Role of vascular endothelial growth factor and placental growth factor in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic mice

Objective: To evaluate the role of vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) in adhesion formation after laparoscopic surgery. Design: Prospective, randomized study. Setting: Academic research center. Animal(s): Female wild-type mice and transgenic mice (n = 110), expressing exclusively VEGF-A(164) (VEGF-A(164/164)) or deficient for VEGF-B (VEGF-B-/-) or for PIGF (PIGF(-/-)). Intervention(s): Adhesions were induced during laparoscopy. To evaluate "basal adhesions" and "CO2 pneumoperitoneum-enhanced adhesions," the pneumoperitoneum was maintained for a minimum (10 minutes) or prolonged (60 minutes) period. The role of PIGF was also evaluated by administration of antibodies. Main Outcome Measurement(s): Adhesions were blindly scored after 7 days. Result(s): In all wild-type mice, CO2 pneumoperitoneum enhanced adhesion formation. In comparison with wild-type mice, basal adhesions were higher in VEGF-A(164/164) mice and similar in VEGF-B-/- and PIGF(-/-) mice. Pneumoperitoneum in did not enhance adhesions in any of these transgenic imice. The effects observed in PIGF(-/-) mice were confirmed in PIGF anti body-treated mice. Conclusion(s): The data demonstrate that the VEGF family plays a role in adhesion formation and confirm that CO2 pneumoperitoneum enhances adhesions. VEGF-A(164) has a direct role in basal adhesions. Absence of pneumoperitoneum-enhanced adhesions in VEGF-A(164/164), VEGF-B-/-, and PIGF(-/-) mice indicates up-regulation of VEGF-A(164), VEGF-B, and PIGF by CO2 pneumoperitoneum as a mechanism for pneumo-peritoneum-enhanced adhesion formation. (C) 2003 by American Society for Reproductive Medicine.