Comparison of electrophysiological and antiarrhythmic effects of vernakalant, ranolazine, and sotalol in canine pulmonary vein sleeve preparations
| Autor: | John K. Gibson, Charles Antzelevitch, Joseph J. Lynch, Serge Sicouri, Marc Pourrier |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Pyrrolidines
Action Potentials Biological Availability Ranolazine Anisoles Pharmacology Piperazines Sodium Channels Membrane Potentials Afterdepolarization Vernakalant chemistry.chemical_compound Dogs Sodium channel blocker Heart Rate Physiology (medical) Atrial Fibrillation Animals Humans Medicine business.industry Sodium channel Cell Membrane Sotalol Isoproterenol Effective refractory period Adrenergic beta-Agonists chemistry Pulmonary Veins Acetanilides Cardiac Electrophysiology Cardiology and Cardiovascular Medicine business Anti-Arrhythmia Agents medicine.drug |
| Zdroj: | Heart Rhythm. 9:422-429 |
| ISSN: | 1547-5271 |
| DOI: | 10.1016/j.hrthm.2011.10.021 |
| Popis: | Background 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. Methods 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. Results 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. Conclusions 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. |
| Databáze: | OpenAIRE |
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