The protective effect of diazoxide on rat hearts during hypothermic preservation

Objective To assess whether diazoxide could enhance myocardial protection during hypothermic preservation of the rat heart. Methods The Langendorff model of isolated rat heart was used. After 30 minutes stabilization, the hearts were stored in 4℃ Celsior cardioplegia solution or Celsior solution containing mitoK_(ATP) opener diazoxide (30?μmol/L) with or without mitoK_(ATP) blocker 5-hydroxydecanoate (5-HD, 100 μmol/L) for 3, 5 or 10 hours followed by 60 minutes reperfusion. The recovery of cardiac function, myocardial enzyme leakage in the coronary effluent and myocardial water content were observed. The myocardial ultrastructure was also determined. Results (1) Diazoxide improved the recovery percent age of left ventricular developed pressure and (±dp/dt_(max)). Moreover, left ventricular end-diastolic pressure was significantly lower in diazoxide treated hearts than hearts in control group after cold preservation for 5, 10 hours, respectively. (2) Compared with the preservation in Celsior solution only, the myocardial enzyme leakage in the coronary effluent was significantly reduced in diazoxide groups. (3) Diazoxide significantly decreased the water content of myocardium and increased coronary flow of the hearts compared to control rat hearts. (4) The cardiac effects of diazoxide were attenuated by 5-HD. (5) Myocardial ultrastructure injury was alleviated. Conclusion The results suggest that diazoxide could enhance myocardial protection during hypothermic preservation of the rat heart, involving the activation of Mitochondrial ATP-sensitive potassium channel.