Abstract 1628: Exercise Training Protects Cardiac Subsarcolemmal and Interfibrillar Mitochondria Against an Ischemia-Reperfusion Injury
Growing evidence suggests that mitochondrial damage during ischemia reperfusion (IR) events critically contribute to cardiac cell damage leading to infarction. On the contrary, exercise training (ExT) has been known to be cardioprotective against an IR insult. Nonetheless, mechanisms responsible for ExT-mediated protection remain unclear. Based upon our previous observation that ExT improves mitochondrial antioxidant capacity, we hypothesized that ExT (treadmill running) would confer cardioprotection via protecting biochemically and morphologically different two subpopulations of mitochondria (subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM)) against an IR. To examine our hypothesis, 4 –5 month-old male Sprague-Dawley rats were used, and an isolated working heart model was chosen to conduct global 40 min ischemia and 45 min of reperfusion. Our results revealed that ExT group maintained higher recovery cardiac work after an IR insult compared with control group (65.9%±2.7 vs. 23.7%±7.2 in con) (n=8, p<0.05). Mitochondrial function (respiratory control ratio) measured from isolated intact mitochondria proved by electron microscopy was significantly higher in both SSM and IFM of ExT group compared with control group (n=8, p<0.05). More importantly, reactive oxygen species (ROS) production measured in physiological condition (50% VO2max) linked by creatin kinase equilibrium was lower in both SSM and IFM of ExT group compared with control group (p<0.05). Additionally, ExT reduced IR-induced mitochondrial lipid and protein oxidative damage and attenuated the release of proapoptotic proteins, cytochrome c and AIF. Our result also showed that ExT improved mitochondrial antioxidant capacity. Collectively, these findings for the first time suggest that ExT-induced cardioprotection is associated with mitochondrial protection, and that this protective mechanism is via enhanced antioxidant capacity. This study provides new insight into a potential mechanism responsible for ExT-induced cardioprotection, and contributes to developing pharmacological or molecular intervention targeting mitochondrial protection to protect the heart.