Prevention of the Localized and Generalized Shwartzman Reactions by an Anticomplementary Agent, Cobra Venom Factor

Abstract

The Shwartzman phenomenon may be defined as the pathologic manifestation of disseminated intravascular coagulation with widespread hemorrhagic necrotic lesions and bilateral renal cortical necrosis induced by the administration of two spaced injections of endotoxic lipopolysaccharide (LPS).I Results of previous investigations indicate that the platelet-LPS interaction with subsequent platelet adherence and release of its contents is primarily responsible for the pathologic alterations of the coagulation system (1--6). Prior treatment of rabbits which renders them thrombocytopenic or leukopenic can regularly protect these animals from the manifestation of Shwartzman lesions (7,8). Stetson found that there was a temporal correlation between thrombocytopenia and the deposition of platelet aggregates in the lung, liver, and spleen after the administration of LPS (1). Furthermore, McKay and Shapiro observed that LPS-induced thrombocytopenia corresponded well with the appearance of a hypercoagulable state (2). Recently, Mustard et al. demonstrated the protection of rabbits from Shwartzman lesions by treatment with acetylsalicylic acid, sulfinpyrazone, or phenyl butazone which are agents that interfere with the platelet release reaction (9-11).Although the mechanism of platelet-LPS interaction remains to be elucidated, Siqueira and Nelson suggested that the complement system is important in this interaction (12). Review of recent reports indicates that plasma factors are required for the platelet-LPS interaction and that these factors are inhibited

Escherichia Coli Bacteremia in the Squirrel Monkey I. EFFECT OF COBRA VENOM FACTOR TREATMENT

“…A fall in hemolytic complement titers has been observed in rabbits and dogs after intravenously administered endotoxin (13)(14)(15)(16). The present studies demonstrated the same phenomenon in monkeys, but the rapidity of the decrease was striking.…”

“…CoF treatment had no influence on the endotoxin-induced neutropenia of the Shwartzman reaction in rabbits but events during the first 4 h postinjection were not reported (16). The accumulation of neutrophils in inflammatory exudates following i.p endotoxin administration was markedly retarded in C5-deficient mice (55).…”

“…both in rabbits and in dogs demonstrate a fall in serum complement titers after the intravenous administration of endotoxin (13)(14)(15)(16).…”

Effects of FUT-175, a New Synthetic Protease Inhibitor on Endotoxin-Induced Disseminated Intravascular Coagulation in Rats

“…On the other hand, it was shown that the complement system plays a role in DIC [13,14], FUT-175 has potent inhibitory effects on C lr and Cl esterase and complementmediated hemolysis by the classical and al ternative pathways [1,15]. Although this an ticomplement activity might contribute in some way to reduce the extent of changes of the coagulation parameters caused by DIC, the exact mechanism requires further investi gation.…”

Simple Methods of Rabbit Hemolytic Complement Component Assays

“…Albino rabbits were injected intravenously with 160 anticomplementary units of CVF [2], Blood samples were obtained from the rabbits at different time intervals for a total period of 15 days. Total, Cl, and C5-9 hemolytic complement component activities were assayed and presented as the percentage of original activity ( fig.…”