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Heart Rhythm. 2012 Mar;9(3):422-9. doi: 10.1016/j.hrthm.2011.10.021. Epub 2011 Oct 20.

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

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Masonic Medical Research Laboratory, Utica, New York 13501, USA.



Vernakalant (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.


Transmembrane 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.


In 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 S(1)-S(1) 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 V(max) in a concentration- and rate-dependent manner. SOT did not significantly affect the effective refractory period, V(max), diastolic threshold of excitation, or the shortest S(1)-S(1) cycle length permitting 1:1 activation. All 3 agents (3-30 μM) suppressed delayed afterdepolarization-mediated triggered activity induced by isoproterenol and high calcium.


In 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.

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