The study was supported by the Sharpe-Strumia Research Foundation and National Natural Science Foundation of China (81070162 and 30971221).
Wenxin Keli Suppresses Ventricular Triggered Arrhythmias via Selective Inhibition of Late Sodium Current
Version of Record online: 25 FEB 2013
©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.
Pacing and Clinical Electrophysiology
Volume 36, Issue 6, pages 732–740, June 2013
How to Cite
XUE, X., GUO, D., SUN, H., WANG, D., LI, J., LIU, T., YANG, L., SHU, J. and YAN, G.-X. (2013), Wenxin Keli Suppresses Ventricular Triggered Arrhythmias via Selective Inhibition of Late Sodium Current. Pacing and Clinical Electrophysiology, 36: 732–740. doi: 10.1111/pace.12109
- Issue online: 4 JUN 2013
- Version of Record online: 25 FEB 2013
- Manuscript Accepted: 28 DEC 2012
- Manuscript Revised: 14 DEC 2012
- Manuscript Received: 7 SEP 2012
- Sharpe-Strumia Research Foundation and National Natural Science Foundation of China. Grant Numbers: 81070162, 30971221
- Wenxin Keli;
- late sodium current;
- early afterdepolarization;
- delayed afterdepolarization;
- triggered activities
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.
Methods and results
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 afterdepolarization (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.