himself for the marathon; he had trained for several months and was well aware of the importance of keeping well hydrated. He had therefore planned to drink two cups of diluted ‘Isostar’ ( mL) each  km, and arranged for his wife to follow him on bicycle to supply it. The air temperature was about – °C on a sunny day. All went well and as planned. After  km he overtook a friend, who he started to compete with. This resulted in him spilling half the fluid he was handed the following – times, but he felt all right until he stopped after . km to get his ration. He drank, and started off again after his friend, but began to stagger. A physician who happened to be nearby had a look at him, but decided that he would be able to run the final  m at a slower pace to complete his run. He ran on, but immediately fell to the ground and blacked out — and came to in the emergency ward, having . L isotonic fluid administered to him in drop infusion. His temperature was then still elevated.

hydration, heat acclimatization and effect of drugs play a role in the tolerance to heat stress [] (see Case story ..).

Prevention and treatment of heat injuries Procedures which improve conditions for heat loss and cardiovascular stability in warm conditions will be protective against heat injury. Since dehydration is a key factor in the development of heat illness, it is important to prevent dehydration by appropriate fluid intake. Water or isotonic fluid sufficient to replace the sweat loss should be drunk during ongoing exercise (see also Chapter .). Two problems arise: firstly, the

Physical Activity and Environment



HEAT Peripheral thermoreceptors

Sweat

SkBF

CO

BF spl, kid, M, fat

Continuing heat

Sweat

PBV

Fl & el

SkBF & V

CBV

TBV

CO BF spl, fat

CVP

Plasma osmolality

Endotoxemia

Tc

SkBF & V

Sweat

Cellular heat shock responses, spherocytosis, etc. Fig. .. Scheme of interacting sequences of events occurring from the beginning of exposure to hot environments to death from heat stroke. Arrows indicate (≠) increase or (Ø) decrease in the parameter. BF = blood flow (spl, kid, M, respectively, Splanchnic, kidney and muscle). CBV = central blood volume. CO = cardiac output. CVP = central venous pressure. DIC = disseminated intravascular coagulation. F1 & el = fluid and electrolytes. PBV = peripheral blood volume. SkBF = skin blood flow. Tc = core temperature. V = volume. (From [].)

Tc

CVP SkBF & V

Tc DIC, acidosis

Coagulative necrosis, other cellular death, cerebral hypoxia

Neural dysfunction

sense of thirst is not a good indicator of water deficit. Persons offered fluid to replace a sweat loss stop drinking before the deficit has been compensated for. This ‘voluntary dehydration’ must be overcome by encouraging persons exercising in warm conditions to drink more than they feel is enough. The other problem is the limitation in the rate of gastric emptying. Fluid is

DEATH

transferred from the stomach to the gut, where absorption takes place at a maximum rate of approximately –. L/h, while sweat rates during exercise in hot conditions may exceed  L/h. This means that even with optimal fluid intake dehydration cannot be totally prevented during prolonged exercise such as marathon running or military activity in warm

 Chapter . Table .. Changes in physical parameters with altitude above sea level (s.l.). Temperature and water content of air

Air pressure

Water content (at 100% saturation)

Air density

Altitude (m)

Atmospheric (mmHg)

PO2 (mmHg)

% of s. l. value

kg/m3

% of s. l. value

°C

g/L

% of s. l. value

0 2000 3400 5500 8800

760 600 500 360 250

159 125 105 75 52

100 79 66 50 33

1.12 1.01 0.87 0.70 0.50

100 90 78 60 45

30 17 +7 –7 –29

33.3 15.4 8.1 3.0 0.5

100 46 24 9 2

climates []. Sports organizations, coaches and physicians responsible for events in hot and especially humid climates should agree on rules for the cancellation of competitions if temperature and humidity exceed certain limits, e.g.  °C, % relative humidity, to prevent heat illness [].

Acclimatization Acclimatization to heat is another important means of protection against heat stress. Stressful environments induce physiologic adaptive changes, which improve tolerance to the stress. When humans are exposed acutely to exercise in hot environments, their heart rate and core temperature increase more than under cool conditions, and their performance and endurance for prolonged exercise is reduced (Fig. ..). A prolonged stay in a hot climate, or repeated daily exposures in climatic chambers over a period of several days to weeks will induce physiologic changes, which include an increase in sweating rate, a lowering of resting core temperature and increased blood volume. These adaptations are beneficial for performance, since they lead to an increased evaporative heat loss, resulting in a lowering of the core and skin temperatures during work in hot environments [,]. Furthermore, the improved filling of the cardiovascular system results in a lower heart rate and improved endurance for exercise. However, in hot humid environments the improved sweating capacity does not help if the physical limits for evaporation of the produced sweat are exceeded.

High altitude Introduction Physical changes and their implications Exposure to high altitude is associated with a reduction in barometric pressure, by one-third at an altitude of  m, by half at an altitude of  m, and by about two-thirds at the altitude of Mount Everest ( m). There is an almost parallel decline in partial pressure of oxygen and air density. Furthermore, temperature declines approximately by  degree per  m of altitude. As a consequence of the decrease in temperature, the water content of fully saturated air decreases dramatically because of falling water vapor pressure (see Table ..). In addition, the thinner overlying atmosphere absorbs less and snowfields reflect more radiation. Therefore solar radiation, especially of short wavelength near the ultraviolet spectrum, is increased at high altitude and calls for special protection of skin and eyes. Table .. also shows that there are already considerable physical changes in the environment at the highest altitudes at which athletes compete or perform classic high-altitude training (– m). In brief, altitude can have the following principal effects on exercise performance.  As long as maximum voluntary power output is not affected, it will enhance performance in short anaerobic events involving high speed because of decreased air resistance.

Physical Activity and Environment  It will decrease performance in events which depend predominantly on aerobic capacity because of a decreased ambient P2. Running over distances longer than about  m will be affected as demonstrated by the results of the Olympic Games held in Mexico City ( m) in .  The lower water content and lower temperature of ambient air may affect performance by exacerbating exercise-induced asthma in athletes with bronchial hyperreactivity or asthma.  At altitudes that are relevant for mountaineers (– m and higher) the danger of acute altitude illnesses (see p. ) and cold injuries (see p. ) will increase. This section will discuss in more detail acute adjustments and acclimatization to hypoxia, the effects of acute and chronic altitude exposure on aerobic performance, and the modalities and efficacy of highaltitude training. In addition, an overview of acute high-altitude illness is given. As cold injuries are not strictly related to hypoxia, they are discussed in a separate section.

Immediate adjustments and acclimatization to hypoxia The energy requirement and thus the O2 demand for performing a given task does not change with altitude. Because of the reduced partial pressure of oxygen, O2 loading of the blood is incomplete at high altitude. The reduced O2 content per volume unit of blood is compensated for at several levels. Ventilation. Ventilation increases immediately and continues to rise further over the first – days at a given altitude. This further rise is called ventilatory acclimatization. As a consequence of this arterial P2 rises considerably during this time. On the other hand, more CO2 will be blown off by the enhanced ventilation causing a relative increase of bicarbonate, i.e. a respiratory alkalosis. This is partially compensated for by increased renal bicarbonate excretion. This leads to a reduction in the blood buffer capacity []. Circulation. Cardiac output and heart rate are increased for a given submaximum workload. With acclimatization this increase declines but heart rate still remains elevated compared to sea level.



Blood. Oxygen-carrying capacity is increased per volume unit of blood, acutely by decreasing plasma volume and in the long range by increases in the number of circulating red cells, i.e. by increasing erythropoiesis through release of erythropoietin from the kidney. Furthermore, ,-diphosphoglycerate (,-DPG) increases in red cells and favors unloading of oxygen in the tissue. This effect may, depending on the altitude, be offset or even overridden by the respiratory alkalosis which favors loading of oxygen in the lung []. Muscle. There are no immediate adjustments in the muscle cell components for hypoxia. Training studies in hypobaric chambers suggest that acclimatization to altitudes below  m may increase capillary density, mitochondrial density, aerobic enzymes and enzyme activities []. Furthermore, increase of myoglobin and other proteins accounts for the augmented buffer capacity of muscle tissue. At altitudes above  m (Himalayan mountaineers) muscle mass, muscle fiber and oxidative capacity of muscle decrease [], a surprising finding, for which the low level of exercise intensity and insufficient nutrition may account.

Aerobic performance Maximum aerobic capacity V˙2 max decreases with acute exposure to high altitude by approximately % per  m above an altitude of  m. In highly trained athletes hypoxia-induced reduction of V˙2 max may be considerably greater (Fig. ..) and it can be detected at altitudes as low as  m [,]. Thus, at elevations of – m at which altitude training is performed, athletes may have a considerably greater reduction of their aerobic capacity than the expected –%. This forces them to reduce the training intensity. This reduction shows, however, considerable interindividual variability []. Despite improved oxygen delivery and utilization with acclimatization the depressed V˙2 max increases little, if at all, with chronic exposure to hypoxia. This lack of improvement can in part be attributed to a reduction in maximal heart rate []. A young healthy mountaineer climbing at  m without supplemental oxygen is left with less than one-third of his sealevel aerobic capacity. Expressed in O2 uptake he is at

 Chapter . 5

5 * Lactate (mmol/L)

0 –5

% ∆VO2max

–10 –15

* Acute altitude

*

4 *

3

† Chronic altitude Sea level

2 * 1

–20

0 –10

–25 –30 –35 –40 –45 45

50

55

60

65

70

75

10

20 30 Time (min)

40

50

Fig. .. Arterial plasma lactate significantly increases at high altitude when exercising at the same absolute workload at · an intensity that elicited % of sea-level V 2 max on day  and day  at an altitude of  m. With acclimatization lactate levels fall significantly but remain elevated compared to sea-level values. From [].

∆VO2maxnorm (ml/kg/min) · Fig. .. Individuals with a higher V 2 max show a greater loss · of aerobic performance (DV2 max) when exercising at a simulated altitude of  m in a hypobaric chamber. From [].

the level observed in patients with severe heart failure ( mL/kg/min) and his rate of climbing is accordingly slow. The maximum power output of this individual is reduced to about . W/kg with maximal values of ventilation of  L/min, with a heart rate of /min and with lactate of . mmol/L []. Despite an arterial oxygen saturation of only %, the ECG is normal. The reduction in maximum heart rate, presumably due to a down-regulation of a-receptors, may protect his heart from ischemia by reducing the maximum workload on the heart.

Submaximum aerobic performance At high altitude the same absolute submaximum workload elicits a higher ventilation, a greater cardiac output and thus a higher heart rate as well as a greater increase in plasma lactate than at low altitude. Acclimatization to high altitude improves submaximum performance as demonstrated by increased endurance time as well as a reduction of heart rate and plasma lactate (Fig. ..) for a given workload [,]. The fact that lactate is higher at a given submaximum exercise level while several studies found maximum lactate to

be reduced compared with exercise at sea level (see data from Mount Everest mentioned above) has been termed the ‘lactate paradox’. This phenomenon, for which there is no clear explanation, has been questioned by recent findings of unchanged maximum lactate levels during the Chacaltaya expedition. In summary, acclimatization to high altitude does not improve the reduced V˙2 max but it enhances performance at submaximum levels. This may help to explain why athletes competing at altitude must train and thereby acclimatize at this altitude prior to the competition. Furthermore, because of changes in the relationship between heart rate and workloads at altitude, it is necessary to adjust heart rate-based recommendations for training intensities.

Training at high altitude for sea-level competition The hypothesis that high-altitude training improves sea-level performance is based on the assumption of beneficial effects by acclimatizing to high altitude and/or hypoxia being an additional training stimulus. Accordingly, three concepts have emerged: • Live high — train high (classic high-altitude training). • Live high — train low (high-altitude houses or hypoxic tents).

Physical Activity and Environment • Live low — train high (training in hypobaric chambers or in normobaric hypoxia). The most important beneficial effect of altitude acclimatization for sea-level performance is the increase in erythropoiesis. Improvements of aerobic capacity after high-altitude training correlate with the increase in red cell mass (RCM). It appears that a significant increase in RCM only occurs when more than  weeks are spent at an altitude equivalent to  m. Interestingly, an exposure of – h at night at an FI2 of .% (equivalent to  m) for  consecutive nights while living and training in normoxia for the rest of the day did not increase RCM []. There are preliminary reports of an increase in RCM by about –% after living – h per day at normobaric hypoxia equivalent to an altitude of  m for  days suggesting that this time and altitude may be sufficient for stimulation of erythropoiesis. Specific ventilation does not change after altitude training indicating that ventilatory acclimatization has no advantage for sea-level performance. The effects of acclimatization on the hemoglobin–O2 affinity and on the plasma volume are rapidly reversible and most likely offer no benefit for sea-level performance. Increases of myoglobin and possibly another muscle protein (karosin) enhance the local buffer capacity of muscle tissue and overcome the potential disadvantage of reduced blood buffer capacity which is due to renal compensation of respiratory alkalosis. It has already been mentioned above that mountaineers living and exercising above altitudes of – m have a loss of muscle mass and a reduction in oxidative capacity. This is mostly a consequence of catabolism due to reduced food intake because of lack of appetite. Regularly exercising on a bicycle ergometer during a chamber study (Operation Everest II, described in reference []) could not prevent muscle loss. Training at high altitude may have several negative aspects like reduction in absolute workload, lack of adequate facilities or locations, unfavorable climate and sleep disturbance. These may offset the benefits of altitude acclimatization. Therefore, the concept of living high and training low has become popular although the evidence in favor of this approach for the elite athlete is at best circ*mstantial. One well-controlled study, published in German only, demonstrated a greater improvement of performance after classic high-altitude training [] and one equally well con-



trolled study found the same after living high and training low [] compared to sea-level training. These studies were performed in moderately well trained athletes (V˙2 max – mL/kg/min). There are no controlled data obtained in elite athletes that unequivocally demonstrate a benefit of either training modality. A recent investigation suggests that there is an individual response to training at high altitude that depends on how much erythropoiesis is increased and on the training intensity that can be maintained at high altitude []. Living in normoxia and training in a hypoxic chamber at simulated altitudes up to  m leads to increases in myoglobin content, oxidative enzymes, capillaries and muscle fiber volume when training is performed at the same absolute workload as in normoxia. Thus, the beneficial effect can be attributed to more intense work rather than to hypoxia itself. Training at the same relative workload in hypoxia vs. normoxia also has no additional effects on endurance performance [].

Acute high-altitude illnesses Unacclimatized healthy individuals who ascend too fast to high altitudes are at risk of developing acute high-altitude illnesses. The faster they climb and the higher they go the greater the chances of developing a serious, possibly life-threatening illness. We distinguish between acute mountain sickness (AMS), an illness dominated by cerebral symptoms which can progress to overt cerebral edema (high-altitude cerebral edema, HACE) and high-altitude pulmonary edema (HAPE). AMS often also precedes the pulmonary form of high-altitude illnesses. There are distinct differences between these entities with regard to aspects of pathophysiology as well as prophylaxis and treatment with drugs (Table ..). Acute mountain sickness (AMS) frequently occurs within – h after rapid ascent to altitudes above – m []. It is characterized by headache, nausea or loss of appetite, fatigue, dizziness and insomnia. AMS usually resolves spontaneously over the next  days when no further gain in altitude occurs. It may also progress to ataxia and clouded consciousness which are early signs of potentially lethal HACE []. The pathophysiology of this illness is poorly understood. While imaging techniques show cerebral edema when HACE is present, the cerebral changes accompa-

 Chapter . Table .. Acute mountain sickness

High-altitude pulmonary edema

Occurrence

Altitude > 2000–2500 m

Altitude > 3000 m

Latency

6–12 h

1–4 days

Leading symptoms

Cerebral symptoms: • Headache • Nausea, vomiting • Neurological abnormalities

Pulmonary symptoms: • Cough • Dyspnea and decreased exercise performance • Rales

Pathophysiology

Low hypoxic ventilatory response Sodium retention Increased cerebral blood flow and permeability of blood brain barrier?

Exaggerated hypoxic pulmonary vasoconstriction

Pre-acclimatization and slow ascent to altitudes > 2500 m (average daily ascent rate: 300–500 m above 2000 m) Acetazolamide: in case of known susceptibility and rapid ascent

Nifedipine: in case of known susceptibility and rapid ascent

Prophylaxis

Exaggerated hypoxic pulmonary vasoconstriction

Therapy

Descent by at least 1000 m of height, supplemental oxygen In addition: Nifedipine

In addition: glucocorticoids Prognosis

• AMS: spontaneous resolution within 1–2 days • HACE: lethal without treatment, prolonged recovery of severe cases at low altitude

nying AMS are subtle and hardly detectable by conventional imaging techniques. There is a large interindividual variability regarding susceptibility to AMS. While usually less than % have AMS (defined as headache and one additional symptom) at an altitude of  m, about –% have AMS after rapid ascent to  m. For prevention it is important that the rate of ascent matches the degree of acclimatization and the individual tolerance. When symptoms occur, a day of rest should be taken. If this is not followed by improvement, one must descend. In severe and often rapidly progressive cases application of supplemental oxygen or treatment in a portable hyperbaric chamber and the administration of dexamethasone (– mg every  h) should be given until descent is possible. Acetazolamide ( ¥  mg) can be taken for prophylaxis when slow ascent in susceptible individuals is not possible. High-altitude pulmonary edema (HAPE) presents after rapid ascent from low altitude within – days

Nifedipine: in case of known susceptibility and rapid ascent

• 50% mortality without therapy • Clinical recovery at low altitude within 1–2 days

[]. It is rarely observed below altitudes of  m and after  week of acclimatization at a particular altitude. In most cases, it is preceded by symptoms of AMS. Early symptoms of HAPE include exertional dyspnea, cough and reduced exercise performance. As edema progresses, cough worsens, and breathlessness at rest and orthopnea occur. Gurgling in the chest and pink frothy sputum indicate advanced cases. There is large interindividual variability in susceptibility to HAPE. Individuals with a proven history of HAPE have a % chance of developing this illness again when the exposure is similar compared to the last episode []. The clinical examination reveals cyanosis, tachypnea, tachycardia, and elevated body temperature, which generally does not exceed . °C. Rales are discrete at the beginning, typically located over the middle lung fields. Often, there is a discrepancy between the minor finding at auscultation compared with the widespread disease on the chest radiograph. In advanced cases, signs of concomitant cerebral edema,

Physical Activity and Environment



Fig. .. Chest radiograph with patchy alveolar pulmonary edema of a -year-old mountaineer with HAPE on admittance to hospital ( m) after evacuation by helicopter from an altitude of  m (left side). Reduction of edema over  h with bed rest and supplemental oxygen (right side).

such as ataxia and decreased levels of consciousness, are frequent findings. There are no characteristic findings in common laboratory examinations. Abnormal results may be due to accompanying dehydration, stress and preceding exercise. Arterial blood gas measurements of four cases of advanced HAPE at  m showed a mean P2 of  mmHg and a mean arterial oxygen saturation of %. These findings demonstrate the severity of this illness. In early cases, values around  mmHg for P2 and % for Sa2 were observed at this altitude. Chest radiographs and CT scans of early HAPE cases show a patchy, peripheral distribution of edema (Fig. ..). Cardiac catheterization of untreated cases of HAPE at high altitude revealed normal wedge pressure and pulmonary artery hypertension (systolic pressure in the order of  mmHg compared to  mmHg in controls at  m). This increased pressure precedes edema formation. Lowering pulmonary artery pressure by nifedipine is effective for treatment and prevention of HAPE. The prevailing hypothesis to explain increased capillary filtration pressure is inhom*ogeneous hypoxic vasoconstriction accounting for increased capillary pressure in areas of overperfusion. Recent investigations by bronchoalveolar lavage suggest that early HAPE is caused by a pressure-induced leak without increased permeability due to an inflammatory reaction. With the exception of the recommended drugs, the prevention and treatment of HAPE resemble those of AMS and are summarized in Table ... The fol-

Table .. How to avoid and treat high-altitude pulmonary edema. Prevention 1 Slow ascent for susceptible individuals (average increase in sleeping altitude of 300–350 m/day above 2000 m). 2 No ascent to higher altitude with symptoms of acute mountain sickness (AMS). 3 Descent when symptoms of AMS do not improve after a day of rest. 4 Under circ*mstances of high risk avoid vigorous exercise when not acclimatized. 5 Nifedipine: 20 mg slow release formulation every 8 h (or 30–60 mg sustained release formulation once daily) for susceptible individuals when slow ascent is impossible. Treatment 1 Descent by at least 1000 m of altitude (primary choice in mountaineering). 2 Supplemental oxygen: 2–4 L/min (primary choice in areas with medical facilities). 3 When 1 and/or 2 not possible: 20 mg nifedipine slow release formulation every 6 h. Portable hyperbaric chamber. Descent as soon as possible.

lowing case history demonstrates that HAPE can be a life-threatening illness from which one recovers rapidly at low altitude. It also demonstrates that a susceptible individual may continue mountaineering even as a mountain guide because HAPE can be avoided with adequate preventive measures (see Case story ..).

