Antiarrhythmic effects of flecainide against canine ventricular arrhythmias induced by two-stage coronary ligation and halothane-epinephrine.
We studied the electrophysiologic effects of flecainide on noninfarcted and infarcted dog hearts and in dogs anesthetized with halothane and administered intravenous epinephrine. Flecainide demonstrated no effect on atrial conduction times, but significantly (p less than 0.05) increased ventricular conduction times in noninfarcted, infarcted, and halothane-epinephrine-exposed dog hearts. Atrial and ventricular effective refractory periods (ERPs) were significantly (p less than 0.05) increased by flecainide. The increase in ERP was more pronounced in infarcted than in noninfarcted dog hearts. Flecainide significantly (p less than 0.05) decreased the echo zone for two or more repetitive ventricular responses in infarcted dog hearts and eliminated all ventricular arrhythmias observed at 48 h after coronary artery ligation. The dose of epinephrine required to induce ventricular arrhythmias in dogs anesthetized with halothane was significantly increased (p less than 0.05) by flecainide. Acute intravenous administration of flecainide to dogs with infarcted hearts produced sinus arrest, transient third-degree heart block, inability to pace, right bundle branch block, and torsade des pointes. Our results provide evidence that flecainide produces its antiarrhythmic effects by increased ventricular ERP and ventricular conduction time. Caution is advised when administering flecainide to patients with previous history of myocardial infarction.
Dobmeyer
D
D
Muir
W W
WW
Schaal
S F
SF
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D004285:Dogs; D004837:Epinephrine; D005260:Female; D005424:Flecainide; D006221:Halothane; D006329:Heart Conduction System / Q000187:drug effects; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D005424:Flecainide; D006221:Halothane; D004837:Epinephrine