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Abstract
Although the development of ileus is widespread and negatively impacts patient outcomes, the mechanism by which ileus develops remains unclear. The purpose of our study was to examine the contribution of myogenic mechanisms to postoperative ileus development and the involvement of inflammation in mediating intestinal smooth muscle dysfunction. Contractile activity and the effects of CXCL1 were studied in a gut manipulation model. Contraction amplitude in the ileum decreased significantly, while tone increased significantly in response to gut manipulation. Differences in contraction amplitude were affected by tetrodotoxin at earlier time points, but not at later time points. Agonist-induced contractions in the small intestine decreased significantly with ileus development. Intestinal transit slowed significantly after the induction of ileus. Myosin light chain phosphorylation was significantly decreased and edema increased significantly in the intestinal wall. Conditioned media from mechanically activated macrophages depressed intestinal contractile activity. CXCL1 (GroA) was significantly increased in the mechanically activated macrophages and intestinal smooth muscle within 1hour after induction of ileus compared with control cells and sham animals, respectively. Treatment with CXCL1 significantly decreased contraction amplitude and agonist-induced contractile activity and increased tone in the small intestine. In the gut manipulation model, treatment with a CXCR2 antagonist prevented the decrease in agonist-induced contractile activity but not contraction amplitude. These data suggest that CXCL1, released from macrophages during intestinal wall stress, can suppress intestinal contractile activity. CXCL1 is a potential target for preventing or treating ileus in trauma patients.
Highlights
Ileus, or depressed intestinal contractile activity, is manifested clini‐ cally as feeding intolerance, one of the most common postoperative complications
Our data suggest that gut manipulation‐induced ileus is mediated, at least in part, by intestinal macrophage secretion of CXCL1
According to the Centers for Disease Control and Prevention, 2.8 million people were hospitalized for traumatic injuries in 2015.22 Feeding intolerance affects more than 30% of moderate to severe trauma patients, and 25% of those patients are diagnosed with ileus.[3]
Summary
Depressed intestinal contractile activity, is manifested clini‐ cally as feeding intolerance, one of the most common postoperative complications. While the effects of intestinal edema on the ENS are unclear, we have shown that intestinal edema alone, in the absence of inflamma‐ tion, inhibits intestinal contractility by downregulating smooth mus‐ cle myosin light chain (MLC) phosphorylation.[10] Edema development results in increased intestinal wall stress.[16] Increased stretch of in‐ testinal smooth muscle cells has been shown to down‐regulate MLC phosphorylation.[17] edema‐induced mechanotransduction in the intestinal smooth muscle layers is one mechanism by which edema causes smooth muscle dysfunction. The purpose of our study was to exam‐ ine the contribution of myogenic mechanisms to the development of postoperative ileus, and the involvement of inflammation in mediat‐ ing smooth muscle dysfunction
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