 Chapter .

Case story 2.3.3 In the summer of  a party of  people led by two mountain guides ascended by cable car from low altitude to  m to climb for several days at altitudes between  and  m. On the third day one of the mountain guides, who was  years old, noticed unusual shortness of breath while climbing to  m, which improved when descending to a hut at  m. There his appetite was reduced, he had headache, felt weak and slept poorly. He did not want to leave a group of  people with only one guide and accompanied the party on the next day to the Margherita Hut ( m). On this ascent, he could not keep up with the group above  m altitude because of severe shortness of breath. He also noticed a dry cough. After he had fought his way up to the hut, he did not recover, was cyanotic and had considerable dyspnea at rest. There were rales over both lungs. He showed truncal ataxia but his consciousness was not clouded. Arterial blood gas analysis, measured by a research team working in the hut, demonstrated severe hypoxemia with a P2 of . mmHg, a P2 of . mmHg and a measured arterial oxygen saturation of %. He was immediately flown out by helicopter to a hospital at  m where the diagnosis of HAPE was confirmed by chest radiography (see Fig. ..). At low altitude, the patient felt immediately bet-

Multiple choice questions  The core temperature during exercise: a reaches a new level after  min exercise b is increased during exercise in proportion to work intensity c rises in proportion to the relative workload of the individual d rises due to an insufficient heat loss e is higher in trained than in untrained athletes at the same work intensity.  The ‘prescriptive zone’ is: a a temperature range where body temperature is independent of environmental temperatures

ter; blood examinations including sedimentation rate and a differential white cell count were normal. He was on supplemental oxygen overnight. When he left the hospital the next morning arterial blood gases without supplemental oxygen showed increased ventilation in order to achieve normoxemia: P2 . mmHg, P2 . mmHg (oxygen saturation %). He continued to work as a mountain guide and had a similar episode of HAPE at the same location on day  after ascending from low altitude with only one night spent at  m. Since then he pays attention to slow ascent (average rate of ascent – m per day above  m) when staying for lengthy periods at altitudes above  m. When slow ascent is not possible, he takes nifedipine,  mg every  h, during ascent until reaching the final altitude. With these measures, he is able to work normally as a mountain guide. He also accompanies groups in the Himalayas and in South America where he reached, without any problems, the top of Aconcagua ( m) after preacclimatizing by climbing the volcanoes in Ecuador (altitude between  and  m). Since  he has had one further episode of threatened HAPE, at an altitude of about  m, which he recognized so early that he was able to descend by himself.

b independent of the activity level c affected by the sweating capacity d the same as ‘comfortable’ temperature conditions e the interval in which shivering responses occur f reduced in water.  In hot conditions: a maximal sweating rate is not so important for endurance performance b competition between muscle and skin blood flows causes an increase in core temperature c fatter individuals tolerate the heat better d the process of heat acclimatization leads to increased blood volume

Physical Activity and Environment e the air humidity has no effect on performance f sweat loss impairs exercise performance.  Heat illness is prevented by: a warming up before physical performance b fluid intake during activity c fluid intake after prolonged activity d training without water for  week e acclimatization to hot conditions.  Cold exposure in humans leads to: a immediate shivering b increase in serum norepinephrine c loss of appetite d extravasation e increased serum FFAs.  With regard to heat production: a it occurs mainly in the muscle b uncoupling proteins are proton channels c adult humans have no uncoupling proteins d specific dynamic action is associated with exercise e drugs increasing cAMP produce heat.  With regard to heat loss and clothing: a radiation is the main avenue for heat loss in winter sports b IREQ index relates to temperature and wind c in winter sports the insulation of clothing is usually – clo units d frostbite begins to develop when WCI is over  W/m2 e cold sensations acclimatize sooner than shivering.  With regard to cold injuries: a ice crystals cause cold injuries b local ointments protect from frostbite c frostbite can be treated by fire d comatose and cold patients should be warmed by active moving.  Immediate adaptive responses to high altitude are: a increase of red blood cell mass b decrease of plasma volume c increase of ventilation d increase of heart rate for a given workload e increase of muscle oxidative capacity.  The following statements about the effects of high altitude on aerobic performance are correct: a V˙2 max decreases. b V˙2 max significantly increases with acclimatization. c Maximal heart rate increases with acclimatization.



d Heart rate for a given workload decreases with acclimatization. e An untrained individual has a greater decrease in aerobic performance than a well-trained individual.  The following statements are correct regarding highaltitude training: a Training at high altitude improves performance at high altitude more than training at low altitude. b Training in a hypobaric chamber is more effective than training in normobaric hypoxia. c Increase in red cell mass is the principal factor for improvement of sea-level performance. d The changes of hemoglobin affinity for oxygen are important for improvement of endurance performance at low altitude. e Training at high altitude improves buffer capacity of muscle tissue.  Acute mountain sickness (AMS): which statements are correct? a The most frequent symptom is vomiting. b When symptoms of AMS occur, a mountaineer must always descend. c Ataxia and decreased consciousness indicate progression to high-altitude cerebral edema (HACE). d Slow ascent is the major preventive measure. e The treatment of choice for HACE is descent, supplemental oxygen and glucocorticosteroids.  High-altitude pulmonary edema (HAPE): which statements are correct? a An inadequate drop in performance accompanied by dyspnea and cough is an early sign of HAPE. b Lowering pulmonary artery pressure is the principle of treatment. c Acetazolamide has been shown to prevent HAPE. d Clinical recovery at low altitude occurs within  or  days. e An individual with a history of HAPE has a high probability of developing HAPE again under similar circ*mstances.

References  Nielsen B. Olympics in Atlanta: a fight against physics. Med Sci Sports Exerc ; : –.  Saltin B, Hermannsen L. Esophageal, rectal and muscle temperature during exercise. Med Sci Sports Exerc ; : –.  Lind AR. A physiological criterion for setting thermal limits for everyday work. J Appl Physiol ; : –.

 Chapter .  Nielsen M. Die Regulation der Körpertemperatur bei Muskelarbeit. Skand Arch Physiol ; : –.  Bittel JHM, Nonotte-Varly C, Livecchi-Gonnot GH, Savourey MJ, Hanniquit AM. Physical fitness and thermoregulatory reactions in a cold environment in men. J Appl Physiol ; : –.  Wilber RL, Rundell KW, Szmedra L, Jenkinson DM, Im J, Drake SD. Incidence of exercise-induced bronchospasm in olympic winter sport athletes. Med Sci Sports Exerc ; : –.  Ricquier D, Fleury C, Larose M et al. Contribution of studies on uncoupling proteins to research on metabolic diseases. J Intern Med ; : –.  Danielsson U. Windchill and the risk of freezing. J Appl Physiol ; : –.  ISO. Ergonomics of thermal environment — cold environments. , Geneva: International Standard Organisation.  Thompson RL, Hayward JS. Wet-cold exposure and hypothermia: thermal and metabolic responses to prolonged exercise in rain. J Appl Physiol ; : –.  ISO/TR-. Evaluation of cold environments — Determination of required clothing insulation (IREQ). , Geneva: International Standard Organisation.  Bruck K, Baum E, Schwennike HP. Cold-adaptive modifications in man induced by repeated short-term cold exposures during a -day and -night cold exposure. Pflügers Arch ; : –.  Leppäluoto J, Korhonen J, Hassi J. Habituation of thermal sensations, skin temperature and norepinephrine in men exposed to cold. J Appl Physiol ; : –.  Mager M, Robinson SM. Substrate mobilization and utilization in fasting men during cold exposure. Bull New Jersey Acad Sci  (symposium issue); –.  Keatinge WR. The effect of repeated daily exposures to cold and of improved physical fitness on the metabolic and vascular responses to cold air. J Physiol ; : –.  Scholander PF, Hammel TH, Lange Andersen K, Logning Y. Metabolic acclimation to cold in man. J Appl Physiol ; : –.  Park YS, Rennie DW, Lee IS et al. Time course of deacclimation to cold water immersion in Korean women divers. J Appl Physiol ; : –.  Young AJ, Myza SR, Sawka MN, Gonzalez RR, Pandolf KB. Human thermoregulatory responses to cold air are altered by repeated cold water immersions. J Appl Physiol ; : –.  O’Brien C, Young AJ, Lee DT, sh*tzer A, Sawka MN, Pandolf KB. Role of core temperature as a stimulus for cold acclimation during repeated immersion in  °C water. J Appl Physiol ; : –.  Vuori I. Sudden death and exercise: effects of age and type of activity. Sport Sci Rev ; : –.  Galloway SD, Maughan RJ. Effects of ambient temperature on capacity to perform prolonged cycle exercise in man. Med Sci Sports Exerc ; : –.

 Sallis R, Chassay CM. Recognizing and treating common cold-induced injury in outdoor sports. Med Sci Sports Exerc ; : –.  Hassi J, Mäkinen T. Frostbite: occurrence, risk factors and consequences. Int J Circumpolar Health ; : –.  Paton B. A history of frostbite treatment. Int J Circumpolar Health ; : –.  Berg U. Human power at subnormal body temperatures. Acta Physiol Scand ; : –.  Nielsen B, Strange S, Christensen NJ, Warberg J, Saltin B. Acute and adaptive responses in humans to exercise in a warm, humid environment. Pflügers Arch ; : –.  González-Alonso J, Teller C, Andersen SL, Jensen FB, Hylding T, Nielsen B. High body temperature causes fatigue during exercise in humans. J Appl Physiol ; : –.  Nielsen B, Hales JRS, Strange S, Christensen JN, Warberg J, Saltin B. Human circulatory and thermoregulatory adaptations with heat acclimation and exercise. J Physiol (Lond) ; : –.  González-Alonso J, Calbert JA, Nielsen B. Metabolic and thermodynamic alterations with dehydration-induced reductions in muscle blood flow in exercising humans. J Physiol (Lond) ; : –.  González-Alonso J, Calbert JA, Nielsen B. Muscle blood flow is reduced with dehydration during prolonged exercise in humans. J Physiol (Lond) ; : –.  Sawka MN. Physiological consequences of hypohydration: exercise performance and thermoregulation. Med Sci Sports Exerc ; : –.  Hales JRS, Hubbard RW, Gaffin SL. Limitation of heat tolerance. In: Fregly MJ, Blatteis CM, eds. Handbook of Physiology, Section , Environmental Physiology. Bethesda MD: American Physiological Society, : –.  Nielsen B, Krog P. Optimal fluid replacement during long lasting exercise in  °C and  °C ambient temperature. Scand J Med Sci Sports ; : –.  Bender PR, McCullough RE, McCullough RG et al. Increased exercise Sa2 independent of ventilatory acclimatization at  m. J Appl Physiol ; : –.  Mairbäurl H, Schobersberger W, Oelz O, Bärtsch P, Eckardt KU, Bauer C. Unchanged in vivo P- at high altitude despite decreased erythrocyte age and elevated ,diphosphoglycerate. J Appl Physiol ; : –.  Terrados N. Altitude training and muscular metabolism. Int J Sports Med ; : S–S.  Hoppeler H, Ceretelli P. Morphologic and metabolic response to chronic hypoxia: the muscle system. In: Fregly MJ, Blatteis CM, eds. Handbook of Physiology, Section , Environmental Physiology . Oxford: Oxford University Press, : –.  Koistinen P, Takala T, Martikkala V, Leppäluoto J. Aerobic fitness influences the response of maximal oxygen uptake and lactate threshold in acute hypobaric hypoxia. Int J Sports Med ; : –.  Chapman RF, Stray-Gundersen J, Levine BD. Individual

Physical Activity and Environment

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   

variation in response to altitude training. J Appl Physiol ; (): –. Gonzalez NC, Clancy RL, Moue Y, Richalet J-P. Increasing maximal heart rate increases maximal O2 uptake in rats acclimatized to simulated altitude. J Appl Physiol ; (): –. Sutton JR, Reeves JT, Wagner PD et al. Operation Everest II: oxygen transport during exercise at extreme simulated altitude. J Appl Physiol ; : –. Maher JT, Jones LG, Hartley LH. Effects of high-altitude exposure on submaximal endurance capacity of men. J Appl Physiol ; : –. Mazzeo RS, Bender PR, Brooks GA et al. Arterial catecholamine responses during exercise with acute and chronic high-altitude exposure. Am J Physiol ; : E–E. Ashenden MJ, Gore CJ, Dobson GP, Hahn AG. ‘Live high, train low’ does not change the total haemoglobin mass of male endurance athletes sleeping at a simulated altitude of  m for  nights. Eur J Appl Physiol ; : –.

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 Levine BD, Stray-Gundersen J. ‘Living high–training low’. effect of moderate-altitude acclimatization with low-altitude training on performance. J Appl Physiol ; (): – .  Mellerowicz H, Meller W, Woweries J et al. Vergleichende Untersuchungen über Wirkungen von Höhentraining auf die Dauerleistung in Meereshöhe. Sportarzt Sportmed ; : –.  Desplanches D, Hoppeler H, Linossier MT et al. Effects of training in normoxia and normobaric hypoxia on human muscle ultrastructure. Eur J Physiol ; : –.  Johnson TS, Rock PB. Acute mountain sickness. N Engl J Med ; : –.  Houston CS, Dickinson J. Cerebral form of high-altitude illness. Lancet ; II ( October): –.  Bärtsch P. High altitude pulmonary edema. Med Sci Sports Exerc ; (): S–S.  Loyd EL. Hypothermia and Cold Stress. London: CroomHelm, .

Chapter 2.4 Nutrition and Fluid Intake with Training LEIF HAM BRÆUS, STEFAN BRA NTH & ANNE RA BE N

Classical reference Ivy JL, Katz AL, Cutler CL, Sherman WM, Coyle EF. Muscle glycogen synthesis after exercise: effect of time of carbohydrate ingestion. J Appl Physiol ; : –. The effect of the time of ingestion of a carbohydrate supplement on muscle glycogen post exercise was examined. The authors investigated  male cyclists who exercised continuously on a cycle ergometer at % V˙2 max interrupted by six -min intervals of % V˙2 max on two separate occasions. A % carbohydrate solution was ingested either immediately post exercise or  hours post exercise. Interestingly, the glycogen synthesis rate after exercise was markedly higher for the group who received carbohydrate immediately after exercise compared with the group that received it  hours after exercise. The slower rate of glycogen storage in the group receiving carbohydrate at a later time point occurred despite the fact that the response in plasma glucose and insulin to carbohydrate loading was similar in the two groups. The study was the first to show in humans that ingestion of a carbohydrate supplement immediately post exercise will result in the most optimal recovery of muscle glycogen storage.

Optimal nutrition for physical training and competition — a challenge for nutritional science In order to perform optimally during daily training as well as during competition, it is essential that an ath-



lete’s habitual diet contains enough of both required nutrients and fluid. An optimal nutrient and fluid status is also important to avoid injuries and to optimize the immune system. Not only nutrient composition, but also timing and frequency of food and fluid intake are critical for optimal performance. One of the reasons for the common idea that athletes need special diets might be based on the misconception that an increased energy turnover per se leads to increased needs for other nutrients. However, this is not necessarily the case. Increased physical exercise is essentially a question of increased energy turnover, while the turnover of essential nutrients is usually not related to energy turnover to such an extent that there is a need for increased intakes. Most studies of food habits have indicated that the nutrient density, i.e. nutrients per energy unit, is the same in low-energy consumers as in high-energy consumers. Thus the increased food intake in physically active individuals will automatically have an increased intake of essential nutrients. To what extent the intake of essential nutrients is a valid problem is consequently mainly due to two factors: (i) are the athletes in energy balance? and (ii) are they eating an optimal, nutritionally balanced diet according to recommendations? For recreational athletes this also means that there is no need for specific supplements or diets to cover their energy needs, as illustrated in Case story .. below. This may also be the case in elite athletes. However their often intensive training programmes in combination with short times for recovery between competitions may call for extra nutritional support.

Nutrition and Fluid Intake

Case story 2.4.1 Energy in long distance biking might be obtained by sport drinks and carbohydrate loading. -year-old, non-athlete male: body weight  kg, height  cm, BMI . kg/m2, body fat %, calculated BMR  kJ, V˙2 max . L/min or . mL/kg/min. He participates in one of the classic Swedish sporting events (Vättern-rundan), a noncompetitive endurance biking race with no exact completion times or publication of results. The-km Vätternrundan is a physically taxing event, as it will take the ordinary participant – h of cycling to complete. Most cyclists start in the evening and thus cycle a large part of the Leg/ km Leg/ km Leg/ km Leg/ km Leg/ km Leg/ km Leg/ km Leg/ km Legs  & / km +  km

Energy turnover (kJ)         

race throughout the night in the dark. The race comprises seven legs and nine stops where refreshments are available. At most stops blueberry soup, coffee, buns, and banana are available, but hot meals are offered after  km (milk, sausage and mashed potatoes, banana) and after  km (lasagne, milk). His mean speed was  km per hour, total energy cost during the race was   kJ (based on heart rate recording) and total energy intake from food and sport drinks during the race was   kJ. His energy balance (in kJ) throughout the race is illustrated in this table. Note the essential energy (and fluid) supplement that is obtained from the sport drinks! Energy intake (kJ)  + *  + *  + *  + *  + *  + *  + *  + * * + *

Total  km     + * * From half bottle of sports drink consumed during each leg. The observed energy deficit ( kJ) corresponds to about  g glycogen which very well might be available, especially if the subject has performed carbohydrate loading before the race. The case illustrates that it is possible even

Are requirement and recommended daily allowances equivalent to optimal nutrition? For each nutrient there is a range of intakes from minimal requirement to prevent nutrient deficiency diseases to toxic levels. Somewhere in between is what is defined as optimal intake. According to the original definition, requirement refers to the minimal nutrient intake needed in order to prevent nutritional deficiency diseases. The recommended dietary allowance is



Energy balance (kJ) – – + + – + – – – –

during energy-demanding endurance performances to cover energy needs by combining carbohydrate loading with optimal food intake during a race.

defined as the mean of the requirement for a special population group +  standard deviations, thereby covering .% of the need of a normal population. In order to compare the requirement vs. an adequate intake some concepts are introduced, as illustrated in Fig. ... A better distinction between the concepts ‘requirement’ and ‘optimal intake’ of nutrients is urgently needed. The mere fact that a more optimal restitution post exercise is reached at a higher nutrient intake does

 Chapter .

1.0

UL

RDA

1.0

AI 0.5

0.5

0 A

B C Observed level of intake

Risk of adverse effects

Risk of inadequacy

EAR

D

Fig. .. Schematic illustration of various concepts used to express requirement and optimal intakes of nutrients. AI, adequate intake; EAR, estimated average requirement; RDA, recommended dietary allowances; UL, tolerable upper limit. (Source: Dietary reference intakes, National Academic Press, Washington, ).

not necessarily mean that there is an increased requirement in athletes as such in order to counteract any potential nutrient deficiency. This further accentuates the need to differentiate between various activity periods, whenever discussing the concept of nutritional perspectives on nutrient turnover in athletes. The daily nutritional requirements of nutrients have very little in common with specific nutritional needs pre-exercise and during exercise for optimal performance, which might also on the other hand be quite different from the nutritional needs post exercise for optimal recovery. Thus an optimal restitution of protein balance in the muscle due to heavy physical exercise might call for increased protein availability in the postexercise period although there is still no risk of protein malnutrition on a normal diet.

Energy requirement vs. nutrient requirement Under normal conditions the body gives priority to covering its energy needs. In situations where its energy needs are not met, it will use all available energy-yielding substances in the food and body stores to cover energy requirements. This also means that the energy need essentially involves quantitative aspects of the dietary intake. The requirement for essential nutrients, i.e. protein, essential fatty acids, minerals and vitamins, is essentially related to fat-free mass and to a small degree to the extent of physical exercise. Thus nutrient requirement is related to age, sex

and body size and refers to a specific need for certain nutrients, involving qualitative aspects of the dietary intake. When the energy intake via the diet, i.e. exogenous energy, does not meet energy requirements, endogenous energy is released from the mobilization of energy stores in the body (glycogen in liver and muscle; fat from subcutaneous and adipose tissue; gluconeogenesis from muscle catabolism). Protein plays a two-fold role. There is (i) a specific nutritional role as source of essential amino acids for protein synthesis, i.e. building up, repairing and maintaining tissues; as well as (ii) a non-specific role as an energy-yielding nutrient. If energy needs are not met, protein will be used as an energy source, no matter whether protein needs are increased and not being met. It is consequently not possible to discuss energy and protein requirements separately. This is of special relevance when discussing nutritional problems in athletes.

Energy density vs. nutrient density The energy density of a diet refers to the amount of energy per weight or volume, while the nutrient density refers to the amount of nutrient in relation to energy, i.e. g/ MJ. Foods rich in fat and sugar have a high energy density, while their nutrient density is low. Persons with a high energy turnover, i.e. endurance athletes, may however cover their nutrient needs even on a diet with low nutrient density if they are in energy balance, while a low nutrient density may be detrimental in low-energy consumers. There are few examples, if any, where athletes consuming a normal diet in amounts relevant to cover their energy needs develop any objective signs of nutrient deficiency.

