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.

Chronic Erythropoietin Treatment Decreases Post-Infarct Myocardial Damage in Rats without Venous Thrombogenic Effect

“…The peroperative parameters of the prethrombotic model were similar to those previously described [20, 21]. In rats with 50% stasis, we found smaller thrombi than those reported in our previously published study.…”

“…A blood sample for hematocrit measurement was taken on EDTA tube at the beginning of the experiment. A prethrombotic state was initiated according to a method previously published [20, 21]. The pressure in the right femoral vein was measured at t0 (bVP).…”

Short-term venous stasis influences routine coagulation testing

“…A wide spectrum of prothrombotic events develops during venous stasis, which culminates in an increased expression of tissue factor in the hypoxemic vasculature, especially in mononuclear phagocytes and smooth muscle cells [17]. Such a thrombogenic potential is mostly time-dependent, however, and usually requires up to 2 h to produce a definitive prethrombotic state [18]. Therefore, it is unlikely that a brief stasis, as induced by up to 3-min tourniquet placing, might be sufficient, at least acutely, to produce additional procoagulant responses and trigger clot formation, besides increasing the concentration of clotting factors.…”

Animal models of venous thrombosis

“…This model, developed in rats (28)(29)(30) and mice (31)(32)(33)(34)(35), involves complete and permanent occlusion of a major vein such as the IVC associated with sacrificing of all side branches distal to the left renal vein (Figure 1A,B). The venous stasis reduces venous flow in the IVC, which is verified by measuring proximal venous pressure (36). Many investigators have used this model to study the effect of antithrombotic interventional anticoagulants by measuring thrombus size and resolution.…”

“…This model is most suited for studying thrombus initiation by platelets interactions and coagulation factors (41). Similarly, this model can also be created in rats (36,43,44).…”