Coromilas James, Costeas Constantinos, Deruyter Bernard, Dillon Stephen M, Peters Nicholas S, Wit Andrew L
Department of Pharmacology and the Center for Molecular Therapeutics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Circulation. 2002 May 14;105(19):2309-17. doi: 10.1161/01.cir.0000016292.14390.16.
K(ATP) channels, activated by ischemia, participate in the arrhythmogenic response to acute coronary occlusion. The function of these channels in border zones of healing infarcts, where arrhythmias also arise, has not been investigated. Do these channels remain maximally activated during infarct healing, or do they downregulate after a period of time? Both might preclude further activation.
Myocardial infarction was produced in dogs by ligation of the left anterior descending coronary artery. Impulse propagation in the epicardial border zone (EBZ) of 4-day-old healing infarcts was mapped during administration of pinacidil, a K(ATP) channel activator, directly into the EBZ coronary blood supply. Pinacidil restored conduction and excitability when the EBZ was initially inexcitable and had large regions of block (6 of 8 experiments). This allowed reentrant circuits to form in the EBZ, causing tachycardia (4 of 8 experiments). In hearts with an initially excitable EBZ, pinacidil shortened the effective refractory period and abolished conduction block at short cycle lengths (7 experiments). This effect prevented initiation of reentry (1 of 2 experiments).
The response to pinacidil indicates that K(ATP) channels in the EBZ remain functional and can be activated to influence electrophysiological properties and arrhythmogenesis.
缺血激活的K(ATP)通道参与急性冠状动脉闭塞后的致心律失常反应。这些通道在愈合梗死灶的边缘区（心律失常也在此处发生）中的功能尚未得到研究。在梗死愈合过程中，这些通道是一直保持最大程度激活，还是一段时间后会下调？这两种情况都可能阻止进一步激活。
通过结扎左冠状动脉前降支在犬身上制造心肌梗死。在将K(ATP)通道激活剂吡那地尔直接注入4日龄愈合梗死灶的心外膜边缘区（EBZ）的冠状动脉供血期间，绘制冲动在EBZ中的传播图。当EBZ最初无兴奋性且存在大片阻滞区域时（8个实验中的6个），吡那地尔恢复了传导和兴奋性。这使得EBZ中形成折返环，导致心动过速（8个实验中的4个）。在最初EBZ有兴奋性的心脏中，吡那地尔缩短了有效不应期，并在短周期长度时消除了传导阻滞（7个实验）。这种效应阻止了折返的起始（2个实验中的1个）。
对吡那地尔的反应表明，EBZ中的K(ATP)通道仍有功能，并且可以被激活以影响电生理特性和心律失常的发生。
