Pharmacokinetics and action of digitoxin and ouabain in the isolated hearts of guinea pigs and rats

: Isolated guinea pig and rat hearts were perfused with 3H-digitoxin and 3H-ouabain. After varying perfusion periods (3-90 min) the glycoside content in the tissue was determined. With digitoxin the tissue/medium-ratio at equilibrium was found to be 14 in guinea pigs and 8 in rats, with ouabain the corresponding values were 2 and 1. In further experiments the efflux of radioactivity from isolated perfused hearts preloaded with 3H-glycosides was measured in 3 min intervals. A compartmental analysis was carried out. The efflux could be described by the sum of two exponentials indicating the existence of two compartments. The half lives of compartment 1 (2.1-4.0 min) and those of compartment 2 (16.8-20.6 min) were similar with both glycosides and both species. The development and decline of the positive inotropic effect in guinea pig hearts exhibited a time course similar to that of the glycoside content in compartment 1: the time for reaching the half maximum effect was 3-4 min with ouabain and 5-6 min with digitoxin. It is suggested that compartment 1 represents the site of the positive inotropic action of cardiac glycosides.