A COMPARISON OF THE ACCUMULATION AND RELEASE OF³H‐OUABAIN AND³H‐DIGITOXIN BY GUINEA‐PIG HEART MUSCLE

Abstract

The tissue uptake and excretion of radioactively labelled cardiac glycosides have been studied in whole animals and also in man (for review, see van Zwieten, 1967). There are, however, only a few reports in the literature of the accumulation of the labelled drugs by isolated organs or tissue slices. Nevertheless such studies with isolated organs would be of great interest, because the pharmacological action of cardiac glycosides can only be studied properly if various extra-cardiac factors can be ruled out. Sjoerdsma & Fischer (1951) described the accumulation of "4C-digitoxin by isolated perfused hearts of various animal species. The uptake of "C-digitoxin by slices of rabbit auricles and ventricles was estimated by Godfraind & Lesne (1967). Systematic investigations of the accumulation and release of 3H-digoxin by beating, isolated guinea-pig atria have recently been carried out (Kuschinsky, Lahrtz, Lullmann & van Zwieten, 1967). In these investigations, the influence of various parameters-for example, the concentration of digoxin in the bath and the frequency of beating of the organs-has been established. The exchange process of tissue-bound digoxin against 3H-digoxin in the bath has been described in a separate paper (Kuschinsky, Lullmann, Schmitz & van Zwieten, 1967). Similar experi- ments on uptake, release and exchange have been carried out with 3H-peruvoside, the a-thevetoside of cannogenin (Kuschinsky, LUllmann & van Zwieten, to be published). The pharmacological and clinical properties of digoxin and peruvoside, whose kinetics of uptake and release by guinea-pig atria we have already studied, lie between those of the two " extremes," digitoxin and ouabain. Digitoxin and peruvoside belong to the inter- mediate category of cardiac glycosides. In animals and in man, digitoxin shows a prolonged action, whereas the duration of the effect of ouabain is comparatively short. It therefore seemed of interest to investigate the uptake and release of 3H-digitoxin and 3H-ouabain by guinea-pig atria. The results of these studies have also been compared with those previously obtained for digoxin and peruvoside. METHODS Guinea-pig isolated atria were prepared and suspended in an organ bath as previously described (Kuschinsky, Lahrtz, Lullmann & van Zwieten, 1967). All experiments were carried out at 30" C. The calcium content of the Tyrode solution was 1.2 m-equiv/l. Throughout the experiments the