Reduction of experimental adhesion formation by inhibition of plasminogen activator inhibitor type 1.
BACKGROUND
Adhesion formation is a common cause of complications following surgery. A reduction in peritoneal fibrinolytic capacity during operation is a key mechanism in the early formation of adhesions. An increase in the main inhibitor of fibrinolysis, plasminogen activator inhibitor type 1 (PAI-1), is a major factor in the loss of fibrinolytic activity. The aim of this study was to investigate if inhibition of PAI-1 could reduce the formation of adhesions after surgery.


METHODS
Mice (n = 53) were subjected to a standard surgical procedure in order to induce adhesion formation to the abdominal side wall. At the conclusion of the operation, fragments for antigen binding of polyclonal rabbit antibody against PAI-1 (PRAP-1) were injected intraperitoneally, at two different concentrations. Control animals received an equal volume of the vehicle (saline). One week after operation adhesion formation was quantified.


RESULTS
Both doses of PRAP-1 significantly reduced adhesion formation compared with the saline control (P = 0.003 and P = 0.002). There were no signs of bleeding in the postoperative period or at reoperation.


CONCLUSIONS
The present observations lend further support to the hypothesis of a pivotal role of fibrinolysis in the early formation of adhesions, and open up new possibilities for adhesion reduction by inhibiting PAI-1.
Falk
K
K
Department of Surgery, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden.
Björquist
P
P
Strömqvist
M
M
Holmdahl
L
L
D000818:Animals; D005260:Female; D051379:Mice; D010529:Peritoneal Cavity / Q000601:surgery*; D017395:Plasminogen Activator Inhibitor 1 / Q000008:administration & dosage*; D000267:Tissue Adhesions / Q000517:prevention & control*
D017395:Plasminogen Activator Inhibitor 1