How to measure energy turnover Figure .. illustrates the various methods that can be used for studies of the various compartments in energy turnover in humans. Energy turnover in the body comprises a conversion of energy between various forms: mechanical energy as represented by physical exercise or muscular work; heat production, which is also called thermogenesis. Sooner or later energy conversions result in heat production, i.e. dietary-induced thermogenesis

Nutrition and Fluid Intake

Ergometers (e.g. bicycle, treadmill)

Direct calorimetry (e.g. room, suit)

Indirect calorimetry: Calculations (food tables)



Direct calorimetry Bomb calorimetry

Calculation (PAL)

Energy in Food intake

Energy out Tissue stores

Tissue stores

External work Heat

Body composition: Densitometry Anthropometry, e.g. skin fold Total water, e.g. bioimpedance, stable isotopes (D218O, 40K)

Losses (urine, faeces)

Indirect calorimetry:

Indirect calorimetry:

Respiratory (O2 /CO2) Doubly labelled water Heart rate Activity records

Calculations (chemical analysis) Direct Calorimetry: Bomb calorimetry

Fig. .. Schematic illustration of the various methods used in studies on energy turnover.

(DIT), work-induced thermogenesis. The efficiency of the body in converting chemical energy to mechanical energy, i.e. physical work, is the same in normal and well-trained individuals, being about %, the remaining % being heat; chemically bound energy, as in food and body stores of glycogen and fat, but also protein. Table .. lists the types of energy stores and their role in exercise as a source for conversion into mechanical energy, as well as differences between trained and untrained individuals. Energy turnover includes oxidation of biological substances, i.e. carbohydrate, fat, protein and alcohol, which yields heat. Energy turnover can thus be measured by analysing the heat produced as a result of the oxidation. This is usually called direct calorimetry and calls for advanced and sophisticated analytical methods, which are of little practical importance in field studies. Energy turnover is consequently usually estimated by means of indirect calorimetry based on

measuring consumption of oxygen or production of carbon dioxide as a result of oxidation of energyyielding substrates. As oxidation is related to blood circulation and indirectly heart rate, a common method of indirect calorimetry measurement, especially in athlete physiology, is based on heart beat registration. The individual relationship between heart beat frequency and oxygen consumption, which is related to physical capacity, can be estimated in the laboratory. It is then possible to estimate the total energy turnover during physical performances using portable heart frequency recorders.

Calculation of energy turnover based on basal metabolic rate (BMR) and physical activity level (PAL) The total energy turnover comprises basal metabolic rate (BMR) as well as the energy needed for daily life, i.e. characteristics of lifestyle including physical activity. Based on large population studies, equations have

 Chapter . Table .. Energy stores, physical activity and training state. Energy stores

Role in exercise

Difference in trained vs non-trained individuals

Muscle glycogen

Important energy source, influences endurance at moderate-intensity exercise This energy source is used to a large extent in: (i) high exercise intensity (ii) short-term exercise (iii) untrained subjects (iv) high intake of carbohydrate in the diet

Training increases the content by approximately 100%

Liver glycogen

Maintenance of blood glucose.To a certain extent, circulating blood glucose is taken up and catabolized in the working muscle

Training increases the content by approximately 100%

Triglycerides in adipose tissue and muscle tissue

Free fatty acids are produced during breakdown of triglycerides Free fatty acids as an energy source are to a large extent used in: (i) low intensity exercise (ii) long-term exercise (iii) trained subjects (iv) high fat intake in the diet

Exercise increases muscle triglyceride content to twice as much, but the percentage of body fat (and absolute fat mass) in the body drops

Muscle protein

Energy deficit leads to increased muscle catabolism due to increased gluconeogenesis. NB Muscle represents > 20% of body energy stores in athletes

Energy deficit leads to more pronounced muscle catabolism in well-trained athletes with low body fat % than in-non-trained individuals with higher body fat %

Exercise: Calculate your own BMR Table .. Calculation of basal metabolic rate based on age, sex and body weight (W). From []. Men

Women

Age

MJ/24 h

kcal/24 h

MJ/24 h

kcal/24 h

0–3 3–10 10–18 19–30 31–60 > 60

0.255 W – 0.226 0.0949 W + 2.07 0.0732 W + 2.72 0.0640 W + 2.84 0.0485 W + 3.67 0.0565 W + 2.04

60.9 W + 54 22.7 W + 495 17.5 W + 651 15.3 W + 679 11.6 W + 879 13.5 W + 487

0.255 W – 0.214 0.0941 W + 2.09 0.0541 W + 3.12 0.0615 W + 2.08 0.0364 W + 3.47 0.0439 W + 2.49

61.0 W – 51 22.5 W + 499 12.2 W + 746 14.7 W + 496 8.7 W + 829 10.5 W + 596

been established in order to calculate BMR with reasonable accuracy based on anthropometric data (weight, length, age and sex) []. It has been postulated that for survival, -h energy

turnover represents about . times BMR, and for a sedentary lifestyle total energy turnover represents about . times BMR (Fig. ..). Various activities in daily life as well as during

Nutrition and Fluid Intake Activity 3600

Total energy requirement (kcal/day)

3000

Activity

HEAVY

2.10

MODERATE

1.78

LIGHT

1.58 HEAVY with desirable MODERATE with desirable LIGHT with desirable MAINTENANCE with 60 min walking/standing INACTNE out of bed SURVIVAL lying continuously

1.40 1.82 1.27 1.84 1.56 1.20 1.40 1.00 1.27 1.20

MAINTENANGE INACTIVE 2000 SURVIVAL BMR

1.00

BMR

1000

65 kg males

55 kg females

Fig. .. Energy turnover expressed as multiples of BMR [].

various forms of physical activities are expressed as multiples of BMR, often characterized as BMR factors [,] or metabolic energy turnover (MET) values (Table ..) [,]. The total energy turnover (ET) per  h can then be calculated based on BMR with the addition of energy for various physical activities based on intensity and duration throughout the day. The relationship between the total energy turnover (ET) and BMR per  h is an indicator of the physical

Exercise: Calculate your own PAL  Calculate your BMR (as above).  Keep a record of your physical activity throughout  h: factor Energy Occupation hours BMR (kJ) e.g. Sleeping  . BMR/  ¥ . Sitting  . BMR/  ¥ . etc.  Estimate total energy turnover per  h (ET).  Your PAL is calculated by dividing ET with BMR.



Table .. Examples of MET values for various athletic activities. From []. Athletic activity

MET value

Badminton, competitive Ballet dancing Basketball, game Bicycle ergometer 100 W Biking > 32 km/h Circuit training Fencing Golf, general Horseback riding, general Ice hockey Jogging, general Orienteering Running, cross-country Running 17 km/h Sailing (Laser) Scuba diving Skiing, cross-country Skiing, competition Soccer, match Squash Skating, competition Swimming, crawl Table tennis Volleyball, beach Weight-lifting, training Wrestling, one match

7.0 6.0 8.0 5.5 16.0 8.0 6.0 4.5 4.0 8.0 7.0 9.0 9.0 18.0 3.0 12.0 7.0 16.5 10.0 12.0 15.0 11.0 4.0 8.0 6.0 6.0

activity level (PAL) of the individual, thus expressing the lifestyle.

Is there a special nutritional problem in training athletes? Elite athletes represent a group of individuals with usually high energy turnover, who experience intensive physical stress. The high energy turnover results in emptying their glycogen depots and in increased fat and protein turnover over shorter or longer intervals. Thus their training and competition schedule dominate their daily life and call for specific energy and nutrient demands and meal patterns. The principle behind any dietary advice to athletes is that priority should be given to covering the energy needs in addition to compensating for fluid losses. It is furthermore essential that all essential nutrients, i.e. vitamins, minerals, essential amino acids and fatty acids, are

 Chapter . consumed not only in adequate amounts, which is usually a minor problem, but also in balanced amounts; the latter might be jeopardized when using food supplements. The meal pattern should always be adjusted to training and competition schedules. However, the effect of physical exercise is not only related to energy turnover as such. Physical exercise also has an impact on substrate utilization and may help the individual to balance his/her body composition, metabolic regulation and homeostasis.

The protein debate In athletic physiology the question as to whether there is a special need for protein in athletes is an ongoing matter of controversy. Critical analyses of the background data, however, show that there are a lot of conflicting opinions. When discussing protein needs, we must be certain that the studies performed have not been influenced by problems with energy deficiency, i.e. that the energy needs are not met []. This is of special concern in athletes with a high energy turnover as the body gives priority to covering its energy needs even when protein turnover is increased. Although it has essentially been the strength athletes that have been engaged in the discussions regarding increased protein needs of athletes, it seems, rather, that protein requirement is in fact a problem of endurance athletes. An increased demand may be due to essentially three reasons. First, it is obvious that training leads to increased muscle mass, which may increase the protein requirement. Secondly, hard physical activity, especially endurance training, may lead to increased breakdown and muscle protein turnover. Thirdly, if energy needs are not met there is an increased gluconeogenesis from muscle protein, leading to muscle protein catabolism and negative nitrogen balance. Recent studies using stable isotope techniques [,] indicate that there seems to exist a compensatory reduction in leucine oxidation in the recovery phase after physical activity. This effect is most pronounced post exercise during fasting and might indicate a homeostatic response in order to preserve body protein. Furthermore, the effect of physical exercise on leucine oxidation seems to be reduced during feeding. This might indicate that increased leucine oxidation in the muscle might be compensated for by increased utilization of dietary

protein. Interestingly earlier results from short-term studies (– h) on protein turnover during physical exercise have not registered any compensatory reduction in leucine oxidation, as they have not continued their measurements long enough after the end of the physical exercise. Both Wolfe and Rennie and their collaborators in a series of papers over the last few decades have also shown that protein turnover is increased during exercise. Nevertheless this does not necessarily mean that protein need is increased. Butterfield and Calloway [] showed that physical activity improved protein utilization and in a recent review Rennie and Tipton [] even suggested that protein metabolism may become more efficient as a result of training.

What do we know regarding gender differences? Certain oscillations in the blood content of sex hormones are necessary in order for women to have a regular menstrual cycle. This also applies to female athletes, though they often have lower levels of these sex hormones than non-trained women [,]. This results in the absence of menstruation — amenorrhea — with the frequency related to exercise volume and intensity. Exercise-induced amenorrhea occurs in nearly % of female endurance athletes [] and in athletes for whom esthetics and low body weight are important (gymnastics, sports with weight categories, dancing). Increase in running volume from  to  km/week for more than  year has resulted in amenorrhea in almost all women. The state of amenorrhea is, however, reversible and there are no indications of reduced fertility in former female elite athletes. Amenorrhea can be counteracted by a simple reduction in exercise volume. There are several indications that an insufficient energy intake influences the development of bleeding disorders. In ballet dancers it is a well-known fact that reduced food intake is associated with amenorrhea. Furthermore, cross-sectional studies have shown that long-distance runners who do not increase their food intake to balance their energy output have a higher prevalence of amenorrhea. Surprisingly, these women do not lose weight in spite of a low energy intake. This may indicate that reduced energy intake is neutralized by a reduction in resting metabolic rate compared with

Nutrition and Fluid Intake non-trained women and trained women with normal menstruation patterns. Measurements of hormones in the blood support these theories, and the absence of bleeding could be an energy-sparing mechanism in women. Underreporting of food intake may also explain why the energy intake is unusually low. The practical importance of the amenorrheal state with reduced plasma levels of sex hormones is a reduction in bone mineral content. In extremely welltrained female endurance athletes, a low bone mineral content close to the limit of fracture is often seen. In men also, intense exercise is known to cause a moderate reduction in sex hormones in the blood [], but it has not yet been clarified whether this has any practical relevance in connection to performance [a] and fertility or whether it relates to a reduced dietary intake. Tarnopolsky has discussed in a series of papers the potential gender differences in substrate utilization during endurance exercise [–]. During moderateintensity long-duration exercise he reported that female athletes showed greater lipid utilization and less carbohydrate and protein metabolism than equally trained males. In studies on substrate utilization and energy turnover in elite cyclists during a -h race we have not been able to show any gender differences in substrate utilization (Branth, Hambraeus et al. in press).



dicate a developing nutrient deficiency state. Physiologic parameters such as decreased muscle strength, prolonged nerve reaction time and reduced immune response, however, may indicate more serious disturbances as a result of deterioration of the nutritional state of an individual. Increased physical exercise is essentially a question of increased energy turnover, while the turnover of essential nutrients is usually not affected to such an extent that there is a need for an increased intake per se, provided the energy needs are covered. The debate as to whether the intake of nutrients in athletes is adequate is usually based on assessments of the dietary intake by various methods. Interestingly numerous food intake studies in elite athletes have been published based on dietary assessments where the energy intake is remarkably low and the discrepancy is obvious if the data are compared to calculated energy turnover from their training log. Thus the first step in analysing any possible nutrient deficiencies in athletes must be based on validation of reported dietary intakes. It is not scientifically relevant to draw any conclusions regarding the possible need for food supplements or increased requirement for specific nutrients in athletes as long as the energy needs are not being met by dietary intake.

Dietary recalls and/or records How to identify nutritional problems in athletes Assessment of nutritional status The nutritional status of an individual can be evaluated by various methods, i.e. anything from recording of dietary intake or analysis of physiologic parameters (i.e. body composition, physical capacity, immune defence system) to biochemical indicators (i.e. plasma levels of nutrients or endocrine response). Each of them will illustrate various stages in the nutritional status. While analysis of dietary intake will indicate potential risks of developing nutrient and energy deficiencies, changes in plasma levels of various nutrients or metabolites can be a result of physiologic adaptation to a changed nutrient balance as well as a serious indicator of nutrient imbalance. Likewise changes in body composition may represent an adaptive mechanism in the homeostatic regulation of metabolism, but also in-

There are several methods used for studies on dietary intake, both retrospective and prospective, based on anything from personal interviews, records and use of food frequency questionnaires to the double portion technique. Each of them has its pros and cons as illustrated in Table ... There is no single golden method for estimation of the dietary intake without error, and the goal of the study is of utmost importance when selecting the optimal method for dietary assessment. Furthermore, different types of errors have different effects in analysis and interpretation. Consequently, data collected by means of one dietary assessment in order to study the intake of one nutrient may not necessarily be as valid in evaluation of the intake of another nutrient. The retrospective methods comprise dietary interviews in order to describe dietary habits from a longerterm perspective. This calls for a skilled interviewer and is time consuming. They can also be based on

 Chapter . Table .. Summary of various methods for dietary assessments. Method

Coverage

Advantage

Disadvantage

Dietary history

All food items or selected items

Long-term perspectives of dietary habits Individual data

Time consuming Skilled interviewer needed Memory demanding Quantitative data difficult to obtain Variations in dietary habits lost

24-h recall

All foods

Relatively rapid and simple Can be repeated Individual data

Selection of interview day critical Quantitative data difficult to obtain Skilled interviewer needed

Food frequency questionnaire (FFQ)

Only listed food items

Rapid and simple Easy to computerize Large groups covered by mail

Restricted number of food items Memory demanding No direct contact with interviewer

Food records

All foods

Individual data Intake during various days Quantitative data

Selection of day critical Dietary intake may be affected Needs resources Time consuming Collaboration necessary

Double portions

All foods

Exact data on nutrient content possible (not dependent on accuracy of food tables)

Dietary intake may be affected Resource demanding Collaboration necessary

repeated -h recalls. In this case it is essential to select various weekdays and training situations and also to be aware of seasonal variations throughout the year. The advantage of retrospective methods is that they do not usually interfere with the subjects’ eating habits, as he/she does not know beforehand that their dietary habits will be analysed. However, the results obtained depend on the skill of the interviewer and on the subject being able to recall his/her dietary intake. In order to cover larger number of individuals, food frequency questionnaires can be used. Such forms can be coded in order to simplify computer analysis. However, the selection of food items is limited, and furthermore there is little personal contact with the subject that would allow the reliability of the data recorded to be assessed. Prospective methods comprise the use of food records, based on weighing all food items consumed or estimated from menu records or by observation. This can be performed over one or several days, usually – days. In the latter case it is essential that the records are performed continuously. A -day food record kept over  consecutive days is far more informative and

reliable than seven isolated -h records made over shorter or longer intervals. All prospective methods may have a more or less pronounced indirect impact on the dietary habits, as the subject is aware that they are being studied.

Validation of dietary assessments Dietary assessment methods will almost without exception result in an underestimation of energy intake. Energy turnover should consequently be evaluated on the basis of studies of energy expenditure based on calculated BMR with the addition of a relevant PAL factor, which is based on the lifestyle including physical activity, and only in exceptional circ*mstances on determinations of energy intake. The energy equation fulfils the first law of thermodynamics: energy cannot be created nor destroyed, it can only be transferred from one form to the other. Available energy from energy intake and tissue breakdown must balance energy turnover if body weight is stable and body composition unchanged over a certain length of time. Thus an objective and reliable reference against which to validate data obtained on dietary intake can be based on a com-

Nutrition and Fluid Intake parison between the observed or registered energy intake (EI) and the theoretical calculations of energy turnover based on calculated BMR with addition of a relevant PAL factor. In Case story .. the flow chart for the estimation of energy turnover is illustrated.

Four different situations of nutritional significance in athletes The mean intake of nutrients in athletes is of less importance and/or interest; rather nutritional problems should be divided into the following subheadings with regard to energy and nutrient intake:  daily intake and food habits (e.g. energy balance, nutrient density);  intake pre-exercise (loading phase) for optimal training effect or performance;  intake during exercise (nutrient and energy maintenance) for optimal performance;  intake post exercise (recovery phase) for optimal restoration of the energy and nutrient stores. Nutritional problems pre-exercise are dominated by the carbohydrate loading as discussed below and in Chapter .. During exercise the dominant problems are compensation for water and electrolyte losses and, if possible, energy turnover. Post-exercise nutrition should be directed towards the most rapid and efficient restoration of body stores and compensation for tissue damages.

Daily intake and food habits in athletes Interestingly numerous published food intake studies in elite athletes are based on dietary assessments where the energy intakes are remarkably low. If the data from their training logs are compared to calculated energy turnover from anthropometric data, the discrepancy is obvious and the use of various forms of compensation for energy adjustments have been proposed. Whether athletes have a tendency to reduce their BMR values as a compensation for insufficient energy intake is still an open question. An increased BMR would in fact have been expected, as both the lower fat content of an athlete’s body compared to that of an untrained individual and the excessive postexercise oxygen consumption (EPOC) should lead to an increased BMR. Data on energy intake from any dietary assessment in athletes who maintain a constant body weight, which does not exceed the minimal energy require-



ment based on BMR and a suitable PAL factor, cannot be considered accurate for analysis of the relationship between dietary intake and health (Case story ..). In case the data should be considered as representative in a long-term perspective, energy balance must have been obtained. It is thus recommended that a validation based on calculated EI/BMR ratios should be included in dietary surveys []. The data must then account for at least the minimal energy needed for sedentary life (BMR ¥ .), with the appropriate addition for physical exercise, otherwise they represent an underestimation. It is then necessary to find out whether the missing energy units are supplied by qualitatively identical dietary components or whether other sources of energy have been consumed and not recorded. Furthermore, to what extent can we assume that the underestimation of dietary intake is the same for all nutrients? An intake of about  g carbohydrate/kg/day is generally recommended for athletes today (Table ..). This corresponds to a total carbohydrate intake of  g per day in a -kg person or to % of total energy (60E%) if daily energy intake is  MJ/day ( g carbohydrate- kJ). This is a considerable amount — both compared to the recommendations for the average population (– E% = – g at  MJ/day) and compared to the average intake of the adult Danish population ( g/day) []. The energy need of an athlete will normally be greater than the energy need of a sedentary person. However, carbohydrates give a higher degree of satiety and feeling of fullness per kJ than fat []. Furthermore,  g carbohydrate contains approximately half as many kJ as  g fat ( kJ/g vs.  kJ/g). It is therefore necessary to consume twice as much carbohydrate than Table .. Nutrient recommendations.

Carbohydrate Fat Protein

Average population * E%

Athletes E%

g/kg/day

55–60 max. 30 10–15

60–65** 20–25 10–15

c. 8 Not defined 1.2–1.7

E%, percentage of total energy. * From [90].

 Chapter .

