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

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Summary

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 2×10−6 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 (a) digoxin-specific Fab are capable of completely removing digoxin from its binding sites, (b) the maximal rate of removal of digitalis glycosides from the (Na++K+)-ATPase is limited by the dissociation rate constant, and (c) 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.

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Abbreviations

Fab:

Fragment antibody binding (digitalis antidote)

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Authors and Affiliations

  1. Medizinische Klinik I der Universität, Klinikum Großhadern, München

    M. Näbauer & E. Erdmann

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  1. M. Näbauer
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  2. E. Erdmann
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Näbauer, M., Erdmann, E. Reversal of toxic and non-toxic effects of digoxin by digoxin-specific fab fragments in isolated human ventricular myocardium. Klin Wochenschr 65, 558–561 (1987). https://doi.org/10.1007/BF01727622

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  • DOI: https://doi.org/10.1007/BF01727622

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