Study of Relative Role of Lysis of Preformed Fibrin and Accretion of New Fibrin on Thrombi in Determining Thrombus Size after rt-PA Bolus
The aim of this study was to evaluate in a rabbit vein thrombosis model the relative role of lysis of preformed fibrin and accretion of new fibrin on thrombi in determining the final thrombus size after the injection of increasing bolus doses of rt-PA. Materials and Methods
Materials: Human ISSI-fibrinogen (FIBI-125 C, 90% clottable; specific activity, 7.1 MBq/mg) was purchased from Sorin Biomedica, Saluggia, Italy. Preliminary studies carried out in our laboratory did not show any difference in our experimental models between rabbit- and human-labeled fibrinogen. Bovine thrombin (RHT 19, lot No. 506009 A) was obtained from Istituto Behring, L’Aquila, Italy, and human thrombin (Ortho Q.F.A., lot No. QFA69) was obtained from Ortho, Milan, Italy. As bovine and human thrombin used to produce experimental thrombi gave identical results in this model in preliminary experiments, bovine thrombin was used in the experiments reported in this article.
All animal studies were performed on New Zealand rabbits and conformed to the guidelines of the American Physiological Society and the Animal Model Subcommittee of the International Society of Thrombosis and Haemostasis. The study was performed in compliance with the animal welfare regulations of the University of Perugia.
Thrombus gmwth-inhibition model: Thrombus growth after a bolus dose of rt-PA was assessed as accretion of “I-fibrinogen onto autologous preformed thrombi. The standard-size nonradioactive thrombi were produced in the external jugular veins of rabbits (weight, 2.5 ±0.1 kg), as previously described.