Thrombolysis with a snake venom protease in a rat model of venous thrombosis.
A fibrin(ogen)olytic protease isolated from the venom of Crotalus atrox (the western diamondback rattlesnake) was tested for thrombolytic activity. The protease, called atroxase, solubilized fibrin when tested on fibrin plates and hydrolyzed fibrinogen rendering it incoagulable with a specific fibrinogenolytic activity of 42 mg fibrinogen/min/mg protein. Atroxase was unable to activate plasminogen. In vivo, fibrinolytic activity was tested on artificial thrombi induced in the posterior vena cava of Sprague-Dawley rats. Thrombolysis was then characterized by angiographic techniques over a period of three hours. Intravenous administration of the protease, at a dosage of 6.0 mg/kg, resulted in thrombolysis within one hour followed by recanalization of the originally occluded vein within two hours. Fibrinogenolytic activity resulted in a 60% decrease in the rat's plasma fibrinogen level. Histological examination of kidney, liver, heart and lung tissue showed no necrosis nor hemorrhage. These results are the first step in evaluating the thrombolytic potential of anticoagulant proteases within C. atrox venom using laboratory animals.
Willis
T W
TW
Department of Biochemistry, Colorado State University, Fort Collins 80523.
Tu
A T
AT
Miller
C W
CW
D000792:Angiography; D000818:Animals; D003435:Crotalid Venoms / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000032:analysis; D005342:Fibrinolysis; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008666:Metalloendopeptidases / Q000627:therapeutic use*; D010447:Peptide Hydrolases / Q000627:therapeutic use*; D010960:Plasminogen Activators / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013924:Thrombophlebitis / Q000188:drug therapy*
D003435:Crotalid Venoms; D005343:Fibrinolytic Agents; D005340:Fibrinogen; D010447:Peptide Hydrolases; D010960:Plasminogen Activators; D008666:Metalloendopeptidases; C057212:atroxase