Deep vein thrombus formation induced by flow reduction in mice is determined by venous side branches

Abstract

BACKGROUND: Interaction between vascular wall abnormalities, inflammatory leukocytes, platelets, coagulation factors and hemorheology in the pathogenesis of deep vein thrombosis (DVT) is incompletely understood, requiring well defined animal models of human disease. METHODS AND RESULTS: We subjected male C57BL/6 mice to ligation of the inferior vena cava (IVC) as a flow reduction model to induce DVT. Thrombus size and weight were analyzed macroscopically and sonographically by B-mode, pulse wave (pw) Doppler and power Doppler imaging (PDI) using high frequency ultrasound. Thrombus size varied substantially between individual procedures and mice, irrespective of the flow reduction achieved by the ligature. Interestingly, PDI accurately predicted thrombus size in a very robust fashion (r² = 0.9734, p < 0.0001). Distance of the insertion of side branches from the ligature significantly determines thrombus weight (r² = 0.5597, p < 0.0001) and length (r² = 0.5441, p < 0.0001) in the IVC, regardless of the flow measured by pw-Doppler with distances <1.5 mm drastically impairing thrombus formation. Occlusion of side branches prior to ligation of IVC did not increase thrombus size, probably due to patent side branches inaccessible to surgery. CONCLUSION: Venous side branches influence thrombus size in experimental DVT and might therefore prevent thrombus formation. This renders vessel anatomy and hemorheology important determinants in mouse models of DVT, which should be controlled for.