FACTORS THAT REGULATE OUABAIN-H⁸ ACCUMULATION BY THE ISOLATED GUINEA-PIG HEART

¹ Department of Pharmacology, The Ohio State University College of Medicine, Columbus, Ohio

Guinea-pig hearts were perfused at constant flow via the aorta with ouabain-H⁸ in concentrations ranging from 1 X 10^-6 M to 1 X 10^-6 M. Perfusion was continued for 64 minutes and was followed by eight minutes of washout. The cardiac uptake showed indications of saturability in this system. The concentration of ouabain in the microsomal fraction was greater than in the heart as a whole, whereas the concentrations in the other particulate fractions were le than that of the heart as a whole. The uptake of ouabain-H⁸ by the guinea-pig heart was directly related to the concentration of sodium ions in the perfusing medium and was inversely related to the concentration of potassium ions in the extracellular medium. The ionic strength of the perfusing medium, independent of the sodium/potassium ratio, also was an important factor determining ouabain uptake. The absence of magnesium or calcium did not significantly influence the uptake of ouabain by the isolated guinea-pig heart. The cardiac uptake of ouabain-H⁸ was reduced in the presence of digitoxin, the effect being greater when the ratio of digitoxin to ouabain in the perfusion medium was increased. From these studies it has been concluded that the cardiac uptake of ouabain falls in the category of carrier-mediated procecesses. It is suggested that digitalis intoxication associated with hypokalemia is due to increased cardiac digitalis uptake.