Colonic Postoperative Inflammatory Ileus in the Rat

Abstract

ObjectiveTo investigate local inflammatory events within the colonic muscularis as a causative factor of postoperative ileus. Summary Background DataSurgically induced intestinal muscularis inflammation has been hypothesized as a mechanism for postoperative ileus. The colon is a crucial component for recovery of gastrointestinal motor function after surgery but remains unaddressed. The authors hypothesize that colonic manipulation initiates inflammatory events that directly mediate postoperative smooth muscle dysfunction. MethodsRats underwent colonic manipulation. In vivo transit and colonic motility was estimated using geometric center analysis and intraluminal pressure monitoring. Leukocyte extravasation was investigated in muscularis whole mounts. Mediator mRNA expression was determined by real-time reverse transcriptase-polymerase chain reaction. In vitro circular muscle contractility was assessed in a standard organ bath. The relevance of iNOS and COX-2 inhibition was determined using DFU or L-NIL perfusion. ResultsColonic manipulation resulted in a massive leukocyte recruitment and an increase in inflammatory mRNA expression. This inflammatory response was associated with an impairment of in vivo motor function and an inhibition of in vitro smooth muscle contractility (56%). L-NIL but not DFU significantly ameliorated smooth muscle dysfunction. ConclusionsThe results provide evidence for a surgically initiated local inflammatory cascade within the colonic muscularis that mediates smooth muscle dysfunction, which contributes to postoperative ileus.Iatrogenic postoperative gastrointestinal dysmotility remains a near-canonical outcome of abdominal surgery. The occurrence of ileus-related complications as well as the "typical" delayed postoperative recovery of intestinal motor activity is associated with a prolonged hospital stay and increased perioperative expense, which has a significant economic impact. 1-3Inhibitory neural reflexes and local inflammatory events within the intestinal muscularis have been proposed to participate in the development of postoperative motility changes. 2,4,5 We have previously shown that surgical manipulation of the small intestine results in the activation of resident muscularis macrophages, which is followed by a massive extravasation of immunocompetent cells into the intestinal muscularis.5 This inflammatory response correlates with the postoperative suppression in jejunal smooth muscle contractile activity.6 However, the resumption of gastrointestinal motility is dependent on the functional cooperation of the entire gastrointestinal tract, and the recovery of the small intestine may arguably not be the crucial gastrointestinal component of surgically induced ileus.

Peroxisome Proliferator-Activated Receptor γ Activation Alleviates Postoperative Ileus in Mice by Inhibition of Egr-1 Expression and Its Downstream Target Genes

“…The surgical procedure was performed under aseptic conditions. Mice underwent midline laparotomy and colonic manipulation (CM), as described previously (Tü rler et al, 2002). In brief, the colon was exteriorized carefully and then compressed for 5 min by use of sterile moist cotton applicators.…”

Impact of CCR7 on the gastrointestinal field effect

“…It has been shown that inflammatory infiltrates and hypomotility also occur in unmanipulated stomach and colon after standardized jejunal manipulation (72). This propagation of the intestinal inflammation to unmanipulated parts of the gastrointestinal tract has been termed as "gastrointestinal field effect" (FE) (72,83). We also observed FE in rodents after orthotopic small bowel transplantation excluding a spinal or supraspinal reflex (3,80,81).…”

“…These detrimental alterations are emphasized as major factors in the development of POI (4, 8, 9, 15, 16, 35-38, 40 -42). We reported a time-and trauma-degree-dependent inflammatory cascade (35,36); infiltration of leukocytes (40 -42, 72, 83), macrophages (21,22,37,87), and immunologically competent cells (35,36,40,67,69,72,81,83); and an upregulation of proinflammatory cytokines within the intestinal muscularis (36, 38 -40, 66, 68, 71, 80 -82, 84, 88). The pharmacological or genetic inhibition of macrophages ameliorated the POI in rodents (87,89).…”

Complication avoidance and management in anterior lumbar interbody fusion

“…17 Animal and human models have suggested that inflammation in the intestinal wall may be directly involved. 18 A consensus conference has reviewed and reported the basic science and some clinical aspects of POI. 19 More details about postulated mechanisms of action and the pathophysiology of POI are presented in subsequent sections.…”