Efficacy of barriers and hypoxia-inducible factor inhibitors to prevent CO(2) pneumoperitoneum-enhanced adhesions in a laparoscopic mouse model

Abstract

Study objective: To investigate the effects of hypoxia-inducible factor (HIF) inhibitors, flotation agents, barriers, and a surfactant on pneumoperitoneum-enhanced adhesions in a laparoscopic mouse model.

Design: Prospective randomized trial (Canadian Task Force classification I).

Setting: Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, Catholic University of Leuven.

Subjects: One hundred fourteen female BALB/c mice.

Interventions: Adhesions were induced during laparoscopy in BALB/c female mice. Pneumoperitoneum was maintained for 60 minutes with humidified CO(2). In 3 experiments the effects of HIF inhibitors such as 17-allylamino 17-demethoxygeldanamycin, radicicol, rapamycin, and wortmanin, flotation agents such as Hyskon and carboxymethylcellulose, barriers such as Hyalobarrier gel and SprayGel, and surfactant such as phospholipids were evaluated.

Measurements and main results: Adhesions were scored after 7 days during laparotomy. Adhesion formation decreased with the administration of wortmannin (p <.01), phospholipids (p <.01), Hyalobarrier Gel (p <.01), and SprayGel (p <.01).

Conclusions: These experiments confirm the efficacy of barriers and phospholipids to separate or lubricate damaged surfaces. They also confirm the role of mesothelial hypoxia in this model by the efficacy of the HIF inhibitor wortmannin.