Reversal of toxic and non-toxic effects of digoxin by digoxin-specific Fab fragments in isolated human ventricular myocardium.

The time course of the reversal of toxic and nontoxic effects of digoxin by digoxin-specific antibody fragments (Fab) was measured in isolated human ventricular myocardium. A concentration of 2 X 10(-6) mol/l digoxin was used to produce positive inotropy followed by mechanical signs of toxicity. After addition of a 1.5-fold higher molar concentration of digoxin-specific Fab, signs of toxicity disappeared within 30 min and digoxin-induced force of contraction decayed with a monoexponential time course with a half-life of 52 min. This rate of decay was almost identical to that observed for the dissociation of the digoxin-(Na+ + K+)-ATPase complex in human heart cell membranes. It is concluded that digoxin-specific Fab are capable of completely removing digoxin from its binding sites, the maximal rate of removal of digitalis glycosides from the (Na+ + K+)-ATPase is limited by the dissociation rate constant, and there is a close correlation between the degree of binding of digitalis glycosides to the (Na+ + K+)-ATPase and the increase in force of contraction.