PREVENTION OF POSTSURGICAL ABDOMINAL ADHESIONS BY POLYPEPTIDES

Sammanfattning: Peritoneal adhesions develop after almost all abdominal surgical interventions and represent an important cause of postoperative intestinal obstruction, abdominal discomfort and infertility. Postoperative adhesions can potentially be reduced by using different antiadhesive agents. In the present study, we hypothesized that a combination of oppositely charged polypeptides could effectively decrease abdominal adhesions. Various polypeptides, including lysozyme, polyglutamate, polylysine and combinations of these were evaluated as compared to hyaluronic acid. A standard wound on the parietal peritoneum in mice was used and the evaluated agents were administered immediately postoperatively. The length of the peritoneal adhesions to the injured area was measured and expressed in percentage of the wound length as evaluated after 7 days. Flow cytometry was performed to evaluate the effect on peritoneal macrophage survival and phagocytic function and Pick test was used to determine peroxide production in order to estimate toxicity and potential impairment of macrophage function. Peritoneal swabs, including the wound area, were stained in order to determine the peritoneal location and clearance of the polypeptides. Electron microscopy was performed to analyze the wound surface and the ultra-structural changes of the phagocytes in cell culture. A reduced dose of polylysine and polyglutamate and local application on the injured peritoneal site were tested prior to the use of polyarginine, representing a potential alternative to polylysine. An ileocolic anastomosis was performed under both ?clean? and ?septic? conditions in the rat. In the presence of tested polypeptides, abdominal adhesions, anastomosis leakage and burst pressure were analysed after 1, 3, 5 and 7 days in the clean anastomosis model and after 7 days in the septic model. The combination of polylysine and polyglutamate significantly reduced postsurgical peritoneal adhesions in all experimental groups. This combination was biodegradable and did not alter the basic functions of peritoneal macrophages and showed no direct cytotoxicity. The insoluble test material specifically adhered to the injured peritoneum, and increased colonic anastomosis safety during the first postoperative days. In conclusion, a strong mechanical connection of the polylysine and polyglutamate complex occurred to the wound, and by prolonged attendance on the surface resulted in an effective prevention against peritoneal adhesions.