Activation of plasma complement by perfluorocarbon artificial blood: probable mechanism of adverse pulmonary reactions in treated patients and rationale for corticosteroids prophylaxis.
Perfluorocarbons have shown promise as clinical blood substitutes. Although early experience in Japan with one such product--Fluosol-DA--has been uncomplicated, we observed an adverse pulmonary reaction in the first American patient to receive it and know of similar reactions in two other Americans so treated. Postulating that activation of plasma complement (C) by the perfluorocarbon emulsion might have caused the reaction, we tested the product to determine if it is an activator of complement. Incubation of Fluosol with plasma led to C3 conversion, decrement in CH50, and generation of C5a-related PMN aggregating activity; EDTA prevented such activation, while EGTA did not, suggesting that it proceeded via the alternative C pathway. Infusion of Fluosol into rabbits produced hypoxemia, neutropenia, thrombocytopenia, and pulmonary leukostasis, mimicking abnormalities previously demonstrated in rabbits receiving infusions of zymosan-activated plasma C. These deleterious responses to Fluosol were diminished by premedicating rabbits with corticosteroids (which had seemed to benefit when used empirically in our patient). In vitro and in vivo, Fluosol's effects were reproduced by Pluronic F-68, the nonionic detergent used to maintain the emulsion stability of Fluosol-DA. We conclude that adverse reactions to Fluosol are probably mediated by C activation and that steroid premedication may prevent them in susceptible patients.
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000368:Aged; D000818:Animals; D001802:Blood Substitutes / Q000009:adverse effects* / Q000627:therapeutic use; D003167:Complement Activation / Q000187:drug effects*; D004338:Drug Combinations / Q000009:adverse effects / Q000627:therapeutic use; D005466:Fluorocarbons / Q000009:adverse effects* / Q000627:therapeutic use; D006098:Granulocytes; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives; D007958:Leukocyte Count; D008171:Lung Diseases / Q000139:chemically induced*; D008297:Male; D011292:Premedication; D011817:Rabbits
D000305:Adrenal Cortex Hormones; D001802:Blood Substitutes; D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination