Selective jejunal manipulation causes postoperative pan-enteric inflammation and dysmotility

Abstract

Background and aims: Small bowel manipulation initiates an intense molecular and cellular inflammatory response within the jejunal muscularis, which causes ileus. The current objective was to investigate pan-enteric inflammatory molecular and functional motility alterations of the muscularis from the unmanipulated stomach and colon initiated by selective jejunal manipulation.

Methods: Rat jejunum was manipulated, and animals sacrificed between 0-24 hours. In vivo gastric emptying, gastrointestinal transit, and in vitro colonic circular muscle recordings were measured. Reverse-transcriptase polymerase chain reaction (RT-PCR) and electromobility shift assay (EMSA) of gastric, jejunal, and colonic muscularis extracts were performed. Whole mounts were histochemically stained for myeloperoxidase leukocytes.

Results: Surgical manipulation suppressed jejunal contractions that were significantly prevented by dexamethasone pretreatment. Selective jejunal manipulation also suppressed in vivo gastric emptying, gastrointestinal transit, and in vitro colonic circular muscle contractility. Nuclear factor interleukin-6 (NF-IL-6) was activated within the gastric and colonic muscularis. RT-PCR showed a 14.9-, 8.1-, and 11.4-fold up-regulation of IL-6 messenger RNA within the jejunal, gastric, and colonic muscularis, respectively. EMSA showed a 30.6-, 14.2-, and 20.8-fold increased activation of signal transducer and activator of transcription (STAT) proteins in jejunal, gastric, and colonic muscularis extracts, respectively. Tumor necrosis factor-alpha, cyclooxygenase-2, and inducible nitric oxide synthase showed a significant up-regulation in the manipulated jejunum, as well as the unmanipulated gastric and colonic muscularis. Neutrophils were significantly recruited into all gastrointestinal regions.

Conclusion: Selective small bowel manipulation leads to a molecular, cellular, and functional pan-enteric "field effect" phenomenon in the unmanipulated gastric and colonic muscularis.