Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Surgery, Adhesion formation, Laparoscopy, Mouse model, PAI-1 antibodies, Reteplase, r-PA, CARBON-DIOXIDE PNEUMOPERITONEUM, TISSUE-PLASMINOGEN-ACTIVATOR, ENDOTHELIAL GROWTH-FACTOR, INHIBITOR TYPE-1, TRANSGENIC MICE, POSTSURGICAL ADHESIONS, MONOCLONAL-ANTIBODY, ENHANCED ADHESIONS, RABBIT MODEL, THROMBOLYSIS, Animals, Disease Models, Animal, Female, Fibrinolytic Agents, Infusions, Parenteral, Mice, Mice, Inbred BALB C, Plasminogen Activator Inhibitor 1, Pneumoperitoneum, Artificial, Recombinant Proteins, Tissue Adhesions, Tissue Plasminogen Activator, 1103 Clinical Sciences, 3202 Clinical sciences

Abstract:

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.