Chi L, Saganek L J, Rogers K L, Mertz T E, Metz A L, Uprichard A C, Gallagher K P
Vascular and Cardiac Diseases Section, Parke-Davis Pharmaceutical Research Division, Ann Arbor, Michigan 48105 USA.
J Pharmacol Toxicol Methods. 1998 Jun;39(4):193-202. doi: 10.1016/s1056-8719(98)00024-0.
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.
本研究的目的是开发并验证一种新的兔静脉血栓形成实验模型。一段3厘米长的硅化聚乙烯（PE）管用作静脉 - 静脉分流器，插入麻醉兔的腹静脉。PE管内有六根棉线，有助于限制管内血流，并作为异物血栓形成表面，血栓可在其上形成。通过连续测量通过腔静脉的血流，可以监测血栓形成的速率，直到血流为零，表明存在完全闭塞性血栓。分流器可以取出，从而能够对血栓进行称重和/或确定其组成。可以在腔静脉中放置第二个分流器，以第二次确定闭塞时间和血栓重量，并将来自第一个分流器的数据用作内部对照标准进行比较。在一个对照组（n = 7）中证明了该技术的可重复性，该组在没有抗血栓干预的情况下使用了两个连续的分流器。在第一次和第二次分流器的研究中，闭塞时间平均分别为20.6±5.2分钟和20.2±5.7分钟（pNS）。净血栓重量（减去棉线湿重）分别为49.0±3.5毫克和47.0±3.3毫克（pNS）。血栓的组织学检查表明，它们主要由纤维蛋白和红细胞组成，与静脉血栓的特征一致。低分子量肝素（LMWH）依诺肝素用作抗血栓干预措施以验证该模型。实现了闭塞时间和血栓重量的剂量依赖性变化，这与凝血参数（凝血酶时间和活化部分凝血活酶时间）的变化以及用耳出血技术测定的出血时间平行。静脉 - 静脉分流模型易于使用、可重复，并且对抗血栓干预有适当反应，表明它对于设计用于静脉血栓栓塞性疾病的抗血栓药物的实验评估应该是有用的。
