A novel model of venous thrombosis in the vena cava of rabbits.
The objective of this study was to develop and validate a new experimental model of venous thrombosis in the rabbit. A 3-cm length of siliconized PE tubing was used as a veno-venous shunt inserted into the abdominal vena cava of anesthetized rabbits. The PE tubing contained six cotton threads which helped to restrict blood flow through the tubing and served as a foreign, thrombogenic surface upon which a thrombus could 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. The shunt can be removed making it possible to weigh the thrombus and/or 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 standard for comparison. Reproducibility of the technique was demonstrated 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 characteristics of venous thrombi. The low molecular weight heparin (LMWH) enoxaparin was used as an antithrombotic intervention to validate the model. Dose-dependent changes in time to occlusion and thrombus weight were achieved which paralleled alterations in coagulation parameters (thrombin time and activated partial thromboplastin time) and bleeding time determined with an ear bleeding technique. The veno-venous shunt model is easy to use, reproducible, and responds appropriately to an antithrombotic intervention, indicating that it should be useful for experimental evaluation of antithrombotic agents designed for venous thromboembolic disorders.
Chi
L
L
Vascular and Cardiac Diseases Section, Parke-Davis Pharmaceutical Research Division, Ann Arbor, Michigan 48105 USA. chil@aa.wl.com
Saganek
L J
LJ
Rogers
K L
KL
Mertz
T E
TE
Metz
A L
AL
Uprichard
A C
AC
Gallagher
K P
KP
D000818:Animals; D001760:Bleeding Time; D001777:Blood Coagulation; D004195:Disease Models, Animal; D017984:Enoxaparin / Q000008:administration & dosage / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D007813:Laparotomy; D008297:Male; D008854:Microscopy, Electron; D011817:Rabbits; D014683:Vena Cava, Superior / Q000473:pathology / Q000503:physiopathology*; D020246:Venous Thrombosis / Q000473:pathology / Q000503:physiopathology*
D017984:Enoxaparin; D005343:Fibrinolytic Agents