STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

An intravenous injection of sodium polyanethol sulfonate, a heparin-like synthetic polymer of large molecular size, into rabbits given endotoxin 2 hours previously, results in the abrupt disappearance from the circulating blood of a large proportion of fibrinogen. The depletion of circulating fibrinogen is prevented by the administration of heparin prior to the synthetic polymer. In animals receiving the polymer alone, or endotoxin alone, no depletion of fibrinogen occurs. It is suggested that the intravascular deposition of fibrinoid and the subsequent necrotizing lesions of the generalized Shwartzman reaction, which occur after the combined injection of endotoxin and synthetic acid polymer, may be due to the intravascular precipitation of fibrinogen by polymer. A qualitative change in fibrinogen, characterized by its precipitability by heparin at low temperature, is regularly demonstrable in plasma between 1 and 4 hours after an intravenous injection of endotoxin. The appearance of this heparin-precipitable fraction is prevented by treatment with heparin before endotoxin. It is not influenced by nitrogen mustard or cortisone. During the period when depletion of circulating fibrinogen is produced by polyanethol, in endotoxin-treated animals, the heparin-precipitable fraction also disappears from the blood. It is suggested that the change in fibrinogen may represent partial polymertization, and the cold precipitability of this material by heparin may be related to its enhanced precipitability, in vivo, by polyanethol. An hypothesis which accounts for certain events in the generalized Shwartzman reaction, based on observations reported in this study, is presented.