title: Antiarrhythmic and antifibrillatory actions of the levo- and dextrorotatory isomers of sotalol.
abstract: The electrocardiographic responses to programmed ventricular stimulation and acute posterolateral myocardial ischemia were studied in conscious dogs treated with the resolved optical isomers of sotalol. Studies were conducted 3-7 days after anterior myocardial infarction to determine the relative contributions of beta-adrenergic receptor blockade and direct Class III electrophysiologic actions in the antiarrhythmic and antifibrillatory actions of the isomers. With cumulative i.v. administration of up to 8 mg/kg, both the beta-blocking levorotatory isomer and the dextrorotatory isomer suppressed the induction of ventricular tachyarrhythmias by programmed stimulation in at least 50% of dogs tested. Both isomers produced equivalent 15-20% increases in normal zone ventricular refractoriness, thereby preventing propagation of programmed ventricular extrastimuli of sufficient prematurity to elicit tachyarrhythmias. The levorotatory isomer of sotalol prolonged the PR interval; the administration of the dextrorotatory isomer increased QTc and, in several dogs, was associated with the development of ventricular ectopy. The prior administration of 8 mg/kg of either optical isomer of sotalol prevented the immediate spontaneous development of ventricular fibrillation in response to ischemia at a distance from the previous site of infarction. These results suggest that alterations in ventricular refractoriness may underlie the antiarrhythmic and antifibrillatory actions of the optical isomers of sotalol and of racemic sotalol.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents; D003327:Coronary Disease / Q000503:physiopathology; D003645:Death, Sudden; D004285:Dogs; D004558:Electric Stimulation; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D013015:Sotalol / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D000889:Anti-Arrhythmia Agents; D013015:Sotalol