A computational analysis of an in vitro vessel wall injury model

Implantation of vascular grafts or stents causes significant injury to the vessel wall. Activated coagulation factors, such as FXa are generated at the injury site. The size of the injury and the flow conditions influence the transport of these activated factors. A simulation model has been developed to evaluate surface bound coagulation inhibitors on medical devices. Tissue factor pathway inhibitor (TFPI) isa potent inhibitor of FXa in vivo. This physiologically relevant in vitro model studies the mechanism by which immobilized rTFPI effectively inhibits TF initiated thrombosis.Computational fluid dynamics was used to develop the model and validated by experiments performed in a parallel plate flow chamber. The lower plate was divided into two zones. The first zone represents fibroblasts that catalyze FXto FXa by TF-FVIIa. The second represents passively absorbed surface bound rTFPI. The efficacy of rTFPI in inhibiting FXa from the injury site was studied under both venous and moderate arterial shear rates. This model extends a previous model to include a more physiologic model of vessel wall injury in which FXa generation by TF:VIIa occurs at the wall upstream of the TFPI coated surface. The previous model estimated a uniform inlet FXa concentration of 20 nM (20% conversion of the approximate physiologic concentration of 100 nM) to the parallel plate chamber.