Pathogenesis of hemorrhage induced by proteinase H from eastern diamondback rattlesnake (Crotalus adamanteus) venom.

The pathogenesis of hemorrhage of a purified hemorrhagic toxin, proteinase H from Crotalus adamanteus venom, was studied. Female, white CD-1 mice were injected intramuscularly with sublethal doses of the hemorrhagic toxin and tissue samples were obtained at 10 min, 1, 3 and 24 hr following injection. Severe local hemorrhage was observed grossly within 10 min. Hemorrhage was observed in the connective tissue of skeletal muscle and within adjacent adipose tissue. Many larger vessels were congested with erythrocytes and platelets. By 3 hr inflammatory cell infiltration was observed and necrosis of some muscle cells was evident. Transmission electron microscopy showed that the capillary endothelium was ruptured, leading to hemorrhage per rhexis. Capillary basal laminae were disorganized and often wholly or partially absent.