Exercise and cardiac preconditioning against ischemia reperfusion injury

Cardiovascular disease (CVD), including ischemia reperfusion (IR) injury, remains a major cause of morbidity and mortality in industrialized nations. Ongoing research is aimed at uncovering therapeutic interventions against IR injury. Regular exercise participation is recognized as an important lifestyle intervention in the prevention and treatment of CVD and IR injury. More recent understanding reveals that moderate intensity aerobic exercise is also an important experimental model for understanding the cellular mechanisms of cardioprotection against IR injury. An important discovery in this regard was the observation that one-to-several days of exercise will attenuate IR injury. This phenomenon has been observed in young and old hearts of both sexes. Due to the short time course of exercise induced protection, IR injury prevention must be mediated by acute biochemical alterations within the myocardium. Research over the last decade reveals that redundant mechanisms account for exercise induced cardioprotection against IR. While much is now known about exercise preconditioning against IR injury, many questions remain. Perhaps most pressing, is what mechanisms mediate cardioprotection in aged hearts and what sex-dependent differences exist. Given that that exercise preconditioning is a polygenic effect, it is likely that multiple mediators of exercise induced cardioprotection have yet to be uncovered. Also unknown, is whether post translational modifications due to exercise are responsible for IR injury prevention. This review will provide an overview the major mechanisms of IR injury and exercise preconditioning. The discussion highlights many promising avenues for further research and describes how exercise preconditioning may continue to be an important scientific paradigm in the translation of cardioprotection research to the clinic.