Endotoxin-vermittelte Dysfunktion der glatten Dünndarm-Muskulatur nach chirurgischen Dickdarmeingriffen

Abstract

BackgroundColonic surgery is associated with a significant delay in intestinal transit. Thus we investigated whether these changes are caused by the downstream barrier of the surgically damaged colon or by small intestinal muscularis alteration itself. Furthermore we evaluate the potential role of gut derived endotoxin in the development of postoperative intestinal dysfunction.Materials and MethodsSD-Rats and Toll-like receptor 4-knockout-mice underwent colonic manipulation. Isolated small intestinal transit was analyzed in animals with ileostomy. The perioperative emigration of intracolonic particles was investigated by lumenal injection of fluorescently labeled LPS and microspheres. The gut was decontaminated prior to manipulation using polymyxin Band neomycin. Mediator mRNA expression was determined by real-time RT PCR. Leukocyte extravasation was investigated in muscularis whole-mounts. In vitro circular muscle contractility was assessed in a standard organ bath. Statistical analysis: unpaired Student t test, p < 0.05, mean ± SEM.ResultsSelective colonic manipulation compared to sham resulted in a significant delay in small intestinal transit (ileostomy-rats). This delay was associated with leukocyte recruitment and an increase in inflammatory mRNA expression within the small intestinal muscularis at 3 hours: IL-6: 1752 fold, ICAM-1: 9 fold, MCP-1: 18 fold, COX-2: 3 fold, iNOS 12 fold). Preoperative gut decontamination prevented this inflammatory response (IL-6: 330 fold, ICAM-1: 5 fold, MCP-1: 6 fold, COX-2: 1 fold, iNOS 2 fold). The small intestinal muscularis after colonic manipulation presented with a 41% inhibition of contractile activity. In contrast, contractions of small intestinal muscle strips after decontamination and colonic manipulation were similar to controls (100 mM: 4.2 ± 0.5 g/mm2/s). Toll-like receptor 4-knockout-mice did not show a significant suppression in smooth muscle contractile activity following colonic surgery compared to control mice.ConclusionsSelective colonic manipulation initiates a distant inflammatory response in the small intestinal muscularis that contributes to postoperative ileus. Furthermore, the data provide evidence that gut derived bacterial products are mechanistically involved in the initiation of this remote inflammatory cascade.