Selective mitochondrial KATP channel activation results in antiarrhythmic effect during experimental myocardial ischemia/reperfusion in anesthetized rabbits
Selective mitochondrial KATP channel activation results in antiarrhythmic effect during experimental myocardial ischemia/reperfusion in anesthetized rabbits
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DOI：
10.1016/s0014-2999(02)01277-3
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发表时间：
2002-02-22
影响因子：
5
通讯作者：
Karanth, KS
中科院分区：
文献类型：
--
作者：
Das, B;Sarkar, C;Karanth, KS
我们研究了在麻醉白化病兔中，在冠状动脉闭塞之前和期间以及缺血再灌注之前和期间给予非膨胀剂量的ATP敏感性K+通道（K-ATP）开放剂（尼可地尔和阿替卡林）和特异性线粒体K-ATP通道阻滞剂（5-羟基癸酸酯）对存活率、缺血/再灌注诱导的心律失常和心肌梗死面积的影响。用可释放的丝线结扎左冠状动脉主干20分钟后再灌注诱发心律失常。在缺血前和缺血期间通过静脉输注尼可地尔（100 mug/kg推注+ 10 mug/kg/min）或阿普卡林（10 mug/kg推注+ 0.1 mug/kg/min）进行早期干预可增加存活率（86%和75% vs.对照组55%），显著降低危及生命的心律失常的发生率和严重程度以及心肌梗死面积。通过5-羟基癸酸酯（5 mg/kg，i. v.推注）预处理家兔，可消除尼可地尔和阿普利卡林的抗心律失常和心脏保护作用。总之，尼可地尔和阿普卡林静脉给药干预（通过选择性激活线粒体K-ATP通道）增加了麻醉家兔在冠状动脉闭塞前和闭塞期间冠状动脉闭塞和再灌注期间的存活率，并表现出抗心律失常和心脏保护作用。(C)2002 Elsevier Science B.V保留所有权利。
We investigated the effects of administration of non-hypotensive doses of ATP-sensitive K+ channel (K-ATP) openers (nicorandil and aptikalim), and a specific mitochondrial K-ATP channel blocker (5-hydroxydecanoate) prior to and during coronary occlusion as well as prior to and during post-ischemic reperfusion on survival rate, ischemia/reperfusion-induced arrhythmias and myocardial infarct size in anesthetized albino rabbits. Arrhythmias were induced by reperfusion following a 20 min ligation of the left main coronary artery with a releascable silk ligature. Early intervention by intravenous infusion of nicorandil (100 mug/kg bolus + 10 mug/kg/min) or aprikalim (10 mug/kg bolus + 0.1 mug/kg/min) just before and during ischemia increased survival rate (86% and 75% vs. 55% in the control group), significantly decreased the incidence and severity of life-threatening arrhythmias and myocardial infaret size. The antiarrhythmic and cardioprotective effects of both nicorandil and aprikalim were abolished by pretreating the rabbits with 5-hydroxydecanoate (5 mg/kg, i.v. bolus). In conclusion, intervention by intravenous administration of nicorandil and aprikalim (through the selective activation of mitochondrial K-ATP channels) increased survival rate and exhibited antiarrhythmic and cardioprotective effects during coronary occlusion and reperfusion in anesthetized rabbits when administered prior to and during coronary occlusion. (C) 2002 Elsevier Science B.V All rights reserved.