Control of Breathing During Exercise

Transcription

1 Control of Breathing During Exercise

2 ii Colloquium Digital Library of Life Sciences This e-book is an original work commissioned for the Colloquium Digital Library of Life Sciences, a curated collection of time-saving pedagogical resources for researchers and students who want to quickly get up to speed in a new area of life science/biomedical research. Each e-book available in Colloquium is an in-depth overview of a fast-moving or fundamental area of research, authored by a prominent contributor to the field. We call these resources Lectures because authors are asked to provide an authoritative, state-of-the-art overview of their area of expertise, in a manner that is accessible to a broad, diverse audience of scientists (similar to a plenary or keynote lecture at a symposium/meeting/colloquium). Readers are invited to keep current with advances in various disciplines, gain insight into fields other than their own, and refresh their understanding of core concepts in cell & molecular biology. For the full list of available Lectures, please visit; All Lectures available as PDFs on our website. Access is free for readers at institutions that license Colloquium. Please info@morganclaypool.com for more information.

3 iii Colloquium Series on Integrated Systems Physiology: From Molecule to Function to Disease Editors D. Neil Granger, Louisiana State University Health Sciences Center Joey P. Granger, University of Mississippi Medical Center Physiology is a scientific discipline devoted to understanding the functions of the body. It addresses function at multiple levels, including molecular, cellular, organ, and system. An appreciation of the processes that occur at each level is necessary to understand function in health and the dysfunction associated with disease. Homeostasis and integration are fundamental principles of physiology that account for the relative constancy of organ processes and bodily function even in the face of substantial environmental changes. This constancy results from integrative, cooperative interactions of chemical and electrical signaling processes within and between cells, organs and systems. This ebook series on the broad field of physiology covers the major organ systems from an integrative perspective that addresses the molecular and cellular processes that contribute to homeostasis. Material on pathophysiology is also included throughout the ebooks. The state-of the-art treatises were produced by leading experts in the field of physiology. Each ebook includes stand-alone information and is intended to be of value to students, scientists, and clinicians in the biomedical sciences. Since physiological concepts are an ever-changing work-in-progress, each contributor will have the opportunity to make periodic updates of the covered material. Published titles (for future titles please see the website,

4 Copyright 2014 by Morgan & Claypool Life Sciences 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, photocopy, recording, or any other except for brief quotations in printed reviews, without the prior permission of the publisher. Control of Breathing During Exercise Susan A. Ward ISBN: paperback ISBN: ebook DOI: /C00108ED1V01Y201406ISP052 A Publication in the Colloquium Series on INTEGRATED SYSTEMS PHYSIOLOGY: FROM MOLECULE TO FUNCTION TO DISEASE Lecture #52 Series Editor: D. Neil Granger, LSU Health Sciences Center, and Joey P. Granger, University of Mississippi Medical Center Series ISSN ISSN X ISSN print electronic

5 Control of Breathing During Exercise Susan A. Ward, D.Phil. Emeritus Professor, Faculty of Biological Science, University of Leeds and Human Bio-Energetics Research Centre, Crickhowell, Powys, United Kingdom COLLOQUIUM SERIES ON Integrated Systems Physiology: From Molecule to Function to Disease #52

6 vi Abstract The control of breathing during exercise remains the source of considerable debate. Classical schemes of the exercise hyperpnea have incorporated elements of proportional feed-back from chemoreceptor sites (carotid body and brainstem) and feed-forward neurogenic (central command and muscle reflex) control. However, the precise details of the control process are still not fully resolved, reflecting in part technical and interpretational limitations inherent in isolating putative control mechanisms in the intact exercising human and also the challenges presented by the ventilatory and gas-exchange complexities encountered at work rates which engender a metabolic (lactic) acidosis. Although some combination of neurogenic, chemoreflex, and circulatory-coupled processes are likely to contribute to the control, intriguingly, the overall system appears to evidence considerable redundancy. This, coupled with the lack of appreciable steady-state error signals in the mean levels of arterial PCO2, PO2, and ph over a wide range of work rates, has motivated the formulation of innovative control models that reflect not only spatial interactions but also temporal interactions (i.e., short-term and longer-term memory ). The challenge remains to discriminate between robust control schemes that (a) integrate such processes within plausible physiological equivalents, and (b) account for both the dynamic and steady-state system response over the entire range of exercise intensities. Key Words exercise hyperpnea, oxygen uptake, carbon dioxide output, exercise intensity, metabolic acidosis, ventilatory requirements, chemoreflexes, central command, muscle reflexes, cardio-circulatory reflexes, redundancy, controller, kinetics

