Thrombolysis for experimental deep venous thrombosis maintains valvular competence and vasoreactivity

Purpose: Thrombolysis protects the structural and functional integrity of vein wall in an experimental model of acute deep venous thrombosis (DVT) immediately after treatment, but late sequelae have not been studied. We designed experiments to compare the effects of thrombolysis and surgical thrombectomy at 4 weeks after the treatment of DVT. Methods: DVT was produced bilaterally in male mongrel dogs by proximal and distal femoral vein ligation. Five dogs underwent sham operation. After 48 hours, the ligatures were removed, and the thrombosis was treated with either Fogarty balloon catheter thrombectomy (shear force, 60 g; n = 6) or catheter-directed urokinase infusion (4000 U/min for 90 minutes; n = 6). At 4 weeks, patency and valvular competence were determined by duplex ultrasound scanning. Thrombogenicity was studied by the measurement of radiolabeled fibrin and platelet deposition. Veins were explanted and prepared for histologic examination, scanning electron microscopy, and functional studies in organ chambers. Results: All veins were patent at 1 month. Recanalized thrombus was observed histologically in four (66%) thrombectomized veins, one (17%) thrombolyzed vein, and none of the sham-operated veins (P = .04). Scanning electron microscopy demonstrated similar luminal endothelial cell loss (11%- 25%) in all three groups. Platelet and fibrin depositions were not different among groups. Valvular incompetence (reflux duration, >0.5 sec) did not differ significantly in the groups (thrombectomized veins, 2 of 12 (17%); thrombolyzed veins, 0 of 12 (0%); P = NS). In organ chamber studies, endothelium-dependent relaxations to calcium ionophore, but not adenosine diphosphate, were inhibited by an antagonist of nitric oxide production after thrombectomy (P < .05, thrombectomy vs sham- and thrombolysis-treated veins). All veins relaxed to exogenous nitric oxide. Conclusion: Both thrombectomy and thrombolysis restored patency and achieved similar valvular competence. Surgical thrombectomy, however, resulted in more residual thrombus and contributed to changes in endothelium-mediated relaxations at 4 weeks. Thrombolysis maintained both structural integrity and endothelial function.