INTERACTION OF PRONETHALOL AND OUABAIN ON CARDIAC RHYTHM AND AUTOMATICITY

¹ Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada

Pronethalol was given to reserpine-pretreated dogs to determine whether it had an effect on ouabain-induced arrhythmias and cardiac automaticity which was independent of its ability to block the cardiac actions of catecholamines. In both reserpine-pretreated and normal dogs, single injections of pronethalol temporarily converted ouabain-induced arrhythmias to sinus rhythm. Maintenance of sinus rhythm required continuous intravenous infusion or repeated doses of pronethalol. Although the antiarrhythmic effect of a single injection of pronethalol was brief, blockade of the chronotropic action of isoproterenol persisted for several hours. Rapid injection of pronethalol always caused a sharp fall in arterial pressure, but reversal of the arrhythmia still occurred when the depressor response was prevented by intraarterial infusion of blood. Conversely, when pronethalol was withheld and the blood pressure was lowered by hemorrhage, the arrhythmias were unaltered. Infusions of pronethalol in reserpinetreased dogs increased the normal sinus rate and the rate of firing of subatrial pacemakers which were elicited by stimulation of the right vagus. This is inconsistent with a generalized cardiac depressant action. The effect of ouabain on the beta adrenergic blocking action of pronethalol in dogs without reserpine pretreatment was also determined. In the absence of beta adrenergic blockade, ouabain inhibited the chronotropic action of isoproterenol, but, in the presence of pronethalol-produced blockade, the action of isoproterenol was enhanced by ouahain. It is concluded that this antiarrhythmic effect of pronethalol is due neither to blockade of the cardiac actions of endogenous catecholamines nor to an unspecific depression of automaticity similar to that caused by quinidine. We suggest that there is a direct pharmacologic antagonism between pronethalol and ouabain in the heart.