New model for in vivo studies of pharmacological interventions with endogenous fibrinolysis: effects of thrombin inhibitors

Seminars in Thrombosis and Hemostasis
S Lenfors, D Gustafsson

Abstract

A new rat model for investigation of the interactions of thrombin inhibitors with endogenous fibrinolysis in vivo is described. The method utilizes the thrombin-like snake enzyme batroxobin, which mainly cleaves the fibrinopeptide A from fibrinogen and activates factor XIII only to a slight degree. Compared to thrombin-formed fibrin, batroxobin-formed fibrin is more readily lysed by plasmin, since it only cross-links fibrin to a minor extent. Radiolabeled fibrinogen (125I) was given intravenously to monitor the effects of batroxobin on fibrinogen and the effects of plasmin on the fibrin formed. Batroxobin was given intravenously in a dose that converted most fibrinogen to fibrin. Five to 10 minutes after batroxobin administration, 125I-activity in the blood decreased, indicating the disappearance of fibrinogen from the circulating blood. At the same time, the 125I activity as measured with a gamma counter increased over the lungs. The fibrin formed in the microvasculature of the lungs started an endogenous fibrinolysis. This could be seen as reappearance of the 125I activity in the blood from fibrin degradation products accompanied by a decrease in the 125I activity over the lungs. When the rats were given tranexamic acid, the ...Continue Reading

Citations

Mar 13, 1999·Thrombosis Research·J Hauptmann, J Stürzebecher
Jul 2, 2005·Expert Opinion on Investigational Drugs·L ChiK P Gallagher
Jul 20, 2011·Blood·Alexi P SuretteDavid M Waisman
Apr 4, 2017·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Bernhard G WeissMartin Canis
Aug 12, 2005·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Shi-Shan MaoJacquelynn J Cook

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