Topically applied tissue factor pathway inhibitor reduced intimal thickness of small arterial autografts in rabbits.

PURPOSE: The purpose of this study was to investigate whether topically applied tissue factor pathway inhibitor (TFPI) reduces intimal thickness and increases long-term patency of small arterial autografts in rabbits. METHODS: An entire 10-mm long section of the left femoral artery was harvested and immersed in saline solution (control group, n = 10), 100 IU/mL of heparin (heparin group, n = 15), or 40 microg/mL of TFPI (TFPI group, n = 15) for 15 minutes. Then the graft was interposed to the right femoral artery. Patency rates were determined by flow measurements throughout the time course of the study, and the grafts were analyzed for measurement of intimal thickness at 3 months after operation. Immunohistochemical analysis was performed to examine whether topically applied TFPI binds to endothelial cells of the grafts. RESULTS: Three-month postoperative patency rates were 10% in the control group, 47% in the heparin group, and 73% in the TFPI group. The TFPI group had a significantly higher patency rate than that of the control group (P <.005). Compared with the heparin group, the TFPI group had a significant reduction in intimal area (0.19 +/- 0.05 mm(2) vs 0.30 +/- 0.09 mm(2), P =.0051), in percentage of stenosis (35.7% +/- 7.7% vs 61.4% +/- 15.8%, P <.0001), and in intimal/media areas ratio (0.64 +/- 0.24 vs. 1.04 +/- 0.33, P =.0051). Immunohistologic analyses confirmed that topically applied TFPI bound to endothelial cells. CONCLUSION: These results indicate that topically applied TFPI reduces intimal thickness and increases long-term patency of small arterial autografts in rabbits.