Xue Xiaolin, Guo Donglin, Sun Hongmei, Wang Dan, Li Jiana, Liu Tengxian, Yang Lin, Shu Juan, Yan Gan-Xin
Department of Cardiology, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
Pacing Clin Electrophysiol. 2013 Jun;36(6):732-40. doi: 10.1111/pace.12109. Epub 2013 Feb 25.
Wenxin Keli is a popular Chinese herb extract that approximately five million Asians are currently taking for the treatment of a variety of ventricular arrhythmias. However, its electrophysiological mechanisms remain poorly understood.
The concentration-dependent electrophysiological effects of Wenxin Keli were evaluated in the isolated rabbit left ventricular myocytes and wedge preparation. Wenxin Keli selectively inhibited late sodium current (INa) with an IC50 of 3.8 ± 0.4 mg/mL, which was significantly lower than the IC50 of 10.6 ± 0.9 mg/mL (n = 6, P < 0.05) for the fast INa. Wenxin Keli produced a small but statistically significant QT prolongation at 0.3 mg/mL, but shortened the QT and Tp-e interval at concentrations ≥ 1 mg/mL. Wenxin Keli increased QRS duration by 10.1% from 34.8 ± 1.0 ms to 38.3 ± 1.1 ms (n = 6, P < 0.01) at 3 mg/mL at a basic cycle length of 2,000 ms. However, its effect on the QRS duration exhibited weak use-dependency, that is, QRS remained less changed at increased pacing rates than other classic sodium channel blockers, such as flecainide, quinidine, and lidocaine. On the other hand, Wenxin Keli at 1-3 mg/mL markedly reduced dofetilide-induced QT and Tp-e prolongation by attenuation of its reverse use-dependence and abolished dofetilide-induced early afterdepolarization (EAD) in four of four left ventricular wedge preparations. It also suppressed digoxin-induced delayed after depolarization (DAD) and ventricular tachycardias without changing the positive staircase pattern in contractility at 1-3 mg/mL in a separate experimental series (four of four).
Wenxin Keli suppressed EADs, DADs, and triggered ventricular arrhythmias via selective inhibition of late INa.
稳心颗粒是一种广受欢迎的中药提取物，目前约有500万亚洲人服用它来治疗各种室性心律失常。然而，其电生理机制仍知之甚少。
在离体兔左心室肌细胞和楔形标本中评估了稳心颗粒的浓度依赖性电生理效应。稳心颗粒选择性抑制晚钠电流（INa），IC50为3.8±0.4mg/mL，显著低于快INa的IC50（10.6±0.9mg/mL，n = 6，P < 0.05）。稳心颗粒在0.3mg/mL时使QT间期有小幅度但具有统计学意义的延长，但在浓度≥1mg/mL时缩短QT间期和Tp-e间期。在基础周期长度为2000ms时，稳心颗粒在3mg/mL时使QRS波时限从34.8±1.0ms增加10.1%至38.3±1.1ms（n = 6，P < 0.01）。然而，其对QRS波时限的影响表现出较弱的频率依赖性，即与其他经典钠通道阻滞剂如氟卡尼、奎尼丁和利多卡因相比，在起搏频率增加时QRS波变化较小。另一方面，在四个左心室楔形标本中，1 - 3mg/mL的稳心颗粒通过减弱多非利特的反向频率依赖性，显著减少多非利特诱导的QT间期和Tp-e间期延长，并消除多非利特诱导的早期后除极（EAD）。在另一个独立实验系列（四个样本均是）中，1 - 3mg/mL的稳心颗粒还能抑制地高辛诱导的延迟后除极（DAD）和室性心动过速，且不改变收缩性的正阶梯现象。
稳心颗粒通过选择性抑制晚钠电流来抑制EAD、DAD及触发的室性心律失常。
