title: Role of the plasminogen system in basal adhesion formation and carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic mice.
abstract: 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.
  
  
  METHODS
  Prospective, randomized study.
  
  
  METHODS
  Academic research center.
  
  
  METHODS
  Seventy female wild-type and transgenic knockout mice for PAI-1 (PAI-1(-/-)), uPA (uPA(-/-)) or tPA (tPA(-/-)).
  
  
  METHODS
  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 pneumoperitoneum.
  
  
  METHODS
  Adhesions were blindly scored after 7 days. Concentrations of PAI-1 and tPA were measured by using enzyme-linked immunosorbent assay.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Surgical Technologies, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium. roger,molinas@uz.kuleuven.ac.be
authors.forename: Carlos Roger
authors.initials: CR
authors.lastname: Molinas
authors.forename: Osama
authors.initials: O
authors.lastname: Elkelani
authors.forename: Rudi
authors.initials: R
authors.lastname: Campo
authors.forename: Aernout
authors.initials: A
authors.lastname: Luttun
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Philippe Robert
authors.initials: PR
authors.lastname: Koninckx
mesh_terms: D000818:Animals; D002245:Carbon Dioxide; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D010535:Laparoscopy / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010537:Peritoneum / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011028:Pneumoperitoneum, Artificial / Q000009:adverse effects; D011446:Prospective Studies; D011897:Random Allocation; D018709:Statistics, Nonparametric; D000267:Tissue Adhesions / Q000378:metabolism* / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D002245:Carbon Dioxide; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator