Use-dependent effects of lidocaine on conduction in canine myocardium: application of the modulated receptor hypothesis in vivo.
Use-dependent effects of lidocaine on conduction in canine myocardium: application of the modulated receptor hypothesis in vivo.
复制标题
利多卡因对犬心肌传导的使用依赖性影响：调节受体假说在体内的应用。
DOI：
10.1161/01.cir.74.1.205
复制
发表时间：
1986
期刊：
影响因子：
37.8
通讯作者：
Hondeghem,LH
中科院分区：
文献类型：
--
作者：
Davis,J;Matsubara,T;Scheinman,MM;Katzung,B;Hondeghem,LH
利多卡因是一种常用的抗心律失常药物，在体外可引起钠通道的使用依赖性阻断，并在体外和体内减慢传导速度。根据抗心律失常药物作用的受体调制假说，利多卡因对静息钠通道的亲和力较低，而对开放和失活的通道亲和力较高。在目前的实验中，我们描述了麻醉犬使用依赖的传导减慢和利多卡因减慢后的恢复。以His-心室传导间期作为传导速度的指标。我们发现，传导时间的延长随着刺激频率的增加而增加。此外，在突然改变刺激频率的情况下，通过两到三次去极化逼近了一个新的稳态传导时间。在停止刺激时，逐渐减少的早搏超前刺激的传导时间呈指数缩短，其终相时间常数为152±115毫秒。这些作用在酸中毒时被利多卡因增强，并被酸中毒的纠正所逆转。结论：利多卡因在体外对动作电位最大上升速度的影响与其在不同频率、节律和pH条件下对动作电位传导的影响相似。尽管这些实验并不是为了验证调制受体假说而设计的，但似乎调制受体假说可以预测利多卡因对体内传导的影响。
Lidocaine is a commonly used antiarrhythmic drug that causes use-dependent blockade of sodium channels in vitro and reduces conduction velocity in vitro and in vivo. According to the modulated receptor hypothesis of antiarrhythmic drug action, lidocaine has a low affinity for rested sodium channels but a high affinity for open and inactivated channels. In the present experiments, we characterized use-dependent conduction slowing and recovery from slowing by lidocaine in anesthetized dogs. The His-to-ventricular conduction interval was used as the indicator of conduction velocity. We found that prolongation of conduction time was greater as the stimulation frequency was increased. Moreover, on abruptly changing the stimulation frequency, a new steady-state conduction time was approached in two to three depolarizations. On discontinuation of stimulation, the conduction time of progressively less premature extrastimuli shortened exponentially with a terminal phase time constant of 152 +/- 115 msec. These effects by lidocaine were enhanced during acidosis and enhancement was reversed by correction of the acidosis. It is concluded that the effects in vivo of lidocaine on conduction under several conditions of rate, rhythm, and pH are similar to its effects on the maximum upstroke velocity of the action potential in vitro. Although these experiments were not designed to validate the modulated receptor hypothesis, it appears that the modulated receptor hypothesis can predict the effects of lidocaine on conduction in vivo.