二氮嗪改善供心超时冷保存效果的实验研究  

The protective effect of diazoxide on rat hearts during hypothermic preservation

作　　者：严志焜[1] 胡志斌[1] 郭炜[2] 潘晓华[1] 吕治林[1] 沈岳良[2] 

机构地区：[1]浙江省人民医院胸心外科,杭州310014 [2]浙江大学医学院生理教研室

出　　处：《中华胸心血管外科杂志》2005年第2期104-107,共4页Chinese Journal of Thoracic and Cardiovascular Surgery

摘　　要：目的　研究二氮嗪在离体大鼠心脏冷保存中的作用,探讨线粒体ATP敏感性钾通道(Mito chondrialATP sensitivepotassiumchannel,MitoKATPC)开放剂在改善供心功能中的可能机制,及超时(超过公认5h)冷保存供心的有效性。方法　SD大鼠随机分7组。对照组、二氮嗪(DE)组,以上两组又各分为冷保存3、5、10h组和DE +5 羟基葵酸盐(5 HD)组。采用Langendorff离体鼠心灌注法,复灌6 0min ,观察心脏血流动力学、冠脉流出液心肌酶漏出量及心肌水含量变化,并做心肌超微结构检查。结果　(1)冷保存3、5、10h后,DE组LVDP、±dp/dtmax、CF恢复率在多个复灌时间点上均优于对照组,且心肌酶漏出量明显减少。(2 )5、10h保存组中,DE处理后LVEDP的变化明显小于对照组。(3)与对照组相比,保存10h后DE组的心肌水含量明显降低,且心肌超微结构优于对照组。(4)与保存5h对照组相比,保存10h后DE组在复灌期可显著抑制LVEDP的增高;仅LVDP和-dp/dtmax恢复率较保存5h对照组低。(5 )DE的上述作用可被Mi-toKATPC的特异性阻断剂5 HD抵消。结论　Celsior保存液中加入DE能明显改善离体大鼠心脏冷保存效果,且供心的冷缺血安全时间可安全延长至10h。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.

关 键 词：保存效果 二氮嗪 实验研究 供心 线粒体ATP敏感性钾通道 Langendorff potassium 离体大鼠心脏 心肌超微结构 channel 心脏血流动力学 LVDP 对照组 冠脉流出液 LVEDP 冷保存 可能机制 SD大鼠 5-羟基 离体鼠心 含量变化 5-HD 

分 类 号：R654.2[医药卫生—外科学]