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Background: Postoperative abdominal adhesions are a major cause of morbidity and mortality. We previously demonstrated the inhibitory effect of sunitinib, a receptor tyrosine kinase inhibitor, on adhesion formation in a murine model, and now investigate its effects in a rabbit model., Methods: Forty New Zealand White rabbits underwent a standard adhesion procedure. Preoperatively, animals were randomized to treatment with sunitinib or saline (control). Animals were treated with a total of 11 daily doses, 1 preoperative and 10 postoperative. One group of 20 animals (group 1) was humanely killed on postoperative day 10, and the other (group 2) on postoperative day 30. After killing, adhesions were scored and abdominal wounds were collected for tensile strength and microvessel density measurements., Results: Sunitinib-treated animals in group 1 had a mean tenacity score of 1.67 ± 0.29 compared with 3.60 ± 0.16 in control animals (P < .01). Similarly, the mean tenacity scores for sunitinib-treated and control animals in group 2 were 0.20 ± 0.20 and 2.70 ± 0.37, respectively (P < .01). The mean uterine involvement scores for sunitinib-treated and control animals in group 1 were 1.44 ± 0.29 and 3.70 ± 0.15, respectively (P < .01), and in group 2 were 0.10 ± 0.10 and 2.70 ± 0.45, respectively (P < .01). There were no differences in ultimate or modular wound tensile strength between sunitinib-treated and control animals., Conclusion: Sunitinib significantly reduces postoperative adhesions in a rabbit model. This therapy may improve postoperative adhesion-related morbidity and mortality., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Postoperative adhesions can cause serious complications after abdominal surgery. This study demonstrates the role of the cholinergic nervous system in the development of postoperative intestinal adhesion., Methods: Postoperative intestinal adhesion was induced by sprinkling talc on the small intestines of rats, and the adhesion rate, histology, and gastrointestinal transit were evaluated. To investigate the involvement of the cholinergic nervous system in postoperative intestinal adhesion, we evaluated choline acetyltransferase (ChAT) activity, muscarinic receptor density, and the preventive effect of a muscarine receptor agonist, bethanechol, on talc-induced intestinal adhesion in rats., Results: Histologic examination revealed inflammation in the intestinal adhesion regions, but no damage was seen in sham-operated rats. The rate of adhesion formation had significantly increased 3-7 days after surgery. The gastrointestinal transit was decreased by about 30% in the talc-induced intestinal adhesion rats. ChAT activity decreased by about 50% in adhesion regions. In contrast, the density of muscarinic receptors was higher in rats with talc-induced intestinal adhesions. Furthermore, bethanechol significantly prevented 30%-41% of adhesion formation in rats with talc-induced intestinal adhesions. This action was inhibited by subcutaneous injection of atropine., Conclusions: Postoperative intestinal adhesion affected the cholinergic nervous system as demonstrated by decreased ChAT activity and increased density of muscarinic receptors. These alterations of gastrointestinal function might be a cause of adhesion formation.

Background: Peritoneal injury sustained at laparotomy may evoke local inflammatory responses that result in adhesion formation. Peritoneal mast cells are likely to initiate this process, whereas vascular permeability/endothelial growth factor (VEGF) may facilitate the degree to which subsequent adhesion formation occurs., Methods: Mast cell deficient mice (WBB6F1-/-), along with their mast cell sufficient counterparts (WBB6F1+/+), underwent a standardized adhesion-inducing operation (AIS) with subsequent sacrifice and adhesion assessment 14 days later in a blinded fashion. Additional CD-1 and WBB6F1+/+, and WBB6F1-/- mice were killed 2, 6, 12, and 24 hours after operation for measurement of VEGF by ELISA in systemic serum and peritoneal lavage fluid. Two further groups of CD-1 mice underwent AIS and received either a single perioperative dose of anti-VEGF monoclonal antibody (10 mug/mouse) or a similar volume of IgG isotypic antibody and adhesion formation 2 weeks later was evaluated., Results: WBB6F1-/- mice had less adhesions then did their WBB6F1+/+ counterparts (median [interquartile range] adhesion score 3[3-3] vs 1.5[1-2] respectively; P < .003). Local VEGF release peaked 6 hours after AIS in both WBB6F1+/+ and CD-1 mice whereas levels remained at baseline in WBB6F1-/- mice. CD-1 mice treated with a single dose of anti-VEGF therapy during operation had less adhesions than controls (2[1.25-2] vs 3[2.25-3], P = .0002)., Conclusions: Mast cells and VEGF are central to the formation of postoperative intra-abdominal adhesions with mast cells being responsible, either directly or indirectly, for VEGF release into the peritoneal cavity after operation. In tandem with the recent clinical success of anti-VEGF monoclonal antibodies in oncologic practice, our observations suggest an intriguing avenue for research and development of anti-adhesion strategy.

