SURGERY 365 DEEP VENOUS THROMBOSIS (DVT) is a significant health problem that affects approximately 5 mil- lion people per year. 1 Chronic venous insufficiency (CVI) is a debilitating problem often resulting from the post-inflammatory sequelae of DVT, and presenting as skin ulceration, hyperpigmentation, and stasis dermatitis. The pathophysiology underly- ing these clinical manifestations is thought to be vein wall fibrosis rendering the vein wall noncom- pliant and valves incompetent, as suggested by a longitudinal duplex study. 2 Thrombosis and inflammation are directly inter- related and are mediated in part by cell adhesion molecules (CAMs) such as P- and E-selectin. 3-7 CAMs are involved with leukocyte rolling, adherence, and transmigration into an area of inflammation, and the cellular mediators that direct this process are many. Furthermore, P selectin is directly involved in early thrombosis, mediating leukocyte-platelet, leukocyte- endothelial, and leukocyte-leukocyte interactions, and has been termed a procoagulant factor. 8 Recent- ly, low molecular weight heparin (LMWH) has been shown to confer some of its anti-inflammatory prop- erties by its anti–P-selectin activity. 9 Prior work in a rat model of deep vein thrombosis (DVT) has shown that LMWH has anti-inflammatory effects at nonan- ticoagulant dosages. 10 Promising work using either P-selectin antibody or P-selectin receptor antagonism (eg, recombi- nant P-selectin glycoprotein ligand, rPSGL-Ig) has been associated with decreased perithrombotic inflammation, increased thrombus dissolution, and decreased vein wall fibrosis. 3-5 However, the media- tors and mechanisms associated with this beneficial effect have not been determined, nor is it clear P-selectin inhibition decreases post- thrombotic vein wall fibrosis in a rat model Porama Thanaporn, BSE, Daniel D. Myers, DVM, Shirley K. Wrobleski, BS, Angela E. Hawley, MS, Diana M. Farris, LVT, Thomas W. Wakefield, MD, and Peter K. Henke, MD, Ann Arbor, Mich Background. Post–deep vein thrombosis (DVT) venous insufficiency is a vexing problem despite effective anticoagulation, and is characterized by vein wall fibrosis. This study tested the hypothesis that P-selectin inhibition would decrease post–thrombotic vein wall fibrosis and associated profibrotic mediators. Methods. A rat stasis model of DVT was used to produce a 2-day-old DVT. Rats then received either intravenous saline (control), rPSGL-Ig (4 mg/kg) once, or daily subcutaneous low molecular weight heparin (LMWH) (0.5 mg/kg). Inferior vena cava wall was harvested 7 days after treatment and processed for thrombus size; leukocyte content; profibrotic mediators by enzyme-linked immunosorbent assay; collagen I and III mRNA expression by semiquantitative real-time polymerase chain reaction; and for collagen protein. Results. Thrombus mass and leukocyte counts were similar between the groups. Treatment with rPSGL-Ig and LMWH resulted in less vein wall collagen (P < .05). rPSGL-Ig treatment (and a similar trend for LMWH) was associated with decreased profibrotic mediators, including less IL-13, MCP-1, bFGH, and transforming growth factor-β (P < .05). Clollagen III gene expression, but not collagen I gene expression, was increased with LMWH treatment (P < .05). Conclusions. P-selectin inhibition with rPSGL-Ig or LMWH decreases post-DVT vein wall fibrosis, and is associated with decreased vein wall profibrotic mediators. This effect is independent of thrombus mass and vein wall leukocytes. (Surgery 2003; 134:365-71.) From the Section of Vascular Surgery, Department of Surgery, Jobst Vascular Laboratory and Unit for Labora- tory Animal Medicine, University of Michigan, Ann Arbor, Mich Presented at the 64th Annual Meeting of the Society of Univer- sity Surgeons, Houston, Texas, February 12-15, 2003. Supported in part by the Society for University Surgeons Junior Faculty Career Development Award (PKH), and the Lifeline Mentored Clinical Scientist Development Award, K08 HL 69780 (PKH) and HL 63148 (TWW). Reprint requests: Peter K. Henke, MD, Section of Vascular Surgery, Department of Surgery, University of Michigan, 2210 Taubman Center, Ann Arbor, MI 48109. © 2003 Mosby, Inc. All rights reserved. 0039-6060/2003/$30.00 + 0 doi:10.1067/msy.2003.249