TNP-470 inhibits intraabdominal adhesion formation

Abstract

Background/purpose: Angiogenesis plays an integral role in wound healing and tissue remodeling. The authors hypothesized that inhibition of angiogenesis would reduce intraabdominal adhesion formation.

Methods: In 98 C57BL6/J mice, a 2-cm midline laparotomy was performed and a 5 mm2 SILASTIC (Dow Corning, Midland, MI) patch fixed to the right side of the peritoneum. Mice were injected with normal saline (n = 54) or TNP-470, an inhibitor of angiogenesis (n = 44; 30 mg/kg every other day over 6 days before surgery until 10 days after surgery). Animals were killed on postoperative days 10, 15, 35, and 55. Adhesions to the SILASTIC (Dow Corning) patch were scored based on their extent, type, and tenacity. Angiogenesis was quantified digitally as the area of vascularized peritoneum over the patch.

Results: At day 10, when TNP-470 was stopped, the percentage of vascularized peritoneum over the patch was less in treatment animals than in controls (P = .004). At day 35, the patch in treatment animals was completely covered by vascularized peritoneum, similar to controls. Adhesions in TNP-470 animals were reduced at day 10 compared with controls (P<.05) and remained reduced off treatment at day 55.

Conclusions: Angiogenesis appears to play an important role in the development of intraabdominal adhesions, because the extent of early neovascularization correlates with adhesion formation. Perioperative treatment with TNP-470, a potent endothelial cell inhibitor, reduced vessel ingrowth over the patch and was associated with a sustained reduction in adhesion formation.