Cheng Yuanna, Li Li, Nikolski Vladimir, Wallick Don W, Efimov Igor R
Department of Cardiovascular Medicine, Desk FF10, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA.
Am J Physiol Heart Circ Physiol. 2004 Jan;286(1):H310-8. doi: 10.1152/ajpheart.00092.2003. Epub 2003 Sep 4.
Investigation of the mechanisms of arrhythmia genesis and maintenance has benefited from the use of optical mapping techniques that employ excitation-contraction uncouplers. We investigated the effects of the excitation-contraction uncouplers 2,3-butanedione monoxime (BDM) and cytochalasin D (Cyto D) on the induction and maintenance of arrhythmia by electric shocks. Electrical activity was optically mapped from anterior epicardium of rabbit hearts (n = 9) during shocks (-100 V, 8 ms) applied from a ventricular lead at various phases of action potential duration (APD). Restitution curves were obtained using S1-S2 protocol and measurement of APD values at 70% of repolarization. Compared with Cyto D, BDM significantly shortened APD at 90% of repolarization, although no significant difference in dispersion of repolarization was observed. Wavelength was also shortened with BDM. In general, shock-induced arrhythmias with BDM and Cyto D were ventricular tachycardic in nature. With respect to shock-induced sustained arrhythmias, the vulnerable window was wider and the incidence was higher with BDM than with Cyto D. There was also a difference in the morphology of ventricular tachycardia (VT) between the two agents. The arrhythmias with BDM usually resembled monomorphic VT, especially those that lasted >30 s. In contrast, arrhythmias with Cyto D more resembled polymorphic VT. However, the average number of phase singularities increased under Cyto D vs. BDM, whereas no significant difference in the dominant frequency of shock-induced sustained arrhythmia was observed. BDM reduced the slope of the restitution curve compared with Cyto D, but duration of arrhythmia under BDM was significantly increased compared with Cyto D. In conclusion, BDM increased arrhythmia genesis and maintenance relative to Cyto D.
心律失常发生和维持机制的研究受益于使用采用兴奋 - 收缩解偶联剂的光学映射技术。我们研究了兴奋 - 收缩解偶联剂2,3 - 丁二酮一肟（BDM）和细胞松弛素D（细胞松弛素D）对电击诱发和维持心律失常的影响。在动作电位持续时间（APD）的不同阶段，从心室导联施加电击（-100 V，8 ms）时，对兔心脏（n = 9）的心外膜前部进行光学映射记录电活动。使用S1 - S2方案并测量复极化70%时的APD值来获得恢复曲线。与细胞松弛素D相比，BDM在复极化90%时显著缩短了APD，尽管在复极化离散度上未观察到显著差异。BDM也缩短了波长。一般来说，BDM和细胞松弛素D诱发的电击性心律失常本质上是室性心动过速。关于电击诱发的持续性心律失常，BDM比细胞松弛素D的易损窗口更宽且发生率更高。两种药物诱发的室性心动过速（VT）形态也存在差异。BDM诱发的心律失常通常类似于单形性VT，尤其是那些持续时间>30 s的。相比之下，细胞松弛素D诱发的心律失常更类似于多形性VT。然而，与BDM相比，细胞松弛素D作用下相奇点的平均数量增加，而电击诱发的持续性心律失常的主导频率未观察到显著差异。与细胞松弛素D相比，BDM降低了恢复曲线的斜率，但BDM作用下心律失常的持续时间比细胞松弛素D显著增加。总之，与细胞松弛素D相比，BDM增加了心律失常的发生和维持。
