TY - JOUR T1 - THE EFFECT OF ACUTE HYPOKALEMIA ON THE MYOCARDIAL CONCENTRATION AND BODY DISTRIBUTION OF TRITIATED DIGOXIN IN THE DOG JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 271 LP - 281 VL - 178 IS - 2 AU - FRANK I. MARCUS AU - LANA NIMMO AU - GEETA G. KAPADIA AU - CARL GOLDSMITH Y1 - 1971/08/01 UR - http://jpet.aspetjournals.org/content/178/2/271.abstract N2 - Cardiac sensitivity to digitalis glycosides associated with reduction in serum potassium concentration has been well documented and is clinically important. This study was done to determine if this sensitivity to digitalis was due to enhanced tissue uptake of digitalis and if hypokalemia would alter the distribution or excretion of digoxin. Dogs were subjected to hemodialysis against a bath potassium of 4 mEq/l (normokalemic dogs) or less than 0.75 mEq/l (hypokalemic dogs). Six normokalemic and six hypokalemic dogs were injected i.v. with 0.35 mg of tritiated digoxin and sacrificed one hour later (protocol A). Nine normokalemic and nine hypokalemic animals were given 0.5 mg of tritiated digoxin, a dose that caused electrocardiographic toxicity in three of the hypokalemic animals (protocol B). Six normokalemic and six hypokalemic dogs were infused with digoxin until toxic, at which time they were sacrificed (protocol C). Since the normokalemic dogs took longer to manifest myocardial toxicity, six additional control dogs were sacrificed at the same time as the hypokalemic animals to compare tissue concentrations of digoxin in dogs infused with the same dose of this glycoside. During hemodialysis and after digoxin was given, the blood pressure, heart rate and electrocardiogram were recorded. Samples of blood were analyzed for sodium, potassium, pH and digoxin concentration. Tissue, blood, urine and bile were analyzed for radioactivity. There was no difference in the myocardial concentration of digoxin between comparable hypokalemic and normokalemic groups. The hypokalemic dogs infused with digoxin exhibited toxicity (three or more consecutive premature ventricular beats) after receiving an average of 39% less digoxin than the normokalemic animals. At that point, the myocardial concentration of digoxin was an average of 35% less than that of the normokalemic dogs. Therefore, myocardial sensitivity to digitalis during hypokalemia could not be due to enhanced cardiac uptake of digoxin. In two of three experiments, the hypokalemic dogs had lower blood concentrations of digoxin than the normokalemic controls. This was usually evident within 15 minutes after digoxin administration and generally persisted. Clinically, we anticipate that the blood concentration of digoxin in hypokalemia may be within the "normal therapeutic range" in the presence of digitalis-induced electrocardiographic toxicity. This may be due to enhanced cardiac automaticity at any given myocardial digoxin level in hypokalemia. © 1971 by The Williams & Wilkins Co. ER -