Modulation of the effects of sotalol on Purkinje strand electromechanical characteristics.
The modulation of the effects of sotalol (30 microM) by two sodium channel blockers, tetrodotoxin (0.07 microM) and lidocaine (50 microM), and by a potassium channel activator, nicorandil (30 microM), were examined. Sotalol alone greatly increased Purkinje fiber transmembrane action potential duration and, in some preparations, induced early after depolarizations. Concurrent with the changes in action potential duration, sotalol also increased isolated Purkinje strand developed force paced at slow rates (0.33 Hz). These sotalol-induced alterations of Purkinje strand electromechanical characteristics were similar to those produced by either veratrine (0.6 or 1.0 micrograms/mL) or by tetraethylammonium (10 mM). The effects of sotalol on action potential duration and force development were reversed by exposure to either tetrodotoxin or nicorandil. Lidocaine also reversed the effects of sotalol on action potential duration and developed force. The sotalol-induced increase in action potential duration and development of early after depolarizations may, therefore, be abated by combination with drugs that either block cardiac sodium channels or that increase membrane potassium conductance. Combination with such drugs may help prevent the adverse arrhythmogenic effects of sotalol.
Lathrop
D A
DA
Department of Pediatrics, University of Cincinnati College of Medicine, OH 45229.
Varró
A
A
D000818:Animals; D004285:Dogs; D004594:Electrophysiology; D006321:Heart / Q000502:physiology; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D013015:Sotalol / Q000494:pharmacology*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014702:Veratrine / Q000494:pharmacology
D007473:Ion Channels; D013757:Tetraethylammonium Compounds; D009536:Niacinamide; D020108:Nicorandil; D008012:Lidocaine; D013015:Sotalol; D014702:Veratrine