Intracardiac electrophysiological study of S-2395 in intact and chemically sympathectomized dogs.
S-2395 is a new, long-acting, non-selective beta-receptor blocking agent without apparent intrinsic cardiodepressive action and no receptor selectivity. Its electrophysiological actions were studied in intact and chemically sympathectomized dogs. In normal dogs, S-2395 very slightly increased atrial monophasic action potential (MAPa) duration, atrioventricular functional (FRP) and ventricular effective (ERP) refractory periods. The onset of the atrial supernormal conduction phenomenon (SNCP) was delayed and the ventricular SNCP was abolished. These results are consistent with the action of low concentrations of beta-blocking agents. In contrast S-2395 reduced the ventricular MAPv and increased the ERP/MAPv ratio of sympathectomized animals. Such modifications are usually seen with concentrations higher than necessary for simple beta-receptor blockade. In conclusion S-2395, like several others beta-blockers, had minor effects on the classical electrophysiological parameters of normal dogs. However, it suppressed ventricular SNCP and had a more pronounced action in sympathectomized dogs who are known to have higher levels of circulating catecholamines and who present post-synaptic supersensitivity. The SNCP has been linked with re-entrant arrhythmias. Considering that beta-blockers prevent arrhythmias specially in hyperadrenergic states, the suppression of the ventricular SNCP by S-2395 could thus be the mechanism by which this drug and possibly other beta-blockers might exert their antiarrhythmic action.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002036:Bundle of His / Q000502:physiology / Q000503:physiopathology; D004285:Dogs; D004594:Electrophysiology; D006321:Heart / Q000502:physiology / Q000503:physiopathology*; D006329:Heart Conduction System / Q000502:physiology / Q000503:physiopathology; D006892:Hydroxydopamines; D011412:Propanolamines / Q000494:pharmacology*; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects; D013876:Thiophenes
D000319:Adrenergic beta-Antagonists; D006892:Hydroxydopamines; D011412:Propanolamines; D013876:Thiophenes; C005632:tertatolol