Viamonte V A, Rosen M R
Department of Pharmacology, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
Circulation. 1990 Jul;82(1):234-43. doi: 10.1161/01.cir.82.1.234.
Premature escape beats induced in conscious dogs with chronic complete atrioventricular block have been defined as escape beats occurring on cessation of overdrive pacing and having a coupling interval to the last paced beat shorter than the coupling interval between the premature escape beat and the second postpacing beat. Triggered activity has been proposed as the primary underlying mechanism. We used standard microelectrode techniques to study the effects of overdrive pacing on normal automatic canine Purkinje fibers to determine if premature escape beats could be induced and if so, to define the underlying cellular mechanism(s). For this purpose, we overdrive-paced Purkinje fibers for 10 and 50 seconds and for 10 and 50 beats at a pacing cycle length (PCL) of 1,000-200 msec. In addition, to help distinguish among major arrhythmogenic mechanisms, we used a matrix of drugs consisting of propranolol, nadolol, lidocaine, ethmozin, and doxorubicin. Fifty-second stimulation trains induced "classic" overdrive suppression of the first three postpacing impulses, whereas 10-second overdrive pacing induced significant overdrive suppression only at a PCL of 200 msec. With 50-beat overdrive pacing and a PCL of 1,000-600 msec, there was overdrive suppression of postpacing impulses, whereas reduced overdrive suppression was observed at a PCL of 400-200 msec. Ten-beat stimulation trains induced a "flat response" of postpacing impulses. Ten- and 50-beat overdrive pacing provoked premature escape beats in 66% of the fibers, with the higher incidence at a PCL of 200 msec for 50-beat stimulation trains. No shortening of the coupling interval of premature escape beats was observed at faster pacing rates. Only lidocaine (which suppresses normal automaticity) abolished premature escape beats. We conclude that normal automaticity is the most likely mechanism underlying premature escape beats in Purkinje fibers with high levels of membrane potential.
在患有慢性完全性房室传导阻滞的清醒犬中诱发的过早逸搏被定义为在超速起搏停止时出现的逸搏,其与最后一个起搏搏动的耦合间期短于过早逸搏与第二个起搏后搏动之间的耦合间期。触发活动被认为是主要的潜在机制。我们使用标准微电极技术研究超速起搏对正常自动性犬浦肯野纤维的影响,以确定是否能诱发过早逸搏,如果可以,则确定潜在的细胞机制。为此,我们以1000 - 200毫秒的起搏周期长度(PCL)对浦肯野纤维进行了10秒和50秒以及10次和50次搏动的超速起搏。此外,为了帮助区分主要的致心律失常机制,我们使用了由普萘洛尔、纳多洛尔、利多卡因、乙吗噻嗪和阿霉素组成的药物矩阵。50秒的刺激序列诱导了前三个起搏后冲动的“经典”超速抑制,而10秒的超速起搏仅在200毫秒的PCL时诱导了显著的超速抑制。在50次搏动的超速起搏且PCL为1000 - 600毫秒时,存在起搏后冲动的超速抑制,而在400 - 200毫秒的PCL时观察到超速抑制减弱。10次搏动的刺激序列诱导了起搏后冲动的“平坦反应”。10次和50次搏动的超速起搏在66%的纤维中诱发了过早逸搏,对于50次搏动的刺激序列,在200毫秒的PCL时发生率更高。在更快的起搏频率下未观察到过早逸搏耦合间期的缩短。只有利多卡因(抑制正常自动性)消除了过早逸搏。我们得出结论,正常自动性是膜电位水平较高的浦肯野纤维中过早逸搏最可能的潜在机制。