Comparative effects of beta-adrenergic blocking drugs on experimental ventricular fibrillation threshold

Recent clinical studies suggest that certain betaadrenergic blocking drugs, such as timolol, may reduce sudden death in patients with ischemic heart disease, but the mechanism has not been established. To assess and compare antifibrillatory effects of beta-blocking drugs as a potential mechanism of sudden death prevention, the ventricular fibrillation (VF) threshold was measured in anesthetized, open-chest dogs before and after 3 minutes of coronary ischemia during intravenous administration of saline solution or 3-fold serial increments (0.003 to 1.0 mg/kg) of 5 beta-blocking drugs with various accessory properties. Ventricular fibrillation occurred in control studies after delivery of a current train of 11.7 ± 7.6 mA in the nonischemic state and 7.0 ± 7.4 mA during ischemia (n = 46). All 5 betablocking drugs but not saline solution caused substantial (average 6-fold) increases (p < 0.001) in the VF threshold under both nonischemic (to 67 ± 30 mA) and ischemic conditions (to 42 ± 31 mA). The maximal VF thresholds attained were similar for individual drugs: timolol, 71, 39 mA (nonischemic, ischemic conditions, n = 10): pindolol, 81, 46 mA (n = 7); propranolol, 58,36 mA (n = 7); metoprolol, 60, 40 mA (n = 7); and labetolol, 67,52 mA (n = 6). The effective doses (mg/kg) at which maximal effects first occurred, however, varied widely: timolol, 0.01 mg/kg; pindolol, 0.1 mg/kg; propranolol, 0.3 mg/kg; metoprolol, 1.0 mg/kg; and labetolol, 1.0 mg/kg. The antifibrillatory potency (mg/kg) generally paralleled known ratios of beta-blocking efficacy, except for timolol's apparently greater potency. Interruption of stellate ganglionic impulses accounted for part of the augmentation in VF threshold. Thus, a substantial antifibrillatory effect accompanies experimental blockade of beta-adrenergics timuli. An increase in VF threshold is suggested as a possible protective mechanism by which beta-blocking drugs reduce sudden death.