Laparoscopic-type environment enhances mesothelial cell fibrinolytic activity in vitro via a down-regulation of plasminogen activator inhibitor-1 activity.
BACKGROUND
Fewer intraperitoneal adhesions have been observed after laparoscopic surgery compared with conventional techniques. The aim of this study is to assess the effect of the pneumoperitoneum on mesothelial cell fibrinolytic activity by use of an in vitro model.


METHODS
Human peritoneal mesothelial cells were seeded onto 24-well plates and incubated in carbon dioxide or helium at 5 mm Hg for 4 hours or standard culture conditions. Supernatant was removed for analysis at 0, 24, 48, and 72 hours after gas incubation and analyzed for plasminogen activator activity, total tissue plasminogen activator (tPA), and total plasminogen activator inhibitor-1 (PAI-1) concentrations by use of an enzyme-linked immunosorbent assay. The effect of different insufflation pressures (0, 7, and 14 mm Hg) was also examined.


RESULTS
Enhanced plasminogen activator activity was observed at 48 hours and 72 hours from cells exposed to CO(2) (P<.04 each) and helium (P<.05 each) compared with control. This was associated with a decrease in PAI-1 concentrations at 48 and 72 hours in both the CO(2) and helium groups compared with control (P<.03 each, CO(2) vs control; and P<.04 each, helium vs control). No changes in tPA levels were observed. Changes in insufflation pressures did not affect plasminogen activator activity.


CONCLUSIONS
These results suggest that incubation of human mesothelial cells with both CO(2) and helium in the absence of oxygen enhances mesothelial cell fibrinolytic activity because of a reduction in PAI-1 concentrations. These changes may participate in the observed reduction in adhesions after laparoscopic surgery relative to open surgery.
Ziprin
Paul
P
Department of Surgical Oncology and Technology, Imperial College School of Medicine, 10th Floor QEQM Building, St. Mary's Hospital, Praed Street, London W2 1NY, United Kingdom.
Ridgway
Paul F
PF
Peck
David H
DH
Darzi
Ara W
AW
D002245:Carbon Dioxide / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D004847:Epithelial Cells / Q000502:physiology*; D005342:Fibrinolysis; D006371:Helium / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D010535:Laparoscopy; D010532:Peritoneal Diseases / Q000517:prevention & control*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D000267:Tissue Adhesions; D010959:Tissue Plasminogen Activator / Q000032:analysis
D017395:Plasminogen Activator Inhibitor 1; D002245:Carbon Dioxide; D006371:Helium; D010959:Tissue Plasminogen Activator