Host Resistance in Hemorrhagic Shock XV. Isolation of Toxic Factor from Hemorrhagic Shock Plasma

Abstract

[dagger]Plasma from normal and shocked dogs was treated with trichloroacetic acid (TCA), and the dialyzed concentrated TCA soluble fraction examined for toxicity and biological activity. Extracts prepared from normal plasma were uniformly inactive, while those from irreversible hemorrhagic shock plasma contained a macromolecular polysaccharide or lipopolysaccharide which resembled bacterial endotoxin in being pyrogenic and leukopenogenic in normal recipients, highly toxic in reversibly shocked recipients, and in its ability to induce tolerance to otherwise lethal degrees of shock trauma and to produce the generalized Schwartzman reaction in suitably prepared recipients. The bacterial origin of this factor was further supported by the observation that this factor was absent from the plasma of animals in shock pretreated with antibiotic non-absorbable orally administered. The absence of this factor in plasma of shocked animals exhibiting "natural" resistance or experimentally induced tolerance to shock is discussed in relation to the endotoxin-neutralizing potential of the reticulo-endothelial system in shock. Arguments against the endotoxin theory of irreversibility in shock, arising from limited observations in germ-free animals, are examined.