Guo Wei, Shen Yue-liang, Chen Ying-ying, Hu Zhi-bin, Yan Zhi-kun, Xia Qiang
Department of Physiology, College of Medicine, Zhejiang University, Hangzhou 310031, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2005 Jul;34(4):331-8. doi: 10.3785/j.issn.1008-9292.2005.04.010.
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.
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.
(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).
Diazoxide as a supplementation in cardioplegia solution could enhance myocardial protection during hypothermic heart preservation via opening of mitochondrial K(ATP) channel.
研究线粒体ATP敏感性钾通道（mitoK(ATP)）开放剂二氮嗪作为心脏停搏液添加剂在大鼠心脏低温保存期间是否能增强心肌保护作用。
采用离体大鼠心脏Langendorff模型。平衡后，心脏在4℃的Celsior心脏停搏液中保存，添加或不添加二氮嗪3或8小时，随后再灌注60分钟。测定心脏收缩功能的恢复、冠状动脉流出液中心肌酶的泄漏以及心肌含水量。同时观察心肌超微结构。
（1）低温保存3小时后，二氮嗪处理可改善大鼠心脏再灌注第2和第4分钟时左心室舒张末压的恢复，并减少心肌酶乳酸脱氢酶（LDH）和肌酸激酶（CK）的泄漏。（2）低温保存8小时后，二氮嗪可改善左心室舒张末压的恢复，并减少再灌注期间心肌酶（LDH、CK和谷草转氨酶）的泄漏。此外，二氮嗪处理的心脏左心室舒张末压明显低于Celsior溶液处理的心脏。（3）低温保存8小时后，与对照组相比，二氮嗪显著降低了心肌含水量并增加了心脏冠状动脉血流量。（4）30μmol/L二氮嗪处理的心脏在低温保存8小时后心肌超微结构损伤减轻。（5）30μmol/L二氮嗪的心脏效应被mitoK(ATP)阻滞剂5-羟基癸酸（100μmol/L）减弱。
二氮嗪作为心脏停搏液的添加剂，可通过开放线粒体K(ATP)通道增强低温心脏保存期间的心肌保护作用。
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