[The protective effect of diazoxide on long-term heart preservation]

Abstract

Prolongation of the duration of heart preservation in vitro is very important in clinical heart transplantation. Previous studies have shown that mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) plays an important role in cardioprotective effect. The purpose of this study was to assess whether the mitoK(ATP) opener diazoxide as an additive to cardioplegia solution could enhance myocardial protection during long-term hypothermic preservation of the rat heart. Langendorff model of isolated rat heart was used. After 30 min stabilization of perfusion, the hearts were stored in Celsior cardioplegia solution at 4 degrees C with (15, 30 and 45 micromol/L) or without diazoxide, a mitoK(ATP) channel opener, for 10 h followed by 60 min reperfusion. The recovery of cardiac contractile function, myocardial enzyme leakage in the coronary effluent, and myocardial water content were determined. The myocardial ultrastructure was also observed. We found that: (1) Diazoxide treatment improved the recovery of left ventricular developed pressure and +/-dp/dt(max) dose-dependently. Left ventricular end-diastolic pressure was significantly lower in diazoxide-treated hearts than that of hearts in Celsior solution after hypothermic preservation for 10 h. (2) Diazoxide at 30 and 45 micromol/L significantly decreased the water content of myocardium and increased coronary flow of the hearts compared to those in control. (3) The leakage of myocardial enzymes (lactate dehydrogenase, creatine kinase and glutamate-oxaloacetate transaminase) in the coronary effluent was significantly reduced in diazoxide-treated hearts. (4) Impairment of myocardial ultrastructure after 10 h hypothermic preservation was alleviated in hearts treated with 30 micromol/L diazoxide. (5) The cardiac effects of 30 micromol/L diazoxide were attenuated by a mitoK(ATP) blocker 5-hydroxydecanoate (5-HD, 100 micromol/L). These results indicate that diazoxide as a supplementation in cardioplegia solution could enhance myocardial protection during long-term hypothermic heart preservation via opening of mitochondrial K(ATP) channel.