In-vitro and in-vivo electrophysiologic effects of encainide.
The intracellular electrophysiologic effects of encainide (E) and its main metabolite, O-desmethyl-encainide (ODE), were studied in guinea-pig papillary muscle preparations and related to the in-vivo electrophysiologic effects observed after intravenous (IV) infusion of E in 11 patients undergoing electrophysiologic study (EPS). At equipotent concentrations of E and ODE, frequency-dependent reductions in Vmax studied at pacing rates of 30-180 beats/min ranged from -11.5% to -53%, with maximum reductions of -53% and -47%, respectively at the highest frequency. The kinetics of onset of use-dependent Vmax reduction were slower for ODE than for E at each studied pacing rate. The kinetics of total recovery from use-dependent block were still slower (120 seconds for E and 300 seconds for ODE at a 90 beats/min pacing rate). These in-vitro electrophysiologic data could explain the marked alterations in intraventricular and atrioventricular conduction observed in humans 60 minutes after IV administration of 1 mg/kg of E over a 15-minute period. The QRS, PA, AH, and HV intervals were significantly increased (p less than 0.01) and the Wenckebach cycle length was increased by 8% (p less than 0.05). Blood pressure, RR, QT, CSNRT, ESACT, ERP, and FRP did not vary significantly. The HV interval was already increased 2 minutes after drug administration, while AH was not increased until 15 minutes after drug administration. There was a positive correlation between the increase of the AH interval and the blood level of ODE.
Libersa
C
C
Department of Pharmacology, Laboratoire de Pharmacologie, Lille, France.
Caron
J
J
Rouet
R
R
D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004562:Electrocardiography; D016700:Encainide / Q000031:analogs & derivatives; D005260:Female; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male
D000813:Anilides; D000889:Anti-Arrhythmia Agents; C033635:O-demethylencainide; D016700:Encainide