Quantitative Adsorption of Antibody by the Isolated Heart and the Intensity of Cardiac Anaphylaxis

Abstract

The present experiments show that the adsorption of antibodies to the guinea pig heart can be achieved by perfusing the heart with rabbit antiovalbumin solutions. The amount of radioactive antibody remaining on the tissue is a definite function of the concentration of antibody in the bulk phase instilled into the coronary circulation. When the antibody-loaded organ is challenged with ovalbumin, the efflux rate of antibody is increased; it is also increased in response to such nonspecific agents as histamine and epinephrine. Since the output rate is not affected when the heart fails to react to rechallenge with antigen, the release of antibody may be entirely dependent upon the mechanical response. The maximal amount.it of histamine-like material that can be produced by the heart undergoing anaphylaxis was found to be 1 x 10 -s moles/Gm./min., estimated as histamine; the minimal amount of antibody necessary to release this quantity was calculated to be 0.343 µg. of specific antiovalbumin/100 mg. of heart. This load can be achieved by perfusing the heart with an antibody solution containing 30 µg. of specific γ-globulin. Perfusion with an antibody solution containing 50 µg./ml. showed the amount of histamine subsequently liberated by the same dose of ovalbumin to be reduced by 50 per cent. The rate and amplitude of contraction were increased to the same absolute values in all cases in which either ovalbumin or histamine was employed to set off the reaction, suggesting that the release of active material at even the low sensitizing doses of antibody used exceeded the ceiling of the physiological response. The decrease in coronary flow was inversely related to the dose of sensitizing antibody and bore little relation to the changes in this parameter induced by the subsequent administration of histamine.