Abstract P81: Role of Mitochondrial Permeability Transition Pore (mPTP) in the Transition from Reversible to Irreversible Myocardial Ischemia and Reperfusion
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 Ca2+ 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.