Budnik Ivan, Kumskova Mariia, Thedens Daniel, Chauhan Anil K
Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.
Department of Radiology, University of Iowa, Iowa City, Iowa, USA.
Res Pract Thromb Haemost. 2025 Aug 13;9(6):103009. doi: 10.1016/j.rpth.2025.103009. eCollection 2025 Aug.
The inferior vena cava (IVC) stenosis model in mice is widely used in venous thrombosis research. However, high variability in thrombus size, reliance on discrete evaluation time points that vary across studies, and the absence of a unified measure of thrombus resolution dynamics hinder the preclinical assessment of candidate treatments designed to accelerate thrombus resolution.
To develop a methodological framework for assessing thrombus resolution dynamics in the IVC stenosis model.
Wild-type mice, neutrophil-specific integrin α9-deficient mice (α9Mrp8Cre), and littermate control (α9) mice were subjected to IVC stenosis. Thrombus resolution was monitored using magnetic resonance angiography on days 2, 7, 14, and 21 postsurgery in the same mouse cohorts. Linear and nonlinear (exponential decay) mixed-effects models were fitted to analyze thrombus resolution.
Ligation of the IVC back branches improved the consistency of thrombus formation in wild-type mice by reducing length variance, independently of surgeon variability. The proportional thrombus resolution rate in wild-type mice was 10.5% per day, with a time to half-maximum thrombus volume of 6.3 days (from day 2 postsurgery). Although neutrophil-specific integrin α9-deficient mice exhibited smaller initial thrombus volumes compared with controls, no difference in thrombus resolution dynamics was observed between the 2 mouse cohorts.
Integrating the IVC stenosis model enhanced by back-branch ligation with serial imaging and statistical modeling to derive unified thrombus resolution metrics-proportional resolution rate and time to half-maximum thrombus volume-provides a robust methodological framework. This framework may facilitate the design of preclinical trials using these metrics as standardized outcome measures.
小鼠下腔静脉（IVC）狭窄模型广泛应用于静脉血栓形成研究。然而，血栓大小的高变异性、依赖于不同研究中各不相同的离散评估时间点，以及缺乏统一的血栓溶解动力学测量方法，阻碍了旨在加速血栓溶解的候选治疗方法的临床前评估。
建立一种评估IVC狭窄模型中血栓溶解动力学的方法框架。
对野生型小鼠、中性粒细胞特异性整合素α9缺陷型小鼠（α9Mrp8Cre）和同窝对照（α9）小鼠进行IVC狭窄手术。在同一小鼠队列中，于术后第2、7、14和21天使用磁共振血管造影术监测血栓溶解情况。拟合线性和非线性（指数衰减）混合效应模型以分析血栓溶解情况。
结扎IVC后支可通过减少长度差异来提高野生型小鼠血栓形成的一致性，且与外科医生的差异无关。野生型小鼠的血栓比例溶解率为每天10.5%，血栓体积减半的时间为6.3天（从术后第2天开始）。虽然中性粒细胞特异性整合素α9缺陷型小鼠的初始血栓体积比对照组小，但在这两个小鼠队列之间未观察到血栓溶解动力学的差异。
将通过后支结扎增强的IVC狭窄模型与系列成像和统计建模相结合，以得出统一的血栓溶解指标——比例溶解率和血栓体积减半时间，提供了一个强大的方法框架。该框架可能有助于设计以这些指标作为标准化结局指标的临床前试验。
