title: The electrolytic inferior vena cava model (EIM) to study thrombogenesis and thrombus resolution with continuous blood flow in the mouse.
abstract: Previously, we presented the electrolytic inferior vena cava (IVC) model (EIM) during acute venous thrombosis (VT). Here, we present our evaluation of the EIM for chronic VT time points in order to determine whether this model allows for the study of thrombus resolution. C57BL/6 mice (n=191) were utilised. In this model a copper-wire, inserted into a 25-gauge needle, is placed in the distal IVC and another subcutaneously. An electrical current (250 μAmp/15 minutes) activates the endothelial cells, inducing thrombogenesis. Ultrasound, thrombus weight (TW), vein wall leukocyte counts, vein wall thickness/fibrosis scoring, thrombus area and soluble P-selectin (sP-sel) were performed at baseline, days 1, 2, 4, 6, 9, 11 and 14, post EIM. A correlation between TW and sP-sel was also determined. A thrombus formed in each mouse undergoing EIM. Blood flow was documented by ultrasound at all time points. IVC thrombus size increased up to day 2 and then decreased over time, as shown by ultrasound, TW, and sP-sel levels. TW and sP-sel showed a strong positive correlation (r=0.48, p<0.0002). Vein wall neutrophils were the most common cell type present in acute VT (up to day 2) with monocytes becoming the most prevalent in chronic VT (from day 6 to day 14). Thrombus resolution was demonstrated by ultrasound, TW and thrombus area. In conclusion, the EIM produces a non-occlusive and consistent IVC thrombus, in the presence of constant blood flow, allowing for the study of VT at both acute and chronic time points. Thrombus resolution was demonstrated by all modalities utilised in this study.
authors.affiliation: Department of Surgery, Section of Vascular Surgery, Conrad Jobst Vascular Research Laboratories, University of Michigan, North Campus Research Complex (NCRC), 2800 Plymouth Road, B26, R251N, Ann Arbor, MI 48105-0654, USA. josediaz@med.umich.edu
authors.forename: Jose A
authors.initials: JA
authors.lastname: Diaz
authors.forename: Christine M
authors.initials: CM
authors.lastname: Alvarado
authors.forename: Shirley K
authors.initials: SK
authors.lastname: Wrobleski
authors.forename: Dallas W
authors.initials: DW
authors.lastname: Slack
authors.forename: Angela E
authors.initials: AE
authors.lastname: Hawley
authors.forename: Diana M
authors.initials: DM
authors.lastname: Farris
authors.forename: Peter K
authors.initials: PK
authors.lastname: Henke
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Wakefield
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Myers
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D003300:Copper / Q000737:chemistry; D004195:Disease Models, Animal; D004558:Electric Stimulation; D007249:Inflammation; D007962:Leukocytes / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology; D019007:P-Selectin / Q000097:blood; D010690:Phlebography; D013927:Thrombosis / Q000473:pathology* / Q000628:therapy*; D013997:Time Factors; D014682:Vena Cava, Inferior / Q000473:pathology*; D020246:Venous Thrombosis
chemical_list: D019007:P-Selectin; D003300:Copper