The effect of digoxin antibody on the washout of tritiated digoxin and its inotropic effect from perfused rabbit hearts.
The reversal of digoxin effects by digoxin antibody (Ab) may be mediated by at least two mechanisms. First, the Ab may simply decrease the concentration of free digoxin in the perfusing medium, or second, the Ab may dislodge digoxin from its receptor. To pursue this problem, rabbit hearts were perfused for 20 min with Krebs-Henseleit solution (K-H) followed by a 30-min perfusion with [3H] digoxin in concentrations of 10(-7), 5x10(-7), and 10(-6) M. The hearts were then washed out with K-H alone or with K-H containing Ab. During washout the effluent was collected at 30-sec intervals and the concentration of [3H] digoxin measured in each sample. Washout was continued until the positive inotropic effect of digoxin had returned to its previous level. The [3H] digoxin washout curves were analyzed on the basis of statistical criteria and yielded three exponential components. During Ab washout the half-times t1/2 of these components were 0-25 +/- 0.07, 1.70 +/- 0.28, and 19.5 +/- 6.9 min, while during K-H washout the values were 0.28 +/- 0.02, 1.49 +/- 0.22, and 11.8 +/- 2.7. The decay of the inotropic effect of digoxin was similar during both washout conditions. The results indicate that the apparent tissue to perfusate concentration gradient for the washout of [3H] digoxin was not increased by Ab...
D000818:Animals; D000906:Antibodies; D001665:Binding Sites; D004077:Digoxin / Q000276:immunology* / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D011817:Rabbits; D011955:Receptors, Drug
D000906:Antibodies; D011955:Receptors, Drug; D004077:Digoxin