Adrenergic and cholinergic mechanisms in digitalis inotropy

In anesthetized dogs, the effects of peripheral cardiac nerves upon cardiotonic steroid-induced contractile force increases were determined by comparing the effects seen with cardiac nerves intact, cardiac denervation, stellate ganglia removed or vagi sectioned. Additionally, structure-activity relationships among four cardiotonic steroids were determined by comparing the contractile force effects of bolus i.v. injections of digitoxigenin (the genin), digitoxigenin-galactose (genin-neutral sugar combination), digitoxigenin-aminogalactose (ASI-222, genin-aminosugar combination) and digoxin. The effects of these drugs upon cardiac rate, mean blood pressure and cardiac contractile force were recorded. Cardiotonic steroids differ in their interaction with cardiac nerves. Digitoxigenin, in addition to its direct contractile force effect on the myocardium, modulates contractile force through adrenergic mechanisms. In contrast, both digoxin and ASI-222 influence their direct inotropic responses through cholinergic mechanisms. Neither adrenergic nor cholinergic mechanisms significantly affect the peak inotropic response of digitoxigenin-galactose. Our data indicate that alterations in both the aglycone and the sugar moieties can significantly alter the contribution of the autonomic nervous system to the contractile force response.