SENSITIZATION TO VENTRICULAR FIBRILLATION. I. SENSITIZATION BY A SUBSTITUTED PROPIOPHENONE, U-0882

¹ Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan

Intravenous administration of the substituted propiophenone U-0882 in anesthetize animals in doses of 10 mg/kg produces a transient depressor effect and concomitant stimulation of respiration. The EKG and direct measurements show that U-0882 prolongs greathy the refractory period of the ventricular myocardium without depressing intractordiac conduction. This compound is also a weak atropine-like blocking agent.

U-0882 followed in 2 to 5 minutes by so subsequent intravenous injection of epinephrine, levarterenol, or isoproterenol induces ventricular fibrillation. Fibrillation may also be produced by electrical stimulation of the right atrium, the right ventricle, or the stellate ganglion after U-0882 sensitization.

Intravenous administration of U-0882 alone in the unanesthetized dog produces spontaneous ventricular fibrillation. This compounds is unusual in that by sensitizing the myocardium it sets the stage for fibrillation and as a result of its central or reflex ations provides the stimulus necessary for the ultimate onset of fibrillation.

U-0882-epinephrine fibrillation is not prevented by Dibenzyline, quinidine, procainamide, or funetional hepateetomy, measures which protect against hydrocarbon-epinephrine fibrillation. Fibrillation from U-0882 is prevented by the previous administration of toxic doses of ouabain or by dichloroisproterenol.

The actions of U-0882 support the hypothesis of continuous conduction as the mechanism for the maintenance of ventricular fibrillation but they speak strongly against the existence of an "excitable gap."