THE EFFECT OF RESERPINE ON THE METABOLISM OF TRITIATED DIGOXIN IN THE DOG AND IN MAN

¹ The Georgetown University Medical Division, District of Columbia General Hospital, Washington, D. C.

Pharmacologic response to digitalis appears to be diminished in the reserpine-pretreated mammalian heart. A lower myocardial concentration of digitalis was postulated to account for the decrease in inotropic response in the reserpine-treated animals. Five dogs were injected i.p. on 2 successive days with 0.1 mg/kg of reserpine. There were six control dogs. All of the animals were given 0.5 mg of tritiated digoxin i.v. and were sacrificed 1 hr later. The concentration of digoxin and metabolites in the heart and spleen was significantly less in reserpine-treated dogs as compared with the controls. In contrast, the renal tissue concentration and urinary excretion of digoxin were greater in the reserpine-treated animals. Increased urinary excretion of digoxin in the reserpine group could not account for the decrease in myocardial concentration of digoxin, since there was also a lower myocardial concentration in reserpine-treated nephrectomized dogs as compared with nephrectomized, untreated controls. No change in digoxin metabolism could be established in normal human subjects after 6 weeks of daily administration of reserpine p.o. in usual clinical doses. A lower myocardial concentration of digoxin in reserpine-treated animals may explain the observed diminished inotropic response to digitalis. These studies provide the first evidence that other pharmacologic agents may be determinants of the myocardial concentration of cardiac glycosides.