Thrombosis with outflow obstruction delays thrombolysis and results in chronic wall thickening of rat veins.
OBJECTIVE
An in vivo model of acute deep venous thrombosis was developed in rats to assess the role of venous thrombosis and outflow obstruction in recanalization and development of secondary wall changes.


METHODS
The left femoral veins of male Sprague-Dawley rats were thrombosed either by means of proximal ligation (obstruction, group A, n = 38) or by means of temporary 24-hour occlusion with a microvascular clamp (unobstructed, group B, n = 20). Right femoral veins served as controls. The rats were killed at intervals over 5 weeks. Wall thickness was compared among groups by means of counting of cells on representative sections through the midvein area. Thrombi were indirectly quantitated with a radiolabeled fibrinogen assay in a parallel series of rats.


RESULTS
Control veins showed no evidence of cellular or structural changes. Early thrombus extension was seen in group A (peak at day 4) followed by recanalization after 2 weeks. Group A veins had marked wall thickening (27 +/- 7 vs 6 +/- 2 cells, p < 0.01, peak at 10 days) consisting of smooth muscle-type, neointimal, and medial cellular proliferations. Within 2 to 3 weeks, local neovascular channels had grown to bypass the outflow obstruction, and resumption of normal cephalad flow was seen. At the same time neointimal proliferation regressed, but medial cellular growth persisted, resulting in chronic wall thickening (11 +/- 3 vs 5 +/- 1 cells, p < 0.01, after 21 days). In contrast, group B veins exhibited no thrombus extension, had significantly less wall thickening (13 +/- 2 vs 5 +/- 1 cells, p < 0.01, peak at 4 days), and did not induce growth of local collateral blood vessels. Within 2 weeks, group B veins regained normal appearance and resumed normal flow.


CONCLUSIONS
Thrombosis of rat femoral veins without chronic obstruction results in rapid lysis of thrombus and transient proliferative changes. In contrast, thrombosis with chronic outflow obstruction results in delayed recanalization, early extension of thrombus, and development of vigorous and persistent proliferative cellular responses. Thrombus-induced chronic wall thickening may be an important factor in development of postthrombotic venous insufficiency.
Division of Vascular Surgery, Stanford University School of Medicine, Calif 94305-5450, USA.
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See-Tho
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Harris
D000818:Animals; D002455:Cell Division; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D014680:Veins / Q000473:pathology*