The pathophysiology of venous thrombosis is complex. One contributory limitation to unraveling the causes of this phenomenon is the lack of longitudinal animal models that can accurately recapitulate the human disease process (1, 2). The purpose of this study was to evaluate the clinical relevance of a mouse model of deep venous thrombosis (DVT) from both a histologic and physiologic perspective. A murine DVT model based on inferior vena cava (IVC) ligation was performed in the following manner. In C57BL/6 mice, A 4-0 surgical silk suture was securely placed around the IVC just below the lowest renal vein, and the ligature was tied to ensure complete ligation of the IVC. The formation of an IVC thrombus was evaluated using digital subtraction angiography at 1 day, 4 days, 7 days, and 30 days. Angiographic images were analyzed for size of thrombus and collateral formation. Tumor thrombus was also analyzed histology for composition. Complete ligation of the IVC resulted in infrarenal IVC thrombosis in the majority (18/20, 90%) of animals at 24 hours. Angiography at 1, 4, 7, and 30 days recapitulated the expected clinical findings of initial acute, expansile thrombus evolving into a diminutive IVC with extensive retroperitoneal and abdominal wall collaterals. Histologic analysis likewise confirmed expected maturation of thrombus over the same time period, with acute thrombus at early time points and collagen-rich, paucicellular tissue at delayed time points. Murine IVC ligation recapitulates human DVT disease progression; the ability to monitor change serially over time through angiography allows for longitudinal investigations into potential interventions to restore patency and evaluate collateral formation.
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Mandal et al. (2024) studied this question.
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