Case story 2.4.2 How to validate dietary assessment by comparing energy intake (EI) and energy turnover (ET) based on BMR and PAL including one practical example Step 

Procedure Collect anthropometric data (age and sex, body weight, height)

  

Verify that body weight has not changed = energy balance Calculate energy intake (EI) from dietary assessment Calculate BMR according to FAO/WHO/UNU  equation Analyse physical activity from training report and lifestyle (hours of sleep, sitting, walking, etc.) Occupation h BMR factor Energy(kJ) Sleep    Cross-country skiing, training    Sitting, reading, TV  .  Walking  .  Miscellaneous  .  Calculate total energy turnover (ET): (a) using BMR factors from physical activity record (see Step ) ET =   kJ (b) using BMR factor for sedentary life (.) ET =   kJ Calculate PAL factor based on: ET (Step a)/BMR(Step ) ET/BMR = . Compare estimated EI from dietary assessment (  kJ) with: (a) estimated BMR ( kJ) EI/BMR = . (b) estimated ET from theoretical calculations of BMR and PAL EI/(BMR ¥ PAL) = .

  

Comments The EI/BMR ratio is ., i.e. the energy intake only covers sedentary life. This is quite different from his PAL according to the lifestyle and training record (.). The difference between ET for sedentary life (  kJ) and that according to the dietary record (  kJ) is  kJ which is energy available for training. Training intensity (MET = ) corresponds to  ¥  =  kJ/h. If this dietary assessment is correct it means that he would only be able to train for / = . h or  min, if it is assumed that he is in energy balance. If on the other hand he is training for the  h recorded in the physical activity diary his daily ET would be , i.e. the recorded EI ( ) would represent only % of ET. These

Example Male,  years, weight  kg, height  cm Stable body weight   kJ  kJ/ h or  kJ/h

values do not fit if he is maintaining his body weight and body composition. If he had been asleep in bed when not training, his ET would have been   kJ. This would mean that his EI should represent a BMR factor of ., which is considered below survival needs. Another solution might be that he must reduce his BMR in order to maintain his body composition and energy balance and not develop a catabolic state. In this case he must reduce his BMR from  to  kJ/h, or % if the BMR factor of . is valid for his sedentary life when not training. The most probable reason for the discrepancy between ET and EI is an underevaluation of his dietary intake!

Nutrition and Fluid Intake



Case story 2.4.3 Energy balance in a 20-year-old tennis-playing female (weight 61 kg, height 165 cm)  Her BMR calculated from anthropometric data was  kJ/ h or  kJ/h.  Her energy intake (EI) based on dietary records was  kJ. Occupation h BMR factor Sleep   Tennis training   Sitting, reading, TV  . Walking  . Miscellaneous  . Total energy turnover (ET) using BMR factors  Her PAL factor was: based on ET/BMR based on EI/BMR  EI in relation to ET from physical activity records

Comments The EI/BMR ratio is ., i.e. the energy intake does not even cover her BMR. This is quite different from her PAL according to lifestyle and training record (.). A dietician (who obviously had no experience or knowledge of athletic physiology) had recommended a low-fat diet, using skimmed milk, low-fat margarine and low-fat yoghurt, and this female started to develop anorexia. Unfortunately this is an authentic case and not an unusual example of misinformation due to lack of

fat in order to obtain the same energy intake. Finally, the so-called nutritious and recommended carbohydrates, which also contribute vitamins, minerals and dietary fiber (starch-rich carbohydrates and fruit), are characterized by a large volume and water content. This type of carbohydrate is therefore much less energy dense than fat, which means that a larger volume of food intake is needed in order to obtain the same energy intake on a carbohydrate-rich diet than on a fat-rich diet. An athlete may therefore find that satiety occurs before the meal is finished and consequently that their intake of energy and carbohydrate is not adequate. Evidence of this also comes from the numerous

 Her physical activity according to training report and lifestyle was as follows:

Energy (kJ)        kJ . . . knowledge that dietary counselling for athletes should be different from that intended for the general public. Low fat diets with low energy density usually lead to difficulties for athletes with high energy turnover in covering their energy needs with reasonable amounts of food. Furthermore the risk factor for cardiovascular disease secondary to fat intake has little relevance for athletes with high energy turnover as long as they are in energy balance.

studies showing a spontaneous decrease in total energy and a reduction in body weight when a carbohydraterich diet is consumed ad libitum for weeks or months [b,,]. From Table .. it can be calculated that you have to eat . kg bread ( slices of rye bread or  slices of wholemeal bread), . kg boiled rice or . kg apples, or drink – L of juice every day in order to obtain  g carbohydrates per day. The volume problem of a very carbohydrate-rich diet can be managed partly through more frequent meals (six to eight per day), and partly by consuming some of the carbohydrates as concentrated carbohy-

 Chapter . drates or fluids such as dried fruits, sugar-rich sweets, juice, energy drinks, glucose or maltodextrin (glucose polymer) solution. In order to obtain essential vitamins and minerals, it is, however, necessary to ensure a daily intake of the nutritious carbohydrates as well. This recommendation is particularly important for subjects with a low fat intake (often women). Since a very high intake of carbohydrates is recommended, the diets of athletes will mostly be based on vegetable food and hence the diet is likely to be semi- or totally vegetarian. It is difficult to design a vegetarian diet, especially a vegan diet (% vegetable), which is sufficient in essential amino acids, vitamins and minerals. The latter applies especially to iron, zinc, calcium and vitamins D and B12. In a lacto-ovovegetarian diet it is relatively easy to obtain essential amino acids, vitamin B12 and calcium, but iron intake is still a problem. This is primarily due to the fact that non-heme iron which is found in vegetables is more difficult to absorb than heme iron which is found in meat []. A vegetarian diet may reduce concentrations of sex hormones even when ideally balanced [,a], but the long-term effects on performance of a vegetarian diet have not been shown [a,].

Nutrient and fluid intake before training/exercise (loading phase) Carbohydrate The focus with regard to athletes’ diets has been on carbohydrate intake in particular, since the body’s glycogen stores are very limited. Although glycogen content is increased about two-fold in a well-trained

athlete compared with a sedentary person (Table ..), the glycogen stores are still a limiting factor for exercise endurance and intensity (see Chapter .). Compared with the fat stores, glycogen stores can supply energy for a few hours of medium-intensity work, whereas fat stores can supply energy for several days. It is also essential to remember that muscle protein also represents a substantial and potential endogenous energy source, constituting about % of the body’s total energy store in a normal individual, probably more in a well-trained athlete. Studies during the past century have also shown quite convincingly, that glycogen stores can be varied according to the dietary composition (Table ..) []. This is of great importance when heavy training takes place once or twice every day. In this case, the stores can be completely replenished if the diet is rich in carbohydrates. Therefore, the goal in dietary advice to athletes has first and foremost been to increase carbohydrate intake. However, it should always be remembered that a diet rich in carbohydrates which still does not meet energy needs is of little use. An increase in muscle and liver glycogen content and an improvement in performance have been seen after the intake of a relatively large carbohydrate meal (approximately  g carbohydrate) – h before training compared with no intake [–]. Previous opinion was that high concentrations of insulin in the blood at the beginning of physical activity (as after intake of carbohydrate – min before training) were a disadvantage because blood glucose during training of medium severity might drop as a consequence of increased glucose absorption in the working muscula-

Table .. Size of glycogen stores on different diets. From []. Size of the glycogen stores Stores

Total weight

Mixed diet*

CHO-rich diet†

Fat-rich diet‡

Liver Muscle

1.2 kg 32 kg

40–50 g 350 g

70–90 g 600 g

0–20 g 300 g

CHO, carbohydrate. * 30 E% fat, 45–50 E% carbohydrate. † 70 E% carbohydrate, 10 E% fat. ‡ 20 E% carbohydrate, 50 E% fat.

Nutrition and Fluid Intake ture []. This risk is lower during intense muscular exercise of short duration (e.g. – min of rowing). Here the release of blood glucose-elevating hormones (counter-regulatory hormones), such as epinephrine, cortisol and growth hormone, is very powerful and can therefore match the extra glucose absorption in the muscle []. Several more recent studies have shown, however, that intake of glucose – min before training (cycling or running) does not result in reduced endurance capacity, sometimes even the contrary (for a review see []).

The glycemic index More recently, not only the amount but also the types of carbohydrate have been included in the dietary guidelines to athletes. The concept of glycemic index (GI) was introduced in  in order to be able to classify carbohydrates according to the postprandial increase in blood glucose []: GI = [ blood glucose area of test food]

[ blood glucose area of white bread] ¥ 100 According to the GI method, carbohydrates can be divided into high, medium and low GI foods. In general, GI is low for foods high in fructose, which have a high amylose/amylopectin ratio, contain large starch particles, are minimally processed or are ingested with fat and protein. However, there is no general rule that complex carbohydrates have a low glycemic index. Thus potatoes may have a high glycemic index while some pasta products have a very low glycemic index []. The GI for some selected foods is shown in Table ... For a more extensive table, see Foster-Powell and Brand-Miller []. Some studies have suggested that low GI or slow carbohydrates should be preferred to high GI carbohydrate before exercise []. However, it seems that carbohydrate intake during exercise eliminates any difference in blood glucose, insulin, substrate oxidation and performance induced by pre-exercise carbohydrate intake [].



Table .. Carbohydrate content and glycemic index (GI)* (where known). From [–].

Glucose Sucrose Fructose Candy Cornflakes, unspecified Muesli, unspecified Liquorice Liquorice allsorts Biscuits, digestive Raisins Chocolate, milk White bread Rye bread, dark Wholemeal bread Rye bread, wholegrain Wine gums Soya beans† Boiled rice, brown† Boiled pasta† Corn Banana Fresh-boiled potatoes† Orange juice Apple/pear Soft drink and syrup Skimmed milk Tomato/cucumber

g/100 g

GI

100 100 100 98 83 71 78 83 66 78 59 51 48 49 49 79 34 25 25 23 21 18 10 13 10 5 6

138 89 31 – 115 96 – 82 93 – 100 89 99 58 – 20 96 45–66 80–87 79–84 80 67 53/47 – 46 –

* Compared to white bread = 100. † GI varies according to method of preparation and temperature during intake.

quate hydration and allow time for excretion of excess ingested water. Of special interest in this context is the fact that glycogen binds . g water per gram of glycogen. Thus during carbohydrate loading it is also essential to have an accurate fluid intake.

Nutrient and fluid intake during training/exercise (maintenance phase) See Case story ...

Fluid

Energy substrates

Fluid stores must be filled before exercise in order to prevent premature dehydration. About  mL of fluid about  h before exercise would promote ade-

The metabolic fuels used during exercise depend on the training duration and intensity, the training state of the athlete, the fuel availability and reserves in the

 Chapter .

Case story 2.4.4 Emergy balance not protein deficiency is the problem in athletes -year-old girl, elite athlete, active mountain biker: body weight . kg, height  cm, BMI ., body fat .%, BMR calculated  kJ, V˙2 max  mL/min ( mL/kg/min). She participates in a test training program involving cycling  km at a mean speed of Intake before race Intake during race Losses during race Balance

Energy (kJ)    –

Please note the pronounced negative energy balance! The protein balance does not represent a problem and it seems that she managed to maintain her fluid balance. (Fluid losses are

body, the previous diet and possible intake during exercise. In general, the use of carbohydrate as substrate increases with increasing exercise intensity and falls with increasing exercise duration (due to depletion of the glycogen stores). Conversely, fat utilization is higher at low exercise intensities (< % V˙2 max) and increases with longer exercise duration (> – h) []. The recommended carbohydrate intake is  g carbohydrate/min, since this is the maximal rate of carbohydrate oxidation during exercise []. A -g/  mL glucose drink at a rate of about  mL/h would be a compromise between fluid intake recommendations and intake rates typically achieved by athletes in competitive situations []. There seem to be no important differences between different moderate to high GI carbohydrate sources ingested during prolonged, moderate-intensity exercise (except for fructose which is very slowly metabolized) []. Furthermore, the food form (fluid vs. solid) seems to be of no importance either. Carbohydrate supplements have not been considered very relevant in exercise bouts lasting less than  h. However, recent studies have shown that in intermittent or high-intensity exercise of <  h, carbohydrate intake may also improve performance [].

 km/h. Duration of race  min. Breakfast before race contained juice, cereals, yoghurt, bread and butter, coffee. Intake during race: sports drinks, chocolate bars and bananas. The nutritional balance at the end of the race could be summarized as follows: Protein (g)    +

Fluid (L) . . . +.

calculated based on weight differences and measurements of body water using bioimpedance.)

Protein Physical exercise leads to an increased protein oxidation in the muscle in absolute terms. However, the contribution of protein to energy turnover is remarkably reduced in relation to carbohydrate and fat. Food intake seems to reduce leucine oxidation during exercise []. The changes in substrate oxidation during exercise at -h energy balance during fasting and feeding is illustrated in Fig. ... A high protein diet seems to have a carbohydratesparing effect as the surplus of protein is converted through gluconeogenesis and contributes to endogenous carbohydrate which is then oxidized. Interestingly a high protein diet also seems to stimulate fat oxidation []. Both these effects might be due to increased glucagon levels in the blood on a high protein diet.

Fat The contribution of fat oxidation increases with improved training state []. But even for the welltrained athlete, the optimal situation during exercise is to maintain carbohydrate supply to the muscles, but slow the depletion of the glycogen stores by increasing the reliance on fatty acids and on glucose supplied from intake of carbohydrate.

Nutrition and Fluid Intake (b) 600

500

500

400

400

J/kg/min

300 200

200

0600

2100

carbohydrate fat protein

0600

Real time (clock hours)

1600 1730

0830 1000 1200

0600

2100

1600 1730

0830 1000 1200

0630

carbohydrate fat protein

0630

100

100 0

300

carbohydrate fat protein

Real time (clock hours) (d)

(c)

100

40

0600

2130

1600 1730

0630 0830 1000 1200

20 carbohydrate fat protein

Real time (clock hours)

60 40 20 0

2130

60

80

1600 1730

80

0630

% of energy expenditure

100

0830 1000 1200

J/kg/min

(a)

% of energy expenditure



Real time (clock hours)

Fig. .. Substrate utilization during exercise in -h energy balance studies at normal and high protein intakes [].

In order to reduce carbohydrate oxidation and spare glycogen stores during exercise, it has been suggested that fat also could be ingested before and/or during work. Medium-chain triglycerides (MCTs) have been investigated in particular, since they are rapidly absorbed and enter the circulation directly through the portal vein. MCTs are rapidly oxidized both at rest and during exercise, especially when ingested with carbohydrate [,]. Conflicting results have, however, been produced, showing either a negative effect, no effect or a glycogen-sparing and performanceenhancing effect of MCTs. Ingestion of  g MCTs was found to contribute –% of energy expenditure, but to have no effect on muscle glycogen breakdown or carbohydrate utilization []. Conversely, a large dose of  g MCTs was found to elevate plasma free fatty acid (FFA), decrease glycogen breakdown and increase performance in a time trial []. However, in another study a negative effect on performance was observed

after intake of  g MCTs alone even though FFA levels were increased. Also the subjects reported gastrointestinal discomfort, which may have been the reason for the decreased performance []. A more recent study showed no effect of carbohydrate + MCT ingestion on time trials after  h of constant-load exercise []. At present, data are therefore too conflicting to conclude whether MCTs should be used or not to enhance performance.

Optimal fluid intake During physical activity fluid is lost at a rate dependent on the degree of work intensity, temperature and humidity of the surroundings. Often athletes have a water loss due to sweating of – L/ h. For elite runners this may amount to .– L in warm surroundings. Studies have shown a tendency to drink too little (involuntary dehydration) since increased thirst during

 Chapter . physical activity does not appear until the subjects dehydrate about % of their body weight. This should be viewed in light of the fact that even a dehydration of –% of body weight reduces performance because of compromised temperature and adjustment of cardiovascular regulation []. It is therefore very important that athletes drink at least as much fluid as they lose. A good rule today is to drink at least every  min during a race. However, how much and what kind of fluid that can be consumed during exercise will vary for each individual and must therefore be decided individually during the actual exercise bout. It is consequently recommended that various kinds of fluids are tested during training in order to find the optimal solution and to try to estimate the water losses by recording body weight changes during the race. To what extent the glycogen-bound water is released and available for the homeostasis of water balance during endurance performance has to be further elucidated. The rate of gastric emptying for fluids depends on the volume and concentration. It is possible to empty c.  mL/ h, but the amount is reduced during intense muscle activity (> % V˙2 max) and with high osmolality in the consumed fluid. The latter is especially important in exercise of longer duration (> – h). As long as the carbohydrate solution is –% it does not, however, affect gastric emptying rate. Newer carbohydrate types (e.g. the glucose polymer maltodextrin) permit an intake of % solutions. This is due to the fact that the osmolality is too low to affect the gastric emptying rate. During prolonged exercise (– h) the fluid should contain carbohydrates and a small amount of electrolytes, primarily in order to increase intestinal absorption of carbohydrate. Even though sodium is lost in sweat, there is no sodium depletion until several hours of work have been performed.

Nutrient and fluid intake after training/exercise (recovery phase) How soon post exercise? Muscle glycogen repletion occurs most rapidly just after exercise. This is due partly to increased glycogen synthase activity and high permeability to glucose, and partly to increased insulin action in the exercised muscle [,]. Hence, the rate of glycogen storage was

Table .. Examples of ‘pick-me-up’ food items for restoration of glycogen depot (all containing  g carbohydrate). 1.5 L sport drink (7% carbohydrate) 0.9 L blueberry soup 2 bananas (peeled) 1.5 dL raisins 1 L orange juice 4 dL cereal mix (muesli) 10 bread slices (wheat) 4 dL oats 0.7 L fruit yoghurt (0.5% fat) 2 L low-fat milk (0.5% fat)

(0 g protein) (3 g protein) (4 g protein) (4 g protein) (10 g protein) (15 g protein) (17 g protein) (20 g protein) (25 g protein) (70 g protein)

found to be four times higher in the first hour after exercise than just  h after end of exercise, when carbohydrate was consumed  or  h post exercise, respectively []. Carbohydrate should therefore be consumed as soon as possible after exercise. Protein consumed in combination with carbohydrate may increase postexercise glycogen synthesis more than carbohydrate alone, due to increased insulin concentrations [,] (Table ..). Recent studies indicate that protein post exercise in the form of protein hydrolysates and amino acid–carbohydrate mixtures [] will also optimize muscle protein recovery or even stimulate protein anabolism and increased muscle mass but this still has to be verified. Fluid intake in connection with exercise must at least compensate for the fluid lost during exercise. Weighing (without any clothes) before and after exercise will show the approximate fluid loss during exercise. The color of an athlete’s urine can also reveal whether overall fluid intake is sufficient.

Is there a need for a special diet post exercise? After moderate-intensity exercise with glycogen depletion, muscle glycogen content (like liver glycogen) is regenerated to a normal level in – days on a mixed diet and in approximately  h on a carbohydraterich diet. Provided that the emptying of the muscle glycogen has been extensive and the following intake of carbohydrate is large, muscle glycogen will be regenerated to higher levels than before exercise (supercompensation). The type of carbohydrate probably plays its most

Nutrition and Fluid Intake important role in the postexercise diet. Thus, one study showed that the glycogen storage rate after glycogen-depleting exercise (.– h at % of V2 max) was higher  h after intake of high GI carbohydrates compared to low GI carbohydrates []. Faster glycogen resynthesis with glucose compared to fructose has also been found during the hours after exercise. After  h, however, no difference between the glycogen resynthesis was found after high or low GI carbohydrates. However, another study showed that after  h a high GI diet increased muscle glycogen stores % more than a low GI diet []. If exercise takes place once or twice daily, it is therefore advisable to choose high GI carbohydrates after training. With exercise only once a day or less and a recovery period of more than  h, the type of carbohydrate does not seem to be important for the training outcome, but this has not yet been completely clarified. A problem often encountered by athletes is a decreased appetite for up to – h after heavy exercise []. To overcome this problem, a carbohydratecontaining drink is advisable. In this way both fluid balance and muscle glycogen can be rapidly restored. It has not yet been clarified, though, if additional protein intake — resulting in a positive nitrogen balance — can be advantageous with respect to muscle building and performance. For most athletes, a sufficient protein intake will not be a problem. This implies, however, that the athletes are in energy balance and consume varied meals containing all the essential amino acids. In types of sport with frequent periods of energy deficiency during training (running, gymnastics, athletics, ballet) as well as for vegetarians (especially vegans), the diet may be low in proteins and insufficient with respect to essential amino acids []. Examples of complete protein combinations are: beans + rice, peas + corn, pulses + bread, cereals + milk or eggs, and potatoes + eggs or milk. One should also bear in mind that the bioavailability of vegetable protein from a fiber-rich diet is estimated to be % lower than the bioavailability of animal protein. Studies on the dietary intake of Kenyan runners by Christensen and collaborators [] were able to show, however, that the high carbohydrate and low fat intake, which was similar to that reported in endurance runners from other low-income countries, was suffi-



cient to cover energy as well as protein intake, including the need of essential amino acids, despite the diet being based on a small range of mainly vegetable food items.

