BEHAVIOUR OF DIGOXIN DIGITOXIN AND DIGITOXIGENIN IN ISOLATED HEART MUSCLE AND IN PLASMA OF RESERPINIZED GUINEA PIGS

The positive inotropic effect, the tissue uptake and the binding to plasma proteins were determined in isolated atria and in plasma of normal and reserpinized guinea pigs for digoxin, digitoxin and digitoxigenin. Some of the experiments were carried out with tritium-labelled cardenolides. 1. The three cardenolides caused the same positive inotropic effect in electrically driven isolated atria from either reserpinized or normal guinea pigs. 2. Pretreatment of the animals with reserpine did not influence the uptake of 3H-digoxin in isolated atria. After pretreatment with reserpine, however, approximately 20% more 3H-digitoxin and 3H-digitoxigenin were taken up. 3. Pretreatment of the guinea pigs with reserpine did not influence the binding of 3H-digoxin to plasma proteins. The binding of 3H-digitoxin and 3H-digitoxigenin to proteins, however, was increased in plasma of reserpinized guinea pigs in comparison with that of untreated control animals. 4. The plasma of reserpinized guinea pigs showed the same osmolality, refraction and total protein content as the plasma of untreated control animals. The plasma electropherogram and also the haemotacrit value of the blood proved to be unaltered in reserpinized guinea pigs. 5. Probably, the pretreatment with reserpine increase the binding capacity of plasma albumin for cardenolides by a mechanism so far unknown. A similar mechanism might cause the increased accumulation by heart muscle tissue. © 1969 Springer-Verlag.