Prominent IKs in epicardium and endocardium contributes to development of transmural dispersion of repolarization but protects against development of early afterdepolarizations
Prominent IKs in epicardium and endocardium contributes to development of transmural dispersion of repolarization but protects against development of early afterdepolarizations
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DOI：
10.1046/j.1540-8167.2002.00172.x
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发表时间：
2002-02-01
影响因子：
2.7
通讯作者：
Antzelevitch, C
中科院分区：
文献类型：
--
作者：
Burashnikov, A;Antzelevitch, C
我们实验室之前的研究表明：(1)i - k比M细胞大得多；(2)与M细胞相比，心外膜和心内膜细胞无法诱导早期去极化后（EAD）活性。本研究检验了这两个特征是相互关联的假设。方法和结果：采用标准微电极和浮动微电极技术记录犬左心室心外膜、M和心内膜区域的跨膜活动。I-Kr阻滞剂E-4031 （1 ~ 10 muM）在NI区分离的组织中引起动作电位持续时间（APD）明显延长并诱导EADs，但在心外膜或心内膜分离的组织中没有引起APD的大范围跨壁弥散。相比之下，I-Ks阻断剂chromanol 293B （10 ~ 30 muM）在所有三种组织类型中均可适度延长无EADs的APD。E-4031（1个muM）和chromanol 293B（30个muM）联合使用可显著延长APD，并在所有三种组织类型中产生EADs。在灌注楔形体中，单独使用E-4031和氯胺醇293B均不能诱发EADs。两种药物联合使用可显著延长所有三个跨壁区域的APD和EADs。结论：我们的研究结果支持了一种假设，即i - k的突出是心外膜和心内膜抵抗部分但不是全部i - k阻滞致心律失常作用的原因。这些数据强调了i - k在犬心脏中的关键重要性，以及当复极储备减少时，电紧张相互作用在最大限度地减少致心律失常底物的发展方面的重要作用。
Introduction: Previous studies from our laboratory demonstrated (1) a much larger I-Ks and (2) inability to induce early afterdepolarization (EAD) activity in epicardial and endocardial cells versus M cells. This study tests the hypothesis that these two characteristics are interrelated.Methods and Results: Standard and floating microelectrode techniques were used to record transmembrane activity from the canine left ventricular epicardial, M, and endocardial regions in isolated tissue slices and arterially perfused wedge preparations. The I-Kr blocker E-4031 (1 to 10 muM) caused prominent prolongation of action potential duration (APD) and induced EADs in tissues isolated from the NI region, but not those from epicardium or endocardium, causing a large transmural dispersion of APD. In contrast, the I-Ks blocker chromanol 293B (10 to 30 muM) produced moderate prolongation of APD without EADs in all three tissue types. The combination of E-4031 (1 muM) and chromanol 293B (30 muM) resulted in profound prolongation of APD and the development of EADs in all three tissue types. In the perfused wedge, neither E-4031 nor chromanol 293B alone could induce EADs. In combination, the two drugs caused significant prolongation of APD and EADs in all three transmural regions.Conclusion: Our results support the hypothesis that I-Ks prominent is responsible for the ability of epicardium and endocardium to resist some but not all of the arrhythmogenic effects Of I-Kr block. The data highlight the critical importance of I-Ks in the canine heart and the significant role of electrotonic interactions in minimizing the development of an arrhythmogenic substrate when repolarization reserve is reduced.