Affiliations: 2nd Medical Clinic, University Medical Center Mainz, Mainz, Germany | Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany | Department of Dermatology, University Medical Center Mainz, Mainz, Germany | German Heart Center and 1st Medical Clinic, Technical University Munich (TUM), Munich, Germany
Note: [] M.B. and T.S. contributed equally to the study and should therefore both be regarded as first authors.
Note: [] M.B. and T.S. contributed equally to the study and should therefore both be regarded as first authors.
Note: [] Corresponding author: Philip Wenzel MD, University Medical Center Mainz, 2nd Medical Clinic and Junior Group “Vascular Biology”, Center for Thrombosis and Hemostasis, Langenbeckstr. 1, 55131 Mainz, Germany. Tel.: +49 6131 170; Fax: +49 6131 179960; E-mail: wenzelp@uni-mainz.de
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.
Keywords: Deep vein thrombosis, mouse model, high frequency ultrasound, side branches
