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.


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.
Molinas
Carlos Roger
CR
Center for Surgical Technologies, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium. roger,molinas@uz.kuleuven.ac.be
Elkelani
Osama
O
Campo
Rudi
R
Luttun
Aernout
A
Carmeliet
Peter
P
Koninckx
Philippe Robert
PR
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
D017395:Plasminogen Activator Inhibitor 1; D002245:Carbon Dioxide; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator