Comparison of electrophysiological and antiarrhythmic effects of vernakalant, ranolazine, and sotalol in canine pulmonary vein sleeve preparations

BackgroundVernakalant (VER) is a relatively atrial-selective antiarrhythmic drug capable of blocking potassium and sodium currents in a frequency- and voltage-dependent manner. Ranolazine (RAN) is a sodium-channel blocker shown to exert antiarrhythmic effects in pulmonary vein (PV) sleeves. dl-Sotalol (SOT) is a β-blocker commonly used in the rhythm-control treatment of atrial fibrillation. This study evaluated the electrophysiological and antiarrhythmic effects of VER, RAN, and SOT in canine PV sleeve preparations in a blinded fashion.MethodsTransmembrane action potentials were recorded from canine superfused PV sleeve preparations exposed to VER (n = 6), RAN (n = 6), and SOT (n = 6). Delayed afterdepolarizations were induced in the presence of isoproterenol and high-calcium concentrations by periods of rapid pacing.ResultsIn PV sleeves, VER, RAN, and SOT (3–30 μM) produced small (10–15 ms) increases in action potential duration. The effective refractory period, diastolic threshold of excitation, and the shortest S1–S1 cycle length permitting 1:1 activation were significantly increased by VER and RAN in a rate- and concentration-dependent manner. VER and RAN significantly reduced Vmax in a concentration- and rate-dependent manner. SOT did not significantly affect the effective refractory period, Vmax, diastolic threshold of excitation, or the shortest S1–S1 cycle length permitting 1:1 activation. All 3 agents (3–30 μM) suppressed delayed afterdepolarization–mediated triggered activity induced by isoproterenol and high calcium.ConclusionsIn canine PV sleeves, the effects of VER and RAN were similar and largely characterized by concentration- and rate-dependent depression of sodium-channel–mediated parameters, which were largely unaffected by SOT. All 3 agents demonstrated an ability to effectively suppress delayed afterdepolarization–induced triggers of atrial arrhythmia.