A study of the antiarrhythmic action of certain beta-blocking agents

Abstract

The effects of the beta-blocking agents, MJ-1999 (sotalol) and practolol, against ouabain and digoxin-induced ventricular rhythm disturbances were studied to evaluate the nature of the action which is involved in the antiarrhythmic action of these beta-blocking agents. Sotalol and practolol, in doses that have been reported to have little effect on cardiac excitability, protected against digoxin-induced arrhythmias. Practolol, but not the low dose of sotalol, protected against ouabain-induced cardiotoxicity. The dose of sotalol necessary to protect against ouabain-induced arrhythmias was five times greater than that necessary to protect against digoxin-induced arrhythmia and has been reported to directly depress cardiac excitability. The maximum rate of ventricular tachycardia produced by ouabain or digoxin was slower in the animals pretreated with practolol but not in those pretreated with sotalol. The slowing in heart rate produced by beta-blocking agents could not be correlated with the protection afforded against either digoxin or ouabain-induced arrhythmia. The data suggest that the capacity of beta-receptor blocking agents to reduce cardiac excitability may not be the only mechanism responsible for their antiarrhythmic action. Both practolol and sotalol protected against digoxin-induced arrhythmias and the only action common to both agents is beta blockade. Therefore, it is suggested that the beta blocking action is responsible for the antiarrhythmic action against digoxin-induced arrhythmias. However, since only practolol protected against ouabain-induced rhythm disturbances in doses which do not depress cardiac excitability and since it differs from sotalol in that it has the capacity to depress adrenergic nervous activity in these doses, it is suggested that the neural depressant action of practolol is responsible, at least in part, for its antiarrhythmic action against ouabain-induced cardiotoxicity.