Accelerated onset and increased incidence of ventricular arrhythmias induced by ischemia in cx43-deficient mice
Accelerated onset and increased incidence of ventricular arrhythmias induced by ischemia in cx43-deficient mice
复制标题
DOI：
10.1161/01.cir.101.5.547
复制
发表时间：
2000-02-08
期刊：
影响因子：
37.8
通讯作者：
Saffitz, JE
中科院分区：
文献类型：
--
作者：
Lerner, DL;Yamada, KA;Saffitz, JE
背景-心肌缺血引起主动膜电流和被动电特性的深刻变化。由于这些复杂的变化发展和进展相伴，它一直是不可能阐明任何一个组成部分的相对贡献，急性缺血诱导的mammogenesis。Cx43+/-小鼠表达50%的正常水平的连接蛋白43（Cx43），主要的心室电偶联蛋白，但在其他方面与野生型（Cx43+/+）小鼠相同。在Cx43+/-和+/+小鼠的embrymogenesis的比较可以提供洞察的作用，在电耦合的变化作为一个独立的变量，在复杂的设置急性ischemia.Methods和Results-Acute缺血引起的左冠状动脉前降支闭塞在离体灌注小鼠心脏。Cx43+/-心脏中自发性室性快速性心律失常（VT）的发生率是Cx43 +/+心脏的两倍多。在近3倍的Cx43+/-心脏中诱导VT。Cx43+/-心脏中自发性VT的多次运行和长时间运行更常见。Cx43+/-心脏的首次VT发作明显较早。室性早搏在Cx43+/-心脏中也更常见。低灌注区的大小是相等的，在两个groups. Conclusions减少表达的Cx43加速发病，并增加冠状动脉闭塞后室性快速性心律失常的发病率，频率和持续时间。因此，减少电耦合本身起着关键作用，在急性缺血诱导的血管生成。
Background-Myocardial ischemia causes profound changes in both active membrane currents and passive electrical properties. Because these complex changes develop and progress concomitantly, it has not been possible to elucidate the relative contributions of any one component to arrhythmogenesis induced by acute ischemia. Cx43+/- mice express 50% of the normal level of connexin43 (Cx43), the major ventricular electrical coupling protein, but are otherwise identical to wild-type (Cx43+/+) mice. Comparison of arrhythmogenesis in Cx43+/- and +/+ mice can provide insights into the role of changes in electrical coupling as an independent variable in the complex setting of acute ischemia.Methods and Results-Acute ischemia was induced in isolated perfused mouse hearts by occlusion of the left anterior descending coronary artery. Spontaneous ventricular tachyarrhythmias (VT) occurred in more than twice as many Cx43+/- hearts than Cx43 +/+ hearts. VT was induced in nearly 3 times as many Cx43+/- hearts. Multiple runs and prolonged runs of spontaneous VT were more frequent in Cx43+/- hearts. Onset of the first run of VT occurred significantly earlier in Cx43+/- hearts. Premature ventricular beats were also more frequent in Cx43+/- hearts. The size of the hypoperfused region was equivalent in both groups.Conclusions-Reduced expression of Cx43 accelerates the onset and increases the incidence, frequency, and duration of ventricular tachyarrhythmias after coronary artery occlusion. Thus diminished electrical coupling per se plays a critical role in arrhythmogenesis induced by acute ischemia.