Evaluation of an Adapted Murine Electrolytic Model of Venous Injury in Wistar Rats: Histopathological Characterization and Challenges in Model Adaptation.

Introduction Murine models are widely used in deep vein thrombosis biomedical studies. The principal large-vessel models include ligature-based and free radical thrombosis models (e.g., the ferric chloride or electrolytic models), with the inferior vena cava and femoral vein being the most commonly used vessels. The femoral vein represents an attractive model target due to surgical accessibility and translational relevance, considering its valve-containing structure and thrombus formation in the direction of blood flow after electrolytic injury. Although mice are the most common experimental animals, laboratory rats offer the advantage of larger and more accessible vascular structures. Therefore, this study aimed to adapt an electrolytic injury model in Wistar rats and to perform a preliminary histopathological characterization of the resulting vascular response, including thrombotic findings. Materials and methods A prospective, interventional, exploratory study was conducted on 24 female Wistar rats, aged 15 months, following institutional and regulatory approvals. Animals were allocated into sham control (n=4), electrolytic injury control (n=4), and two treated electrolytic injury groups receiving enoxaparin or rivaroxaban (n=8 each). The electrolytic injury consisted of a direct electrical current (3 Volts, 90 seconds) applied to the exposed surface of the femoral vein. Animals in the electrolytic injury control group were euthanized on day 1, while sham and treated animals were euthanized on day 7. Vascular samples underwent histopathological analysis (hematoxylin-eosin and van Gieson elastica stains). Based on recorded findings, two novel semiquantitative scores were developed: the venous wall injury score (VWIS) and the inflammation score (IS). The scores were further compared between treatment groups and between samples with and without detected thrombus. Results The main histopathological findings included changes in all vascular layers, occasional necrosis, and mural and/or perivascular inflammatory infiltrates of variable severity. Thrombus presence was detected in one out of four animals from the electrolytic injury control group one day after the procedure, and in five out of 16 animals from the treatment electrolytic injury group seven days after the procedure. Comparison of VWIS and IS at day 7 showed no statistically significant differences between enoxaparin- and rivaroxaban-treated rats. However, VWIS at day 7 was significantly higher in samples containing thrombus compared to those without detected thrombus. Conclusion This pilot exploratory study developed and evaluated a modified electrolytic model of venous thrombosis in Wistar rats. The model induced histopathological changes in both the femoral artery and vein, with variable thrombus occurrence, and inflammatory modifications of the venous wall and perivascular tissue. Thrombi detection was associated with a significantly higher VWIS. Further standardization and validation using larger sample groups, different time points, and various model-related conditions (electrical current parameters and therapeutic management), supported by in vivo thrombus visualization techniques, are required for reproducible thrombus induction and reliable treatment comparisons.