Hide E J, Thiemermann C
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, UK.
Cardiovasc Res. 1996 Jun;31(6):941-6.
To investigate the effect of the ATP-sensitive potassium (KATP) channel inhibitor sodium 5-hydroxydecanoate (5-HD) on the reduction in myocardial infarct size afforded by ischaemic preconditioning in the sodium pentobarbitone rabbit.
New Zealand white rabbits were anaesthetised with sodium pentobarbitone and subjected to 60 min occlusion of the first antero-lateral branch of the left coronary artery (LAL) followed by 120 min reperfusion. Ischaemic preconditioning was achieved by a single episode of 5 min LAL occlusion followed by 15 min reperfusion prior to the 60 min occlusion. 5-HD (5 mg kg-1), an ischaemia selective KATP channel inhibitor, was administered into the left ventricle as a bolus injection 10 min prior to the onset of ischaemic preconditioning. Injection of Evans blue dye was used to determine the area of the left ventricle at risk and infarct size was determined by incubation of the area at risk with nitro-blue tetrazolium.
There were no significant differences between groups in haemodynamics or area at risk. Ischaemic preconditioning resulted in a significant reduction in infarct size (27 +/- 8%) when compared to control animals (55 +/- 3%; P < 0.05). Pretreatment of animals with 5-HD completely abolished the cardioprotection seen with ischaemic preconditioning (50 +/- 6%).
These results support the hypothesis that the cardioprotection afforded by ischaemic preconditioning in the pentabarbitone anaesthetised rabbit is dependent on the opening of KATP channels.
研究三磷酸腺苷敏感性钾(KATP)通道抑制剂5-羟基癸酸钠(5-HD)对戊巴比妥钠麻醉兔缺血预处理所致心肌梗死面积减小的影响。
用戊巴比妥钠麻醉新西兰白兔,阻断左冠状动脉前降支第一对角支60分钟,随后再灌注120分钟。缺血预处理通过在60分钟阻断前单次阻断左冠状动脉前降支5分钟随后再灌注15分钟来实现。在缺血预处理开始前10分钟,将缺血选择性KATP通道抑制剂5-HD(5mg/kg)作为单次推注注入左心室。注射伊文思蓝染料以确定左心室危险区面积,通过将危险区与硝基四氮唑蓝孵育来确定梗死面积。
各组间血流动力学或危险区面积无显著差异。与对照动物(55±3%)相比,缺血预处理导致梗死面积显著减小(27±8%;P<0.05)。用5-HD预处理动物完全消除了缺血预处理所见的心脏保护作用(50±6%)。
这些结果支持以下假说,即在戊巴比妥钠麻醉兔中,缺血预处理所提供的心脏保护作用依赖于KATP通道的开放。