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. Antibodies with average intrinsic affinity constants for ouabain and acetyl strophanthidin of the order of 108 M-1 were raised in rabbits challenged by repeated injection of a conjugate of ouabain covalently linked to a poly D,L-alanyl derivative of human serum albumin. Effects were assessed in terms of time-course and extent of inotropy reversal, influence of experimentally induced ventricular failure, digitalis-antibody concentration relations, influence of digitalis-antibody complex on response to additionally added digitalis, and relation of antibody effects on digitalis-induced automaticity and contracture to reversal of inotropy. Specific antibody (but not control antibody) in 1.1-1.5-fold molar excess over cardioactive steroid concentrations blocked positive inotropic effects of ouabain and acetyl strophanthidin, and gradually reversed established contractile effects of these agents with a mean time for half-reversal of ouabain-induced inotropy of 124±6 (SEM) min and 37±3 min for half-reversal of acetyl strophanthidin-induced inotropy. Papillary muscles from cats with right ventricular failure induced by chronic pulmonary artery constriction responded similarly. Both normal and failing muscles returned to but not below levels of contractility existing before cardioactive steroid exposure, and time for half-reversal of inotropy by antibody was significantly shorter than time for half-reversal after removal of ouabain or acetyl strophanthidin by muscle bath washout alone. Presence of ouabain- or acetyl strophanthidin-antibody complex did not alter the myocardial contractile response to subsequently added cardioactive steroids.
Herman K. Gold, Thomas W. Smith
Title and authors | Publication | Year |
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Annual Reports in Medicinal Chemistry
JJ Liu, TW Lee |
Annual Reports in Medicinal Chemistry Volume 46 | 2011 |
Monoclonal antibodies to T-2 toxin. In vitro neutralization of protein synthesis inhibition and protection of rats against lethal toxemia
G Feuerstein, JA Powell, AT Knower, KW Hunter |
Journal of Clinical Investigation | 1985 |
New Advances in the Assessment and Treatment of Digitalis Toxicity
TW Smith |
The Journal of Clinical Pharmacology | 1985 |
Digoxin Specific Antibody (Fab) Fragments in 34 Cases of Severe Digitalis Intoxication
A Smolarz, E Roesch, E Lenz, H Neubert, P Abshagen |
Journal of Toxicology: Clinical Toxicology | 1985 |
Part III Digitalis glycosides: Mechanisms and manifestations of toxicity
TW Smith, EM Antman, PL Friedman, CM Blatt, JD Marsh |
Progress in Cardiovascular Diseases | 1984 |
Part II Digitalis glycosides: Mechanisms and manifestations of toxicity
TW Smith, EM Antman, PL Friedman, CM Blatt, JD Marsh |
Progress in Cardiovascular Diseases | 1984 |
Part I Digitalis glycosides: Mechanisms and manifestations of toxicity
TW Smith, EM Antman, PL Friedman, CM Blatt, JD Marsh |
Progress in Cardiovascular Diseases | 1984 |
Digoxin-specific antibody fragments and a calcium antagonist for reversal of digoxin-induced mesenteric vasoconstriction
T Hess, G Scholtysik, R Salzmann, W Riesen |
Journal of Pharmacy and Pharmacology | 1983 |
Extracellular versus intracellular digoxin action on bovine myocardium, using a digoxin antibody and intracellular glycoside application
P Hess, P Müller |
The Journal of Physiology | 1982 |
The effectiveness of digoxin-specific F(ab‘)2-antibody fragments in the treatment of digitoxin poisoning: experimental investigations in the cat
T Hess, G Scholtysik, W Riesen |
European Journal of Clinical Investigation | 1980 |
Immunogenicity and kinetics of distribution and elimination of sheep digoxin-specific IgG and Fab fragments in the rabbit and baboon
TW Smith, BL Lloyd, N Spicer, E Haber |
Clinical & Experimental Immunology | 1979 |
Contrasting rates of reversal of digoxin toxicity by digoxin-specific IgG and Fab fragments
BL Lloyd, TW Smith |
Circulation | 1978 |
Effects of sheep digoxin-specific antibodies and their Fab fragments on digoxin pharmacokinetics in dogs
VP Butler, DH Schmidt, TW Smith, E Haber, BD Raynor, P Demartini |
Journal of Clinical Investigation | 1977 |
Reversal of Advanced Digitoxin Toxicity and Modification of Pharmacokinetics by Specific Antibodies and Fab Fragments
HR Ochs, TW Smith |
Journal of Clinical Investigation | 1977 |
PRODUCTION AND PROPERTIES OF DIGOXIN-SPECIFIC ANTIBODIES
VP Butler, DH Schmidt, JF Watson, JD Gardner |
Annals of the New York Academy of Sciences | 1974 |
DISCUSSION PAPER: USE OF ANTIBODIES IN THE STUDY OF THE MECHANISM OF ACTION OF DIGITALIS
TW Smith |
Annals of the New York Academy of Sciences | 1974 |
Cardiac Glycosides
DG Friend |
New England Journal of Medicine | 1962 |