Spontaneous and inducible ventricular arrhythmias after myocardial infarction in mice
Spontaneous and inducible ventricular arrhythmias after myocardial infarction in mice
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DOI：
10.1016/s1054-8807(03)00152-2
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发表时间：
2004-05-01
影响因子：
3.7
通讯作者：
Yamada, KA
中科院分区：
文献类型：
--
作者：
Betsuyaku, T;Kanno, S;Yamada, KA
导读：间隙连接的重塑与心肌梗死（MI）后室性心律失常的发展有关，但电偶联减少的具体作用尚不清楚。我们使用connexin43空等位基因（Cx43(+/-)）杂合的小鼠心脏来解决这个问题。方法：为了确定Cx43缺陷小鼠在慢性缺血性心脏病的情况下是否会增加自发性室性心律失常，在左冠状动脉前降支结扎或假手术后2天或9周，将射频发射器植入野生型和Cx43（+/-）小鼠。记录心肌梗死后1周和10周未麻醉、不受约束小鼠的心电图。心肌梗死后1周和10周切除离体灌注心脏，施加程序性电刺激诱发心律失常。结果和结论：心肌梗死表现出更多自发性和诱导性心律失常，但在野生型和cx43缺陷小鼠之间没有显著差异。在体内表现出自发性室性心动过速（VT）的心脏比在体外诱导的少，这表明在离体心脏中诱导VT的结构和功能底物可能不足以在体内启动和维持持续的VT。先前的研究表明，在急性局部缺血时，cx43缺陷小鼠比野生型小鼠表现出更多的VT。心肌梗塞小鼠心律失常增加。然而，cx43缺陷小鼠的偶联减少并没有显著增强心肌梗死后自发性或诱导性VT。(C) 2004 Elsevier Inc。版权所有。
Introduction: Remodeling of gap junctions has been implicated in development of ventricular arrhythmias following myocardial infarction (MI) but the specific contribution of reduced electrical coupling is not known. We addressed this question using hearts from mice heterozygous for a connexin43 null allele (Cx43(+/-)). Methods: To determine whether Cx43-deficient mice exhibit increased spontaneous ventricular arrhythmias in the setting of chronic ischemic heart disease, radiofrequency transmitters were implanted in wild-type and Cx43(+/-) mice 2 days or 9 weeks after left anterior descending coronary artery ligation or sham operations. ECGs were recorded from unanesthetized, unrestrained mice 1 and 10 weeks after MI. Isolated, perfused hearts excised 1 and 10 weeks after MI were subjected to programmed electrical stimulation to induce arrhythmias. Results and conclusions: Hearts with infarcts exhibited more spontaneous and inducible arrhythmias, but there was no significant difference between wild-type and Cx43-deficient mice. Fewer hearts exhibited spontaneous ventricular tachycardia (VT) in vivo than were inducible in vitro, suggesting that structural and functional substrates for inducible VT in isolated hearts may not be sufficient for initiation and maintenance of sustained VT in vivo. Previous studies have shown that Cx43-deficient mice exhibit more VT than wild-type mice during acute regional ischemia. Mice with MI exhibit increased arrhythmias. However, reduced coupling in Cx43-deficient mice does not significantly enhance spontaneous or inducible VT after MI. (C) 2004 Elsevier Inc. All rights reserved.