Effect of Reteplase and PAI-1 antibodies on postoperative adhesion formation in a laparoscopic mouse model.
BACKGROUND
Postoperative adhesions remain an important clinical problem, accounting for infertility, chronic pain and bowel obstruction. Its prevention is still inadequate and overall poorly understood. The aim of this study was to investigate the effect of Reteplase (a recombinant plasminogen activator, r-PA) and of PAI-1 antibodies upon adhesion formation in a laparoscopic model.


METHODS
Pneumoperitoneum-enhanced adhesions were induced by performing a bipolar lesion in female BALB/c mice and by using pure and humidified CO(2) as insufflation gas for 60 min. In experiment 1, four doses of 0.125, 0.25, 0.5 and 1 mg/0.5 ml r-PA and one and two doses of 1 mg r-PA were administrated i.p. Two control groups were included, one without any treatment and the second one receiving four times 0.5 ml of saline. In experiment 2, four doses of 0, 1, 10 and 100 microg/0.5 ml r-PA were administrated i.p. In experiment 3, PAI-1 neutralising and non-neutralising antibodies were injected i.p. after performing the lesion on day 0 and days 2 and 4. Adhesions were scored after 7 days.


RESULTS
Adhesion formation was less with the administration of four doses of 1 microg r-PA (proportion, p < 0.04, Wilcoxon). An increase in adhesion formation was observed when higher number of doses and amounts of r-PA were used (Proc GLM, eight groups, two variables, p = 0.05 for the amount of r-PA and p < 0.02 for the number of doses administrated). No effect was observed with the PAI-1 antibodies.


CONCLUSIONS
Low-dose i.p. administration of rPA is effective in the prevention of adhesions in a laparoscopic mouse model.
Binda
Maria Mercedes
MM
Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium. Mercedes.Binda@gmail.com
Hellebrekers
Bart W J
BW
Declerck
Paul J
PJ
Koninckx
Philippe Robert
PR
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D007263:Infusions, Parenteral; D010535:Laparoscopy / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D017395:Plasminogen Activator Inhibitor 1 / Q000276:immunology*; D011028:Pneumoperitoneum, Artificial / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage; D000267:Tissue Adhesions / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*
D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; C087896:reteplase; D010959:Tissue Plasminogen Activator