Frequency- and time-dependent depression of ventricular distal conduction by two novel antiarrhythmic drugs, cibenzoline and flecainide.
The effects of two novel antiarrhythmic drugs, cibenzoline and flecainide, known to exert potent inhibitory effects on sodium channel, were investigated on intraventricular conduction in anaesthetized, closed-chest dogs. During this study, in which the heart was electrically stimulated, the pacing period was gradually reduced in the 500-200 msec range, and the pacing rate was abruptly altered (2 sec) or sustained (8 to 10 sec) in order to study the possible frequency- and time-dependency of the depression of conduction. In addition to the electrocardiogram, the conduction time was recorded in the ventricular contractile tissue between an electrode advanced to the apex and the pacing electrode positioned near the base. Effective refractory period (ERP) was concurrently measured according to the extrastimulus method, and the monophasic action potential (MAP) recorded. The drugs were infused at a rate of 0.2 mg/kg/min over a 10 min period after a 4.0 mg/kg loading dose. Conduction time was lengthened by approximately 50% at low frequencies and 100% at high frequencies. Widening of the ORS complexes paralleled this lengthening, whereas the drugs tended only to prolong ERP, without preventing its shortening induced by acceleration. Cardiac disorders were aggravated when high pacing rates were maintained for 8 to 10 sec.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D005424:Flecainide / Q000494:pharmacology*; D006321:Heart / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D005424:Flecainide; C032151:cifenline