title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: 2nd Medical Clinic, University Medical Center Mainz, Mainz, Germany Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.
authors: Moritz
authors: M
authors: Brandt
authors: Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.
authors: Tanja
authors: T
authors: Schönfelder
authors: Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany Department of Dermatology, University Medical Center Mainz, Mainz, Germany.
authors: Melanie
authors: M
authors: Schwenk
authors: Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany Department of Dermatology, University Medical Center Mainz, Mainz, Germany.
authors: Christian
authors: C
authors: Becker
authors: Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.
authors: Sven
authors: S
authors: Jäckel
authors: Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.
authors: Christoph
authors: C
authors: Reinhardt
authors: German Heart Center and 1st Medical Clinic, Technical University Munich (TUM), Munich, Germany.
authors: Konstantin
authors: K
authors: Stark
authors: German Heart Center and 1st Medical Clinic, Technical University Munich (TUM), Munich, Germany.
authors: Steffen
authors: S
authors: Massberg
authors: 2nd Medical Clinic, University Medical Center Mainz, Mainz, Germany Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.
authors: Thomas
authors: T
authors: Münzel
authors: German Heart Center and 1st Medical Clinic, Technical University Munich (TUM), Munich, Germany.
authors: Marie-Luise
authors: ML
authors: von Brühl
authors: 2nd Medical Clinic, University Medical Center Mainz, Mainz, Germany Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.
authors: Philip
authors: P
authors: Wenzel
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014682:Vena Cava, Inferior / Q000473:pathology / Q000503:physiopathology*; D020246:Venous Thrombosis / Q000473:pathology / Q000503:physiopathology*
keywords: Deep vein thrombosis; high frequency ultrasound; mouse model; side branches