Background: Postoperative peritoneal adhesion formation causes a multitude of disorders, including bowel obstruction and infertility., Methods: To test whether fibrin sealant inhibits adhesion formation, mice were given an intraperitoneal injection of talc (to induce adhesions) after which sealant was administered. Seven and 14 days later, the thickness of connective tissue between the fragmented mesothelium and the abdominal muscle was measured., Results: At both 7 and 14 days after talc administration, talc-treated mice had a 6-fold increase in connective tissue thickness over vehicle alone (P < .05). Although fibrin sealant alone failed to trigger peritoneal pathologic conditions, administration of sealant to talc-treated mice inhibited connective tissue deposition by 80% at 7 and 14 days (P < .05). Additionally, delaying fibrin sealant administration up to and including 72 hours after talc treatment results in comparable inhibition of connective tissue deposition, as does treatment immediately after talc exposure., Conclusions: This study demonstrates that fibrin sealant inhibits peritoneal inflammation and peritoneal adhesion formation with use of a quantitative assay of connective tissue deposition. In addition, this is the first report to document the administration of fibrin sealant into the closed abdomen. The success of these studies suggests that fibrin sealant will block peritoneal adhesions when administered laparoscopically. Finally, because fibrin sealant is therapeutic even when administered after the initiation of peritoneal inflammation, it suggests that it may be efficacious in patients who present with adhesions or those undergoing multiple operations.

Background: Peritoneal adhesions continue to be a significant cause of postoperative complications. Elucidating the origin of these adhesions has been hampered by the lack of a reproducible animal model. The purpose of this study was to create a standardized model in which a single, specific adhesion could be objectively measured. With this model the kinetics of adhesion formation were then evaluated. A variety of potential antiadhesive agents were then tested and compared., Methods: In this study a reproducible, quantitative rat model was developed that used uniform defects on the peritoneal wall and cecal surface. The resulting adhesions were subsequently scored, and their strength was measured with a tensiometer. An evaluation of the kinetics of peritoneal adhesion formation was obtained by using a timed removal of silicone elastomer sheeting held between the two injured surfaces. The following antiadhesive agents were evaluated: Ringer's lactate solution; dextran 70 (32%); modified carboxymethylcellulose (1.0% and 2.0%); an absorbable barrier of specially knitted material composed of oxidized regenerated cellulose; fibrin sealant; silicone elastomer film; and expanded polytetrafluoroethylene membrane., Results: Evaluation of the kinetics of peritoneal adhesion formation indicated that the susceptibility for adhesion formation was significantly decreased or eliminated after the first 36 hours. Evaluation of antiadhesion agents indicated that the magnitude of adhesion prevention was directly proportional to the agent's ability to remain at the site of injury during the critical period of adhesion formation. Permanent barriers (silicone elastomer film, expanded polytetrafluoroethylene membrane) provided the greatest antiadhesion effect but were not believed to be ideal agents because they remained at the site of injury well after the critical period of adhesion formation. The incidence of adhesion formation for the other agents was as follows: control (34 of 34), Ringer's lactate (12 of 12), absorbable barrier of knitted cellulose (10 of 10), 32% dextran 70 (8 of 12), 1% carboxymethylcellulose (6 of 12), fibrin sealant (4 of 9), and 2% carboxymethylcellulose (4 of 12)., Conclusions: The efficacy of antiadhesion agents appears to be related to the agent's viscosity, ability to coat the wound surface, and residence time at the site of injury. In this rat model an agent that remained on the injured surfaces for at least 36 hours after injury appeared to be more effective in reducing adhesion formation than an agent with a shorter residence time.