The isolation of digoxin-specific antibody and its use in reversing the effects of digoxin.
Specific antibodies to digoxin were isolated from antisera of sheep immunized with a digoxin-human serum albumin conjugate. The antibody was purified by adsorption to an immunoadsorbent, synthesized by coupling a ouabain-ribonuclease conjugate to bromoacetyl-cellulose, followed by elution with 25 mM ouabain. Ouabain was dissociated from antibody by denaturation in 6 M guanidine. The renatured antibody bound 1.6 mol of digoxin per mol and had an association constant of 1.6 x 10(8) M(-1). At near-stoichiometric concentrations, either purified antibody to digoxin, or its papain-digested product (Fab-Fc), reversed digoxin-induced: (a) inhibition of (86)Rb transport in human erythrocytes, (b) increase in developed tension in isolated guinea-pig atrial strips, and (c) ventricular tachycardia in intact dogs, and also corrected digoxin-induced automaticity in isolated guineapig atrial strips.
D000327:Adsorption; D000818:Animals; D000906:Antibodies / Q000302:isolation & purification*; D001665:Binding Sites; D001692:Biological Transport; D002482:Cellulose; D002498:Centrifugation; D002850:Chromatography, Gel; D004077:Digoxin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006325:Heart Atria; D006801:Humans; D007106:Immune Sera; D007114:Immunization; D007120:Immunochemistry; D066298:In Vitro Techniques; D010042:Ouabain; D010206:Papain / Q000378:metabolism; D011489:Protein Denaturation; D012260:Ribonucleases; D012413:Rubidium / Q000378:metabolism; D012756:Sheep; D013610:Tachycardia / Q000139:chemically induced
D000906:Antibodies; D007106:Immune Sera; D010042:Ouabain; D004077:Digoxin; D002482:Cellulose; D012260:Ribonucleases; D010206:Papain; D012413:Rubidium