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Nikos C. Apostolopoulos Stretch Intensity and the Infl ammatory Response: A Paradigm Shift Stretch Intensity and the Inflammatory Response: A Paradigm Shift Nikos C. Apostolopoulos Stretch Intensity and the Inflammatory Response: A Paradigm Shift Nikos C. Apostolopoulos University of Toronto Toronto, ON, Canada ISBN 978-3-319-96799-8 ISBN 978-3-319-96800-1 (eBook) https://doi.org/10.1007/978-3-319-96800-1 Library of Congress Control Number: 2018961999 © Springer Nature Switzerland AG 2018 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland I dedicate this book to my constant companions, my daughters, Thalia Sofia and Justine Francis. Preface “The true nature of knowledge is experiment… What is now prove’d was once only imagin’d” William Blake 1757–1827 Although nature may have buried her secrets deep, she has not entirely hidden them. As scientists, we are curious, often investigating for information and insight in order to enlighten ourselves with that which lies beyond her veil. In order to gain a glimpse, we use imagination, intuition, and invention, but mostly enthusiasm and perseverance, the qualities of an undying desire to make clear that which has so often eluded us, but through intuition, we know truly exists. At times, we walk and occupy the nether zone between reality and illusion in order to bridge the gap between the outer and the inner worlds. This is a sensitive chaos that we attempt to explain through the language of mathematics (numbers, equations, statistics, etc.), believing that this will make the invisible visible. The belief is that, by solving the formation of this now visible pattern, frozen in time and space through observation, one will obtain a better idea into nature’s function and activity. Similar to Parzifal’s quest for the Holy Grail and how he refused to be raised in the dark forest, we chal- lenge ourselves to learn and discover the mysteries and the inner workings of the human body. Parzifal was faced with the dilemma of whether to respond to the plight of the fisher king, Astofar, or to hold steadfastly true to the code of the knights. His adherence to the code cost him several more years of wondering before fulfill- ing his task. Just seeing the Holy Grail is not enough; we have to ask about it, mak- ing inquiries while approaching our task with an open and unbiased mind, breaking old thought patterns and codes in order to advance, to be the biographers of a much- needed paradigm shift. Toronto, ON, Canada Nikos C. Apostolopoulos vii Acknowledgements “Truth is the offspring of silence and meditation. I keep the subject constantly before me and wait ‘til the first drawings open slowly, by little and little, into a full and clear light.” – Sir Isaac Newton While researching and writing this manuscript, I found myself meandering in and out of numerous moments of contemplation, for such was the nature of the work at hand. Bathed in silence, I had pensive periods that allowed for necessary reflections as to how best to proceed. During these moments, my thoughts drifted to and about those who had gone before, the pioneers who paved the way. Enquiring about the property of things, the forming of hypotheses, and the designing of experiments, they were responsible for making clear that which was observed or intuitively believed. With enthusiasm, perseverance, and the need to know, they were instru- mental in laying the foundation from which this manuscript was made manifest. The quote by Sir Isaac Newton best sums up their influence: “If I have seen further it is only by standing on the shoulders of giants…”. Although the opportunity has yet to present itself to meet with these individuals, I would nonetheless like to acknowledge their contributions to my thought processes and to science as a whole. Distinguished Professors Donald E.  Ingber (Harvard University) and James G. Tidball (UCLA) have had a profound influence on my knowledge and under- standing of the response of the cell and muscle tissue. Professor Ingber’s compel- ling work on the concept of mechanotransduction has been pivotal in formulating my thoughts about the effect of mechanical force (i.e., stretching intensity) on mus- cle tissue and cells. In other words, how the magnitude of the stretch can manifest a biochemical response. Professor James G. Tidball provided the stepping stone from which to relate the effects of this mechanical stress on the recovery and regeneration of muscle tissue. For the inflammatory response, both acute and chronic, the cyto- kines, and C-reactive proteins, I am indebted to the work of Professor Emeritus Irving Kushner (Case Western University). His work has made these complex con- cepts simple and coherent. The groundbreaking research on calpains by Professor Angelo Belcastro (York University, Canada) was the keystone, connecting my hypothesis with the magnitude of stretching intensity to inflammation. Moving ix x Acknowledgements across the pond to Europe, two distinguished researchers stand out: Clinical Professor Michael Kjaer (Institute of Sports Medicine, Copenhagen) and Professor Dr. Matthias Chiquet (University of Bern). Their research has been immensely valu- able in formulating thoughts regarding the response of the extracellular matrix (ECM) to