Effect of WenxinKeli and quinidine tosuppress arrhythmogenesis in an experimental model of Brugada syndrome

Yoshino Minoura,MD,PhD,BrianK.Panama,PhD,VIadisIavV.Nesterenko,PhD,
Matthew Betzenhauser,PhD,HectorBarajas-Martinez,PhD,DanHu,MD,PhD,JoseM.DiDiego;MD;
Charles Antzelevitch,PhD,FHRS
(From the Masonic Medical Research Laboratory, Utica, New York.)

Background: Wenxin Keli(WK),a Chinese herb extract,is reported to be effective in the treatment of atrial and ventricular cardiac arrhythmias. Recent studies suggest that WK inhibits the transient potassium out ward current (Ito).

Objeot:  To examine the effectiveness of WK, alone and in combination with quinidine, to suppress arrhyth mogenesis in an experimental model of Brugada syndrome (BrS).

Methods:  Action potential and electroca rdiographic recordings were obtained from epicardia land endocardia Isites of coronary- perfused caninerightv entricular wedge preparations.The Ito agonist NS5806(10-15 NM) was used to pharmacologically mimic a genetic predisposition to BrS.

Results: The Ito agonist induced Phase2 reentry (P2R) in 139 preparations and polymorphic ventricular tachycardia (pVT) in 11/19 wedge preparations.WK(lOg/L)suppressed P2R and pVT in 100%(3/3) of preparations.A lower concentration of WK(5g/L) suppressed P2R in 60% (3/5) and pVT in 50%(2/4),but in combination with a low concentration of quinidine(5 NM), was 100% effective in suppressing P2R and pVT Quinidine alone suppressed P2R and pVT in 60%(3/5) and 50%(2/4), respectively, and incombination with WK(5g/L) suppressed P2R and pVT by 80% (4/5) and 75%(3/4), respectively. WK reduced Ito, the L-type calcium current,and contractility in single cardio myocytes,but dose-dependently increased contractility in intact wedge prepara一tions, an effect mimicked by tyramine. Conclusions Our data provide support. for the hypothesis that WK, particularly in combination with quinidine, effectively suppresses arrhythmogenesis in an experimental model of Br5 via
inhibition of Ito and indirect adrenergic sympathomimetic effects.

Keywords:  Transient outward potassium channel current; Positive inotropic effect; Cardiac arrhythmias; Suddendeath;wenxin keli