Abstract
Introduction: Vernakalant was approved as an anti-atrial fibrillatory drug by EMA and Health Canada but not by FDA due to its cardiovascular adverse events including bradycardia and hypotension. We characterized its electropharmacological profile in vivo with the isoflurane-anesthetized beagle dogs and in vitro with the rat aorta.
Methods: Vernakalant (0.3 and 3 mg/kg/10 min) was intravenously administered to the dogs in the absence (n=5) and presence (n=4) of α-adrenoceptor blocker phentolamine. Next, the in vitro vascular effect of vernakalant on the rat aorta was assessed by its cumulative application in concentrations of 0.001-100 μmol/L (n=13 preparations).
Results: Vernakalant suppressed the sinus automaticity, ventricular contractility and atrioventricular nodal as well as intraventricular conduction, whereas it increased the total peripheral vascular resistance, preload to the left ventricle and mean blood pressure. It delayed the ventricular repolarization in a reverse frequency-dependent manner; the extent of prolongation of early and late repolarization was similar. It also prolonged the atrial and ventricular effective refractory period similarly. Pretreatment of phentolamine hardly affected those results. Meanwhile, vernakalant did not induce the contraction of aorta in vitro.
Conclusion: Vernakalant exerted α-adrenodceptor-independent vasoconstrictor action only in vivo. It also showed electrophysiological effects on the atria and ventricles to a similar extent, which resembles those of dl-sotalol and bepridil.
