Topical Tissue Factor Pathway Inhibitor Improves Free-Flap Survival in a Model Simulating Free-Flap Errors

ABSTRACT

Free flap failure is frequently due to tension, twisting, kinking, or compression of the vascular pedicle after the anastomosis is completed. A rabbit model simulating these errors was used to evaluate the capacity of topically-applied tissue factor pathway inhibitor (TFPI) to prevent microvascular thrombosis. The rabbit ear was isolated on the central artery and vein. The artery was transected, shortened, repaired, and twisted 360° around the vein. Immediately following the anastomosis, TFPI in concentrations of 1,4,10, or 40 μg/ml was irrigated across the lumen. Topically-applied control buffer and heparin (50 U/ml) were compared to TFPI. Treatment with control buffer resulted in a 20 percent survival rate Topically-applied heparin improved the survival rate to 60 percent (p <0.05). In contrast, TFPI in concentrations of 4,10, and 40 μg/ml yielded survival rates of 89,100, and 97 percent, respectively. This was significantly greater than the heparin-treated ears (p <0.05). TFPI in a concentration of 40 μg/ml was effective in preventing arterial thrombosis when applied for as little as 30 sec; 4 μg/ml was effective in preventing thrombosis when applied for 10 min. These results support the use of TFPI as a topical irrigation solution to help prevent microvascular arterial thrombosis in free-flap surgery.