Active Voice: Exercise-induced Cardioprotection
By Scott K. Powers, Ph.D., Ed.D., FACSM; Andreas N. Kavazis, Ph.D.; John C. Quindry, Ph.D., FACSM
Viewpoints presented in SMB commentaries reflect opinions of the authors and do not necessarily reflect positions or policies of ACSM.
Scott Powers, Ph.D., is the UAA Endowed and Distinguished Professor of Applied Physiology and Kinesiology at the University of Florida. His research interests include exercise-induced protection of cardiac and skeletal muscle against stress and the mechanisms responsible for disuse skeletal muscle atrophy.
Andreas Kavazis, Ph.D., is an Assistant Professor of Kinesiology at Mississippi State University. His main research focuses on cardiac mitochondrial adaptations following endurance exercise training.
John Quindry, Ph.D., is an Associate Professor of Kinesiology at Auburn University. His research interests include understanding oxidative stress and mechanisms of exercise-induced cardioprotection against various cardiac pathologies including ischemia-reperfusion injury.
See the March 2012 issue of Medicine & Science in Sports & Exercise® (MSSE) for two articles related to this topic, which were authored by these three scientists and others from their research teams: “Exercise protects cardiac mitochondria against ischemia-reperfusion injury” and “Evaluation of arrhythmia scoring systems and exercise-induced cardioprotection”.
Cardiovascular disease and specifically ischemia-reperfusion (IR) injury, i.e., heart attack, remains the major cause of death in the industrialized world. Developing strategies to reduce the incidence and severity of IR injury is vital. Numerous investigations clearly demonstrate that regular endurance exercise protects the myocardium during heart attacks. Heart attack protection is a cellular phenomenon which extends to clinically relevant outcomes including tissue preservation, muscle pump function and ventricular arrhythmia prevention (see Miller et al., March, 2012 issue of MSSE).
Interestingly, as few as five consecutive days of moderate-intensity exercise protects against heart attack-induced cardiac damage similar to the protection provided by long duration exercise training (weeks to months). Like other health benefits of exercise, this exercise-induced cardioprotection is lost if there is an extended period of detraining (e.g., 18 days). Although it is clear that endurance exercise induces a cardioprotective phenotype, the biochemical mechanisms underpinning this phenomenon are not fully known. Several mechanisms have been proposed, e.g., alterations in coronary circulation, increased myocardial expression of endoplasmic reticulum stress proteins, increased cardiac cyclooxygenase-2 activity, up-regulation of myocardial heat shock proteins, improved cardiac antioxidant capacity, cardiac mitochondrial adaptations, and/or elevation of myocardial ATP-sensitive potassium channels. These mechanisms have been tested independently in scientific studies over the last decade and many have been eliminated as central to exercise-induced cardioprotection.
However, current evidence suggests that elevated myocardial levels of mitochondrial antioxidants and increased expression of ATP-sensitive potassium channels are both contributors to exercise-induced cardioprotection against IR injury. Specifically, recent findings reveal that endurance exercise fortifies a key antioxidant enzyme defense; manganese superoxide dismutase (MnSOD) found in mitochondria that scavanges damaging oxidants in the myocardium during heart attacks. Importantly, several investigators have reported that an exercise-induced increase in MnSOD in the heart is essential in blunting arrhythmias and cardiac damage during IR.
Moreover, endurance exercise evokes beneficial changes in mitochondrial protein content and activity (for further detail, see Kavazis et al., 2008 and Quindry et al., 2010). Specifically, Kavazis et al. performed experiments in vitro where cardiac mitochondria were isolated from sedentary and endurance exercised animals. Mitochondria were then exposed to an exogenous oxidant challenge. Results indicate that endurance exercise results in a lower maximal rate of mitochondrial damage (i.e., opening of the permeability transition pore) in both subsarcolemmal and intermyofibrillar cardiac mitochondria. Quindry et al. have further shown that exercise-induced activation of cardiac mitochondrial ATP-sensitive potassium channels prevent arrhythmias and oxidative stress during surgicallyinduced heart attacks.
Collectively, these findings indicate that the exercised myocardium undergoes endogenous adaptations that improve tolerance against IR insults and that many of the protective mechanisms are central to the mitochondria. In one of our recently published papers that appeared in the March issue of MSSE (Lee et al., 2012), we further demonstrated that exercise-induced cardioprotection is mediated, at least in part, through a mitochondrial phenotype that resists IR-induced damage. These exciting findings provide mechanistic understanding of exercise as medicine against heart attack damage and highlight the mitochondria as a focal point of exercise-induced cardioprotection.