Morphine Postconditioning Protects Against Reperfusion Injury: the Role of

Background/Aims: The purpose of this study was to investigate the implications of protein kinase C-epsilon (PKCe), Extracellular Signal-regulated Kinase 1/2 (ERK1/2) and mitochondrial permeability transition pore (mPTP) in myocardial protection induced by morphine postconditioning (MpostC). Methods: The isolated rat hearts were randomly assigned into one of eight groups. Hearts in time control (TC) group were constantly perfused for 105min. Hearts in ischemia-reperfusion (I/R) group were subjected to 45 min of ischemia followed by 1 h of reperfusion. MpostC was induced by 10 min of morphine administration at the onset of reperfusion. eV 1-2 (an inhibitor of PKCe) and PD (an inhibitor of ERK1/2) was administered with or without morphine during the first 10 min of reperfusion following the 45 min of ischemia. I/R injury was assessed by functional parameters, creatine kinase-MB (CK-MB) release and infarct size (IS/AAR). Additional hearts were excised at 20 min following reperfusion to detect the membrane-specific translocation of PKCe, ERK1/2 phosphorylation, mitochondrial permeability transition (MPT) and cytochrome C (Cyt-c) release. Results: MpostC markedly reduced infarct size (IS/AAR), CK-MB release, and improved cardiac function recovery. However, these protective effects were partly abolished in the presence of eV 1-2 or PD. Compared to TC group, the membrane translocation of PKCe, ERK1/2 phosphorylation, mPTP opening, and Cyt-c release were significantly increased in I/R hearts. MpostC further increased the membrane translocation of PKCe and ERK1/2 phosphorylation, and significantly inhibited mPTP opening