The cocoa flavanol (−)‐epicatechin exerts its cardioprotective effects by protecting myocardial bioenergetics

Targeting the mitochondria during ischemia reperfusion (IR) may confer cardioprotection and lead to improved clinical outcomes. This study tested the potential of the cocoa flavanol (−)‐epicatechin (EPI) to exert cardioprotection during IR via modulation of mitochondrial function. Ischemia was induced in rats via a 45 min occlusion. Reperfusion was allowed for 1h, 48h, or 3 wks. EPI (10 mg/kg) was administered IV 15 min prior to reperfusion for the single dose group and again 12h later for the double dose group. Controls received water. A single dose of EPI significantly reduced infarct size by 27% and 28% at 48h and 3wk, respectively, compared to controls. Double EPI treatment further decreased infarct size at 48h (80% reduction), which was sustained at 3 wk (52% reduction). In order to assess if this cardioprotection was mediated by protection of mitochondrial function, mitochondria were isolated from the left ventricle of sham, IR, and IR+EPI animals 1h after ischemia. IR animals had a significant decrease in mitochondrial O 2 consumption, significant increase in mitochondrial Ca 2+ levels, and decreased ATP and NADH pools. Epicatechin protected against these changes and had levels similar to sham animals. Taken together, the results suggest that EPI appears to enhance myocardial bioenergetics to confer cardioprotection. This study addresses an important topic related to the identification of mechanisms of action of an inexpensive, yet apparently effective dietary supplement for the potential treatment of cardiovascular disease. This work was supported by NIH 1R24DK092154 and Cardero Therapeutics.