Although previous studies have demonstrated that the electrophysiologic effects of many antiarrhythmic agents can be reversed by catecholamines, the susceptibility of amiodarone to such reversal is unknown. The objective of this study was to compare the relative degree of reversal of the electrophysiologic effects of quinidine and aminiodarone by epinephrine infusions that result in plasma epinephrine levels similar to those achieved during various physiologic stresses. Twenty-nine patients who had inducible sustained monomorphic ventricular tachycardia and underwent electropharmacologic testing with quinidine and amiodarone were enrolled in the study. The variables measured before and during an epinephrine infusion (25 or 50 ng/kg per min) included the sinus cycle length, mean arterial pressure, QT interval and effective refractory period at drive train cycle lengths of 600 and 400ms. The effective refractory period measured at a drive train cycle length of 600 ms shortened less during amiodarone therapy (2 ±2%) than during quinidine therapy (6 ± 4%) or than in the baseline state (6 ± 4%; p < 0.01). Similar results were obtained during evaluation of the effective refractory period at a cycle length of 400 ms. Epinephrine infusion, at both 25 and 50 ng/kg per min, completely reversed the effects of quinidine partially reversed the effects of amiodarone on the effective refractory period. The effects of epinephrine on the sinus cycle length and QT interval were similar in the baseline state and in conjunction with quinidine and amiodarone. Twenty-four patients underwent programmed ventricular stimulation during amiodarone therapy alone and in conjunction with either a 25- or a 50-ng/kg per min infusion of epinephrine. None of the five patients whose ventricular tachycardia was suppressed by amiodarone had sustained ventricular tachycardia induced during an epinephrine infusion. The ventricular tachycardia cycle length in patients with persistently inducible ventricular tachycardia also did not change after an epinephrine infusion. No patient receiving long-term amiodarone therapy has had a recurrence of ventricular tachycardia during a mean follow-up interval of 9 ± 4 months. The results of this study demonstrate that amiodarone is more resistant than quinidine to reversal of its electrophysiologic effects by epinephrine. This resistance may be due to the beta-adrenergic blocking properties of amiodarone and may explain, at least in part, the drug's unique long-term effectiveness in treating malignant ventricular arrhythmias.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine