EFFECT OF ISOPROTERENOL ON FACILITATION OF ELECTRICAL DEFIBRILLATION BY E-4031

To determine whether isoproterenol could reverse enhancement of electr ical defibrillation effectiveness by class III antiarrhythmic agents, we measured the internal defibrillation threshold (DFT) in 12 anesthet ized dogs during infusion of (a) saline (baseline), (b) isoproterenol, (c) isoproterenol + E4031 (a new class III anti-arrhythmic agent), an d (d) E4031 alone. The isoproterenol infusion was adjusted so that hea rt rate (HR) was at least 30 beats/min greater than baseline. E4031 wa s given as a 40-mu g/kg bolus at the beginning of the third stage of t he study, followed by constant infusion at 2 mu g/kg/min. Eight dogs c ompleted the study. Although the energy-based DFT was not affected by isoproterenol (from 6.1 +/- 1.5 to 6.0 +/- 1.7 J), it was decreased to 3.7 +/- 1.6 J in the third stage by infusion of E4031 and isoproteren ol (p < 0.01 vs. baseline and vs. isoproterenol). After the discontinu ation of isoproterenol in the fourth stage, i.e., during infusion of E 4031 alone, DFT was 3.4 +/- 1.6 J (p < 0.01 vs. baseline and vs. isopr oterenol). Therefore, isoproterenol did not antagonize the effect of E 4031 on the DFT, suggesting the possible clinical usefulness of class III agents for facilitating defibrillation even in the presence of aug mented sympathetic activity.