Effect of digitalis on response of the ventricular pacemaker to sympathetic neural stimulation and to isoproterenol

Abstract

It is established that digitalis antagonizes the chronotropic effect of adrenergic stimulation of the heart, and this finding suggests that the sympathetic nervous system does not play a significant role in ventricular arrhythmias produced by digitalis. However, this antagonism has been established by testing the response of the sinus nodal pacemaker to digitalis and adrenergic stimulation. Since clinically significant digitalis-induced arrhythmias are ventricular in origin, the response of the ventricular pacemaker seems the more critical variable. To test this hypothesis, we applied two types of adrenergic stimulation before and after ouabain administration to anesthetized dogs with complete atrio-ventricular block. Ouabain in a dose of 40 μg/kg caused no significant change in the increase in heart rate produced either by electrical stimulation of postganglionic sympathetic nerves or by isoproterenol administration. In 6 of the 12 dogs ventricular tachycardia developed after digitalis administration at levels of adrenergic stimulation that did not cause arrhythmia before the drug was given. These results indicate that digitalis does not affect the chronotropic response to adrenergic stimulation of ventricular pacemakers. Moreover, the heart exposed to digitalis appears to be sensitized to the arrhythmogenic effects of adrenergic stimuli.