title: Development of an experimental model of pre-thrombosis in rats based on Wessler's principle using a calibrated venous stasis.
abstract: We have developed a model of a pre-thrombotic state in rats based on venous stasis induced by partial ligature of the inferior vena cava. The degree of stenosis was calibrated by using variations in upstream venous pressure. Different degrees of stasis were tested in order to obtain a pre-thrombotic state. Increasing doses of thromboplastin were infused. The thrombogenic potential of this model was evaluated by measuring thrombus weight and by the increase in levels of thrombin-antithrombin complexes. A pre-thrombotic state was induced by 2 h of exposure to a 40% stasis obtained by increasing by 40% the upstream venous pressure (mean thrombus weight, 0.2 +/- 0.6 mg). In these conditions of stasis, low doses of thromboplastin induced venous thrombosis (mean weight, 23 +/- 20 mg; P < 0.05). The increase in thrombus size was correlated to the rise in thrombin-antithrombin levels (r = 0.53, P < 0.001). In conclusion, we have developed the first animal model in which venous stasis can be calibrated by varying the degree of stenosis of the inferior vena cava. This model could be used to study the kinetics of biological markers of hypercoagulability, to study the pathogeny of thrombosis or to evaluate the therapeutic efficacy of new drugs in pre-clinical trials.
authors.affiliation: Service de Médecine Interne A, Hôtel Dieu, CHU Nantes, Nantes Cedex, France. pierre.pottier@sante.univ-nantes.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Pottier
authors.forename: Bernard
authors.initials: B
authors.lastname: Planchon
authors.forename: Flôrence
authors.initials: F
authors.lastname: Truchaud
authors.forename: Georges
authors.initials: G
authors.lastname: Leftheriotis
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Herbert
authors.forename: Luc
authors.initials: L
authors.lastname: Bressolette
authors.forename: David
authors.initials: D
authors.lastname: Trewick
authors.forename: Norbert
authors.initials: N
authors.lastname: Passuti
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002138:Calibration; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D029968:Escherichia coli Proteins / Q000097:blood; D006487:Hemostasis / Q000187:drug effects; D006490:Hemostatics / Q000008:administration & dosage / Q000494:pharmacology; D026901:Membrane Transport Proteins / Q000097:blood; D051381:Rats; D019851:Thrombophilia / Q000139:chemically induced; D013925:Thromboplastin / Q000008:administration & dosage / Q000494:pharmacology; D013927:Thrombosis / Q000139:chemically induced; D014680:Veins; D014682:Vena Cava, Inferior
chemical_list: D029968:Escherichia coli Proteins; D006490:Hemostatics; D026901:Membrane Transport Proteins; C408585:twin-arginine translocase complex, E coli; D013925:Thromboplastin