Abstract 191: Endothelial Dysfunction Potentiates Deep Venous Thrombosis in a Mouse Model of Sepsis

Objective: Sepsis is a strong risk factor for the development of deep venous thrombosis (DVT). However, little is understood about the underlying pathobiology responsible for this phenomenon. This study was undertaken to evaluate the endothelial response of cellular adhesion molecules (CAM) involved in early thrombogenesis in a mouse model of sepsis. Methods: Wild-type mice underwent treatment with vehicle or LPS (10mg/kg), or followed by inferior vena cava (IVC) ligation to generate a venous thrombus (VT). Tissue and plasma were harvested at 2 hours post-intervention and were assessed for CAMs, thrombus size, and markers of extracellular DNA (NETs). Pre-treatment (12 hours prior and at time of thrombosis) with P/E selectin (sel) and ICAM exogenous inhibition was undertaken. Antibody depletion was accomplished in selected mice with anti-Ly6G antibody. To understand leukocyte trafficking to the vein wall under sepsis conditions, a separate group of animals underwent LPS or vehicle injection followed by intravital fluorescence microscopy of rhodamine-6G-labeled leukocytes. Results: Pre-thrombosis, IVC CAMs (P-sel p=0.15, E-sel, p Conclusions: In a mouse model of endotoxemia, CAM elevation and leukocyte trafficking occurs in the serum and local vein wall; and with stasis insult, larger VT form. Inhibitor experiments suggest that ICAM may be central to the sepsis related early VT, while PMNs and P/E sel may be less important. CAM inhibition may be a unique strategy to prevent sepsis-associated DVT.