Local irrigation with tissue factor pathway inhibitor inhibits intimal hyperplasia induced by arterial interventions

D. M. Brown, N. M. Kania, E. T. Choi, L. A. Lantieri, E. N. Pasia, T. C. Wun and R. K. Khouri
Department of Surgery, Washington University School of Medicine, St Louis, Mo., USA.

OBJECTIVE: To evaluate the capacity of local irrigation with tissue factor pathway inhibitor (TFPI) to inhibit vessels from neointimal lesion formation following intimectomy or balloon angioplasty. DESIGN: The common carotid arteries in New Zealand white rabbits were subjected to either intimectomy or balloon angioplasty. INTERVENTION: Before restoring blood flow, the lumina of the vessels were irrigated with 1 mL of Dulbecco phosphate-buffered saline either with TFPI (100 micrograms/mL [TFPI group, n = 10]) or without TFPI (control group, n = 10). MAIN OUTCOME MEASURES: The area of neointimal formation and the ratio of the intimal to medial areas (I/M) were determined from elastin-stained sections. RESULTS: The area of neointima and the I/M ratio were not significantly different at 2 weeks postoperatively. However, at 4 weeks, TFPI-treated vessels demonstrated a significant reduction in the neointimal lesion 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 surface 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 hypothesize that TFPI binds to the injured vessel surface and inhibits the cascade of thrombotic events that promote intimal hyperplasia.

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