ANTIARRHYTHMIC ACTIONS OF 4-(2-HYDROXY-3-ISOPROPYLAMINOPROPOXY)-ACETANILIDE (ICI 50,172) IN THE DOG HEART-LUNG PREPARATION

¹ Department of Pharmacology, Marquette School of Medicine, Milwaukee, Wisconsin

The antiarrhythmic activity of 4-(2-hydroxy-3-isopropylaminopropoxy)-acetanilide (ICI 50,172), a beta adrenergic blocking agent, was investigated in the dog heart-lung preparation (HLP). ICI 50,172 (0.5 mg) decreased the positive inotropic and chronotropic effects of epinephrine, indicating a blockade of the beta adrenergic receptors with this dose. A 0.5-mg dose of ICI 50,172 prevented the ventricular fibrillation resulting from a combination of halothane (1%) and epinephrine (50 µg) in the HLP. A total dose of 2 mg of ICI 50,172 was needed to antagonize the multifocal ventricular tachycardia produced by a combination of halothane, epinephrine and mechanical elevation of the aortic pressure. These data suggest that the mechanism of induction of pressure-dependent ventricular tachycardia is different from that of pressure-independent ventricular fibrillation. Pretreatment of the HLP with 25 mg of ICI 50,172 did not modify the dose of ouabain necessary to induce multifocal ventricular tachycardia. ICI 50,172 was also ineffective, in doses up to 50 mg, against ouabain-induced ventricular tachycardia in this preparation. It is concluded that ICI 50,172 can selectively antagonize adrenergically induced cardiac arrhythmias in the HLP.