Evaluation of the role of IKACh in atrial fibrillation using a mouse knockout model
Evaluation of the role of IKACh in atrial fibrillation using a mouse knockout model
复制标题
DOI：
10.1016/s0735-1097(01)01304-3
复制
发表时间：
2001-06-15
影响因子：
24
通讯作者：
Clapham, DE
中科院分区：
文献类型：
--
作者：
Kovoor, P;Wickman, K;Clapham, DE
我们试图研究I-KACh在心房纤颤（AF）中的作用以及特异性I-KACh拮抗剂的潜在电生理效应。迷走神经刺激易患AF，但I-KACh在AF的产生和特定的I-KACh阻滞的电生理学效应的具体作用还没有studied.METHODS成年野生型（WT）和I-KACh缺陷敲除（KO）小鼠的情况下和存在的毒蕈碱受体激动剂卡巴胆碱进行了研究。KO小鼠的电生理功能进行了比较与WT小鼠的一个特定的I-KACh拮抗剂的潜在影响进行评估。结果心房颤动持续平均为5.7 +/- 11分钟，在卡巴胆碱的存在下，在10 14 WT小鼠中开始，但不是在没有卡巴胆碱。在KO小鼠中不能诱导房性心律失常。两种小鼠均不能诱发室性快速性心律失常。与WT小鼠相比，KO小鼠在卡巴胆碱和窦性周期长度后的窦房结恢复时间更短，心室有效不应期更长。KO和WT小鼠的AV结功能无显著差异。结论I-KACh的激活易诱发AF，I-KACh的缺乏可预防AF。特异性I-KACh阻滞剂可能用于治疗AF，对房室结或心室无显著不良影响。（美国科尔心脏病学杂志2001;37：2136-43）（C）2001年美国心脏病学会。
OBJECTIVES We sought to study the role of I-KACh in atrial fibrillation (AF) and the potential electrophysiologic effects of a specific I-KACh antagonist.BACKGROUND I-KACh mediates much of the cardiac responses to vagal stimulation. Vagal stimulation predisposes to AF, but the specific role of I-KACh in the generation of AF and the electrophysiologic effects of specific I-KACh blockade have not been studied.METHODS Adult wild-type (WT) and I-KACh-deficient knockout (KO) mice were studied in the absence and presence of the muscarinic receptor agonist carbachol. The electrophysiologic features of KO mice were compared with those of WT mice to assess the potential effects of a specific I-KACh antagonist.RESULTS Atrial fibrillation lasting for a mean of 5.7 +/- 11 min was initiated in 10 of 14 WT mice in the presence of carbachol, but not in the absence of carbachol. Atrial arrhythmia could not be induced in KO mice. Ventricular tachyarrhythmia could not be induced in either type of mouse. Sinus node recovery times after carbachol and sinus cycle lengths were shorter and ventricular effective refractory periods were greater in KO mice than in WT mice. There was no significant difference between KO and WT mice in AV node function.CONCLUSIONS Activation of I-KACh predisposed to AF and lack of I-KACh prevented AF. It is likely that I-KACh plays a crucial role in the generation of AF in mice. Specific I-KACh blockers might be useful for the treatment of AF without significant adverse effects on the atrioventricular node or the ventricles. (J Am Coll Cardiol 2001;37:2136-43) (C) 2001 by the American College of Cardiology.