Studies on digitalis. XIV. Influence of cardiac norepinephrine stores on the response of isolated heart muscle to digitalis.

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 in the normal muscles and 2.65 ±0.50 g/mm 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). In addition to these changes in isometric tension, strophanthidin increased the maximum velocity of contraction (VmBI) 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