Linear dose response and quantitative attenuation by potassium of the inotropic action of acetylstrophanthidin

To evaluate the nature of the inotropic dose response of digitalis and to determine the effects of potassium on this response, isometrically contracting isolated supported right ventricular cat papillary muscles were studied relative to their peak tension and peak dT/dt increases to physiologic cumulative doses of acetylstrophanthidin (ACS) in different extracellular potassium concentrations in the muscle bath. The inotropic dose response to ACS was observed to be linear in cumulative glycoside concentrations ranging from 0.40 to 4.23 × 10^-7 M ACS in 3.5 mM K⁺ medium and also from 1.22 to 7.47 × 10^-7 M ACS in 7.0 mM K⁺ medium. The influence of potassium alterations in the muscle bath from the low to the high K⁺ concentrations prior to ACS resulted in marked attenuation of the positive inotropic property of ACS. From these data, it is concluded that the dose inotropic response of digitalis is linear, with small doses producing proportionally the same effects as larger doses, and that extracellular potassium markedly influences this linear dose response such that higher K⁺ concentrations considerably attenuate the positive inotropic response of digitalis.