Effect of STH-2 cardioplegic solution containing levosimendan on ischemia-reperfusion injury in isolated rat hearts

Abstract

Objective To investigate the effect of STH-2 cardioplegic solution containing levosimendan on ischemia-reperfusion (I/R) injury in isolated rat hearts. Methods Thirty-two male Wistar rats weighing 250-300 gwere anesthetized with intraperitoneal 3% pentobarbital 30 mg/kg. The hearts were rapidly excised and perfused with oxygenated (95% O2-5% CO2) K-H solution for 30 min in a Langendorff apparatus and then divided into 4groups (n = 8 each) according to the composition of cardioplegic solution: group Ⅰ control (group C) was perfused with STH-2 cardioplegic solution; group Ⅱ , Ⅲ and Ⅳ were peffused with STH-2 cardioplegic solution containing levosimendan 0.03 μmol/L (L1), 0.3 μmol/L (L2) and levosimendan 0.3 μmol/L + glibenclamide 10 μmol/L (L2+ G) respectively. The isolated hearts were first perfused with different cardioplegic solutions for 2 h and then with K-H solution for 30 min. The coronary effluent was collected before ischemia (baseline) and at 10, 20 and 30 min of reperfusion for measurement of creatine kinase (CK) and lactate dehydrogenase (LDH)activities. Myocardial specimens were obtained from apex at 30 min of reperfusion for determination of myocardial ATP and MDA contents and SOD activity. Results Perfusion with STH-2 cardioplegic solution significantly increased CK and LDH activities and MDA content, and significantly decreased SOD activity. Levosinendan 0.03or 0.3 μmol/L significantly attenuated the cardioplegia-induced increase in LDH,CK and SOD activities and MDA content. The protective effects of levosimendan on myocardium against I/R injury were reversed by glibenclamide to some extent. Conclusion Levosimendan can protect myocardium from I/R injury in a dose-dependent manner by opening KATP channel. Key words: Pyridazines; Cardioplegic solutions; Myocardial reperfusion injury