Electrophysiologic properties of perhexiline.
Perhexiline maleate (Pexid), a promising clinical antiarrhythmic and antianginal drug, was evaluated for its electrophysiologic effects on the entire conduction system of the intact canine heart throughout a wide range of therapeutic and potentially toxic doses. Intracardiac conduction times were measured by bipolar intramyocardial and transvenous endocardial electrodes before and following the intravenous administration of each dose of perhexiline maleate, 3 mg/kg every 30 min for a total of 4 doses in 7 open-chest anesthetized dogs. Eight animals served as controls in which similar operative technique and electrophysiologic variables were recorded after infusion of the maleate diluent. In addition, the effects of perhexiline on atrial and ventricular thresholds to electrical stimulation were recorded, as well as the QRS and QT intervals, sinus rate, and rhythm disorders. It was observed that perhexiline did not significantly (p greater than .05) alter sinus rate, QT interval, QRS duration, PR interval, intra-atrial conduction time, atrioventricular nodal conduction time, and His-Purkinje conduction velocity. The drug did not affect the cardiac threshold to electrical stimulation of less than 0.1 ma. No ectopic atrial or ventricular activity emerged during the accumulated influence of the agent. From this study, it is concluded that perhexiline does not exert deleterious actions on the conduction system of the intact canine heart. In view of the negligible toxic effects and its efficacy in treating ventricular tachyarrhythmias in patients, the drug deserves further clinical evaluation.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002036:Bundle of His / Q000502:physiology; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D006321:Heart / Q000502:physiology; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D010480:Perhexiline / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*
D010880:Piperidines; D010480:Perhexiline