The role of dietary supplements Is there a need for food supplements? Subnormal levels of one or more nutrients in body fluids cannot be taken as an indicator that there is a nutrient deficiency which calls for food supplements, unless the energy needs are covered. Several studies indicate that subnormal levels of nutrients can be restored by means of a well-balanced diet consumed in adequate amounts to cover energy requirements. The motivation for athletes to use supplements can be divided into various categories:  use of supplements for optimal training effect, e.g. use of certain amino acids stimulating the release of growth hormone;  supplements to be used during competition, e.g. use of bicarbonate to counteract acidosis;  use of preparations for optimal restoration, e.g. creatinine for training effect at repetitive strength training;  use of supplements to increase psychological capacity, e.g. B vitamins against agony, branched chain amino acid supplements to counteract central tiredness, antioxidants against muscle tissue damage. In all these circ*mstances there is a gray area between physiologic demands and doping effects, an issue which is still not resolved. There are also various forms and types of supplements. Complete supplements represent an alternative to conventional food which are often used in clinical dietetics for tube feeding of patients with gastrointestinal problems. These products may be used as ‘convenience foods’ for athletes who have problems fitting their meal pattern around their training schedule. Food supplements comprising vitamins and minerals are often used. It is, however, essential that they are balanced in a defined mixture, usually as a multiple of the recommended intakes. Otherwise there is a risk that imbalanced intakes will cause problems. Energy supplements, often drinks or cakes with high energy density, usually based on carbohydrate, are often used to cover high energy turnover. However, there is a

 Chapter . potential risk of high energy density products leading to nutrient imbalance as a result of low nutrient density of the diet. Finally there are the ergogenic supplements which usually include megadoses of vitamins, minerals, stimulators (e.g. caffeine), and others (e.g. creatinine, Q, ginseng), in order to increase physical and mental capacity. In these cases we are also in the gray area between physiologic demands and doping effects. Excessive dietary intake of certain minerals and trace elements may impair the balance of other minerals due to interactions affecting intestinal absorption; e.g. zinc intake above  mg per day impairs copper and iron metabolism and high iron supplementation impairs the uptake of other minerals, e.g. zinc. A high protein intake has also been reported to be deleterious for calcium, phosphorus, zinc and copper requirements.

Fat More recently, a renewed interest in fat-rich diets as an ergogenic aid has emerged. Thus, several studies have investigated whether fat oxidation can be increased and thereby glycogen breakdown prolonged during exercise if the athlete is habituated to a more fat-rich diet instead of the recommended carbohydrate-rich diet [–]. The overall message from these studies seems to be, however, that a fat-rich diet consumed for at least  weeks does not improve performance or increase glycogen stores. On the contrary, a carbohydrate-rich diet still seems to be superior to a fat-rich diet. A daily intake of at least  E% fat should be consumed in order to obtain enough essential fatty acids and fat-soluble vitamins in the diet. However, up to – E% fat would still ensure enough calories for carbohydrate and protein in the diet.

Protein Protein is also metabolized during exercise, although to a lesser degree than carbohydrate and fat as long as the athlete is in energy balance. Furthermore, sufficient carbohydrate stores and carbohydrate administration during exercise have a sparing effect on protein utilization. It is recommended that an endurance athlete should consume .–. g protein/kg body weight/day, while strength-training athletes should

consume .–. g protein/kg body weight/day [] although the scientific evidence for a raised protein requirement in the diet is questioned by others. At a total energy intake of  MJ/day, where the protein intake corresponds to  E%, this means an intake of  g protein or . g protein/kg body weight in a -kg man, i.e. well above these recommendations. Most athletes even in their normal diet have >  E% protein and a higher energy intake than  MJ. Thus there is no need for extra protein supplements in their diet in order to cover a protein requirement of .–. g/kg body weight/day. Of greater interest is, however, to what extent a more optimal muscle protein restoration could be obtained if protein is given post exercise. This, however, still has to be further elucidated.

Minerals Minerals and trace elements constitute about % of the body. The dominant part is calcium phosphate in the skeleton, representing almost –% of body mass, while the trace elements constitute less than .%. As the latter play an essential role in the metabolic function of the body, trace elements represent essential nutrients which must be consumed regularly, albeit in small amounts. Today  minerals and trace elements have been identified as essential, but recommended daily allowances (RDA) have only been established for seven of these: calcium, iodine, iron, magnesium, phosphorus, selenium and zinc. Intense physical exercise has been shown to increase the losses of minerals and trace elements in urine, sweat and feces to varying degrees. The magnitude of the losses is dependent not only on the type and intensity of exercise and individual homeostatic control, but also on the nutritional situation (nutrient intake and nutrient status of the individual). It is still an open question as to how to measure mineral status in an individual, as plasma levels are usually not appropriate indicators and may even be misleading due to the homeostatic regulation in the body. It is generally agreed that moderate physical activity does not adversely affect mineral status when recommended amounts of minerals and trace elements are consumed in a mixed diet with a normal nutrient density []. Diets with high energy density and low nutrient density (often called empty calories), i.e. high

Nutrition and Fluid Intake carbohydrate and/or high fat diets, may potentially lead to deficiencies of essential nutrients for some athletes with high physical activity. Other risk groups are those engaged in sports which favor low body weights, leading to restricted dietary intakes (e.g. gymnasts, endurance runners). Nevertheless, very few studies have so far indicated reduced physical performance due to trace element deficiencies, with the exception of iron-deficiency anemia.

Calcium Calcium is the most abundant mineral in the body, which contains about .–. kg. Approximately % of the body calcium is located in the skeleton, which serves as an important calcium depot, while the remaining % occurs as calcium ions of relevance for neuromuscular function. Severe hypocalcemia can cause serious muscle cramps and heart arrhythmias. However, there are no reliable data available concerning the potential effect of calcium supplementation in the treatment of muscle cramps in athletes. The homeostasis of calcium is tightly regulated by a complicated hormonal system in which vitamin D plays an important role. Peak bone mass is achieved by the age of –  years. An inadequate calcium intake before this age, which is common in many young females, may lead to consequences later in life with osteoporosis and fractures. Weight-bearing exercises such as running and weight-lifting have been shown to increase peak bone mass, especially before puberty, but are probably not as important as calcium intake. A physically active lifestyle throughout life does however have a positive effect on bone mass and a lifelong adequate calcium intake of over  mg/day reduces the risk for later osteoporosis []. A positive interaction between exercise and calcium has also been shown in young subjects but it seems likely that the calcium intake has to exceed  mg, which many athletes do not achieve []. Athletes with stress fractures have been found to have low bone density associated with low calcium intake []. In contrast calcium supplements ( mg/day) given to military recruits did not prevent stress fractures []. In osteoporosis, prophylactic studies indicate that an effect is obtained only when more than  mg are given in supplements. There



are no studies or other evidence that calcium supplementation could give athletes any physical performance benefits. On the contrary, excess calcium intake may inhibit iron absorption.

Iron The total content of iron in the body is – g. Iron is stored in the body bound to a protein, ferritin, and serum ferritin is considered to reflect total body iron stores. Transferrin is a transport protein in plasma and is usually only saturated with iron to %. The saturation decreases during iron depletion, but total transferrin content, often referred to as total iron binding capacity, is also increased during chronic infections and pregnancy, leading to a lower saturation. Serum iron is influenced by many factors including physical exercise and it is not considered as a suitable indicator of iron status of the individual. Iron occurs in two forms in the diet: in an inorganic form in vegetable sources, non-heme iron, as well as in an organic form, heme iron, from animal products, i.e. meat and blood products. The absorption of non-heme iron is relatively low and inhibited by, for example, bran, cellulose, pectin and phytic acid, while protein such as meat and ascorbic acid enhance absorption. Heme iron has a higher bioavailability and this is not influenced by antinutrients to the same extent. Iron supplements are widely used by athletes but gastrointestinal side-effects are common, which decrease compliance and make the treatment complicated. Low dose iron supplementation seems to be a good practice (approximately  mg elemental Fe/day) []. The daily loss of iron is small (c.  mg/day for men and  mg/day for women — menses) because of an effective recycling system. In addition iron absorption increases when iron stores are depleted as occurs during growth and menstrual bleeding (up to  mg/day). Hence, recommendations have been fixed at  mg/day for men and  mg/day for women, respectively. An increased incidence of reduced serum ferritin has been shown in many studies among athletes, where runners are most affected, especially females, but most types of training can affect serum ferritin concentration. However, most studies have shown that a low serum ferritin level without manifest anemia does not seem to affect performance capacity. Furthermore, low serum ferritin concentrations may only reflect a

 Chapter . shift of iron from stores to functional compartments, e.g. myoglobin in muscle. Moreover, the widespread low or subnormal hemoglobin and hematocrit, often reported especially among endurance athletes, has been called ‘sports anemia’. However, in most cases this is probably caused by physiologic adaptation with expanding baseline plasma volume (dilution pseudoanemia) due to the repetitive acute loss of plasma volume during intense physical exercise []. In addition, intensive prolonged or muscle-damaging exercise evokes an acute phase response which, among other reactions, causes a fall in serum iron and rise in ferritin levels. This makes the interpretation of iron status in athletes difficult. Several suggestions have been proposed to explain how iron status can be affected by physical exercise, including increased gastrointestinal blood losses by hemorrhage erosions or ischemic colitis and/or reduced absorption. Hematuria occurs but is uncommon, and iron losses in the urine are small. Hemolysis due to erythrocyte rupture during strenuous training, especially running, where erythrocytes may be crushed within the foot, is also suggested as an explanation. There is also a possibility of increased red cell turnover and there might be increased red cell mass by training. Iron losses through sweat have been estimated to be –% of absorbed iron per day during  h exercise and thus might be a problem for those with low iron intake and marginal stores []. The incidence of iron-deficiency anemia has not been shown to be high in athletes. Most studies have so far also shown that non-anemic iron depletion as well as iron supplementation does not seem to increase physical performance. However, some limited data suggest that female athletes with low ferritin values could benefit from iron supplementation [,] but this still has to be clarified. Increased iron intake by diet should always be the first choice. Three groups have, however, been identified to be at greater risk for developing iron deficiency: female athletes, distance runners and vegetarian athletes. Attention has, however, to be focused on the fact that excess iron appears to lead to oxidative stress and may therefore aggravate exercise-induced oxidative stress. It could also be deleterious for those with the genetic disease hemochromatosis []. Furthermore, excess iron intake may reduce uptake of other trace elements, in

particular zinc, and cause nutritional imbalances. Consequently iron supplementation to athletes should only involve small doses and should only be used when iron-deficiency anemia is properly documented by laboratory assessments [].

Zinc Zinc is a component of more than  enzymes involved in carbohydrate, fat and protein turnover. They are necessary for the immune system as well as for the endocrine response and protection against free radicals. Zinc is of vital importance for metabolic turnover during physical exercise. About % of the zinc is intracellular; only .% of the total body content of zinc occurs in plasma while % is located in muscles. Thus the measurement of plasma zinc levels as an indicator of zinc status can be questioned. Zinc needs for athletes are still not clarified although exercise may result in increased zinc losses in sweat and urine []. There is, however, so far no evidence that zinc supplementation may enhance physical performance in humans. It has however, been suggested that zinc depletion could increase exercise-induced stress, e.g. decreased immune defence and muscle damage secondary to changes in membrane stability []. Zinc supplementation is common among athletes. However, zinc overdose (>  mg) may impair immune function as well as iron and copper status [].

Magnesium Magnesium is involved in more than  metabolic reactions of relevance for substrate turnover and utilization. It is also involved in neuromuscular, cardiovascular, immune and endocrine function, and has an antioxidant role. Magnesium deficiency has been shown to occur in a wide variety of clinical conditions associated with oxidative stress, e.g. cardiovascular disorders and diabetes, where magnesium supplementation may be beneficial []. In athletes it has been suggested that magnesium deficiency is a contributing factor to exercise-induced muscle cramps, but this is still not proven. Serum magnesium is a poor indicator of magnesium status and there are still no reliable methods available for evaluating magnesium status. Although magnesium is excreted in the sweat, even during profuse sweating the

Nutrition and Fluid Intake magnesium losses are relatively small, probably due to an effective redistribution of magnesium within the body, especially thanks to the homeostatic control of the kidney. There might, however, be increased magnesium turnover and urinary losses during long and intensive training periods and stress []. So far there are, however, no studies that show that magnesium supplementation is beneficial for athletes despite the fact that magnesium has an essential function in energy turnover in the body.

Chromium Although chromium is considered as an essential nutrient, its biologic role is still not fully understood. Strenuous exercise has been shown to increase urinary excretion of chromium markedly [], but whether this leads to a risk of developing chromium deficiency is not known.

Selenium Selenium functions as an antioxidant alone in the detoxification of heavy metals in the body and as a cofactor of the antioxidant enzyme glutathione peroxidase. Dietary selenium deficiency increases tissue oxidative damage and it seems that selenium has a sparing effect on tissue levels of vitamin E. However in experimental studies selenium deficiency does not impair endurance capacity in rats and supplementation in humans has no effect on physical performance []. Selenium has also been shown to be important for the immune system. This is of special concern in the Scandinavian countries, which have selenium-poor soils, and has led to specific programs to add selenium to fertilizers in Finland in order to increase the dietary intake of selenium. In this context it is of interest that it has been shown that selenium status in Swedish athletes is subnormal and lower than in Finnish athletes [].

Sodium As sodium plays an essential role in the regulation of fluid balance, prolonged strenuous exercise, especially in a hot environment, may result in acute sodium losses which lead to heat exhaustion or even heat cramps []. The daily intake of sodium is usually quite accurate and sodium replacement is seldom necessary during exercise. There is also an adaptation process in the

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body during heat environment leading to less sodium losses in sweat and urine, but if the athlete is not acclimatized, losses of sodium and minerals in a hot environment may be considerable.

Vitamins Vitamins are essential nutrients which must be supplied on a regular basis. They are involved in many metabolic pathways, which often are stressed during intensive exercise, and include coenzymes essential in the metabolic system as well as antioxidants. Consequently it has been shown that a low vitamin status can reduce physical performance [] although, to date, no controlled studies have shown that vitamin supplementation increases performance. Exercise appears to increase the turnover and losses of some B vitamins. Some studies indicate that nutritional status is impaired in some active individuals with insufficient energy intake and/or poor nutrient density in their diet such that it is deficient in certain B vitamins, i.e. thiamine, riboflavin and vitamin B6.

Oxidative stress and antioxidants Oxygen is essential for human life and necessary for energy production, but in some forms it can be damaging to the body as reactive oxygen species (ROS): free radicals. The majority of ROS are produced in the mitochondrial electron transport chain during energy production. Physical exercise augments the production of free radicals and other forms of reactive oxygen species. End-products of oxidative damage are observed in the blood and tissues after acute intensive exercise as well as signs of decreased levels of antioxidants in some studies. Strenuous exercise may manifest an imbalance between the production of ROS and antioxidant defences, resulting in an oxidative stress situation in the body []. In fact there is some evidence which implicates ROS as an underlying cause of exercise-induced muscle fatigue and damage. During an acute bout of strenuous exercise the immune system is activated and produces a substantial amount of ROS, which may cause an inflammatory process. The immune system produces ROS to kill bacteria and viruses. During b-oxidation of large amounts of fat, as occurs during starvation, there is a substantial production of ROS; this also occurs during oxidation of amino acids through degradation of xanthine to uric

 Chapter . acid. In addition there is a ROS production during the autooxidation of catecholamines []. The body has created an extensive protective system against these potentially damaging species, the antioxidant system. If the production of free radicals is large enough to overcome the antioxidant defence system, oxidative stress will ensue. Training seems to induce an adaptation with elevation of antioxidant protection through increased levels of the key antioxidant enzymes: the zinc-containing superoxide dismutase, iron-containing catalase and selenium-containing glutathione peroxidase. Training also seems to reduce signs of oxidative stress. Important dietary sources of antioxidants include vitamins C and E, carotenoids, zinc and selenium, whereas uric acid, bilirubin, ubiquinone (Q) and the thiol glutathione are important endogenous antioxidants. It is not yet fully known whether the body’s natural antioxidant defence system is sufficient to counteract the increase of free radical production during intense exercise. There is, however, evidence that antioxidant consumption increases during excessive prolonged exercise, but not to what extent. Some studies have reported that supplementation with antioxidants, such as vitamins C and E and thiol compounds (e.g. N-acetyl-cysteine and a-lipoic acid) might have some protective properties against tissue damage induced by oxidative stress []. Antioxidant supplements have, however, not been shown to increase performance. The balance between ROS production and availability of antioxidants plays a very important role in maintaining an intact immune system. Antioxidant deficiencies have been shown to impair immune function and supplementation has been shown to improve protection against infections in some studies. However, megadoses and unbalanced supplementation with antioxidants may be deleterious as they may cause autoxidation and increased tissue damage and suppress immune functions []. Thus recommendations for athletes should give priority to increasing the dietary intake of food items containing naturally occurring antioxidants, such as vegetables and fruits.

some of these are included in the list of doping drugs, such as caffeine (max  mg/mL is allowed in urine) and alcohol. Among the (still) legal and most often used diet supplements are creatine, Q, antioxidants and ginseng. The daily need of creatine is approximately  g/ day and it is covered through both the diet and the body’s own production (through the amino acids arginine and methionine). In the diet, creatine is found especially in meat (c.  g/kg), fish and to a smaller extent in milk (– mg/L). If the intake of creatine is increased, the muscle tissue will reach a saturation limit after approximately  days whereafter the surplus is excreted in the urine. An increased intake of creatine may have a positive effect, especially after shortterm explosive exercise []. Athletes who consume a well-balanced diet do not, however, need a creatine supplement. Q (ubiquinone or vitamin Q) works as an electrotransporter in the respiratory chain of the mitochondria where it is involved in the energy-producing processes. Furthermore, studies have shown that Q has antioxidative qualities. During physical activity, the content of Q in plasma lipoproteins is reduced. This may be due to an increased incorporation of Q into the heart and skeletal muscle, or because Q is used or excreted in the intestine. Q supplementation is known to have a positive effect on the heart muscle of patients with particular heart diseases, but no studies have yet shown that athletes who consume a varied diet need additional Q. Ginseng (Russian root) has been shown to have an ability to prevent tiredness and increase work capacity. However, there are also studies which have not been able to show this positive effect. In general, the effects of the diet supplements mentioned above have not been fully investigated for either possible positive qualities or toxicity, side-effects and long-term effects. Furthermore, the type of sport may influence the possible effects.

Practical dietary advice In training camps and abroad

Ergogenic substances A number of diet-related supplements have been credited with the ability to improve performance. Today

• In a training camp or at competitions it is not always possible to obtain the diet you are used to. It is therefore essential that you are prepared and plan in advance in

Nutrition and Fluid Intake order to keep to your normal dietary habits and meal order as far as possible. It is often possible to discuss the matter with your coach and to contact the hotel staff in advance to discuss your needs. • Bring your own food (raisins, bread, biscuits) and some nutritionally well-balanced convenient food items in suitable portions if you know in advance that the food may be of poor quality. If you do not get enough food, it may be necessary to eat food of poor nutritional value, such as chocolate, crisps and sweets. • Make sure that you consume plenty of bread together with the hot meal. It is always possible to get bread. Otherwise: insist on having bread! Pasta is another alternative that you can bring with you in order to get enough carbohydrate. • Make sure that there is plenty of food and ask for more if you do not feel full. • Make sure that it is possible to have a snack between meals, such as fresh fruit.

Important guidelines while abroad • Buy bottled water if the tap water is not drinkable, but be sure that the bottle has been carefully sealed by the factory. Boil the tap water whenever you are uncertain of its quality. • Never have ice in your drinks as it comes from tap water and may have been stored under less than hygienic conditions. • Do not eat dishes containing mayonnaise or egg. • Avoid eating fresh vegetables and raw fruits. Do not eat salad and cold mixed dishes. In a lot of countries, e.g. in Asia, the water is so polluted that bacteria in fresh vegetables may cause illness. Furthermore, avoid dishes which have been heated for a while and left to cool down. • Eat only fruits which have a ‘natural wrapping’, such as bananas and oranges, and peel them yourself. Otherwise peel the fruit (e.g. apples, pears) yourself carefully. Do not eat ‘ready-made’ fruit salad. • Do not eat ice-cream, or cakes with cream or filling, no matter how nice they look. • Be sure that meat, fish, egg and chicken dishes are thoroughly boiled or fried. Do not eat raw meat.

