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(Circulation. 1973;48:830.)
© 1973 American Heart Association, Inc.

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The Inotropic Effects of Digoxin in Hyperkalemia

Relation to (Na⁺,K⁺)-ATPase Inhibition in the Intact Animal

ROBERT H. GOLDMAN M.D.¹; D. JOHN COLTART M.D.¹; JOEL P. FRIEDMAN M.D.¹; GAETON T. NOLA ¹; DAVID K. BERKE M.D.¹; ESTHER SCHWEIZER ¹; DONALD C. HARRISON M.D.¹

¹ From the Cardiology Division, Stanford University School of Medicine, Stanford, California.

The effects of hyperkalemia on the inotropic properties of digoxin were studied in anesthetized mongrel dogs. With preload, afterload and heart rate maintained constant in dogs who received atropine and practolol to block cardiac reflexes, 0.08 mg/kg digoxin increased the first derivative of the left ventricular pressure curve (LV dp/dt) 53.1 ± 8.3% (SEM) in normokalemic animals but only 9.5 ± 2.5% in hyperkalemic animals at 60 min. This decrease in the inotropic effects of digoxin by hyperkalemia was accompanied by significant decreases in both total left ventricular digoxin concentration and microsomal-bound digoxin. (Na⁺, K⁺)-ATPase was inhibited 43.3 ± 2.4% in normokalemic animals but only 27.4 ± 2.5% in hyperkalemic animals (P < 0.01), while (Mg⁺⁺)-ATPase levels were similar in normokalemia and hyperkalemia. In animals not given digoxin, hyperkalemia had no effect on either LV dp/dt or (Na⁺, K⁺)-ATPase. There was a good correlation between the positive inotropic effects of digoxin and percent inhibition of (Na⁺, K⁺)-ATPase.

These studies provide further support for the importance of (Na⁺, K⁺)-ATPase inhibition and microsomal-bound digoxin in determining the inotropic effects of digoxin. Hyperkalemia alters the inotropic effects of digoxin by decreasing binding of digoxin to a microsomal cell fraction containing (Na⁺, K⁺)-ATPase activity.

These studies also provide support for the importance of reflex withdrawal of sympathetic tone in modifying the inotropic properties of digoxin in normokalemic and hyperkalemic animals.

Key Words: ATPase inhibition • In vivo digoxin binding • Left ventricular digoxin • Microsomal-bound digoxin

Submitted on April 4, 1973
Accepted on June 11, 1973