LOCAL IRRIGATION WITH TISSUE FACTOR PATHWAY INHIBITOR INHIBITS INTIMAL HYPERPLASIA INDUCED BY ARTERIAL INTERVENTIONS

Objective: To evaluate the capacity of local. irrigation with tissue f actor pathway inhibitor (TFPI) to inhibit vessels from neointimal lesi on formation following intimectomy or balloon angioplasty. Design: The common carotid arteries in New Zealand white rabbits were subjected t o either intimectomy or balloon angioplasty. Intervention: Before rest oring blood flow, the lumina of the vessels were irrigated with 1 mL o f Dulbecco phosphate-buffered saline either with TFPI (100 mu g/mL [TF PI group, n=10]) or without TFPI (control group, n=10). Main Outcome M easures: The area of neointimal. formation and the ratio of the intima l to medial areas (I/M) were determined from elastin-stained sections. Results: The area of neointima and the I/M ratio were not significant ly different at 2 weeks postoperatively. However, at 4 weeks, TFPI-tre ated vessels demonstrated a significant reduction in the neointimal le sion and the I/M ratio compared with those of controls, following both angioplasty and intimectomy. Transmission electron microscopy showed a lack of platelet aggregation and thrombus formation at the intimal s urface in the TFPI-treated vessels. Conclusions: Local irrigation with TFPI at the time of arterial interventional therapy inhibits intimal hyperplasia following either balloon angioplasty or intimectomy. We hy pothesize that TFPI binds to the injured vessel surface and inhibits t he cascade of thrombotic events that promote intimal hyperplasia.