Summary Elite athletes represent a group of individuals with an unusually high energy turnover who experience inten-

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sive physical stress, and who regularly increase their fat and protein turnover and empty their glycogen depots. Training and competition schedules dominate their daily life and call for specific energy and nutrient requirements as well as meal patterns. Many athletes, especially in endurance sports, have problems satisfying their energy needs through a conventional diet according to recommendations. The principle behind any dietary advice to athletes is that energy needs should be covered and fluid losses compensated for. All nutrients, i.e. vitamins, minerals and fatty acids, should be consumed in adequate and balanced amounts. The meal pattern should also be adjusted to the training/competition schedule. Furthermore, based on all available scientifically sound data the diet should take into account the specific demands that occur as a result of various physical and psychological stresses during training and competition. Special attention should also be given to the characteristics of each phase of training and competition within each specific type of athletic performance, i.e. strength as well as endurance sports. This may call for dietary counselling regarding diet composition, meal order and meal frequency as well as energy-rich food supplements. A high energy intake is no guarantee per se that the need for essential nutrients is being satisfied. Increased use of energy-dense food items (empty calories) leads to a diet with low nutrient density. The role of dietary intake for optimal performance can be divided into the following categories: (i) dietary habits in general (energy balance, nutrition density); (ii) intake of nutrients before competition (loading phase); (iii) intake of nutrients during performance (maintenance phase); and (iv) intake of nutrients after performance (recovery phase). Dietary recommendations for the general population may not be valid for elite athletes as a high intake of carbohydrate and dietary fiber leads to bulkiness. A low fat intake leads to problems in supplying energy needs. A high intake of PUFA and iron may lead to increased formation of free radicals and increased need for antioxidants. There are also various levels of motivation for the use of supplements: (i) for optimal training effect, e.g. amino acids stimulating growth hormone; (ii) use during competition, e.g. bicarbonate against acidosis; (iii)

 Chapter . for optimal restoration, e.g. creatine for training effect at repetition; and (iv) to increase psychological capacity, e.g. B vitamins against agony, branched chain amino acids against central tiredness. Subnormal levels of one or more nutrients in body fluids cannot be taken as an indicator that there is a nutrient deficiency unless it is known that the energy needs are being adequately fulfilled. Subnormal levels of nutrients can usually be restored by means of a well balanced diet consumed in adequate amounts.

Multiple choice questions  Resynthesis of muscle glycogen after prolonged endurance exercise depends on: a only complex carbohydrate being taken b intake of carbohydrate in a liquid form c immediate intake of carbohydrate after exercise d ensuring a high carbohydrate content in the food intake for the following  h.  With regard to an athlete’s diet it is important to: a have a high fat content in the diet b have a minimum intake of  g protein/kg body weight/day c ensure obligatory administration of antioxidants d ensure that over % of the daily energy intake is from carbohydrate.  With regard to energy intake during exercise it is correct that: a a solution with around % carbohydrate will provide the best source of carbohydrate during exercise b carbohydrate intake during exercise helps prolong endurance by emptying the glycogen stores at a lower rate c energy intake only plays a role during exercise if it lasts for more than  h d fat intake will help improve fat combustion and therefore improve endurance.  With regard to supplementation in regularly training individuals it is correct that: a all training female athletes will need iron implementation in order not to become anemic b magnesium deficiency can easily be detected by blood sample c extra administration of vitamin B will increase performance d vitamins C and E might have some protective properties against tissue damage from oxidative stress.

References 

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responses to exercise in humans: influence of hypoxia and physical training. Am J Physiol ; : R–R. Hawley JA, Burke LM. Effect of meal frequency and timing on physical performance. Br J Nutr ;  (Suppl.): S–S. Jenkins DJA, Wolever TMS, Taylor RH, Barker H et al. Glycemic index of foods: a physiological basis for carbohydrate exchange. Am J Clin Nutr ; : –. Björk I, Liljeberg H, Östman E. Low glucaemic-index foods. Br J Nutr ;  (Suppl.): S–S. Foster-Powell K, Brand Miller J. International tables of glycemic index. Am J Clin Nutr ; : S–S. Thomas DE, Brotherhood JR, Brand JC. Carbohydrate feeding before exercise: effect of glycemic index. Int J Sports Med ; : –. Burke LM, Claassen A, Hawley JA, Noakes TD. Carbohydrate intake during prolonged cycling minimizes effect of glycemic index of preexercise meal. J Appl Physiol ; (): –. Romijn JA, Coyle EF, Sidossis LS, Gastaldelli A, Horowitz JF, Endert E, Wolfe RR. Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. Am J Physiol ; : E–E. Hawley JA, Dennis SC, Noakes TD. Oxidation of carbohydrate ingested during prolonged exercise. Sports Med ; : –. Noakes TD. Fluid replacement during exercise. Exerc Sport Sci Rev ; : –. Jeukendrup A, Brouns F, Wagenmakers AJM, Saris WHM. Carbohydrate-electrolyte feedings improve  h time trial cycling performance. Int J Sports Med ; : –. Forslund AH, El-Khoury AE, Olsson RM, Sjödin AM, Hambraeus L, Young VR. Effect of protein intake and physical activity on -h pattern and rate of macronutrient utilization. Am J Physiol ;  (Endocrin Metab ): E–E. Hurley BF, Nemeth PM, Martain WH, Hagberg JM, Dalsky GP, Holloszy JO. Muscle triglyceride utilization during exercise: effect of training. J Appl Physiol ; : –. Massicotte D, Peronnet F, Brison GR, Hillaire-Marcel C. Oxidation of exogenous medium-chain free fatty acids during prolonged exercise — comparison with glucose. J Appl Physiol ; : –. Jeukendrup AE, Saris WHM, Schrauwen P, Brouns F, Wagenmakers AJM. Metabolic availability of medium chain triglycerides co-ingested with carbohydrates during prolonged exercise. J Appl Physiol ; : –. Jeukendrup AE, Saris WHM, Brouns F, Halliday D, Wagenmakers AJM. Carbohydrate (CHO) metabolism after ingestion of CHO and medium-chain triglycerides (MCT) during prolonged exercise. Metabolism ; : –. Van Zeyl CG, Lambert EV, Hawley JA, Noakes TD, Dennis SC. Effects of medium-chain triglyceride inges-

 Chapter .

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

  

  







  



tion on fuel metabolism and cycling performance. J Appl Physiol ; (): –. Jeukendrup AE, Thielen JJHC, Wagenmakers AJM, Brouns F, Saris WHM. Effect of MCT and carbohydrate ingestion during exercise on substrate utilization and subsequent cycling performance. Am J Clin Nutr ; (): –. Goedecke JH, Elmer-English R, Dennis SC, Schloss I, Noakes TD, Lambert EV. Effects of medium-chain triacylglycerol ingested with carbohydrate on metabolism and exercise performance. Int J Sports Nutr ; : –. Maughan RJ. Fluid and electrolyte loss and replacement in exercise. J Sports Sci ; : –. Garetto LP, Richter EA, Goodman MN, Ruderman NB. Enhanced muscle glucose metabolism after exercise in the rat: the two phases. Am J Physiol ; : E–E. Price TB, Rothman DL, Taylor R, Avison MJ, Shulman GI, Shulman RG. Human muscle glycogen resynthesis after exercise: insulin-dependent and -independent phases. J Appl Physiol ; : –. Ivy JL, Katz AL, Cutler CL, Sherman WM, Coyle EF. Muscle glycogen synthesis after exercise: effect of time of carbohydrate ingestion. J Appl Physiol ; : –. Zawadzki K, Yaspelkis B III, Ivy J. Carbohydrate–protein complex increases the rate of muscle glycogen storage after exercise. J Appl Physiol ; : –. Van Loon LJC, Saris WHM, Kruijshoop M, Wagenmakers AJM. Maximizing postexercise muscle glycogen synthesis: carbohydrate supplementation and the application of amino acid or protein hydrolysate mixtures. Am J Clin Nutr ; : –. Van Loon LJC, Kruijshoop M, Verhagen H, Saris WHM, Wagenmakers AJM. Ingestion of protein hydrolysate and amino acid-carbohydrate mixtures increases postexercise plasma insulin responses in man. J Nutr ; : –. Kiens B, Raben AB, Valeur AK, Richter EA. Benefit of dietary simple carbohydrates on the early postexercise muscle glycogen repletion in male athletes. Med Sci Sports Exerc ; : . Burke LM, Collier GR, Hargreaves M. Muscle glycogen storage after prolonged exercise: effect of glycemic index of carbohydrate feedings. J Appl Physiol ; : –. King NA, Burley VJ, Blundell JE. Exercise-induced suppression of appetite: effects on food intake and implications for energy balance. Eur J Clin Nutr ; : –. Acosta PB. Availability of essential amino acids and nitrogen in vegan diets. Am J Clin Nutr ; : –. Christensen DL, van Hall G, Hambræus L. Food intakes in Kalenjin runners in Kenya: a field study. In: Sport Science in a Changing World of Sports, nd Annual Congress of the European College of Sport Science. Copenhagen, Denmark, – August : –. Lambert EV, Speechly DP, Dennis SC, Noakes TD. Enhanced endurance in trained cyclists during moderate

      

    

   

  

intensity exercise following  weeks adaptation to a high fat diet. Eur J Appl Physiol ; : –. Pruett EDR. Glucose and insulin during prolonged work stress in men living on different diets. J Appl Physiol ; : –. Helge JW, Richter EA, Kiens B. Interaction of training and diet on metabolism and endurance during exercise in man. J Physiol ; : –. Lemon PWR. Effect of exercise on protein requirements. J Sports Sci ; : –. Armstrong LE, Maresh CM. Vitamin and mineral supplements as nutritional aids to exercise performance and health. Nutr Rev ; : –. Weaver CM. Calcium requirements of physically active people Am J Clin Nutr ;  (Suppl.): S–S. Specker BL. Evidence for an interaction between calcium intake and physical activity on change in bone mineral density. J Bone Min Res ; : –. Myburgh KH, Hutchins J, Fataar AB, Hough SF, Noakes TD. Low bone density is an etiological factor for stress fractures in athletes. Ann Intern Med ; : –. Schwellnus MP, Jordan G. Does calcium supplementation prevent bone stress injuries? A clinical trial. Int J Sports Nutr ; : –. Beard J, Tobin B. Iron status and exercise. Am J Clin Nutr ;  (Suppl.): S–S. Weight LM. Sport anemia: does it exist? Sports Med ; : –. Clarkson PM. Micronutrients and exercise. Antioxidants and minerals. J Sports Sci ; : –. Rowland TW, Deisroth MB, Green GM, Kelleher JF. The effect of iron therapy on exercise capacity of non-anemic iron deficient adolescent runners. Am J Dis Child ; : –. Yoshida T, Ido M, Chida M, Ichioka M, Makiguchi K. Dietary iron supplement during physical training in competitive distance runners. Med Rehab ; : –. Jenkins RR, Krause K, Schoufield LS. Influence of exercise on clearance of oxidant stress products and loosely bound iron. Med Sci Sports Exerc ; : –. Van Rij AM, Hall MT, Dohm G, Bray J, Porioes WJ. Change in zinc metabolism following exercise in human subjects. Biol Trace Element Res ; : –. König D, Weinstock C, Keul J, Northhoff H, Berg A. Zinc, iron and magnesium status in athletes. Influence on regulation of exercise induced stress and immune function. Exerc Immun Rev ; : –. Fosmire G. Zinc toxicity. Am J Clin Nutr ; : – . Begona MK, Moorkens G, Vertommen J, Noe M, Nève J, De Leeuw I. Magnesium status and parameters of magnesium. J Am Coll Nutr ; : –. Seelig MS. Consequences of magnesium deficiency on the enhancement of stress reactions: preventive and therapeutic implications. J Am Coll Nutr ; : –.

Nutrition and Fluid Intake 

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   

Anderson RA, Bryden NA, Polansky MM, Deutster PA. Exercise effects on chromium excretion of trained and untrained men consuming a constant diet. J Appl Phys ; : –. Sen KC, Packer L. Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr ;  (Suppl.): S–S. Wang W-C, Heinonen O, Mäkelä A-L, Mäkelä P, Näntö V, Branth S. Serum selenium, zinc and copper in Swedish and Finnish orienteers. A comparative study. Analyst ; : –. Armstrong LE, Maresh CM. The exertional heat illness: a risk of athletic participation. Med Exerc Nutr Health ; : –. Manroe MM. Effects of physical activity on thiamine, riboflavin, and vitamin B requirements. Am J Clin Nutr ;  (Suppl.): S–S. Li Li J. Antioxidants and oxidative stress in exercise. Proc Soc Exp Biol Med ; : –. Clarkson PM, Thompson SH. Antioxidants. what role do

 



  

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they play in physical activity and health? Am J Clin Nutr ;  (Suppl.): S–S. Niess AM, Dickhuth HH, Northoff H, Fehrenbach E. Free radicals and oxidative stress in exercise — immunological aspects. Exerc Immun Rev ; : –. Greenhaft PL, Casey A, Short AH, Søderlund K, Hultman E. Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man. Clin Sci ; : –. Sandström B, Aro A, Becker W, Lyhne N, Pedersen JI, Pórsdóttir I. Nordic Nutrition Recommendations. Nordiska Ministerrådet, Köpenhamn. Nord Livsmedel: . Møller A. The Composition of Foods, th edn. Copenhagen: Levnedsmiddelstyrelsen, . Jenkins DJA, Wolever TMS, Jenkins AL, Josse RG, Wong GS. The glycemic response to carbohydrate foods. Lancet ; : –. Jenkins DJA, Wolever TMS, Jenkins AL. Starchy foods and glycemic index. Diabetic Care ; : –.

Chapter 2.5 Ergogenic Aids (Doping) and Pharmacologic Injury Treatment ULRICH FRE DB E RG, TI MO S ÄPPÄ LÄ , RASMUS DA MS GAA RD & MI CHA E L KJ ÆR

Classical reference 5.0

L/min

Ekblom B, Berglund B. Effect of erythropoietin administration on maximal aerobic power. Scand J Med Sci Sports ; : –. The effect of subcutaneous injections of recombinant human erythropoietin (rhEPO) on the circulatory response to submaximal and maximal exercise was studied in healthy males. The study was the first to describe the ergogenic effect in well-trained humans of exogenous rhEPO. Seven weeks of rhEPO resulted in increased [Hb] from  g/L to  g/L and in parallel maximal V2 increased from . to . L/min (Fig. ..). The improvement in V˙2 max by rhEPO administration was similar to that obtained by acute elevation of [Hb] with red blood cell reinfusion. After stopping rhEPO administration V˙2 max gradually returned to the initial value over – weeks. Interestingly, systolic blood pressure at  W increased after rhEPO treatment.

4.5 4.0

3.5 –2

2

4

6 Weeks

8

10

12

Fig. .. Maximal oxygen uptake before and after rhEPO administration in eight healthy young individuals.

found in an English sports lexicon, and included both the medical use and the moral implications. Gradually the term adopted a wider usage and in reference to sport, it became known as ‘doping’. In today’s sporting context, doping refers to the use by athletes of banned substances or methods that may enhance performance.

Doping and ergogenic drugs Ancient and modern drug use Introduction The use of prohibited ergogenic aids to enhance sporting performance is referred to as doping (Table ..). The word ‘dope’ arises from the Dutch word ‘doop’ which means sauce or cream. In South Africa the word referred to a drink that was used as a stimulant in religious ceremonies and during intensive hard work. In  the word appeared for the first time in an English dictionary, referring to a mixture of opium and narcotics used in horses. In  the term ‘doping’ was



In the third century  Greek athletes prepared different mushrooms in the belief that it would enhance their performance. Similarly the Roman gladiators used stimulants for faster recovery after injury and chariot racers fed their horses ‘potent’ mixtures. Members of the Inca people chewed coca leaves before engaging in particularly intensive physical activities and Vikings have been said to eat fly agaric when fighting battles. Various stories about the use of different drugs by athletes emerge from the nineteenth

Ergogenic Aids and Pharmacologic Treatment Table .. Overall effect of ergogenic agents and procedures. Substances above the full line represent abandoned doping substances, whereas procedures and substances below the line represent legal or limited-legal approaches (caffeine below the allowed limit). Substance

Mechanism and effect

Blood doping Erythropoietin Anabolic steroids GH/IGF-I Beta-adrenergics Beta-blockers Amphetamine

· Hgb and V O2 max (10–15%) · Hgb and V O2 max (10–15%) Protein synthesis and strength (10–30%) Protein synthesis and strength (?) Protein synthesis and strength (5%) Central (5–10%) Central (3–5%)

Altitude Caffeine Creatine Bicarbonate

· Hgb and V O2 max (3–6%) Metabolism (5–15%), contraction (2–4%) Metabolism (3–5%), strength (10–20%) Neutralize acidosis (3–4%)

GH, growth hormone; Hgb, hemoglobin; IGF-I, insulin-like growth factor 1.

century when sport became more organized and sophisticated, reflecting the industrialization and urbanization of society; drugs included strychnine, nitroglycerine, opium, alcohol, coca leaves and caffeine. The majority of stories were related to cycling and other endurance sports. The events leading to a banning of drugs in sports are listed in Table ...

The Olympic Movement Anti-Doping Code The use of drugs to improve athletic performance is strictly prohibited in sports, mainly on the grounds of fair play and health. From an ethical and moral standpoint doping contravenes the fundamental principles of Olympism, sports as well as medical ethics and is thus forbidden. Furthermore, recommending, proposing, authorizing, condoning or facilitating the use of any substance or method covered by the definition of doping or trafficking therein is also forbidden. The International Olympic Committee (IOC) has considered the philosophy of control and the types of drugs to be classified as doping agents, and has established suitable methods for testing. These are included in the Olympic Movement Anti-Doping Code and may be changed by the IOC Executive Board. Legally



licensed athletes are bound by the regulations of their international federations. The regulations of the different federations vary in the details of their sanctions and restricted drugs. The IOC list of banned substances and methods consists of stimulants, narcotics, anabolic agents, diuretics and peptide hormones, masking agents, blood doping and manipulations (Table ..).

Doping agents and their function Substances used to increase performance can be classified according to the parameters they will influence, i.e. (i) increasing endurance and aerobic capacity, (ii) increasing muscle mass and strength, (iii) decreasing feelings of fatigue and nervousness and (iv) improving recovery processes (Table ..).

Stimulants (amphetamine, ephedrine, cocaine and caffeine) Substances belonging to this group range from the potent amphetamines to the weaker caffeine and ephedrine. The substances are called sympathomimetics and imitate the effects of the stress hormones epinephrine and norepinephrine. Amphetamines were synthesized first in  and were initially commercially available as a nasal decongestant. They cause the release of excitatory neurotransmitters, such as dopamine, to stimulate the central nervous system (CNS). The main effects on the CNS include wakefulness, alertness and a decreased sense of fatigue, mood elevation, increased self-confidence and a decreased appetite. The physical effects include increased heart rate, redirection of blood flow from the gastrointestinal tract to the muscles, and an increased fat metabolism. Amphetamine carries a high potential of tolerance, i.e. dosage has to be increased after prolonged use to induce the same effect. Although several CNS-acting stimulants are suspected to be performance enhancing, amphetamine is among the few that has been evaluated scientifically and has been shown to improve performance by –% []. Ephedrine’s effect on the CNS is weaker than that of amphetamine and controlled studies on its effect are few. Evidently ephedrine has an energy expenditure enhancing effect which has been used in treatment of obesity, and thus could potentially — although this is unsubstantiated — lead to fat loss in athletes. Cocaine has not

 Chapter . Table .. Chain of events finally leading to the banning of drugs in sport and the establishment of the independent World Anti-Doping Agency (WADA). 1896 The first recorded death was in 1896 when a cyclist,Arthur Linton, collapsed and died after finishing the first ever Paris Roubaix apparently after an overdose of strychnine

1963 The Council of Europe set up a Committee on drugs but couldn’t decide on a definition of doping.The first ever antidoping law was approved in France and 2 years later in Belgium

1904 The first near death in modern Olympics where a marathon runner,Thomas Hicks, was using a mixture of brandy and strychnine No specific date Most drugs involved alcohol and strychnine. Heroin, caffeine and cocaine were also widely used until heroin and cocaine became available only on prescription

1966 The first doping controls were carried out by FIFA during the World Championship in soccer in England

1930s Amphetamines were produced and quickly became the choice over strychnine.A wide use of amphetamine among soldiers was seen during the Second World War 1950s The production and use of synthetic testosterone explains the extreme improvements in weight-lifters from the Soviet team at the World Championship in 1954.Accordingly the potent effect of testosterone and synthetic derivatives such as dianabol became common knowledge 1952 One of the first noticeable doping cases involving amphetamines, which occurred at the Winter Olympics. Several speed skaters became ill and needed medical attention 1960 At the Olympics in Rome, Danish cyclist, Kurt Jensen, collapsed and died from an amphetamine overdose

been found to have any performance-enhancing effect in athletes. Although this drug could contribute to a subjective feeling of ‘doing well’, the effects on peripheral reflexes of cocaine could in fact impair performance. The effect on the CNS of amphetamine may lead to a distortion of the user’s perception of reality and impairment of judgement, which may cause an athlete to continue participation while injured or exhausted leading to worse injuries or collapse. Other acute sideeffects are headaches, insomnia, convulsions, halluci-

1967 The IOC took action after the death of Tommy Simpson (due to the illegal taking of amphetamines) in the Tour de France 1968 The IOC decided on a definition of doping and developed a banned list of substances.Testing began at the Olympic games 1988 At the Seoul Olympics, Ben Johnson tested positive for a banned anabolic steroid, was stripped of his gold medal and was suspended for 2 years 1999 The World Conference on Doping in Sport held in Lausanne on 2–4 February 1999 produced the Lausanne Declaration on Doping in Sport.This document provided for the creation of an independent international antidoping agency to be fully operational for the Games of the XXVII Olympiad in Sydney. Pursuant to the terms of the Lausanne Declaration, the World Anti-Doping Agency was established on 10 November 1999 to promote and coordinate the fight against doping in sport internationally

nations and paranoia and ultimately death due to ruptured blood vessels in the brain, heart attacks, heart rhythm abnormalities and heat stroke. Chronic sideeffects consist of dyskinesia, compulsive and repetitive behaviors, schizophrenia and death from ruptured blood vessels throughout the body. Caffeine, even in moderate doses (– mg/kg body weight) that do not exceed the accepted amount of caffeine in the urine, will result in improved performance. Earlier results indicated that the primary effect of caffeine was to stimulate an increase in circulating

Ergogenic Aids and Pharmacologic Treatment Table .. Performance-enhancing drugs. Performance aim

Ergogenic agent or method

Endurance

Erythropoietin Blood doping Hemopure/oxyglobin Caffeine

Strength (Body composition)

Anabolic steroids Growth hormone Insulin-like growth factor 1 Beta-adrenergic

Central fatigue Restitution (Nervousness) (Pain)

Amphetamine Ephedrine/cocaine Beta-blockers ACTH/cortisol Local anesthetics Glucose/insulin Alcohol

Anti-test

Effect 5–15%

10–30%

3–5%

Diuretics Probenecid/epitestosterone Human choriogonadotrophin Saline infusion



catecholamines which in turn mobilized free fatty acids (FFA) from adipocytes and improved muscular fat metabolism, sparing glycogen stores and improving endurance performance . However, more recently it has been shown that other mechanisms are also active, in that an enhanced performance effect of caffeine can be demonstrated in the absence of changes in catecholamines, and is found even in sports lasting only – min where fat metabolism does not play any major role. The effect has also been demonstrated in vivo in spinal cord injured individuals who underwent electrical stimulation of paralyzed muscle indicating that effects were local on the muscle rather than related to the brain, epinephrine or fatty acid mobilization [].

