CORRELATION BETWEEN DECLINE OF POSITIVE INOTROPIC EFFECT AND LOSS OF CARDIAC GLYCOSIDES FROM ISOLATED ATRIA DURING WASH-OUT

The rate at which the positive inotropic effect of ouabain, digoxin and digitoxin diasppears from guinea-pig isolated atria during wash-out has been determined quantitatively. This rate was compared with the decrease in total tissue concentration during the wash-out procedure, previously established by means of tritium-labelled cardiac glycosides. The positive inotropic effect had entirely disappeared at 20-30 min; no important differences were observed between the glycosides studied. The decrease in total tissue concentration occurred more slowly. Calculations have shown that it is probably the rate at which the glycosides diffuse out of the extracellular space which governs the decrease in pharmacological effect. This disapearance of the positive inotropic action is not determined by the decline in total tissue concentration. The results suggest that the different duration of action of cardiac glycosides in vivo is caused by differences in elimination and/or metabolism and not by differences in fixation to heart muscle. © 1969.