Update on the electrolytic IVC model for pre-clinical studies of venous thrombosis

Abstract

Essentials Three key updates are provided on the electrolytic inferior vena cava model (EIM). The originally described stimulator equipment has been discontinued; we developed an alternative. The fibrinolytic system and the current and time dependency of the EIM was characterized. EIM allows the investigation of the fibrinolytic system, critical for endovascular therapies. Background: The electrolytic inferior vena cava model (EIM) is a murine venous thrombosis (VT) model that produces a non-occlusive thrombus. The thrombus forms in the direction of blood flow, as observed in patients. The EIM is valuable for investigations of therapeutics due to the presence of continuous blood flow. However, the equipment used to induce thrombosis in the original model description was expensive and has since been discontinued. Further, the fibrinolytic system had not been previously studied in the EIM. Objectives: We aimed to provide an equipment alternative. Additionally, we further characterized the model through mapping the current and time dependency of thrombus resolution dynamics, and investigated the fibrinolytic system from acute to chronic VT. Results: A voltage to current converter powered by a direct current power supply was constructed and validated, providing an added benefit of significantly reducing costs. The current and time dependency of thrombus volume dynamics was assessed by MRI, demonstrating the flexibility of the EIM to investigate both pro-thrombotic and anti-thrombotic conditions. Additionally, the fibrinolytic system was characterized in EIM. Centripetal distribution of plasminogen was observed over time, with peak staining at day 6 post thrombus induction. Both active circulating plasminogen activator inhibitor-1 (PAI-1) and vein wall gene expression of PAI-1 peaked at day 2, coinciding with a relative decrease in tissue plasminogen activator and urokinase plasminogen activator. Conclusions: The EIM is a valuable model of VT that can now be performed at low cost and may be beneficial in investigations of the fibrinolytic system.