Dissociation of the inotropic effect of digitalis from its effect on atrioventricular conduction.

The relation between sequential changes in left ventricular contractility and atrioventricular (A-V) nodal conduction and refractoriness was assessed in open chest dogs during intravenous administration of acetylstrophanthidin (5 mug/kg) at 5 minute intervals until toxic arrhythmias developed. At each time interval, high fidelity left ventricular pressure, its electronic derivative (dP/dt) and a His bundle electrogram were simultaneously recorded and the A-V nodal refractory period was measured by graded trains of stimuli. Animals were studied with an intact autonomic state (Group I), with pharmacologic blockade of both the beta adrenergic and parasympathetic system (Group II) and with parasympathetic blockade (Group III). Whereas contractility increased in response to small doses of digitalis, displaying a linear dose-response relation independent of autonomic tone, A-V nodal transmission indexes responded minimally to less than 50 percent of the toxic dose of digitalis, and the response was dependent upon autonomic tone. These results indicate a dissociation between the effects of digitalis on contractility and A-V transmission in that the major drug action on the ventricular contractile mechanism is a direct, linear one in contrast to the nonlinear response of A-V nodal transmission, which is predominantly mediated through the autonomic system. Clinically, these observations imply that the optimal dose and serum level of digitalis required to treat congestive heart failure may differ significantly from those required to treat supraventricular tachycardias, the therapeutic response of the latter being largely determined by the underlying autonomic tone.