Beta-2 agonists These drugs are used for treatment of asthma (see Chapter .) and do not improve aerobic performance in lung-healthy individuals. However, it has been documented that b-agonists administered orally have an anabolic effect. Clenbuterol increases muscle hypertrophy and decreases fat deposition in animals, and several studies on b2-agonists in humans have shown increased strength gains [].

Beta-blockers Table .. The IOC list of prohibited classes of substances and methods. I Prohibited classes of substances A Stimulants B Narcotics C Anabolic agents D Diuretics E Peptide hormones, mimetics and analogs II Prohibited methods A Blood doping B Pharmacologic, chemical and physical manipulation III A B C D E

Classes of substances prohibited in certain circ*mstances Alcohol Cannabinoids Local anesthetics Corticosteroids Beta-blockers

By reducing sympathetic activity b-blockers cause a marked reduction in the maximal heart rate and thus reduce V˙2 max by –% which is clearly unfavorable in the case of any components of a sport that demand circulatory loading. On the other hand, b-blockers have been shown to cause an improvement in pistol shooting, ski jumping and musical performance of –% [].

Anabolic androgen steroids These substances, especially the hormone testosterone, are the doping substances most widely used for improving muscle mass and strength in association with regular training. Initially evidence for its effect was minor, due to the use of very small doses, but later studies have confirmed a significant effect. Body composition changes, with increased fat-free mass and reduced body fat. Some of this effect can be seen even without training, but is relatively more pronounced when added to resistance training [–]. Doses used

 Chapter . Table .. Overview of anabolic steroids. Drug

Administration

Side-effects

Comments

Testosterone esters

i.m. (in water) Subling/derm (oil)

Some risk of hepatotoxic and lipid effects Androgenic effects

Very potent, cleared rapidly

Stanozolol

Oral

Low hepatotoxic risk Very little fluid retention

Cleared slowly

Oxandrolone

Oral

Low androgen risk Very little fluid retention

Regarded as potent with few side-effects

Nandrolone

i.m. (in oil)

Low androgen risk

Regarded as potent with few side-effects

are variable depending upon the drug type, but it is not uncommon to use – mg/day for men and –  mg/day for women. A study of female body builders who all had trained for  years showed that those who took anabolic steroids intermittently for around  years had markedly more muscle mass than the control group. Furthermore, reports on former German Democratic Republic athletes who took anabolic substances for several years estimated that improvements in already well trained athletes were up to –% with regard to throwing events in track and field []. Interestingly, women performing running distances of ,  and  m also gained up to –% improvement. Finally, in a well-controlled study,  weeks of  mg/week testosterone enanthate administered to healthy young males resulted in markedly enhanced muscle growth in the group that received the drug []. Drug users often use a mixture of steroids, or have preference for specific types of steroids, e.g. testosterone enanthate, nandrolone decanoate, stanozolol, oxymetholone or oxandrolone. This is due to differences in the profile of the various drugs with regard to effect vs. side-effects, especially anabolic vs. androgenic effects. Whereas some substances have a low androgen side-effect and are thus preferred by women users, other drugs are cleared more rapidly from the body, lowering the risk of being caught in a doping test (Table ..). In general the side-effects associated with androgen abuse are three-fold: (a) hepatotoxic effects; (b) androgenic and reproductive side-effects; and (c) other effects on lipid and carbohydrate metabolism as well as

Table .. Side-effects associated with intake of anabolic steroids in well-trained athletes ( mg testosterone daily over  months). Data from Alen et al. Int J Sports Med ; : –.

ASAT (U/L) Testicular volume LH (IU/L) Sperm count (millions/mL) HDL cholesterol (mmol/L) LDL cholesterol (mmol/L) Hct (%)

Before

3 months

30 ± 3 19 ± 2 5.0 ± 2.4 55 ± 15 1.5 ± 0.2 3.1 ± 0.5 45 ± 2

46 ± 7* 13 ± 1* 2.5 ± 2.1* 2* 0.6 ± 0.1* 4.1 ± 0.9* 48 ± 2*

ASAT, aspartate aminotransferase; LH, luteinizing hormone; HDL, high-density lipoproteins; LDL, low-density lipoproteins; Hct, hematocrit.

psychologic effects. As substances are metabolized in the liver and are often used in high doses, it is clear that toxic parenchymal effects on the liver can occur, and elevation of aminotransferases is one of the first signs of anabolic substance abuse (Table ..) []. In addition, liver pathology such as cholestasis, blood cysts and primary liver tumors are observed. Suppression of sex hormones as well as testicular atrophy and infertility can be observed after only  months of abuse, and although these effects are thought to be reversible after drug use ceases, good long-term studies of chronic abusers are lacking. Male athletes often take human chorionic gonadotrophin (hCG) in order to maintain endogenous synthesis of substances needed for spermatogenesis. Administration of large amounts of

Ergogenic Aids and Pharmacologic Treatment testosterone can in males result in formation of estrogen and thus development of gynecomastia, and many male abusers take estrogen antagonists to counteract this. In women androgenous side-effects lead to virilization including a deepened voice, increased facial hair and cl*toral hypertrophy []. Hair loss including balding has been observed in both female and male athletes. Likewise skin problems with acne appear in a dose-dependent manner in both sexes. Changes in blood lipid profile are seen rapidly after androgen intake commences, and interestingly the cholesterol profile after  months of use seems more unfavorable than in untrained healthy individuals []. Likewise a dramatic change in insulin sensitivity has been seen, providing the basis for development of glucose intolerance. Good studies are, however, lacking with regard to reversibility, as well as to any later development of cardiovascular disease and/or type II diabetes. Psychologic side-effects have been difficult to assess, but studies have suggested an increase in psychologic pathologies such as anxiety, psychosis, irritability, aggression and violent behavior []. The exact mechanisms are not obvious but could be related to changes in neurotransmitter systems or hypogonadism.

Diuretics These substances are used in sports where body weight is important such as wrestling, boxing, light-weight rowing and horse riding, and weight loss of several percent has been observed overnight, resulting in unfavorable dehydration and subsequent reduced performance (see Chapter .). Previously, diuretics were also used for diluting the urine in order to pass doping tests, but today the determination of the urine mass weight has stopped this.

Human growth hormone (hGH) and insulin-like growth factor (IGF-I) Intake of growth hormone (GH) has been used for years in the belief that it has an anabolic effect on skeletal muscle. It has been demonstrated that GH administration in GH-deficient individuals can improve fat-free body mass and thus muscle, and animal studies have documented a GH-mediated stimulation of muscle hypertrophy. In spite of this, there have been no studies robustly documenting any muscle massincreasing effect of GH in addition to strength training



in either untrained or well-trained individuals []. What has been shown is an enhancing effect of GH on lipid oxidation and thus on body composition. Growth hormone administration results in several side-effects, in both the short and long term. Immediate sideeffects are fluid accumulation in the legs and carpal tunnel syndrome, whereas impaired glucose metabolism (glucose intolerance), hyperlipidemia and cardiomegaly can develop with long-term misuse. IGF-I has become used as a doping substance but no good experiments have documented any major effect of its administration in relation to muscle growth and performance.

Erythropoietin (rhEPO) The development of erythropoietin in recombinant form to use in patients with anemia has led to it totally replacing blood doping as the doping choice in endurance athletes. It has been demonstrated in both untrained and well-trained athletes with normal hematocrit and hemoglobin values that rhEPO can increase hemoglobin concentration, endurance performance, maximal aerobic power and arterial pressure during exercise [–]. Improvements by rhEPO administration are similar to those seen previously with blood transfusion, and it is thus likely that improvements in real sports performance are equally as good as those achieved by blood transfusion (see also Classical reference). It has been documented that performance in cross-country skiing and -km running has been shown to be increased by –% up to –  days after blood transfusion. More recently it has been shown in monkeys that genetic engineering was able to produce erythropoietin in muscle and that hematocrit rose. Unfortunately, the increase in hemoglobin production led to a rise to unacceptably high levels. However, the finding points to the fact that genetic doping could very well be used in the future for other categories of doping substances. Another area of interest for doping attempts is the production of stable hemoglobin without erythrocytes from bovine blood (hemopure, oxyglobin) which is being developed for emergency cases involving blood loss. Use of this formulation is expected to provide higher oxygen uptake and delivery capacity in athletes, and is likely to become a used substance within the next few years.

 Chapter . Legal substances or procedures In addition to the doping substances described above, it is clear that legal approaches can also result in performance enhancement. With regard to endurance, it has been documented that altitude training, especially if training is carried out at a moderate altitude (~  m) and the rest of the time is spent at a somewhat higher altitude (~  m), can result in some marginal improvement. Furthermore, the use of artificial low-oxygen ‘altitude’ houses has been shown to increase Hb concentration and hematocrit, if sufficient time is spent in hypoxia (> – h). The improvement is, however, not as large as that seen with rhEPO. The intake of bicarbonate has been shown to result in a small improvement in performance of events such as the -m run where both aerobic and anaerobic systems are heavily taxed. One of the most debated substances lately has been creatine (Cr), and its performance-enhancing effects. Research indicates that Cr supplementation (initially  g/day followed by – g/day) can increase muscle PCr content in some individuals. Exercise performance involving short periods of extremely powerful activity can be enhanced, especially during repeated bouts of activity [], whereas performance in aerobic exercise is not influenced. Furthermore, it has been demonstrated that Cr results in increased improvement of muscle strength with strength training but the mechanism behind this has not been discovered []. So far there are no documented gastrointestinal, renal or muscle side-effects associated with Cr intake.

Doping analyses Doping analyses have been used for doping control in a variety of sports for some  years now []. National and international sports associations and their antidoping authorities are responsible for the selection of the athletes to be tested, for maintaining the testing organization and for handing down judgements. Athletes are tested at competitions and during training (out-of-competition tests). To ensure the quality and reliability of testing, the protocol of sample collection is clearly specified and standardized. At present in most sports, only urine is collected from an athlete as a doping sample. The sample is divided between two glass bottles, each of which bears a distinguishable code. To guarantee the security of processing and stor-

age of the test samples, the bottles are sealed and transported to the laboratory in special containers. The analysis itself has to rely on an adequate sample collection. In some countries certified quality systems for doping control based on ISO- series standards and International Anti-Doping Arrangement (IADA) standards for doping control have been established already and in several other countries quality certification is in progress. Analysis in all official doping control tests is carried out exclusively in doping control laboratories accredited by the IOC, at present  in the world. The laboratories follow the guidelines and procedures set by the IOC. The accreditation must be reapplied for each year. In the near future, WADA, founded by the IOC and nations throughout the world in , will take the leadership in organizing and harmonization of worldwide doping control.

Methods of detection The requirements of the IOC for the accreditation of doping laboratories include sophisticated instrumentation. Most of the methods are based on gas chromatography and sensitive and selective detectors. Development of analytic techniques and instrumentation has been fast in recent years allowing ever better resolution, identification and detection of smaller and smaller amounts of analytes with sufficient certainty. High-resolution and tandem mass spectrometry, liquid chromatography combined with mass spectography (HPLC/MS) with various configurations and even gas chromatography/combustion/ carbon isotope ratio mass spectrometry (GC/C/ CIRMS) are coming into routine use [–]. The IOC list of banned substances consists of numerous compounds with a wide range of chemical structures. The actual laboratory analysis consists of two steps: screening and confirmation analysis. From seven to nine separate analytic procedures are needed to cover all banned substances. After screening, all suspected samples are reanalyzed by gas chromatography/mass spectrometry (GC/MS) to provide fully reliable results. Some peptide hormones with large molecules such as human chorionic gonadotrophin (hCG) are still detected by immunoassays since sufficiently sensitive mass spectrometry methods are not yet available.

Ergogenic Aids and Pharmacologic Treatment However, if appropriately standardized and validated methods are used, investigators should be able to detect self-administration of hCG in men as reliably as anabolic steroids and testosterone are now being detected by mass spectrometry methods []. Reliability of the doping result is of crucial importance. The consequence of a false finding of doping in an innocent athlete is personal disaster. Therefore, the ratio of true-positive to false-positive doping results must be extremely high. The personal opinion of the author is that .% of the cases decided as ‘doping’ should be true positive. Because approximately   doping tests performed annually in the whole world yield more than  positive findings the application of the .% principle would lead to false positive tests of one or two non-users throughout the world each year. All tests used for doping control purposes should be well validated. The positive predictive value (PPV) of the test can be estimated by routine measures using Bayesian rule [] provided that the sensitivity and specificity of the test have been studied. The accurate value is, however, hardly ever obtained since the relative number of drug users has a marked effect on PPV. IOC requirements for doping laboratories guarantee that the reliability of the doping tests is high in general. This in no way precludes the existence of various uncertainties in the test results (or in judgements).

Testing of some doping agents of interest Non-physiologic agents Misuses of central nervous system stimulants, narcotic analgesics and b-blocking agents are all controlled at competitions only, and are easily controlled by the present analytic techniques, e.g. []. Sensitivities of the assays are nearly % for these agents, and analyses are reliable and specific. The ion mass spectrum indicative of the parent drug or its metabolite detected from the sample can be considered as a fingerprint of the banned substance in the body. Since stimulants, narcotics and b-blocking agents are allowed to be used during the training period for therapeutic purposes there is a risk for careless athletes of stopping the treatment too late before the competition to give sufficient time for elimination of the drug from the body. Such cases do not lead to sanctions and



Table .. Summary of urinary concentrations above which IOC-accredited laboratories must report findings for specific substances. Caffeine Carboxy-THC Cathine Ephedrine Epitestosterone Methylephedrine Morphine 19-Norandrosterone 19-Norandrosterone Phenylpropanolamine Pseudoephedrine Testosterone/epitestosterone ratio

> 12 mg/mL > 15 ng/mL > 5 mg/mL > 5 mg/mL > 200 ng/mL > 5 mg/mL > 1 mg/mL > 2 ng/mL in males > 5 ng/mL in females > 10 mg/mL > 10 mg/mL >6

in order to decrease this risk the IOC has set limits for urinary concentrations of e.g. ephedrine and ephedrine derivatives for which the laboratories declare the results as negative (Table ..). Similar to this, morphine positive samples are reported to doping authorities only when the urinary morphine concentration exceeds a certain limit. The rationale for this is that several unbanned antidiarrheals and narcotics, e.g. codeine, are metabolized in part into morphine. Ingestion of poppy seeds may also be the reason for the existence of small amounts of morphine in urine. Caffeine which is daily consumed in many beverages and foods belongs to the list of prohibited substances. The definition of a positive result depends on the concentration of caffeine in urine. This concentration may not exceed  mg/L. The restricted level is only occasionally exceeded by common habitual intake []. In any case, excretion of caffeine into urine shows large interindividual variation due to several factors including differences in genetically determined enzyme profile [,]. Before doping sanctions based on urinary caffeine concentrations can be considered reliable much more research is needed. Anabolic steroid agents are used during the training period and therefore out-of-competition tests are of utmost importance to reveal the users. Conventional urine testing for anabolic steroids reliably identifies either the banned drug, its metabolites or both by GC/MS [,]. Increased knowledge of their metabolism has made it possible to select metabolites with

 Chapter . long elimination half-lives and different from naturally occurring steroids for monitoring. On the other hand, the recent development of high-resolution equipment has lowered the detection limit for these agents. Accordingly, the number of anabolic steroidpositive findings has clearly increased over the last few years. Moreover, very small amounts of nandrolone metabolites, which may be physiologic in certain conditions (e.g. pregnancy) can be detected nowadays and the IOC has set the maximum allowable urine concentrations for these substances. It is well known that use of anabolic androgenic steroids has a long-term influence on the production and excretion of various endogenous steroids. In looking at methods of broadening the time window of detection of anabolic androgen use, the influence of these steroids on the hormone to hormone ratios derived from the measurement of several endogenous steroid hormones and metabolites (‘urinary steroid profile’) has been considered (see []). It has been shown that when appropriately calibrated the chemometric evaluation of urinary steroid profiles makes a distinction between control and user groups and may delineate androgenic steroid users directly from the routine screening procedure []. Validation of the procedure and confirmation of the results may be laborious. Further, the procedure is extremely vulnerable to exogenous manipulation. Therefore, steroid profile and chemometric methods are not in official use.

Physiologic agents There are two possible strategies for revealing doping with an agent which naturally occurs or may occur in some physiologic conditions in the human body. The more laborious way to find the solution is to make quantitative determinations of the agent itself, e.g. growth hormone (GH), and of a number of potential ‘markers’ of its effects. In the case of GH such markers could be e.g. insulin-like growth factor (IGF-I) and IGF binding proteins. Measurements should be made in the blood and urine. Samples should be taken in rest and exercise situations from healthy subjects with varying demography and athletes representing different sports. The results should be submitted to extensive statistic modelling and analysis to obtain reference values or indexes with sufficient reliability to reveal the

exogenous use of the agent. The second way is more challenging: attempt to set up a method which allows discrimination between the endogenous and exogenous molecule. The current assay methods for testosterone do not distinguish synthetic (exogenous) testosterone from physiologic (endogenous) testosterone. Detection of doping with testosterone is based on measuring the testosterone to epitestosterone ratio (T/E) in urine by GC/MS []. The T/E ratio in healthy males who have not used testosterone is usually lower than or around .. Athletes who have a urinary T/E ratio >  are suspected of testosterone doping. The difficult aspect of the T/E test is that a small number of males have been found with T/E ratios in the range – in the absence of testosterone administration [] and a strict application of the T/E >  criterion would falsely classify these subjects as testosterone users. Attempts to distinguish testosterone users from non-users in this population have included measuring the urinary ratio of testosterone to luteinizing hormone, measuring serum testosterone/hydroxyprogesterone ratio, carrying out the ketoconazole test, measuring different ratios of testosterone and epitestosterone sulfate and glucuronide conjugates as well as measuring several ratios based on testosterone precursors and metabolites. At present, sports authorities do not act on the basis of a single result T/E > , instead additional tests are carried out on the suspected athlete to follow the changes in the T/E ratio which has been to found to be relatively stable in healthy drug-free males. Not only may the current methodology applied to reveal testosterone doping lead to erroneous reporting of cases in which the T/E ratio >  might be natural due to a physiologic or pathologic condition, it may also miss the cases with urinary T/E <  in which exogenous testosterone, alone or together with epitestosterone and/or hCG, might have been used. Therefore assays for exogenous testosterone would be more reliable if identification of injectable testosterone esters, occurring in the body only after the use of testosterone preparations, were possible. Recently, a promising method utilizing HPLC/ MS analysis of serum testosterone esters has been published []. With further development a method might be adopted in sports doping control provided that blood samples will be allowed to be collected.

