Evidence for Adrenergic Mediation of Ouabain induced Arrhythmias in the Guinea Pig

Oubain in a dose of 7.5 μg/min. was infused intravenously into urethane anaesthetized guinea pigs weighing from 250–500 g. The incidence of cardiac fibrillation and the cardiotoxic dose (fibrillation, cardiac arrest) were determined in groups of (1) untreated controls. (2) adrenalectomized, (3) reserpinized, 5 mg/kg subcutaneously, (4) reserpinized + adrenalectomized, (5) reserpinized + noradrenaline pretreated animals (100 μg/kg intravenously 15 min. before ouabain). All animals were kept at a constant rectal temperature of 34°. The pressor response to tyramine (0.1 and 1 mg/kg intravenously) was tested during the same experimental conditions. All animals died in fibrillation except those in (4) in which only 50% showed fibrillation. The sensitivity to ouabain (minimal fibrillatory dose, LD100) was only slightly decreased in (2) while the LD100 was increased from 239 ± 10 μg/kg to 375 ± 15 μg/kg in (3) and 466 ± 17 μg/kg in (4). Infusion of noradrenaline into reserpinized animals caused a partial recovery of the normal ouabain sensitivity as the LD100 decreased from 375 ± 15 μg/kg to 302 ± 11 μg/kg (P < 0.001). The pressor response to tyramine showed features almost similar to the ouabain sensitivity except that the sensitivity to tyramine could not be regained by a noradrenaline infusion in reserpinized guinea pigs. The results indicate that the ouabain cardiotoxicity in the guinea pig is at least to some extent mediated through a release of catecholamines and may explain the species dependent difference in potency of some β‐adrenergic blocking agents on ouabain arrhythmias.