Molecular and Functional Contractile Sequelae of Rat Intestinal Ischemia/Reperfusion Injury1

Hierholzer, Christian; Kalff, Jörg C.; Audolfsson, G.; Billiar, Timothy R.; Tweardy, David J.; Bauer, Anthony J.

doi:10.1097/00007890-199911150-00006

Cited by 108 publications

(88 citation statements)

References 38 publications

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“…23 The paradigm of the present study and our previous work is that inflammatory events within the muscularis externa, caused by intestinal handling, directly modulate smooth muscle contractile activity and subsequently changes in transit. 5,6,8,24 Similar to our reported observations in the small intestine, the data from the present study confirm an association between surgical trauma, leukocyte infiltration, and smooth muscle dysfunction within the colonic muscularis. Based on this and our previous work, we propose that activated resident as well as recruited leukocytes release kinetically active mediators that directly modulate motility.…”

Section: Discussionsupporting

confidence: 91%

Colonic Postoperative Inflammatory Ileus in the Rat

Türler¹,

Moore²,

Pezzone³

et al. 2002

Annals of Surgery

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122

106

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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.

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Section: Discussionsupporting

confidence: 91%

Colonic Postoperative Inflammatory Ileus in the Rat

Türler¹,

Moore²,

Pezzone³

et al. 2002

Annals of Surgery

Self Cite

122

106

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“…When groups 1 and 3 were compared, it was seen that they did not show such a strong adhesion as NB2CA. Hierholzer et al [22] also demonstrated that intestinal ischemia/reperfusion injury in rats results in a molecular and cellular inflammatory response within the intestinal muscularis and in a decrease in muscle contractions. As a result, this inflammatory response during ischemia-reperfusion has the effect of forming strong intra-abdominal adhesions.…”

Section: Discussionmentioning

confidence: 97%

Effects of N-Butyl-2-Cyanoacrylate on High-Level Jejunojejunostomy

Ensari

Genç²,

Çakmak³

et al. 2009

Eur Surg Res

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Background: Morbidity and mortality due to anastomotic complications in gastrointestinal surgery remain important problems. The tissue adhesive N-butyl-2-cyanoacrylate (NB2CA) is used in many fields of surgery. This study was designed to assess the effects of NB2CA on high-level jejunojejunostomy. Materials and Methods: Forty male albino Wistar rats were divided into 4 groups of 10 each. The groups were treated as follows: group 1 underwent only a jejunojejunostomy, group 2 underwent jejunojejunostomy followed by NB2CA application around the anastomosis, group 3 underwent jejunojejunostomy after a 60-min ischemia and a 60-min reperfusion, and group 4 underwent jejunojejunostomy after a 60-min ischemia and a 60-min reperfusion followed by NB2CA application around the anastomosis. At postoperative day 7, the subjects in all groups were sacrificed. Intra-abdominal adhesions, anastomotic complications and anastomotic burst pressures (ABP) were recorded. Results: The analysis of all the groups for adhesion scores and ABP showed statistical significance (p < 0.001). Conclusions: The use of NB2CA had positive effects in terms of increasing ABP both with and without the initial ischemia- reperfusion insult. However, it had the adverse effect of significantly increasing the number of intra-abdominal adhesions.

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“…In the present study, we investigated mediators that are specifically known to initiate leukocyte recruitment, to be involved in transplantation-associated problems and to modulate smooth muscle function in rodent models of ischemia/reperfusion and intestinal manipulation (24,25).…”

Section: Discussionmentioning

confidence: 99%

Resident Macrophages are Involved in Intestinal Transplantation-Associated Inflammation and Motoric Dysfunction of the Graft Muscularis

Schaefer

Tahara

Schmidt

et al. 2007

American Journal of Transplantation

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Gut manipulation and ischemia/reperfusion evoke an inflammatory response within the intestinal muscularis that contributes to dysmotility. We hypothesize that resident macrophages play a key role in initiating the inflammatory cascade. Isogenic small bowel transplantation was performed in Lewis rats. The impact of recovery of organs on muscularis inflammation was investigated by comparing cold whole-body perfusion after versus prior to recovery. The role of macrophages was investigated by transplantation of macrophage-depleted gut. Leukocytes were counted using muscularis whole mounts. Mediator expression was determined by real-time RT-PCR. Contractility was assessed in a standard organ bath. Both organ recovery and ischemia/reperfusion induced leukocyte recruitment and a significant upregulation in IL-6, MCP-1, ICAM-1 and iNOS mRNAs. Although organ recovery in cold ischemia prevented early gene expression, peak expression was not changed by modification of the recovery technique. Compared to controls, transplanted animals showed a 65% decrease in smooth muscle contractility. In contrast, transplanted macrophagedepleted isografts exhibited significant less leukocyte infiltration and only a 19% decrease in contractile activity. In summary, intestinal manipulation during recovery of organs initiates a functionally relevant inflammatory response within the intestinal muscularis that is massively intensified by the ischemia reperfusion injury. Resident muscularis macrophages participate in initiating this inflammatory response.

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Molecular and Functional Contractile Sequelae of Rat Intestinal Ischemia/Reperfusion Injury1

Abstract: I/R injury evokes a molecular and cellular inflammatory response within the intestinal muscularis that is associated with a subsequent decrease in intestinal motility.

Cited by 108 publications

References 38 publications

Colonic Postoperative Inflammatory Ileus in the Rat

Colonic Postoperative Inflammatory Ileus in the Rat

Effects of N-Butyl-2-Cyanoacrylate on High-Level Jejunojejunostomy

Resident Macrophages are Involved in Intestinal Transplantation-Associated Inflammation and Motoric Dysfunction of the Graft Muscularis

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