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PubMed1955

Studies on the generalized Shwartzman reaction. VI. Production of the reaction by the synergistic action of endotoxin with three synthetic acidic polymers (sodium polyanethod sulfonate, dextran sulfate, and sodium polyvinyl alcohol sulfonate).

Lesions indistinguishable from those of the generalized Shwartzman reaction occured in rabbits when a single intravenous injection of Gram-negative bacterial endotoxin was accompanied, or followed, by an injection of one of the following synthetic, heparin-like, acidic polymers-sodium polyanethol sulfonate, dextran sulfate, or sodium polyvinyl alcohol sulfonate. These reactions were produced by doses of polymer or of endotoxin which were without demonstrable effect when given singly. Heparin, in those similar to those previously shown to protect rabbits against the lesions of the generalized Shwartzman reaction, prevented the reaction to the combined injection of endotoxin and acidic polymers. Nitrogen mustard, which was previously shown to prevent the lesions of the generalized Shwartzman reaction from occurring after two intravenous injections of endotoxin, had no protective action against the lesions produced by the combined injection of endotoxin and polymer. Cortisone did not affect the reaction to endotoxin and polymer. The role of fibrinogen in the reaction under study is discussed in the paper which follows.

Animals↗
PubMed1955

Studies on the generalized Shwartzman reaction. VII. The role of fibrinogen in the deposition of fibrinoid after combined injections of endotoxin and synthetic acidic polymer.

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.

Animals↗