BACKGROUND: Vanoxerine produces potent block of cardiac hERG, sodium, and L-type 
calcium channels. Block is strongly frequency dependent, is unassociated with 
transmural dispersion of repolarization, and occurs at concentrations safe in 
humans. Therefore, we proposed that vanoxerine might be antiarrhythmic. In these 
studies, we tested the hypothesis that vanoxerine would terminate induced atrial 
fibrillation (AF) and atrial flutter (AFL) in dogs with sterile pericarditis 
(SP).
METHODS AND RESULTS: In 9 SP dogs, 11 episodes each of sustained (>10 minutes) 
AF and AFL were induced. Electrophysiological studies were performed before and 
after infusion of vanoxerine, which effectively terminated AF and AFL in 19 of 
22 episodes. Simultaneous multisite mapping during 3 AF and 3 AFL episodes 
demonstrated that termination of each arrhythmia occurred with termination of 
the driver (a reentrant circuit) following an increase in tachycardia CL. Except 
for conduction in an area of slow conduction in the driver's reentrant circuit, 
vanoxerine did not significantly affect intraatrial or atrioventricular 
conduction time, QRS duration, or QT/QTc intervals. Ventricular refractoriness 
prolonged minimally during ventricular pacing at 400 and 333 ms (176 +/- 16 ms 
to 182 +/- 16 ms; 173 +/- 11 ms to 178 +/- 18 ms, respectively). Vanoxerine 
minimally increased (mean 0.7 mA) atrial stimulus threshold for capture.
CONCLUSIONS: Vanoxerine effectively terminated induced, sustained AF and AFL in 
the canine SP model, and produced insignificant or minimal changes in 
refractoriness, conduction time, or stimulus threshold, consistent with little 
proarrhythmic risk.