STUDIES ON THE GENERALIZED SHWARTZMAN REACTION : IV. PREVENTION OF THE LOCAL AND GENERALIZED SHWARTZMAN REACTIONS WITH HEPARIN

In order to explore the hypothesis that the occurrence of thrombosis of small blood vessels is an essential stage in the development of the local and generalized Shwartzman reactions, the effect of heparin was studied. Aqueous heparin, administered intravenously, and "depot" heparin, injected subcutaneously, prevented completely the occurrence of the local and generalized Shwartzman phenomena. The amounts of heparin required for protection were similar to the amounts required to produce sustained incoagulability of the blood of rabbits for a period of at least 4 hours. The local and generalized Shwartzman reactions were prevented when heparin was given at the time of provocation, but not when heparin was administered during the period of preparation. Heparin prevented the development of bilateral cortical necrosis of the kidneys following a single intravenous injection of meningococcal toxin in rabbits previously treated with cortisone or thorotrast. Hemorrhagic necrosis of the skin which follows an intradermal injection of toxin in thorotrast-treated rabbits was also prevented by heparin. Provocation of the dermal Shwartzman reaction with glycogen, saline suspension of rabbit liver, and human serum was prevented by treatment with heparin. Heparin itself, in the preparations and dosages used, had no consistent effect on either white blood cell or platelet counts. Heparin had no effect on the occurrence of polymorphonuclear leukopenia which follows an intravenous injection of meningococcal toxin. Treatment with heparin did not interfere with the lethal effect of single, large doses of meningococcus toxin. In animals in which bilateral cortical necrosis of the kidneys was prevented by heparin, occlusion of the glomerular capillaries by "fibrinoid" material did not occur. These observations support the concept that vascular occlusion plays an essential role in the development of the local and generalized Shwartzman reactions.