Abstract

Background—Several clinical trials have shown that vernakalant is effective in terminating recent onset atrial fibrillation (AF). The electrophysiological actions of vernakalant are not fully understood. Methods and Results—Here we report the results of a blinded study comparing the in vitro canine atrial electrophysio-logical effects of vernakalant, ranolazine, and dl-sotalol. Action potential durations (APD50,75,90), effective refractory period (ERP), post repolarization refractoriness (PRR), maximum rate of rise of the action potential (AP) upstroke (Vmax), diastolic threshold of excitation (DTE), conduction time (CT), and the shortest S1-S1 permitting 1:1 activation (S1-S1) were measured using standard stimulation and microelectrode recording techniques in isolated normal, non-remodeled canine arterially perfused left atrial preparations. Vernakalant caused variable but slight prolongation of APD90 (Pnot significant), but significant prolongation of APD50 at 30 mol/L and rapid rates. In contrast, ranolazine and dl-sotalol produced consistent concentration- and reverse rate-dependent prolongation of APD90. Vernakalant and ranolazine caused rate-dependent, whereas dl-sotalol caused reverse rate-dependent, prolongation of ERP. Significant rate-dependent PRR developed with vernakalant and ranolazine, but not with dl-sotalol. Other sodium channel-mediated parameters (ie, Vmax, CT, DTE, and S1-S1) also were depressed significantly by vernakalant and ranolazine, but not by dl-sotalol. Only vernakalant elevated AP plateau voltage, consistent with blockade of ultrarapid delayed rectified potassium current and transient outward potassium current.