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.
D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D004077:Digoxin / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007700:Kinetics; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010210:Papillary Muscles / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors
D007140:Immunoglobulin Fab Fragments; D011955:Receptors, Drug; C027082:digitalis receptor; C050199:digoxin antibodies Fab fragments; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase