Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation

Epidemiologic investigations have shown that exercise reduces morbidity and mortality from coronary artery disease. In this study, using a rat model, we attempted to determine whether exercise can reduce ischemic injury to th e heart and elucidate a mechanism for the cardioprotective effect of exerci se. Results showed that exercise significantly reduced the magnitude of a m yocardial infarction in biphasic manner. The time course for cardioprotecti on resembled that of the change in manganese superoxide dismutase (Mn-SOD) activity. The administration of the antisense oligodeoxyribonucleotide to M n-SOD abolished the expected decrease in infarct size. We showed that the l evel of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL- 1 beta) increased after exercise. The simultaneous administration of the ne utralizing antibodies to the cytokines abolished the exercise-induced cardi oprotection and the activation of Mn-SOD. Furthermore, TNF-alpha can mimic the biphasic pattern of cardioprotection and activation of Mn-SOD. An antio xidant completely abolished cardioprotection and the activation of Mn-SOD b y exercise or the injection of TNF-alpha as well as exercise-induced increa se in TNF-a! and IL-1 beta. The production of reactive oxygen species and e ndogenous TNF-alpha and IL-1 beta induced by exercise leads to the activati on of Mn-SOD, which plays major roles in the acquisition of biphasic cardio protection against ischemia/reperfusion injury in rats.