Why the study?
Does digoxin-specific antibody reverse the biological and toxic effects of digoxin in preclinical models?
Does digoxin-specific antibody reverse the biological and toxic effects of digoxin in preclinical models?
Purified digoxin-specific antibodies and Fab fragments rapidly reverse the toxic effects of digoxin, including life-threatening ventricular tachycardia, providing the foundational evidence for clinical use of digoxin immune Fab.
Answers are grounded in this paper and cite their sources.
Reverses digoxin-induced VT rapidly in dogs; extends antibody-fragment evidence but leaves open human translation.
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.
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Curd et al. (1971) studied this question.
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