Action of Digitalis on the Nonfailing Heart of the Dog

¹ From the Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Bethesda, Maryland

Ouabain induces a moderate increase in the contractility of the nonfailing heart of the dog with a complete circulatory system in doses which do not produce electrocardiographic signs of digitalis intoxication. The increased contractility was demonstrated both by the increase in ventricular contractile force and by the higher ventricular function curves obtained after administration of ouabain. The drug also increased systemic peripheral resistance and blood pressure, decreased systemic output, heart rate, left and right atrial pressures, and produced only small, variable changes in left ventricular stroke work. The reduction in systemic output and left atrial pressure and the absence of substantial changes in stroke work after ouabain appeared to be the result of a decrease in venous return to the heart. Evidence for this interpretation was obtained from experiments in which left atrial pressure was kept constant during the actions of ouabain by infusing 100–300 cc of whole blood. Under these conditions, ouabain brought about moderate increases in systemic output and left ventricular stroke work as well as in contractile force even though the changes in heart rate and blood pressure were comparable to those obtained in experiments in which left atrial pressure was uncontrolled. The data presented indicate that ouabain has two primary hemodynamic effects in the normal animal, namely, a direct cardiac stimulant action and a peripheral action resulting in a decreased venous return. The relationship of these findings to the mechanism of action of digitalis in congestive heart failure is discussed.

Note:
with the assistance of William M. Butler, Jr.