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Effects of flecainide acetate on ventricular tachyarrhythmia and fibrillation in dogs with recent myocardial infarction



Effects of flecainide acetate on ventricular tachyarrhythmia and fibrillation in dogs with recent myocardial infarction



Pharmacology 35(4): 181-193



The antiarrhythmic and antifibrillatory actions of the class IC antiarrhythmic agent flecainide acetate were examined in urethane-anesthetized dogs with recent myocardial infarction. The intravenous administration of flecainide in a loading dose of 1.0 mg/kg (n = 7) or 2.0 mg/kg (n = 6), followed by a maintenance infusion of 1.0 mg/kg/h to achieve plasma drug concentrations considered clinically therapeutic, failed to significantly elevate the electrical threshold current required to provoke ventricular fibrillation at infarct zone, border zone and non-infarct zone stimulation sites in postinfarction dogs. In 8 dogs which responded to baseline programmed stimulation with inducible sustained ventricular tachycardia, flecainide administered as 1.0 or 2.0 mg/kg loading doses followed by a 1.0 mg/kg/h maintenance infusion failed to prevent ventricular tachycardia initiation in any animal tested, although the post-treatment ventricular tachycardia cycle lengths were prolonged compared to baseline values (pre: 178 +/- 11 ms vs post: 202 +/- 17 ms, p less than 0.05). Flecainide administration apparently facilitated the induction of newly sustained ventricular tachycardia in 3 previously noninducible postinfarction dogs. The development of acute posterolateral ischemia at a site remote from previous anterior myocardial infarction resulted in the development of ventricular fibrillation in 4 of 11 (36%) saline-treated postinfarction dogs vs a cumulative 10 of 12 (83%) flecainide-treated, baseline noninducible postinfarction dogs (p less than 0.05 vs saline-treated). The incidence of sudden ischemic ventricular fibrillation was 7 of 7 (100%) among flecainide-treated baseline inducible postinfarction dogs. These data suggest that flecainide acetate may have only limited efficacy in preventing ventricular tachycardia or ventricular fibrillation soon after myocardial infarction.

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Accession: 005304344

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PMID: 3118399


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