Rys Ryan N, Blostein Mark D, Lemarié Catherine A
Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University.
Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University; Department of Medicine, Jewish General Hospital, McGill University.
J Vis Exp. 2018 Apr 13(134):57392. doi: 10.3791/57392.
Venous thrombosis is a common condition affecting 1 - 2% of the population, with an annual incidence of 1 in 500. Venous thrombosis can lead to death through pulmonary embolism or results in the post-thrombotic syndrome, characterized by chronic leg pain, swelling, and ulceration, or in chronic pulmonary hypertension resulting in significant chronic respiratory compromise. This is the most common cardiovascular disease after myocardial infarction and ischemic stroke and is a clinical challenge for all medical disciplines, as it can complicate the course of other disorders such as cancer, systemic disease, surgery, and major trauma. Experimental models are necessary to study these mechanisms. The stasis model induces consistent thrombus size and a quantifiable amount of thrombus. However, it is necessary to systematically ligate side branches of the inferior vena cava to avoid variability in thrombus sizes and any erroneous data interpretation. We have developed a non-invasive technique to measure thrombus size using ultrasonography. Using this technique, we can assess thrombus development and resolution over time in the same animal. This approach limits the number of mice required for quantification of venous thrombosis consistent with the principle of replacement, reduction, and refinement of animals in research. We have demonstrated that thrombus weight and histological analysis of thrombus size correlate with measurement obtained with ultrasonography. Therefore, the current study describes how to induce deep vein thrombosis in mice using the inferior vena cava stasis model and how to monitor it using high frequency ultrasound.
静脉血栓形成是一种常见疾病，影响着1%至2%的人群，年发病率为1/500。静脉血栓形成可通过肺栓塞导致死亡，或导致血栓后综合征，其特征为慢性腿痛、肿胀和溃疡，或导致慢性肺动脉高压，进而造成严重的慢性呼吸功能损害。这是仅次于心肌梗死和缺血性中风的最常见心血管疾病，对所有医学学科来说都是一项临床挑战，因为它会使其他疾病（如癌症、全身性疾病、手术和重大创伤）的病程复杂化。研究这些机制需要实验模型。淤滞模型可诱导出大小一致且数量可量化的血栓。然而，有必要系统性地结扎下腔静脉的侧支，以避免血栓大小出现差异以及任何错误的数据解读。我们开发了一种使用超声测量血栓大小的非侵入性技术。利用该技术，我们可以在同一只动物身上评估血栓随时间的发展和溶解情况。这种方法根据研究中动物替代、减少和优化的原则，限制了静脉血栓形成定量所需的小鼠数量。我们已经证明，血栓重量和血栓大小的组织学分析与超声测量结果相关。因此，本研究描述了如何使用下腔静脉淤滞模型在小鼠中诱导深静脉血栓形成，以及如何使用高频超声对其进行监测。