Ergogenic Aids and Pharmacologic Treatment The most promising approach for confirming the abuse of exogenous testosterone is based on gas chromatography/combustion/carbon isotope ratio mass spectrometry (GC/C/CIRMS) in which the changes in carbon isotope ratios (13C/12C) of urinary testosterone, its precursors and metabolites are detected []. Synthetic testosterone is derived from chemical sources whilst physiologic testosterone is of natural origin with a much higher carbon isotope ratio. Accordingly, decreased isotope ratio is indicative to a great extent of the use of exogenous testosterone. High costs may restrict the adoption of this method into routine use, as well as the lack of knowledge of the effects of dietary habits, variability of different pharmaceutical batches, etc. on the results []. The pregnancy hormone human chorionic gonadotrophin (hCG) has so far been measured by commercial immunoassays. According to the IOC recommendations hCG should be determined by two different immunoassays. Since hCG-like immunoreactivity occurs at low concentration in the plasma and urine of normal healthy males the analyses are quantitative in nature. Some uncertainties are included in the different immunoassays because hCG occurs in various molecular forms including the intact hCG heterodimer, its free a and b subunits, proteolytically cleaved forms and fragments, and these different forms cross-react to various degrees in immunoassays. Therefore, in each laboratory the assay procedure for urinary hCG has to be validated carefully in control and athletic populations before running the tests routinely. After the appropriate validation the selfadministration of hCG can be reliably detected [] provided that pregnancy or diseases associated with endogenous hCG production are excluded. Although human growth hormone (hGH) is easily measured by simple immunoassays the fact is that there are currently no valid methods of detecting its abuse. Based on quantitative determination of urinary hGH by immunoassays detection of hGH doping would be feasible provided that urine samples could be obtained in the basal states without exogenous intake []. The problem is that renal clearance of the hGH increases drastically during strenuous effort preventing relevant interpretation of the results. GH- is a European multinational research project, the aim of which is to produce an indirect method of revealing



hGH doping by measuring hGH, growth factors, IGF binding protein and connective tissue metabolites as potential markers []. As for testosterone, the 13C/ 12 C isotope ratios have been measured for natural hGH and commercial recombinant rhGH products in an attempt to differentiate endogenous and exogenous origins of the hGH by high-performance liquid chromatography/isotope ratio mass spectrometry (HPLC/IRMS) []. However, only one preparation studied differed markedly from natural hormone in its carbon isotope ratio. Further, the low renal clearance of GH reduces the applicability of this concept. The assay might work better with serum GH. So far, there are no reliable methods available to reveal the abuse of hGH. Erythropoietin (EPO) is a physiologic glycoprotein hormone involved in the regulation of erythropoiesis. The pharmaco*kinetics and pharmacodynamics of recombinant human EPO (rhEPO) are well clarified []. The produced rhEPO is hom*ogenous with respect to the peptide sequence of natural EPO, but rhEPO contains heterogeneous carbohydrate moiety and this difference in carbohydrate structure is an important factor for identifying the administration of exogenous rhEPO [] as is the consequent difference in electric charges of natural EPO and rhEPO detectable by electrophoresis [,]. At the Sydney Olympic Games a combination of an indirect method utilizing blood samples [] and a direct method utilizing urine samples [] was used for the first time in a preliminary manner to reveal the use of rhEPO. Validation of methods reliable for doping control purposes is in progress.

Pharmacologic treatment of sports injuries The objective for medical treatment of sports injuries is primarily to shorten the rest period by reducing inflammation and pain so active rehabilitation can start as soon as possible before the deconditioning rest period has seriously reduced the physical properties of the soft tissues. Medical treatment is therefore only an adjuvant therapy in the overall management of sports injuries. The main treatment is ‘active’ rest and gradual rehabilitation within the limits of pain. If you are not familiar with the principles of rehabilitation, do not use medicine in the treatment of sports injuries.

 Chapter . The indications for using medicine in sports medicine are (i) pain control: simple analgesics (e.g. paracetamol), non-steroid anti-inflammatory drugs (NSAIDs) and weak opioids (e.g. tramadol) and (ii) inflammation control: NSAIDs and corticosteroids.

when in the acute phase of a viral illness [,]. Fever indicates an infection and sports activity must be stopped and temperature normalized before resuming sports activity.

Administration Simple analgesics and weak opioids Indications Analgesics can be used to a limited extent to reduce the pain in minor injuries when there is no risk of aggravating the injury by continuing the sports activity, for example hematomas under nails and excoriations. Of course analgesics can be used to reduce all forms of pain if the sports activity is stopped. Because of its few side-effects paracetamol is recommended.

Pharmacodynamics Paracetamol has an analgesic and antipyretic effect. Mode of operation is partly unknown but it seems probable that it has both a peripheral and central component.

Paracetamol – g – times daily by oral administration. Rectal administration gives a slower but longer effect.

Conclusion Because of the very few side-effects of paracetamol it is recommended as the drug of choice in treatment of pain without inflammation.

NSAIDs NSAIDs are widely used in sports medicine (i) to control pain, (ii) as anti-inflammatory agents that presumably allow early activity that speeds the healing process, and (iii) to decrease inflammation presumably to speed healing directly.

Indications Pharmaco*kinetics Ninety per cent is absorbed and maximal plasma concentration of paracetamol is reached after .– h after oral administration. The duration of effect is – h. Only % of paracetamol is absorbed by rectal administration.

Adverse events In contrast to weak opioids and acetylsalicylate derivatives paracetamol at the recommended dose has virtually no side-effects [a].

Contraindications Analgesics should never be used to allow an athlete to continue a sports activity when there is a risk of aggravating the injury. Paracetamol and other analgesics with antipyretic effects must never be used to reduce the body temperature before sports activity. Several viral infections can invade heart muscle and produce myocarditis. This risk of myocarditis is increased in strenuous physical activity during the acute phase of viral infection, and there are reports of spontaneous death and serious complications occurring in previously fit young adults who undertake vigorous exercise

Tendon injuries. Several randomized, placebocontrolled short-term studies of NSAID treatment in acute tendon injuries have been done. Healing was slightly more rapid and inflammation slightly decreased in treated patients compared with placebotreated patients in most studies [–], while no effect was found in other studies [,], and some studies showed increased instability and reduced range of motion []. Acute muscular injuries (strains and contusions). Only a few animal studies [,], and a single double-blind, placebo-controlled human study [] are available. Increased contractile force was found in the NSAIDtreated muscles early following the injury, but the treatment was associated with a delayed degradation of damaged tissue later on and a delayed muscle regeneration. Similarly, muscle regeneration appeared to be slowed by the NSAID treatment. The human study showed no beneficial effect. Myositis ossificans. One study showed that ossifications after non-cemented total hip arthroplasty appeared significantly less frequently in patients postoperatively

Ergogenic Aids and Pharmacologic Treatment treated with anti-inflammatory drugs []. No studies concerning athletes exist. Chronic muscle and tendon injuries. There is no convincing scientific support in literature for using NSAID treatment in chronic muscle and tendon injuries [,].

Pharmacodynamics NSAIDs have analgesic, antipyretic and anti-inflammatory effects. NSAIDs act by inhibiting the synthesis of prostaglandins, which are capable of mediating the inflammatory response following injury by the enzyme cyclooxygenase (COX). Two isoforms are now recognized. COX-, which is constitutively expressed, sustains the routine physiologic function of prostaglandins, including gastric mucosal protection. COX- is induced chiefly in response to pathologic processes, including pain and inflammation. Prostaglandins synthesized by the inducible COX- isoform mediate acute inflammatory responses in animal models. NSAIDs are non-isoform specific, inhibiting both the COX- and COX- isoforms. Since prostaglandins are involved in the maintenance of gastrointestinal (GI) mucosal integrity and since only the COX- isoform is present in the normal GI mucosa, the GI toxicity of NSAIDs has been proposed to result largely from inhibition of COX- activity. The therapeutic effects of NSAIDs may be primarily attributable to COX- inhibition. By selective inhibition of the COX- enzyme it is possible to reduce inflammation almost entirely without serious GI side-effects. A recent animal study [] indicates that a new isoform of the enzyme cyclooxygenase (COX-) has anti-inflammatory activity equivalent to or greater than that seen with steroids [] and can be an important part of the regeneration process.

Pharmaco*kinetics All NSAIDs are almost completely absorbed after oral administration and the half-life in the body (t 1/2) is from a few hours to more than  day.

Adverse events Adverse GI effects are frequently seen in patients who are given NSAIDs and include dyspepsia, nausea and ulcer. The new selective COX- inhibitors are



largely free of serious GI side-effects. Serious adverse events are rare, but anaphylactic shock, nephritis and aplastic anemia are described. Only very few sideeffects are associated with the use of topical NSAIDs (allergy).

Contraindications In healthy athletes only allergy is a contraindication. Be careful with ulcer disease, hypertension and insufficiency of the kidney, heart and liver.

Administration Oral administration is recommended. A few placebocontrolled studies [–] all suggest that topical NSAIDs may indeed be significantly better than placebo in treating acute injuries although the blood concentration after topical administration will reach less than % of levels after oral or intramuscular administration []. There is no scientific support in literature for using intramuscular administration. No scientifically based conclusion as to the ideal time to start and the ideal duration of NSAID treatment can be drawn.

Discussion It remains controversial whether inhibiting the acute inflammatory response is of uniform advantage. Pain and disability following the injury are at least in part due to the inflammatory response. Decreasing the inflammation decreases the symptoms and may allow earlier rehabilitation. On the other hand, inflammatory cells are responsible for clearing away cell debris and necrotic muscle fibers. Without this phagocytic function healing, in particular regeneration, may not be able to begin. Studies involving anabolic steroids (which are not allowed in sport) and muscle injuries have found increased numbers of progenitor cells [a] and more rapid healing and restoration of force []. Interestingly, both studies found this was associated with an initial increase in inflammatory cells. This suggests that the initial inflammatory response is indeed a crucial part of the healing response. The future will show whether the new isoform of the enzyme cyclooxygenase (COX-) can be an important part of this regeneration process. Inhibiting the enzyme cyclooxygenase can theoretically result in a reduced spontaneous regeneration after an injury.

 Chapter . Conclusions Although several clinical trials indicate that treatment with NSAIDs has some effect in sports injuries it is not clear that the difference between NSAIDs and placebo is clinically significant and clear-cut indications cannot be given. The indication for suppressing the acute inflammatory response is questionable. Theoretically it could reduce regeneration of the injured tissue. Adverse events after oral NSAIDs are common, but rarely serious. With this background it does not seem reasonable to recommend the use of NSAIDs routinely in acute muscle and tendon injuries. If treatment with NSAIDs is indicated, topical administration is recommended whenever possible. When systemic treatment is indicated it seems rational to use a COX- inhibitor because of the fewer side-effects although there is no documentation of the effect in athletes. If treatment with NSAIDs is misused as a ‘pain killer’ in order to send athletes back to full sport activity without rehabilitation and correction of training failures the medical treatment can indirectly result in a chronic injury.

Other pharmaceutical agents Systemic injected heparin has been used in the treatment of peritendinitis crepitans. At the moment there is little scientific basis for this treatment [] and the adverse events are so serious that the treatment cannot be recommended []. Local injections of polysulfated glycosaminoglycan [], one of the constituents of the base substance, and the protease inhibitor aprotinin [], have been used in the management of peri- and intratendinous pathologies. For these experimental treatments also there is currently little scientific basis.

Corticosteroids No legal treatment in sport has been so controversial as local injected corticosteroids. Intratendinous injection of corticosteroid has resulted in some animal studies in a directly deleterious effect on the tendon [–], and should be unanimously condemned. Obviously not all studies agree [–]. No proof of any deleterious effect of peritendinous injections exists in the literature [–]. Generally the literature concerning injection of local corticosteroids is very sparse and too many conclusions are based on poor scientific evidence.

Injection of corticosteroids is used in sports medicine: (i) to decrease acute inflammation in bursitis, tendovaginitis and peritendinitis; and (ii) to reduce the deleterious effect of chronic inflammation in chronic overuse symptoms.

Indications Arthritis. Intra-articular injected corticosteroid is one of the most widespread treatments in rheumatology. Placebo-controlled studies have proved the effectiveness of the treatment in arthritis [,]. Chronic tendinopathy. There are only very few randomized, placebo-controlled studies concerning the effect of local corticosteroids and chronic tendon injuries, but some effect has been recognized in the treatment of tennis elbow [,], rotator cuff tendinitis [] and plantar fasciitis []. Often the effect has been of short duration. Newer randomized, doubleblind, placebo-controlled studies [a,b] have shown a significant effect of ultrasound-guided peritendinous injection of long-acting corticosteroids in athletes with the most severe ultrasonography-verified jumper’s knee or Achilles tendinopathy. Despite having had symptoms for an average of 1/2 years % of the athletes were free of symptoms after  months but only % were free of symptoms after  months. The increased tendon diameter and the edema evaluated by ultrasonography were highly significantly reduced every week for the first  weeks following an injection despite the fact that the tendons were never totally normalized after the maximum of three peritendinous corticosteroid injections. The high frequency of relapse of symptoms in the study can be explained by the very aggressive training involving starting running a few days after injection. Another explanation could be the degenerative changes in the tendon. Although there is only sparse documentation of inflammatory cells in biopsies from chronically affected tendons the significant reduction in edema and thickness of the treated tendons is most likely due to a reduction in the inflammatory process. The corticosteroid seems to reduce the inflammation and edema of the tendon, but steroid cannot, however, repair the degenerative changes. When maximal training intensity is resumed the degenerative changes will cause relapse of the inflammation. A third explanation of the relapse

Ergogenic Aids and Pharmacologic Treatment of symptoms could be the limited duration of the steroid effect. Peritendinitis. A retrospective study reported significant reduction in pain after corticosteroid injection for peritendinitis []. No controlled studies exist. Myositis ossificans. One article has reported seven cases demonstrating the beneficial effect of local corticosteroid injection in myositis ossificans []. No controlled studies exist. Bursitis. The effect of injected corticosteroid in bursitis is safe but sparsely documented []. Muscle strain. To date, there are no reported human or animal studies where corticosteroids have been injected locally into strained muscle.

Pharmacodynamics The mechanism of the anti-inflammatory action of corticosteroid is not completely understood, but corticosteroids inhibit both the early vascular phase of inflammation and the late inflammatory and regenerative phase. Corticosteroids seem to modulate the inflammation not only through an effect on prostaglandin production but also by modulating the cytokine activity in both the parenchymal tissue and the cellular components.



above mentioned study [a,b] where Achilles and patellar tendons were injected, nearly % had atrophy, which disappeared in most cases after  months and in no cases caused embarrassing symptoms. Generally this atrophy seems to do little harm and recedes with time. Systemic effects from the corticosteroid are only a theoretical risk. Although locally injected corticosteroids are designed to be most effective where they are injected, a proportion of the substance penetrates to the bloodstream, and flushing, menstrual disturbances and fluctuations in blood glucose have been reported. Anaphylactic shock is a theoretical complication which doctors must be prepared to treat since cortisone allergy is a rare but possible form of allergy. Unintended injection in total or partial ruptured Achilles tendons is not unheard of [,]as the diagnosis can be difficult without ultrasonography and it is impossible to feel the erroneous intratendinous injection in degenerated tendons (see Figs ..–..). Unintentional damage to other structures is minimized when ultrasound-guided injections are used. The doping supervisors must be informed if the athlete is chosen for doping control during the  weeks following an injection.

Pharmaco*kinetics Most preparations are microcrystallic suspensions of glucocorticoid esters. The less soluble the preparation the longer the duration of effect and the higher the risk of systemic effect. The long-acting corticosteroid triamcinolone has effects lasting for  weeks.

Adverse events Introduction of infection is a possible adverse effect when using local steroid injection therapy. However, this risk can be almost completely eliminated by using a meticulous aseptic, no-touch technique, and by avoiding injections in areas with suspected infection. Atrophy of the overlying skin with telangiectasia and increased hyperesthesia or hypoesthesia and transparency or subcutaneous fat necrosis is often seen when subcutaneous structures are injected. In the

Fig. .. Athlete with jumper’s knee before injection. The erroneous placement of the needle inside the thick inflamed tendon is seen. The black arrows show the superficial border of the inflamed patellar ligament. The white arrows show the needle.

 Chapter . Administration

Fig. .. The same athlete as in Fig. .. before injection. After correction the correct peritendinous placement of the needle is seen. The white arrows show the needle.

Dilute the corticosteroid with local anesthetic before the injection. The diluted solution decreases the risk of adverse effects, and the anesthetic-induced disappearance of pain helps to confirm the diagnosis. The literature on the comparative efficacy of different preparations, doses and number of injections is scanty [,]. Price et al. [] concluded in a double-blind study that more rapid relief of symptoms of tennis elbow was achieved with  mg triamcinolone than with  mg hydrocortisone and there was less need to repeat injections in the former group, and Vogel [] showed an increase in the tensile strength of tendons after corticosteroid injections, but repetition of injections progressively weakened the tendons, suggesting a relationship between cumulative dose and the adverse effect. Systemic treatment with corticosteroids is not allowed in sports and no studies in the literature find any beneficial effects of this treatment. Corticosteroids may also be delivered with phonophoresis or iontophoresis [,]. The literature is also unclear concerning the efficacy and potential side-effects when corticosteroids are used in this manner. These are common physical therapy modalities used especially to treat some of the most chronic problems in athletes, such as tendinopathy or bursitis.

Discussion

Fig. .. The same athlete as in Fig. .. after injection. The injection fluid is seen peritendinous. The white arrows show the peritendinous corticosteroid and local anesthesia.

Contraindications Avoid injection in areas with suspected infection. Active tuberculosis is an absolute contraindication. There is not enough practical or scientific experience with local injection with corticosteroids in children. Injecting children for sports injuries is almost never indicated.

Peritendinous injection of corticosteroids can be used as an adjuvant therapy of severe chronic tendon injuries. The main treatment is of course ‘active’ rest and gradual rehabilitation for several months within the limits of pain. Only when the injured structure is trained to withstand the maximal stress, should full sports activity be allowed. If the athlete does not follow the rules for graduated rehabilitation over several months after a chronic injury and returns to full sports activity before the weakened tissue is strong enough, there is of course a risk of rupturing the tissue. Incorrect rehabilitation is obviously the greatest risk in treating athletes with local corticosteroid injections. It is necessary to verify the diagnoses by ultrasonography (or MRI) and make the injection under ultrasonographic guidance especially when the big tendons are being treated (Achilles and patellar tendons and the

Ergogenic Aids and Pharmacologic Treatment plantar fascia). If there is no effect from one ultrasound-guided steroid injection there is no indication for a second (or third) injection. If there is a partial effect it might be reasonable to repeat the injection once or twice at –-week intervals.

Conclusions Local injection of corticosteroids seems to be an effective treatment in acute bursitis, tenosynovitis, peritendinitis, plantar fasciitis and (traumatic) arthritis even though the documentation is sparse. Performed where indicated, on the basis of an ultrasonography-verified diagnosis, ultrasoundguided peritendinous injection with a long-acting corticosteroid is safe and can be a powerful supplement to the basic rehabilitation of severe chronic tendon injuries when normal conservative rehabilitation has failed. If the treatment is misused to send athletes back to full sport after a few weeks the medical treatment can indirectly result in chronic injuries.

Summary Medical treatment is only an adjuvant therapy in the overall management of sports injuries. On the basis of a correct diagnosis and indication medical treatment can reduce the deconditioning rest period so that active rehabilitation can start as soon as possible before the physical properties of the soft tissues are seriously impaired. Before full participation in sports activities a period with gradual increased rehabilitation with respect for pain is necessary to reduce the risk of relapse of symptoms. Without this period of active rehabilitation medical treatment can be misused and increase the risk for chronic injuries. The use of ergogenic aids is subject to doping regulations, and urine analysis provides the basis for detection of several doping agents. In endurance sports use of erythropoietin (–% improvement) and in power sports anabolic steroids (–% improvement) is documented to improve performance but simultaneously to cause major side-effects.

d intra-articular injection e peritendinous injection.  In chronic tendinopathy in the groin unalleviated by rest and graduated training it seems reasonable to try the following medical treatment: a paracetamol b weak opioids c heparin d NSAIDs e local injected steroid.  Why should ultrasound be used when local steroid injection is planned? a For correct diagnosis. b To decrease the risk of unintended puncture of vessel and nerves. c To decrease the risk of erroneous intratendinous injection. d To decrease the risk of skin atrophy. e To allow evaluation of the effect of treatment.  What are the documented risks after a peritendinous injection of corticosteroid? a Skin atrophy. b Tendon rupture. c Adrenal suppression. d Fat necrosis. e Unintended injection in other structures.  What are possible facts concerning acute inflammation after injury? a It is necessary for clearing away cell debris and necrotic muscle fibers. b It is necessary for regeneration and healing. c It causes pain. d Treatment with anti-inflammatory drugs reduces the risk for myositis ossificans (after hip arthroplasty). e When left unchecked it can lead to a chronic situation and destruction of tendons and surrounding tissue resulting in ruptures of tendons, scar tissue and adherence.

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