TNP-470 inhibits intraabdominal adhesion formation

Background/Purpose: Angiogenesis plays an integral role in wound healing an d tissue remodeling. The authors hypothesized that inhibition of angiogenes is would reduce intraabdominal adhesion formation. Methods: in 98 C57BL6/J mice, a 2-cm midline laparotomy was performed and a 5 mm(2) SILASTIC(R) (Dow Coming, Midland, MI) patch fixed to the right sid e 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 po stoperative days 10, 15, 35, and 55. Adhesions to the SILASTIC(R) (Dow Corn ing) patch were scored based on their extent, type, and tenacity. Angiogene sis was quantified digitally as the area of vascularized peritoneum over th e patch. Results: At day 10, when TNP-470 was stopped, the percentage of vascularize d 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 anim als were reduced at day 10 compared with controls (P <.05) and remained red uced off treatment at day 55. Conclusions: Angiogenesis appears to play an important role in the developm ent of intraabdominal adhesions, because the extent of early neovasculariza tion correlates with adhesion formation. Perioperative treatment with TNP-4 70, a potent endothelial cell inhibitor, reduced vessel ingrowth over the p atch and was associated with a sustained reduction in adhesion formation. J Pediatr Surg 35.. 189-196 Copyright (C) 2000 by W.B. Saunders Company.