EFFECT OF CHRONIC ORAL MORICIZINE AND INTRAVENOUS EPINEPHRINE ON VENTRICULAR-FIBRILLATION AND DEFIBRILLATION THRESHOLDS

The purpose of this study was to determine the effects of chronic oral moricizine therapy and physiological doses of epinephrine on ventricu lar fibrillation and defibrillation thresholds using an implantable tr ansvenous/subcutaneous defibrillation system in a pig model. Thirteen pigs completed the three phases of the study. After a baseline study o n day 1, the animals were randomized to receive moricizine 10-15 mg/kg tid or placebo for seven doses, at which time the protocol was repeat ed on day 4. The same protocol was again repeated on the same day afte r infusion of physiological doses of epinephrine. Multiple ventricular fibrillation and defibrillation thresholds were measured during each study. Moricizine did not alter ventricular fibrillation nor defibrill ation thresholds, whereas epinephrine increased the ventricular defibr illation threshold from 20.8 J to 23.7 J (P < 0.05). In addition, we o bserved an increase in both ventricular fibrillation (19.7 J vs 12.6 J ; P < 0.05) and defibrillation (20.8 J vs 17.8 J; P (0.05) thresholds over the 4 days of the study. These findings suggest that moricizine m ay be a safe antiarrhythmic agent to use in patients with implantable cardioverter defibrillators, and that elevated endogenous epinephrine may render defibrillation more difficult.