[HTML][HTML] In vivo analysis of antithrombotic effectiveness of recombinant hirudin on microvascular thrombus formation and recanalization

F Roesken, B Vollmar, M Rücker, D Seiffge… - Journal of vascular …, 1998 - Elsevier
F Roesken, B Vollmar, M Rücker, D Seiffge, MD Menger
Journal of vascular surgery, 1998Elsevier
Purpose: This study was undertaken to evaluate in vivo the effect of recombinant hirudin (r-
hirudin [HBW 023]), a potent thrombin inhibitor, on the process of microvascular thrombus
formation and recanalization. Methods: Thrombosis was induced photochemically in distinct
arterioles (n= 25) and venules (n= 30) of the ear of 16 hairless hr/hr mice (8 to 10 weeks old,
25 to 30 g of body weight). r-Hirudin (1 mg/kg of body weight) was administered
intravenously directly before thrombus induction; saline-treated animals served as controls …
Purpose
This study was undertaken to evaluate in vivo the effect of recombinant hirudin (r-hirudin [HBW 023]), a potent thrombin inhibitor, on the process of microvascular thrombus formation and recanalization.
Methods
Thrombosis was induced photochemically in distinct arterioles (n = 25) and venules (n = 30) of the ear of 16 hairless hr/hr mice (8 to 10 weeks old, 25 to 30 g of body weight). r-Hirudin (1 mg/kg of body weight) was administered intravenously directly before thrombus induction; saline-treated animals served as controls. Thrombus formation (i.e., first platelet deposition at the endothelial lining [FPD]; inner luminal diameter reduction to 50% [D/2]; complete vessel occlusion [CVO]), vessel recanalization, microcirculatory parameters, and leukocyte-endothelial cell interaction were analyzed by means of intravital fluorescence microscopy.
Results
Hirudin significantly delayed the process of thrombus formation compared with saline-treated controls in both arterioles (FPD: 381 ± 80 vs 137 ± 25 seconds, P < 0.05; D/2: 627 ± 49 vs 501 ± 71 seconds; CVO: 925 ± 78 vs 854 ± 60 seconds) and venules (FPD: 173 ± 11 vs 59 ± 4 seconds; D/2: 342 ± 54 vs 228 ± 27 seconds; CVO: 541 ± 85 vs 344 ± 43 seconds; P < 0.05). In addition, r-hirudin-treated animals showed an increased rate of vessel recanalization at 24 hours after thrombus induction (arterioles: 54% [7 of 13] vs 0% [0 of 12], P < 0.05; venules: 77% [10 of 13] vs 53% [9 of 17]), whereas microcirculatory parameters and leukocyte-endothelial cell interaction were not affected.
Conclusion
Our data indicate that r-hirudin not only counteracts the process of thrombus formation but also promotes vessel recanalization, thus supporting its use in clinical microvascular surgery. (J Vasc Surg 1998;28:498-505.)
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