Immunological protection against digoxin toxicity

Schmidt, Donald H.; Butler, Vincent P.

doi:10.1172/jci106558

Cited by 61 publications

(22 citation statements)

References 21 publications

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“…Experimental animals immunized with synthetic digoxin-protein conjugates form antibodies with speciThese studies have been presented in part to the Scientific Session of the American Heart Association at Atlantic City, N. J., 11 November 1973 (1). Dr Received for publication 10 February 1976 and in revised form 21 October 1976. ficity for the unconjugated digitalis glycoside, digoxin (2).…”

Section: Introductionmentioning

confidence: 99%

“…In vitro, antibodies to digoxin or to other cardiac glycosides are capable of removing these glycosides from mammalian cells (3,4) and of preventing or of reversing many of the pharmacologic and toxic effects of the glycosides on such cells (3)(4)(5)(6)(7)(8)(9)(10). In vivo, antidigoxin antibodies are capable of preventing or of reversing lethal digoxin intoxication in experimental animals (11)(12)(13). These properties of digoxin-specific antibodies have prompted consideration of the possibility that these antisera might be of clinical value in the reversal of severe digoxin intoxication in man (5,7,9,12,13).…”

Section: Introductionmentioning

confidence: 99%

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Effects of sheep digoxin-specific antibodies and their Fab fragments on digoxin pharmacokinetics in dogs.

Butler¹,

Schmidt²,

Smith³

et al. 1977

J. Clin. Invest.

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A B S T R A C T Intact sheep antidigoxin antibodies and their Fab fragments have both been found to exert profound effects on digoxin pharmacokinetics in [3H]digoxin-treated dogs. Both classes of molecule remove digoxin from the extravascular space and sequester it in the circulation in protein-bound form, a form in which the digoxin is presumably inactive. These two classes of molecule differ, however, in that the intact antibody molecules interfere with digoxin excretion, thereby promoting the retention of the glycoside; this retained digoxin is eventually released in free, active form when the administered antibody is metabolically degraded. In contrast, urinary excretion of digoxin continues in Fab-treated dogs, with significant quantities of digoxin being excreted promptly in the urine in complex with Fab fragments. These differences in urinary excretion, together with the probable decreased immunogenicity of sheep antidigoxin Fab fragments, suggest that such fragments possess potential advantages over intact antibody molecules for use in the therapy of life-threatening digoxin intoxication in man.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of sheep digoxin-specific antibodies and their Fab fragments on digoxin pharmacokinetics in dogs.

Butler¹,

Schmidt²,

Smith³

et al. 1977

J. Clin. Invest.

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“…Schmidt and Butler showed that immunization with a digoxinserum albumin conjugate substantially increased the resistance of rabbits to potentially lethal doses of digoxin (14). They further determined that passively administered digoxin-specific antibody could reverse established cardiac digoxin toxicity in the dog (4), a finding confirmed in our own laboratory (3,5).…”

Section: Discussionmentioning

confidence: 55%

Reversal of Ouabain and Acetyl Strophanthidin Effects in Normal and Failing Cardiac Muscle by Specific Antibody

Gold¹,

Smith²

1974

J. Clin. Invest.

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A B S T R A C T Isolated cat right ventricular papillary muscles were used to study the effects of antibodies with high affinity for ouabain and acetyl strophanthidin on myocardium exposed to these cardioactive steroids. strophanthidin-antibody complex did not alter the myocardial contractile response to subsequently added cardioactive steroids.Spontaneous automaticity occurring as a toxic response to ouabain or acetyl strophanthidin in eight muscles was rapidly reversed by specific antibody at a time when positive inotropic effects were still fully manifest. Early contracture was also reversed by specific antibody. These studies provide further support for the concept that cardiac glycoside-specific antibodies are capable of reversing established cellular effects of cardioactive steroids. INTRODUCTIONSeveral recent studies have shown that cardiac glycosidespecific antibodies can reverse established effects of digitalis glycosides in biological systems (1-3). In addition to reversal of cardiac glycoside-induced effects on in vitro systems, it has been demonstrated that advanced cardiac digoxin toxicity in the intact dog can be reversed by digoxin-specific antibody (4, 5).To assess the effect of cardiac glycoside-specilic antibody on digitalis-treated myocardium, we have studied the effects of ouabain-specific antibody on isolated cat right ventricular papillary muscles exposed to ouabain and acetyl strophanthidin. In the experiments to be described, special attention has been directed to (a) the time-course of reversal of digitalis-induced inotropy by antibody and its relation to reversal of inotropy by washout alone; (b) the effect of congestive heart failure, induced by chronic pulmonary artery constriction, on papillary muscle responses to digitalis and specific antibody; (c) the relation of cardioactive steroid concentration to specific antibody concentration required to reverse established effects; (d) the question of whether

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“…Technically the development of a vaccine to prevent krimpsiekte is quite feasible (Butler & Chen 1967;Schmidt & Butler 1971). Antibodies have been raised against digoxin, a cardenolide cardiac glycoside.…”

Section: Introductionmentioning

confidence: 99%

A potential krimpsiekte vaccine.

Botha¹,

Crafford²,

Butler³

et al. 2011

Poisoning by Plants, Mycotoxins and Related Toxins

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Krimpsiekte, a chronic form of cardiac glycoside poisoning, is an important plant-induced intoxication of small stock in South Africa. It is caused by cumulative, neurotoxic bufadienolides, such as cotyledoside. A cotyledoside-bovine serum albumin conjugate was synthesized to immunize animals. The efficacy of the cotyledoside-conjugate in inducing an immunological response was ascertained in rabbits (n = 4) and sheep (n = 4) by determining cotyledoside antibody titres with an ELISA using cotyledoside-hen ovalbumin as antigen. The formation of anticotyledoside antibodies was induced in both rabbits and sheep following immunization with the cotyledoside-protein conjugate. Protection provided by the vaccine was demonstrated by challenging sheep (n = 4) with repeated, daily doses of cotyledoside (0.015 mg/kg) administered intravenously, commencing 45 days after the initial vaccination. One control animal died on Day 3 of the challenge period and the other was severely affected after administration of the third cotyledoside dose. The immunized ewes (n = 2) remained clinically unaffected and the challenge was suspended following six daily injections. Vaccination as a means of preventing krimpsiekte seems to be quite feasible and deserves further investigation.

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Immunological protection against digoxin toxicity

Cited by 61 publications

References 21 publications

Effects of sheep digoxin-specific antibodies and their Fab fragments on digoxin pharmacokinetics in dogs.

Effects of sheep digoxin-specific antibodies and their Fab fragments on digoxin pharmacokinetics in dogs.

Reversal of Ouabain and Acetyl Strophanthidin Effects in Normal and Failing Cardiac Muscle by Specific Antibody

A potential krimpsiekte vaccine.

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