A NOVEL MODEL OF VENOUS THROMBOSIS IN THE VENA-CAVA OF RABBITS

The objective of this study was to develop and validate a new experime ntal model of venous thrombosis in the rabbit. A 3-cm length of silico nized PE tubing was used as a veno-venous shunt inserted into the abdo minal vena cava of anesthetized rabbits. The PE tubing contained six c otton threads which helped to restrict blood now through the tubing an d served as a foreign, thrombogenic surface upon which a thrombus coul d develop. By continuously measuring blood flow through the vena cava, the rate of thrombus development can be monitored until zero flow is achieved indicating that a completely occlusive thrombus is present. T he shunt can be removed making it possible to weigh the thrombus and/o r determine its composition. A second shunt can be placed in the vena cava to make a second determination of time to occlusion and thrombus weight, using the data from the first shunt as an internal control sta ndard for comparison. Reproducibility of the technique was demonstrate d in a control group (n = 7) in which two successive shunts were used without an antithrombotic intervention. In studies with the first and second shunts, time to occlusion averaged 20.6 +/- 5.2 min and 20.2 +/ - 5.7 min (pNS), respectively. The net thrombus weights (less the wet weight of the cotton threads) were 49.0 +/- 3.5 mg and 47.0 +/- 3.3 mg (pNS). Histologic examination of the thrombi indicated that they were largely composed of fibrin and red blood cells, consistent with the c haracteristics of venous thrombi. The low molecular weight heparin (LM WH) enoxaparin was used as an antithrombotic intervention to validate the model. Dose-dependent changes in time to occlusion and thrombus we ight were achieved which paralleled alterations in coagulation paramet ers (thrombin time and activated partial thromboplastin time) and blee ding time determined with an ear bleeding technique. The veno-venous s hunt model is easy to use, reproducible, and responds appropriately to an antithrombotic intervention, indicating that it should be useful f or experimental evaluation of antithrombotic agents designed for venou s thromboembolic disorders. (C) 1998 Elsevier Science Inc.