Tritiated digoxin metabolism after prior treatment with propranolol or diphenylhydantoin sodium

Digitalis-induced arrhythmias can be suppressed by intravenous potassium, diphenylhydantoin sodium and propranolol. As it is known that hyperkalemia can interfere with the myocardial uptake of digoxin, this study was performed to determine whether diphenylhydantoin sodium or propranolol could exert any antiarrhythmic effect by altering the metabolism of 3H-digoxin and, in particular, the accumulation of the glycoside by cardiac muscle. Three groups of anesthetized dogs were given 6 muCi 3H-digoxin per kilogram intravenously, and in two groups 15 mg/kg diphenylhydantoin sodium or 3 mg/kg propranolol were injected intravenously 15 minutes prior to the glycoside. The concentration of labelled digoxin was measured in plasma up to one hour, and then tissues were removed and analyzed for digoxin content. Diphenylhydantoin sodium did not influence myocardial uptake of digoxin. It is considered its suppressant action on digitalis-induced arrhythmias is not due to any effect on the cardiac accumulation of digoxin. Propranolol did reduce the myocardial uptake of digoxin, but this was not considered of sufficient magnitude to be the main factor in suppressing arrhythmias induced by digitalis. These studies provide evidence that both diphenylhydantoin sodium and propranolol do not have a suppressant effect on digitalis-induced arrhythmias by virtue of any significant interference with the uptake of digoxin by myocardial tissue.