Intra-cardiac remote ischemic post-conditioning attenuates ischemia-reperfusion injury in rats

It remains unknown whether brief occlusion and relaxation of remote non-infarct-related coronary arteries limits infarct size. We tested the hypothesis that repetitive, brief, non-infarcting ischemia in one remote myocardial region, applied before sustained reperfusion to another intra-cardiac vasculature following infarcting ischemia, attenuates ischemia-reperfusion injury.

In anesthetized open-chest rats, the left main coronary artery (LCA) was occluded for 30 min followed by sustained relaxation for 120 min. All rats were randomly allocated to six groups (n=8):

without other interventions; Intra-cardiac remote ischemic post-conditioning (R-Post): before LCA relaxation, 3 cycles of 10 s ischemia by occluding the circumflex branch and 10 s reperfusion by relaxing it were applied; Atractyloside (Atr): given intravenously with atractyloside, an opener of the mitochondrial permeability transition pore; R-Post + Atr; Classical ischemic post-conditioning (Post): 3 cycles of 10 s reperfusion followed by 10 s ischemia were applied before 120 min of LCA relaxation; Sham: without LCA occlusion. We evaluated infarct size, cardiac function, cardiomyocyte ultrastructure and inflammatory processes.

Compared with CONTROL, at the end of sustained reperfusion, R-Post and Post had smaller infarcts (respectively, 49%+/-5% vs. 32%+/-6% and 26%+/-5%, p<0.05), higher left ventricular +/-dP/dt(max), slighter ultrastructural damage, lower malondialdehyde activity and higher superoxide dismutase activity in plasma and myocardium, and lower myeloperoxidase activity in myocardium. R-Post-induced cardioprotection was abrogated by atractyloside.

Intra-cardiac remote ischemic post-conditioning attenuates myocardial ischemia-reperfusion injury, and inhibition of the mitochondrial permeability transition pore opening may be involved in this cardioprotection.