Biologic Effects of Specific Antibodies in Reversing the Pharmacologic and Toxic Effects of Digoxin

Abstract

By virtue of their ability to bind the cardiac glycoside, digoxin, with high specificity and affinity (Butler and Chen, 1967; Smith et al., 1970), antidigoxin antibodies are capable (Table 31.1) of acting as specific antagonists of digoxin, both in vitro and in vivo (Butler, 1970; Butler et al., 1973; 1974; Smith, 1974; Smith et al., 1977; Butler et al., 1977b). In vitro, antibodies to digoxin are capable of preventing the uptake of digoxin by rat renal cortical slices (Watson and Butler, 1972) and by human erythrocytes (Watson and Butler, 1972; Gardner et al., 1973). In inhibiting digoxin uptake by human red blood cells, digoxin-specific antibodies prevent the glycoside from exerting a pharmacologic effect on these cells in that, after a brief incubation with antidigoxin antibodies, digoxin is unable to inhibit the influx of potassium (Watson and Butler, 1972; Gardner et al., 1973) or of rubidium (Curd et al., 1971) into erythrocytes; antibodies to proscillaridin (also a cardiac glycoside) exert a similar effect on rubidium uptake (Belz et al., 1973). Antibodies to digoxin and to ouabain, another cardiac glycoside, have been shown to be capable of preventing the corresponding cardiac glycosides from exerting their positive inotropic effects on isolated cat papillary muscle strips (Skelton et al., 1971; Gold and Smith, 1974).

Supported in part by grants from the United States Public Health Service (HL 10608; HL 18003) and the New York Heart Association.

Recipient of an Irma T. Hirschl Career Scientist Award.

Established Investigator of the American Heart Association.