The Isolation of Digoxin-Specific Antibody and Its Use in Reversing the Effects of Digoxin
Abstract
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 × 108 M-1. At near-stoichiometric concentrations, either purified antibody to digoxin, or its papain-digested product (Fab-Fc), reversed digoxin-induced: (a) inhibition of 86Rb 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.
