Murine model of large-vein electrolytic injury induction of thrombosis with slow resolution

Abstract

Deep vein thrombosis (DVT) and its sequela, pulmonary embolism, occur at a rate of 1 per 1000person/year. Experimental models for evaluation of DVT have many short-comings, such as mechanical occlusion or stenosis to cause thrombosis, rather than the clinical scenario of thrombosis causing occlusion/stenosis. The goal of this study was to develop a model of flow-based large-vein thrombosis with resistance to resolution, to model clinical DVT behavior. Adult male C57Bl/6 mice underwent thrombus induction via an electrolytic injury to the femoral vein (3V positive current for 90s), with subsequent intra-vital fluorescence quantitation of platelet and fibrin accumulation through the first 60min, and final histomorphometric volume evaluation at 1, 7, 14, and 28days. Platelet accumulation at the injury site was comparable to a milder electrolytic injury, whereas fibrin was greatly augmented by 60min in the more severe injury model. Thrombi showed persistent presence at 1 and 7days, with remodeling to a stenotic fibrosis that encroached into the lumen at 14 and 28days. The thrombotic/fibrotic volume within the femoral vein fell by 23% from 1 to 7days, but had a residual presence at 28days that was 31% the 1-day volume. This new model may provide an alternative approach to evaluating DVT persistence and therapeutic inhibition, to develop a better understanding of the clinical progression of DVT to thrombophlebitis.