Comparative Effects of Antiarrhythmic Drugs on the Ventricular Fibrillation Threshold

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Abstract
The purpose of this study was to compare the effects of several different antiarrhythmic drugs on the ventricular fibrillation threshold (VFT). Experiments were performed on open-chest dogs anesthetized with pentobarbital. The VFT was measured on the right ventricle by scanning the vulnerable period with a single 10-ms electrical stimulus. The following antiarrhythmic drugs were each given intravenously to eight different dogs: procainamide (25 mg/kg). lidocaine (2 mg/kg + 70 μg/kg/min), flecainide (3 mg/kg), timolol (0.1 mg/kg), clofilium (1 mg/kg), dl-sotalol (5 mg/kg), and bethanidine (4 mg/kg). The drugs resulted in the following increases in the VFT: procainamide, 33 ± 13%; lidocaine, 21 ± 5%; flecainide, 38 ± 10%; timolol, 19 ± 6%; clofilium, 14 ± 6%; sotalol, 33 ± 10%; and bethanidine, 69 ± 15%. The changes in VFT were all significant (p < 0.01) except for clofilium. Only procainamide and sotalol caused stimulus-induced runs of nonsustained polymorphic ventricular tachycardia that spontaneously reverted to sinus rhythm after 4 s or more. In individual experiments, the occurrence of nonsustained polymorphic tachycardia that resembled ventricular fibrillation could not be correlated with a change in the VFT. In addition, there appeared to be no relationship between a drug-induced increase of the VFT and alterations in the QRS duration, the QT interval, or the ventricular effective refractory period. Bethanidine had the greatest effect on the VFT, in spite of the fact that this drug shortened the ventricular effective refractory period. The results suggest that the ability of an antiarrhythmic drug to alter the VFT cannot be based on the electrophysiologic actions of the drug. Furthermore, the VFT may not provide an accurate index of a drug's antifibrillatory activity.