Role of the plasminogen system in basal adhesion formation and carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic mice

Objective: To evaluate the role of plasminogen activator inhibitor-1 (PAI- 1), urokinase plasminogen activator (uPA), and tissue-type plasminogen activator (tPA) in adhesion formation after laparoscopic surgery. Design: Prospective, randomized study. Setting: Academic research center. Animal(s): Seventy female wild-type and transgenic knockout mice for PAI-1 (PAI-1(-/-)), uPA (uPA(-/-)) or tPA (tPA(-/-)). Intervention(s): Standardized lesions to induce peritoneal adhesions were performed during laparoscopy. To evaluate basal adhesions and pneumoperitoneum-enhanced adhesions, the pneumoperitoneum was maintained for 10 minutes or 60 minutes, respectively. Peritoneal biopsy samples were obtained during and after 60 minutes of carbon dioxide prieumoperitoneum. Main Outcome Measure(s): Adhesions were blindly scored after 7 days. Concentrations of PAI-1 and tPA were measured by using enzyme-linked immunosorbent assay. Result(s): In PAI-1, uPA, and tPA wild-type mice, pneumoperitoneum, enhanced adhesions. Compared with wild-type mice, basal adhesions were fewer in PAI-1(-/-) mice and more in uPA(-/-) and tPA(-/-) mice. Pneumoperitoneum did not enhance adhesions in these transgenic mice. PAI-1 concentration increased after 60 minutes of pneumoperitoneum whereas tPA concentration did not change. Conclusion(s): Impaired fibrinolysis increases basal adhesions. The absence of pneumoperitoneum-enhanced adhesions in PAI-1(-/-), uPA(-/-), and tPA(-/-) mice and the increase in PAI-1 expression indicate that PAI-1 up-regulation by carbon dioxide pneumoperitoneum is a mechanism of pneumoperitoneum-enhanced adhesion formation. (C)2003 by American Society for Reproductive Medicine.