The infarct size-limiting effect of ischemic postconditioning (IPOC) is suppressed in isolated hyperhomocysteinemic (Hhcy) rat hearts: The reasonable role of PKC-δ

BackgroundRecently we have demonstrated that the cardioprotective potential of ischemic postconditioning (IPOC) against ischemia and reperfusion (I/R)-induced myocardial injury was markedly suppressed in hyperhomocysteinemic (Hhcy) rat hearts. The present study investigated the possible role of PKC-δ in Hhcy-induced suppression of myocardial infarct size-limiting effect of IPOC.MethodsIsolated Langendorff's perfused normal and Hhcy rat hearts were subjected to 30-min global ischemia (I), followed by 120-min reperfusion (R). The myocardial damage was assessed by measuring the infarct size, and analyzing the release of LDH and CK-MB in coronary effluent. The oxidative stress in the heart was assessed by measuring lipid peroxidation and superoxide anion generation.ResultsThe I/R produced myocardial injury in normal and Hhcy rat hearts by increasing myocardial infarct size, LDH and CK in coronary effluent and oxidative stress. Hhcy rat hearts exhibited enhanced I/R-induced myocardial injury and high oxidative stress as compared to normal rat hearts subjected to I/R. The IPOC (six brief episodes of I/R, 10 s each) afforded cardioprotection against I/R-induced myocardial injury in normal rat hearts; but IPOC-mediated cardioprotection was abolished in Hhcy rat hearts. Treatment with rottlerin (10 μM), a selective inhibitor of PKC-δ, did not affect the cardioprotective effect of IPOC in normal rat hearts; but its treatment significantly restored the myocardial infarct size-limiting effect of IPOC in Hhcy rat hearts.ConclusionThe high oxidative stress produced in Hhcy rat hearts during reperfusion may activate PKC-δ, which may be responsible for impairing the infarct size-limiting potential of IPOC in Hhcy rat hearts.