Effects of Tocainide Enantiomers on Experimental Arrhythmias Produced by Programmed Electrical Stimulation

Abstract

Summary: The enantiomers of tocainide, a Class Ib antiarrhythmic agent, have recently been shown to exhibit differences in antiarrhythmic activity and pharmacokinetic characteristics. The present study examined the antiarrhythmic and electrophysiological effects of SR tocainide, S tocainide, and R tocainide on arrhythmias in a conscious canine arrhythmia model and compared the results with placebo. Using up to three extrastimuli, programmed electrical stimulation was performed in conscious dogs, 7-30 days after coronary artery ligation. Each treatment was assessed for its ability to abolish sustained ventricular tachycardia, prevent nonsustained ventricular tachycardia, and protect against death (ventricular fibrillation), in groups of six dogs. In the placebo group, arrhythmias in four of six dogs remained unchanged, and two dogs died. SR tocainide prevented the arrhythmia in three of six dogs (mean effective dose, 21.3 mg/kg), one remained unchanged, and two died. S tocainide prevented the arrhythmia in four of six dogs (mean effective dose, 7.1 mg/kg), one remained unchanged, and one died (p < 0.05 compared with placebo). R tocainide prevented the arrhythmia in five of six dogs (mean effective dose, 9.0 mg/kg), one remained unchanged, and none died (p < 0.01 compared with placebo). PR intervals, QRS durations, and corrected QT intervals were unaffected by any treatment and there was no change in effective or functional refractory periods. These results indicate that the enantiomers of tocainide are more effective than the racemic mixture in abolishing ventricular arrhythmias and in preventing death in this model; no additive antiarrhythmic effect occurs with the racemic mixture, and adverse effects may be potentiated.