The Postsurgical Inflammatory Ileus of the Colon: Differential Role of Kinetically Active Mediators
Abstracts
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Background: Inflammatory events within the small intestinal muscularis have been proposed to participate in the development of postoperative ileus. However, the underlying pathophysiological mechanisms in the colon, as the crucial component for recovery of gastrointestinal motor function after surgery, are still largely unknown. Aims: To define postoperative inflammatory changes within the colonic muscularis and to identify co-expressed kinetically active mediators with functional significance. Methods: SD-Rats (180-220g) underwent selective colonic manipulation or a combined small intestinal and colonic manipulation. Mediator mRNA expression was determined by real-time RT-PCR. Leukocyte extravasation was quantified in muscularis whole-mounts. In vivo transit and colonic motility was estimated using geometric center analysis (GC) and intralumenal pressure monitoring at 24 hours. In vitro circular muscle contractility was assessed in a standard organ bath. The functional relevance of iNOS and COX-2 inhibition was determined using DFU or L-NIL perfusion. Statistical analysis: unpaired Student t test, p<0.05, mean ? SEM. Results: Colonic manipulation resulted in a massive leukocyte recruitment and an increase in inflammatory mRNA expression in the colonic muscularis (IL-6: 46 fold, ICAM-1: 8 fold, MCP-1: 47 fold, COX-2: 12 fold, iNOS 764 fold). This inflammatory response was associated with a significant impairment of intestinal transit (GC=6.5 ? 0.7 versus 9.5 ? 0.3). After surgical manipulation the colonic contractile amplitudes were markedly diminished (> 50% compared to sham) and more variable in amplitude and frequency. Muscle strips from surgically manipulated colons compared to shams showed a significant impairment in the bethanechol stimulated contractile response (3.4 ? 0.6 versus 7.4 ? 1.4 grams/mm2/sec at 100 µmol/L). L-NIL significantly ameliorated colonic and small intestinal smooth muscle dysfunction whereas DFU only improved postoperative small intestinal circular muscle contractions. Conclusions: The results provide evidence for a surgically initiated inflammatory response within the colonic muscularis that contributes to postosurgical ileus. We demonstrate that the postoperative iNOS expression plays a key role in inhibiting colonic circular smooth muscle motor function. Furthermore, regional differences in the direct functional effects of COX-2 generated eicosanoids are clearly evident within the small and large intestines. |
