Liquid And Barrier Anti-adhesive Materials For Reducing Pelvic Adhesions In A Rabbit Doule Uterine Born Model: A Basic Research

Objective Randomized controlled prospective study using the rabbit double uterine horn model was carried out to assess time-course of pelvic adhesions, as well as, the effect of two different anti-adhesive materials in reducing adhesions compared with controls. The possible mechanisms of the anti-adhesive materials were also investigated. Materials and Methods 330 Japanese white rabbits underwent laparotomy followed by uterine horn incision. Two anti-adhesive materials were applied randomly to treatment animals versus controls. Animals were euthanized after 3 to 42 days at five time points. Adhesion formation was scored both grossly and histopathologically. Time-course of adhesion formation was also observed. NF immunohistochemical staining was used to identify nerve fibers. Peritoneal fluids were collected for detection of tPA concentrations using ELISA kits.Results1. The surgical procedure was smooth. Rabbit double uterine horn model helped evaluation of pelvic adhesions in a 3-dimension fashion. With the similarity of fibrinolytic system between the rabbit and human, rabbit double uterine horn model made the ideal model for assessment of postoperative adhesions following gynecological surgeries. Each of the three means—gauze abrasion, needle holder clamping and direct uterine incision could induce postoperative pelvic adhesions, among which direct uterine incision the best to mimic conditions after gynecological operations.2. Under normal circumstances, degradation of filmy fibrinous adhesions by locally released proteases of the fibrinolytic system occurs within 72 hours of injury. If disturbed, the fibrous adhesion would follow. And regeneration of the mesothelium is complete within 7 days. Collagen—an important matrix reaches its peak by day 14, therefore day 14 makes a good observation point for this component. Anti-adhesive materials are supposed to be absorbed completely by day 28, and their effect and disappearance can be confirmed at this time point. Whether their effect can be maintained after absorption of the anti-adhesive materials is investigated in 42 days.3. Within 7 days, extent and type of pelvic adhesions increased slightly, afterwards the extent reduced, while the type scores remained stable. Between 14～28 days, extent and type of the adhesions both progressed. Tenacity of adhesions increased during 3～14 days, and reached a plateau later on. But after 28 days, the tenacity decreased in a pattern similar to the previous two parameters. In histopathological examination, inflammation regressed with time. Fibrosis decreased in 28 days, but elevated slightly afterwards, while neovascularization remained stable since day 7.4. There were reductions in adhesion formation in 3 days when anti-adhesive materials was delivered. In 1 week and afterwards, fibrosis was less obvious in treatment groups. Barrier anti-adhesive material showed better results at some points, but at the end of 42 days the two materials were equally effective for reducing pelvic adhesions in the rabbit double uterine horn model.5. NF immunohistochemical staining confirmed the growth of nerve fibers into the adhesions in 1 week with a similar distribution pattern as neovascularization.6. tPA concentrations also changed with time, which reached its peak in 2 weeks.7. But investigation showed no significantly difference among the 3 groups when tPA concentrations in peritoneal fluids were concerned.Conclusions1. The animal model showed a good example of postoperative pelvic adhesions after direct uterine horn injury and thus made a suitable model for studying site-specific adhesions.2. Observation at 3 days,1 week,2 weeks,4 weeks and 6 weeks respectively provided a full picture of the adhesion formation process.3. Both gross and histopathological scores of the induced adhesions showed a time-course.4. Treatment groups showed significant reduction in adhesion scores compared to the control at several points, which confirmed their effectiveness through some different mechanisms.5. The growth of nerve fibers in pelvic adhesions may be the reason for postoperative pain.6. tPA concentrations in peritoneal fluids changed with time.7. However no significant difference was shown between treatment groups and the controls, implying regulation of fibrinolytic system might not be a mechanism for their adhesion preventing effect.