Effect of heart preservation solution containing pinacidil on mitochondrial function in isolated rat hearts / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effect of heart preservation solution containing pinacidil on mitochondrial function in isolated rat hearts. Methods One hundred and twenty pathogen-free SD rats of both sexes weighing 250-350 g were used in this study. The animals were anesthetized with intraperitoneal pentobarbital 65 mg/kg. Their hearts were immediately removed and perfused in a Langendorff apparatus. Left ventricular enddiastolic pressure was measured from a fluid-filled latex balloon inserted in the left ventricle. The isolated hearts were randomized into 5 groups (n = 24 each)group Ⅰ was perfused with cardioplegic solution HTK; group Ⅱ with HTK containing pinacidil (a non-specific sarcKATP and mitoKATP channel opener) 0.5 mmol/L; group Ⅲ with HTK containing pinacidil 0.5 mmol/L + 5-HD (a selective mitoKATP channel blocker) 100 μmol/L; group Ⅳ with HTK containing pinacidil 0.5 mmol/L + HMR-1098 100 μmol/L (a selective sarcKATP channel blocker) and group Ⅴ with HTK containing pinacidil 0.5 mmol/L + 5-HD 100 μmol/L + HMR-1098 100μmol/L. The isolated hearts were perfused with simple HTK or HTK containing pinacidil or pinacidil + 5-HD and/or HMR 20 ml/kg at 10 ml/min and then removed from Langendorff apparatus and dipped into the same HTK solution for 8 h at 4 ℃followed by 60 min reperfusion. The respiratory function of mitochondria (respiratory control rate (RCR), the rate of oxygen consumption in state 3/state 4 and P/O) was measured at the end of equilibration (T1) after 8 hpreservation (T2) and at the end of 60 min reperfusion (T3). The CK-MB and LDH activities and cTnI expression in myocardium was detected at T1 and T3. The ultrastructure of myocardium was examined at T3. Results Perfusion suspension-reperfusion (PS/R) significantly decreased mitochondrial respiratory function (RCR, P/O and rate of O2 consumption in state 3) and increased myocardial cTnI concentration and CK-MB and LDH activities at T3 compared with baseline at T1 in group Ⅰ. Pinacidil significantly increased mitochondrial respiratory function (RCR, P/O and rate of O2 consumption in state 3) and decreased myocardial cTnI concentration and CK-MB and LDH activities in group Ⅱ as compared with group Ⅰ-indicative of protective effect of pinacidil on mitochondria against PS/R injury. The protective effect of pinacidil against PS/R injury was attenuated by 5-HD and/or HMR1098. The myocardial damage was slightest in group Ⅱ . Conclusion Both sarcolemmal and mitochondrial KATPchannel are involved in the protective effect of pinacidil against PS/R-induced myocardial damage during heart preservation.