ALTERATION OF THE BODY DISTRIBUTION OF TRITIATED DIGOXIN BY ACUTE HYPERKALEMIA IN THE DOG

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

The purpose of this study was to determine whether an increase in extracellular potassium concentration influences tissue concentration of digoxin in vivo, and whether potassium can displace digoxin from the heart and other organs. 1) In one group of experiments, hyperkalemia was produced prior to the injection of digoxin and was continued for 1 hr or 4 hr before sacrifice. This increased serum potassium concentration to the range of 6 to 9 mEq/liter. There was less digoxin in the myocardium of the hyperkalemic animals in the 1- and 4-hr studies. In the 4-hr studies, digoxin concentration was lowered in the kidney and increased in the skeletal muscle. Blood concentrations of digoxin were higher in the controls during most of the 4-hr period. The potassium-infused dogs excreted more digoxin only during the longer experiments. 2) In another group of experiments, infusion of potassium chloride was begun 70 min after i.v. digoxin and continued for 150 min. This elevated serum potassium to the range of 6.5 to 7.8 mEq/liter. The hyperkalemic animals showed no statistical difference from controls in the concentration of digoxin and metabolites in the myocardium or other tissues, the excretion of digoxin in bile and urine or the concentration of digoxin in the blood at the time of sacrifice. It is postulated that the change in body distribution of digoxin in the dog made hyperkalemic prior to the administration of digitalis may be explained in part by competitive inhibition of potassium and digitalis for similar receptor sites. Once digitalis is bound to the cell, hyperkalemia does not alter its retention. The mechanism of action of potassium in reversing digitalis-induced arrhythmias may be other than physical displacement of digitalis from the heart.