Different patterns of autonomic nerve activity produced by a polar vs. a neutral cardiac glycoside

Digitalis agents react with various peripheral reflex receptor areas (i.e., carotid artery baroreceptors and cardiac mechanoreceptors) to alter autonomic nerve activity. Physical characteristics of these reflex receptors differ and thus they may respond differently to polar and neutral cardenolides. Our purpose was to determine the effect of progressive i.v. infusion of either ASI-222, a polar aminocardenolide agent, or digoxin, a neutral cardenolide, on cardiac sympathetic, efferent vagal, and carotid sinus nerve activity. Digoxin or ASI-222 were infused into anesthetized dogs at dose rates which caused cardiac arrhythmias in about 2 hr. Nerve activities were monitored and recorded by a system of differential amplifiers and by a digital storage oscilloscope. Infusion of ASI-222 progressively reduced sympathetic nerve activity (approximately 55%) through the toxic dose; sympathetic nerve activity remained depressed even through the onset of cardiac arrhythmias. Digoxin also depressed cardiac sympathetic nerve activity but only at intermediate dose levels; sympathetic activity rose near the toxic dose. Digoxin increased both carotid sinus and vagal efferent nerve activity with progressive doses. In contrast, ASI-222 did not alter carotid sinus and efferent vagal nerve activity. In summary, digoxin activates carotid sinus baroreceptors; ASI-222 does not. Digoxin and ASI-222 produce different profiles of changes in cardiac autonomic nerve activity and appear to differ in autonomic reflex receptor interactions.