On the basis of studies on cardiac tissue removed from animals treated with antiadrenergic drugs, a number of investigators have suggested that the positive inotropic response to digitalis requires norepinephrine in the cardiac muscle. In the present study the action of strophanthidin was studied in isolated papillary muscles obtained from normal cat hearts, from chronic, totally cardiac-denervated, norepinephrine-depleted hearts, and from reserpine-treated, norepinephrine-depleted cats. Complete force-velocity and length-tension curves were recorded. Following the addition of strophanthidin (1.0/xg/ml) to the bath, maximum isometric tension rose by averages of 2.17 ±0.32 g/mm 2 in the normal muscles and 2.65 ±0.50 g/mm 2 in the muscles from the denervated cats, but increased significantly less (P<0.05) in the muscles from the reserpine-treated animals (1.09 ±0.36 g/mm 2 ). In addition to these changes in isometric tension, strophanthidin increased the maximum velocity of contraction (V mBI ) to a comparable extent in normal and denervated muscles, with a smaller elevation of Vm^ in reserpine-treated muscles. Strophanthidin reduced the absolute refractory period to an equal extent in all three groups of muscles. From a comparison of the inotropic responses of the muscles from normal and cardiac-denervated cats it is concluded that cardiac norepinephrine stores and neural integrity are not essential for the positive inotropic effect of strophanthidin or for its effects on the duration of the absolute refractory period. However, it appears that prior reserpine treatment may interfere with the inotropic response to digitalis by a mechanism other than norepinephrine depletion.
ADDITIONAL KEY WORDS reserpine strophanthidinforce-velocity curve absolute refractory period anesthetized cats cardiac denervation myocardial contractility inotropic action of glycosides • It has been suggested that the digitalis glycosides release norepinephrine (NE) from cardiac sympathetic nerves and that intact stores of the neurotransmitter are therefore required in order for these drugs to exert their full positive inotropic effect. This work was aided by grants from the John A. Hartford Foundation and U. S. Public Health Service Grants HE-06312 and HE-K3-05616.Accepted for publication March 9, 1966. suggestion has been based primarily on the demonstration of a reduced response to digitalis in cardiac muscle which had been depleted of its NE stores by reserpine or guanethidine, or in which the response to released NE was blocked with dichloroisoproterenol.1 -6 These studies do not, however, exclude the possibility that actions of these drugs, other than NE depletion or adrenergic blockade are responsible for the diminished effectiveness of digitalis. Chronic total denervation of the heart results in profound depletion of cardiac NE stores 6 and provides an opportunity to study the effects of digitalis 326