7 vii Contents 1. Introduction Ventilatory Requirements Pulmonary CO 2 Clearance Arterial PCO2 Set-Point Physiological Dead Space Interactions Ventilatory Responses Moderate Exercise Phase Phase Phase Heavy and Severe Exercise Breathing Pattern Ventilatory Control Neural Control Central Command Short-Term Potentiation Long-Term Modulation Muscle Reflex Control Cardio-Circulatory Control Cardiodynamic Control Peripheral Vascular Control Humoral Control Central Chemoreflex Control Moderate Exercise Phase

8 viii CONTROL OF BREATHING DURING EXERCISE Phase Phase Heavy and Severe Exercise Peripheral Chemoreflex Control Moderate Exercise Phase Phase Phase Heavy and Severe Exercise Other Control Schemes Redundancy Optimization Conclusions References... 73

9 1 c h a p t e r 1 Introduction The condition of exercise is not a mere variant of the condition of rest, it is the essence of the machine. Joseph Barcroft [1] ( Features in the Architecture of Physiological Function, Cambridge Univ. Press, p. 286, 1934) 1. INTRODUCTION There is little question that breathing or, more specifically, ventilation the rate at which air enters or leaves the lung increases when we exercise. More importantly, however, is the recognition that it increases in a quite particular way that is, to maintain arterial blood gas and acid base homeostasis in the face of the demands imposed by the energetic requirements of the muscular force generation necessary to support the exercise task. Thus, over the wide range of work rates that are aerobically supported ( moderate intensity) in humans at sea level, the partial pressures of CO 2 and O 2 and the ph in the arterial blood (Pao 2, Paco 2 and pha, respectively) remain at or close to their resting levels (reviewed in [2, 3, 4, 5]), 1,2,3 despite substantial increases in metabolic rate, because of a close matching of ventilation to the exchange rates of O 2 and CO 2 at the lungs the O 2 uptake 1 An alternative opinion has been expressed more recently, however [6]. 2 The corresponding responses in other mammalian species such as ponies and goats differ, however, with ventilation typically being in excess of pulmonary gas exchange requirements, resulting in sustained decreases in PaCO 2 and increases in pha (reviewed in [2, 3]). 3 Hyperventilation can occur transiently at exercise onset, especially in excitable subjects; this is more common in treadmill than cycle ergometry.

10 2 CONTROL OF BREATHING DURING EXERCISE (V o 2 ) and CO 2 output (V co 2 ). 4 And at higher work rates which require an additional anaerobic contribution to energy provision ( high intensity), ventilation has the additional and competing challenge of providing compensation for the metabolic (largely lactic) acidosis. 5 Ventilation is therefore not arbitrarily set, but rather is a controlled variable. What is far less certain, however, is how its control is effected, any serious discussion of which has to accommodate the underlying ventilatory requirements of the particular exercise task and the profiles of the actual ventilatory response achieved each of which is dependent on the intensity of the exercise. Evidence is presented for and against the involvement of the major putative control mechanisms, with the primary focus being on studies in humans, although animal studies are drawn upon where this is felt to be appropriate. This article is intended to provide a comprehensive, but not necessarily exhaustive, review of what is still in many regards a contentious field; the interested reader is referred to references [7] and [8] for an in-depth historical background. A deliberate citations strategy is to lean toward review articles, not that they themselves should be taken as sources of primacy but rather to provide avenues toward key original research articles. 4 Here and subsequently, the superimposed dot over a particular variable (e.g., volume, V ) follows the mathematical convention of signifying its rate of change, most usually with respect to time (t) i.e., dv/dt or V. 5 Acidosis indicates an increased acidity in tissues which may include blood; acidemia specifically indicates an increased acidity in blood.