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 ventricular fibrillation and defibrillation thresholds using an implantable transvenous/subcutaneous defibrillation system in a pig model. Thirteen pigs completed the three phases of the study. After a baseline study on 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 repeated on day 4. The same protocol was again repeated on the same day after infusion of physiological doses of epinephrine. Multiple ventricular fibrillation and defibrillation thresholds were measured during each study. Moricizine did not alter ventricular fibrillation nor defibrillation thresholds, whereas epinephrine increased the ventricular defibrillation threshold from 20.8 J to 23.7 J (P < 0.05). In addition, we observed 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 may be a safe antiarrhythmic agent to use in patients with implantable cardioverter defibrillators, and that elevated endogenous epinephrine may render defibrillation more difficult.
Pharand
C
C
Department of Pharmacy Services, Hartford Hospital, CT 06115, USA.
Goldman
R
R
Fan
C
C
Chow
M
M
Kluger
J
J
D000284:Administration, Oral; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D017147:Defibrillators, Implantable; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D007262:Infusions, Intravenous; D016293:Moricizine / Q000008:administration & dosage / Q000494:pharmacology*; D013552:Swine; D013566:Sympathomimetics / Q000008:administration & dosage / Q000494:pharmacology*; D014693:Ventricular Fibrillation / Q000503:physiopathology / Q000628:therapy*; D016276:Ventricular Function / Q000187:drug effects / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D013566:Sympathomimetics; D016293:Moricizine; D004837:Epinephrine