Role of erythropoietin in ischemic postconditioning induced cardioprotection in hyperlipidemic rat heart

Abstract

ObjectiveIschemic postconditioning (IPOC) is an endogenous cardioprotective phenomenon, which gets attenuated during the hyperlipidemia. It has been documented that erythropoietin (EPO), a glycoprotein, produces IPOC-like cardioprotection through common signaling pathway such as PI-3K pathway. The aim of this study has been designed to investigate the role of EPO in IPOC induced cardioprotection in hyperlipidemic rat heart. Materials and methodsHeart was isolated from hyperlipidemic rat and mounted on Langendorff's apparatus, subjected to 30min ischemia and 120min reperfusion. IPOC was mediated by four cycles of 5min reperfusion and 5min ischemia. The infarct size was estimated using TTC stain and coronary effluent was analyzed for LDH and CK-MB release to assess the degree of myocardial injury. ResultsFour cycles of IPOC produces cardioprotection noted in terms of decrease in infarct size and decrease in the release of LDH and CK-MB in normal rat heart. However, IPOC-induced cardioprotection was completely attenuated in isolated heart obtained from hyperlipidemic rat. Perfusion of EPO (1U/ml) significantly restored the attenuated cardioprotection in hyperlipidemic rat heart, which was completely blocked by perfusion of LY294002 (10μM), a selective inhibitor of PI-3K. ConclusionThus, it is suggested that EPO restores the attenuated cardioprotective effect of IPOC in hyperlipidemic rat heart by the activation of PI-3K signaling pathway.