[Protective effect of mitochondrial ATP-sensitive potassium channel opener on rat heart during hypothermic preservation].

OBJECTIVE: To investigate whether the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) opener diazoxide as an additive to cardioplegia solution could enhance myocardial protection during hypothermic preservation of the rat heart. METHODS: The Langendorff model of isolated rat heart was used. After equilibrium, the hearts were stored in Celsior cardioplegia solution at 4 degree with or without supplement of diazoxide for 3 or 8 h followed by 60 minutes 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. RESULT: (1) Treatment of diazoxide improved the recovery of left ventricular developed pressure and decreased the leakage of myocardial enzymes, lactate dehydrogenase (LDH) and creatine kinase (CK), at the 2nd and 4th minute of reperfusion of rat heart after hypothermic preservation for 3 h. (2) After hypothermic preservation for 8 h, diazoxide improved the recovery of left ventricular developed pressure and decreased the leakage of myocardial enzymes (LDH, CK and glutamic oxalic transaminase) during reperfusion. Moreover, left ventricular end-diastolic pressure was significantly lower in diazoxide-treated hearts than that of hearts in Celsior solution. (3) Diazoxide significantly decreased the water content of myocardium and increased coronary flow of the hearts compared with those in control after hypothermic preservation for 8 h. (4) Impairment of myocardial ultrastructure after 8 h hypothermic preservation was alleviated in hearts treated with 30 mol/L diazoxide. (5) The cardiac effects of 30 mol/L diazoxide were attenuated by a mitoK(ATP) blocker 5-hydroxydecanoate (100 micromol/L). CONCLUSION: Diazoxide as a supplementation in cardioplegia solution could enhance myocardial protection during hypothermic heart preservation via opening of mitochondrial K(ATP) channel.

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

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.

[Follow-up of twelve cases of heart transplantation].

OBJECTIVE: To observe the effects of heart transplantation. METHODS: Twelve patients undergoing orthotopic heart transplantation, one of which underwent combined heart and kidney transplantation (HKT), from June 1997 to June 2002 were followed up to observe the complications, work ability, life quality and psychic status. RESULTS: One of the 12 patients died of acute rejection and one died of acute renal failure during perioperative period. Ten cases (83.3%) survived the operation. Then one of the 10 patients died of acute rejection due to stopping Cellcept 7 months after operation; and the other 9 patients had lived well for 1 to 9 years, of which one recipient undergoing HKT survived for nearly 3 years. One year after operation the 9 patients showed class I heart function (NYHA), and all resumed their original work. One patient suffered from schizophrenia 1 week after operation. After the operation every year all cases were to receive coronary angiography with the results showing thinner coronary artery and less lateral branches, and myocardium, emission computed tomography (ECT) scanning that revealed local ischemia in anterior or posterior myocardium in 2 cases 4 and 5 years after respectively, however, no symptom of coronary artery disease was seen in all patients. Two cases, including the one receiving HKT, had symptoms of diabetes mellitus. Two patients thoracotomy during the perioperative period because of cardiac tamponade or too much blood drainage. All cases suffered from right heart failure, mouth ulcer and hypertension due to taking CsA and they had to take antihypertension drug to control their blood pressure. No malignant tumor had been found. CONCLUSION: Heart transplantation is an effective treatment for end-stage dilated cardiomyopathy. But many complications may follow. Some of them may endanger patients' life, and others may affect the quality of life. To trace the patients closely and deal with various complications in time will improve the effect of cardiac transplantation.