ATP-sensitive potassium channel modulators: both pinacidil and glibenclamide produce antiarrhythmic activity during acute myocardial infarction in conscious rats.
ATP-sensitive potassium channel modulators: both pinacidil and glibenclamide produce antiarrhythmic activity during acute myocardial infarction in conscious rats.
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ATP 敏感的钾通道调节剂：吡那地尔和格列本脲在清醒大鼠急性心肌梗死期间均产生抗心律失常活性。
DOI：
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发表时间：
1996
影响因子：
3.5
通讯作者：
J. Papp
中科院分区：
文献类型：
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作者：
I. Leprán;I. Baczkó;A. Varró;J. Papp
我们研究了吡那地尔（一种 ATP 敏感的钾通道开放剂）和格列本脲（一种 ATP 敏感的钾通道抑制剂）对清醒大鼠冠状动脉结扎后心律失常和心源性猝死发生率的影响。通过收紧先前放置的松散丝结扎线来闭塞左冠状动脉主干。在对照组 (n = 25) 中，冠状动脉结扎后分别只有 40% 和 24% 的动物存活 15 分钟和 16 小时。静脉注射 0.1、0.3 或 1 mg/kg 吡那地尔预处理可使前 15 分钟的存活率分别提高至 67% (n = 15)、70% (n = 20) 和 67% (n = 12)，前 16 小时的存活率分别提高至 60%、55% 和 67%。格列本脲预处理 (5.0 mg/kg i.p.) 将两个时间点的存活率提高至 87% (n = 16)。两种类型的预处理均显着降低了危及生命的心律失常的发生率，并增加了未出现任何心律失常的存活动物数量。总之，本研究结果表明，在清醒大鼠中，吡那地尔预处理和格列本脲预处理，尽管它们明显具有不同的作用机制，但在实验性心肌梗死急性期的心律失常和心源性猝死方面可能会导致非常相似的最终结果。
We investigated the effects of pinacidil, an ATP-sensitive potassium channel opener, and of glibenclamide, an ATP-sensitive potassium channel inhibitor, on the incidence of arrhythmias and sudden cardiac death after coronary artery ligation in conscious rats. Occlusion of the left main coronary artery was produced by tightening a previously placed loose silk ligature. In the control group (n = 25) only 40% and 24% of the animals survived for 15 min and 16 hr after coronary artery ligation, respectively. Intravenous pretreatment with 0.1, 0.3 or 1 mg/kg pinacidil increased the survival rate to 67% (n = 15), 70% (n = 20) and 67% (n = 12) in the first 15 min and to 60%, 55% and 67% in the first 16 hr, respectively. Glibenclamide pretreatment (5.0 mg/kg i.p.) improved the survival rate at both time-points to 87% (n = 16). Both types of pretreatment significantly decreased the incidence of life-threatening arrhythmias and increased the number of animals that survived without developing any arrhythmia. In conclusion, the present findings demonstrate that in conscious rats, pretreatment with pinacidil and pretreatment with glibenclamide, although they obviously have different mechanisms of action, may result in a very similar final outcome with respect to arrhythmias and sudden cardiac death during the acute phase of experimental myocardial infarction.