Antivascular endothelial growth factor therapy prevents peritoneal adhesion formation without adversely affecting wound strength or anastomotic integrity

Abstract

Abstract Background Postoperative intra-abdominal adhesion formation remains a significant cause of complications in surgical patients. To date, no agent has been shown consistently to block adhesion formation; preliminary evidence has shown that intra-abdominal adhesion formation is angiogenesis dependent. Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis and promotes vascular leakage. This study determined whether a specific VEGF monoclonal antibody (mAb) could prevent postoperative adhesion formation without affecting wound and anastomotic integrity. Methods After developing a standardized peritoneal injury which resulted in a reproducible adhesion model, 40 CD-1 mice were randomized and treated intraperitoneally with either VEGF mAb (n = 20) or immunoglobulin (Ig) G isotype control mAb (n = 20) at the time of abdominal closure. Animals (n = 10 per group) were killed on postoperative day 14, and the development of intra-abdominal adhesions was determined and graded blindly using well established criteria. Animals (n = 10 per group) were also killed 10 days after operation, and laparotomy wounds and gastrointestinal anastomoses were assessed by tensiometry. Statistical analyses were performed using the Mann–Whitney and Fisher's exact tests. Results Treatment with VEGF mAb resulted in a significantly lower incidence of adhesion formation compared with control animals (P < 0·001). Furthermore, intergroup analysis for the presence of marked adhesions (grade 2 or 3) demonstrated that mice treated with VEGF mAb had a significantly lower incidence of advanced adhesions compared with controls (10 versus 90 per cent). Laparotomy wound and gastrointestinal anastomotic strength were similar between groups. Conclusion This study demonstrates that the formation of postoperative intra-abdominal adhesions is attenuated following the administration of VEGF mAb without adversely affecting wound strength or anastomotic integrity.