Protection of Mitochondrial Function During Ischemia Reperfusion

Cardiovascular diseases (CVDs) are the primary cause of death globally. Numerous studies have indicated that flavonoid-rich foods and beverages have cardioprotective capabilities. We have previously demonstrated that the cocoa flavanol epicatechin (EPI) reduces infarct size and improves long-term left ventricular structure/function after ischemia reperfusion (IR).  It has been shown that targeting the mitochondria during IR may confer cardioprotection and lead to improved clinical outcomes. Thus, the potential of EPI to exert cardioprotection during IR via modulation of mitochondrial function was tested. Rats underwent 45 min ischemia and 1h, 48h or 3wk reperfusion. EPI (10 mg/kg) or water was administered IV 15 min prior to reperfusion for the single dose group and again 12h later for the double dose group. The results show that a single dose of EPI significantly reduced infarct size by 27% and 28% at 48 h and 3 wk, respectively, compared to controls. Double EPI treatment further decreased infarct size at 48 h (80% reduction), which was sustained at 3 wk (52% reduction). Mitochondria were isolated from the left ventricle of sham, IR, and IR+EPI animals 1h after ischemia to look at mitochondrial structure/function. IR animals had a significant decrease in mitochondrial O₂ consumption, significant increase in mitochondrial Ca²⁺ levels, and decreased ATP and NADH pools. EPI protected against these changes and had levels similar to sham animals. In conclusion, IV EPI may be conferring cardioprotection by preservation of myocardial energetics with effects that can be reinforced by the use of multiple doses.