Abstract P81: Role of Mitochondrial Permeability Transition Pore (mPTP) in the Transition from Reversible to Irreversible Myocardial Ischemia and Reperfusion

Abstract

Introduction . The aim of this study was to evaluate the role of mitochondrial permeability transition in the transition from reversible to irreversible injury following increasing times of ischemia- reperfusion. Methods . Rat hearts (n=72) were perfused according to Langendorff technique, arrested and submitted to global warm ischemia during 0 (sham), 10, 20, 30, 40 or 60 minutes at 37°C, and 60 min of reperfusion. Infarct size was evaluated by TTC staining and CK and LDH release. Functional recovery was assessed by rate-pressure product (RPP). Mitochondria were isolated to assess Ca 2+ resistance capacity (CRC) of the MPTP. Results . a transition from reversible to irreversible ischemia occurred between 20 and 30 minutes of warm ischemia. Hearts ischemic for less than 20 minutes exhibited better functionnal recovery with RPP averaging 31264±1341 and 28578±2176 mmHg/beats/min, respectively. In contrast, hearts that underwent 30, 40 and 60 min of ischemia displayed dramatic RPP decrease, averaging 12183±1895, 7411±578 and 4916±698 mmHg/min, respectively (p<0.001 vs 20 minutes ischemia). CK and LDH release and TTC staining confirmed absence of infarction with ischemia < 20 min (Panel A). In line with this, mean CRC was significantly reduced when ischemia lasted more than 20 minutes (p<0.001, Panel B). Conclusion . This study shows a parallel evolution between the alteration of mitochondrial calcium retention capacity of the appearance of irreversible damage in the reperfused heart.