Effects of ischemia postconditioning on ischemia-reperfusion injury and reperfusion injury salvage kinase signal transduction pathways in isolated mouse hearts / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the effects of ischemia postconditioning (IPC) on ischemia-reperfusion (I/R) injury and associated reperfusion injury salvage kinase (RISK) signal transduction pathways changes in isolated mouse hearts.</p><p><b>METHODS</b>Langendorff perfused C57/BL mouse hearts were divided to 6 groups (1) control 30 min global ischemia and 2 h reperfusion (I/R); (2) IPC with 3 episodes, IPC with 3 episodes of 10 s of ischemia and 10 s reperfusion after 30 min ischemia and before 2 h reperfusion; (3) IPC with 6 episodes, IPC with six episodes of 10 s of ischemia and 10 s reperfusion after 30 min ischemia and before 2 h reperfusion; (4) delayed IPC, IPC with 3 episodes of 10 s of ischemia and 10 s reperfusion after 30 min ischemia and at one minute after reperfusion; (5) IPC + ERK1/2 inhibitor PD98059 (10(-5) mol/L for 15 min); (6) I/R + ERK1/2 inhibitor PD98059 (10(-5) mol/L for 15 min). The effects of IPC on hemodynamics, coronary artery flow, creatine kinase (CK) and lactate dehydrogenase (LDH) release, myocardial SOD, MDA, phospho-protein kinase (P-ERK1/2) and phospho-protein kinase B (P-Akt) as well as myocardial infarction size were measured.</p><p><b>RESULTS</b>IPC with 3 episodes and IPC with 6 episodes significantly and equally improved myocardial function, increased myocardial SOD, reduced CK and LDH release and myocardial infarction size compared with IR group (all P < 0.01) while these parameters were similar between I/R hearts and delayed IPC hearts. IPC significantly increased myocardial ERK1/2 phosphorylation, PD98059 inhibited the phosphorylation of ERK1/2 and abolished the cardioprotective effects induced by IPC.</p><p><b>CONCLUSIONS</b>IPC obviously attenuated I/R injury in isolated mouse hearts, the cardioprotection of IPC was not enhanced because of increasing of IPC episodes and disappeared in delayed IPC. The cardioprotective effects of IPC were mediated through ERK1/2-MAPK signal transduction pathway.</p>