mechanical stress. The ECM provides the structural framework, contrib- uting to the mechanical stability of tissues as well as acting as a substrate for cell adhesion. When a mechanical stimulus is imparted on the body, this imparts infor- mation to the cells, resulting in their subsequent response. However, a common denominator to a lot of the material mentioned above is the work of the pioneer and visionary, the late Buckminster Fuller. Science owes a major debt to this individual. His abridgement of the concepts of tension and integrity, tensegrity, is the founda- tion for the response of the cell to mechanical force(s). Continuous tensional behav- iour, an interplay between tension and compression from the macro to the cellular level, is the basis for how the magnitude of stretching affects muscle tissue and cells, and is responsible for the significance of the inflammatory response. In conclusion, no acknowledgement would be complete without mentioning those who have had a direct impact on me. Besides my immediate family and clos- est friends, a heartfelt gratitude goes out to Professor Emeritus Dr. Jack Taunton (University of British Columbia, Canada) and Professor Michael J. Plyley (Brock University, Canada). Both were instrumental in pushing me out of my comfort zone, encouraging me to test the waters in order to grow as a scientist and therapist. To my coach and mentor, Andy Higgins (University of Toronto), our numerous discussions and his advice held me steadfast and true to my goals both professionally and per- sonally. Finally, like everything, true friendship possesses a quality of its own. It is unique, it listens openly, it is not afraid to speak the truth, and it is not envious but selfless, with a great willingness to be truly present. These characteristics define my oldest friend and esteemed colleague, Professor Peter Pericles Trifonas (University of Toronto). During times of great trepidation, our numerous walks and talks were the light at the end of the tunnel, and for this I am truly indebted. Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2 Literature Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 The Definition of Stretching and Its Measurement . . . . . . . . . . . . . . . . . . 6 Classification of Stretches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Static . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Ballistic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Dynamic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Proprioceptive Neuromuscular Facilitation (PNF) . . . . . . . . . . . . . . . . 11 Macroscopic and Microscopic Information Processing Levels: Macroscopic—Muscle, Tendon, and Myotendon Unit (MTU) . . . . . . . . 12 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Muscles, Tendons, and MTU . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Macroscopic and Microscopic Information Processing Levels: Microscopic—Force, Cells, Tissue, and the Extracellular Matrix (ECM) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 Force, Cells, and Tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 The Extracellular Matrix (ECM) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 The Strain Factors of Stretching: Intensity, Duration, and Frequency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 Inflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 Neutrophils, Macrophages, Cytokines, and Acute Phase Response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 Inflammation and Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 Mechanotransduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 Stretching and Inflammatory Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 xi xii Contents 3 Study One: Acute Inflammatory Response to Stretching . . . . . . . . . . 131 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 Power Calculations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 Biomarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 Statistical Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 RMANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 Effect Sizes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 4 Study Two: Stretch Intensity vs. Inflammation: Is There a Dose-D ependent Association? . . . . . . . . . . . . . . . . . . . . . . . 145 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146 Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146 Power Calculations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146 Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146 Blood Biomarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 Statistical Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 RMANOVA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 Effect Sizes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 Secondary Analysis: Linear Regression (30–90 and 60–90% Maximum ROM) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156 5 The Effect of Different Passive Static Stretching Intensities on Perceived Muscle Soreness and Muscle Function Recovery Following Unaccustomed Eccentric Exercise: A Randomised Controlled Trial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162 Statistical Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166

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