Validation of a mouse adhesion reduction model using Seprafilm®

Introduction: Most initial trials of antiadhesion technologies are currently carried out in rats or rabbits. This paper describes a simple, reliable technique for producing intraperitoneal adhesions in the mouse. This model has been validated using a hyaluronan/carboxymethyl-cellulose (HA/CMC) barrier (Seprafilm®; Genzyme, Somerville, NJ) currently in clinical use. Methods: Adult, FVB mice were anesthetized with isoflurane. Celiotomy was performed in each mouse and the cecum and abdominal wall were abraded with sandpaper in a standardized manner. The mice either received no treatment or the cecum was wrapped in the HA/CMC membrane. Treatment groups were assigned, after abrasion, by coin toss. One (1) week later, the mice were euthanized and the adhesions were scored by two trained investigators blinded to the treatment group of each animal and the other investigator's adhesion score. Results: Maximum adhesion grades were significantly lower (p = 0.009, Wilcoxon rank-sum) for the HA/CMC group (median = 0; s = 1.21; n = 18) than for the control group (mean = 2; s = 0.85; n = 24). The risk of any adhesion formation for the HA/CMC group was only half (relative risk [RR] = 0.51, 95% confidence interval [CI] = 0.30-0.87) as large as the risk of adhesion formation in the control group. Eight (8) mice (16%) died during the experiment. The risk of death was 8 times higher for mice treated with HA/CMC membrane than for the controls (RR = 7.7; 95% CI = 1.0-57), suggesting that treatment with HA/CMC could have increased the risk of mortality. Conclusions: This simple technique for adhesion formation is reliable and allows fast throughput of animals. The extent of adhesion prevention with HA/CMC membrane suggests that trials of adhesion prevention technologies in this model system may mirror those seen in humans.