Endogenous endotoxin participates in causing a panenteric inflammatory ileus after colonic surgery

Andreas Türler, Christoph Schnurr, Atsunori Nakao, Sandra Tögel, Beverley A. Moore, Noriko Murase, Jörg C. Kalff, Anthony J. Bauer

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

OBJECTIVE: To investigate muscularis inflammation and endogenous endotoxin as causes of postoperative ileus. BACKGROUND: Postoperative inflammatory ileus of the colon is associated with a significant delay in gastrointestinal transit. We investigated whether these changes are caused by the downstream obstructive barrier of the surgically altered colon or by small intestinal muscularis inflammation itself. Furthermore, we evaluated the mechanistic role of gut derived endotoxin in the development of postoperative intestinal dysfunction. METHODS: Rats underwent surgical manipulation of the colon. Isolated gastrointestinal transit was analyzed in animals with ileostomy. The perioperative emigration of intracolonic particles was investigated by colonic luminal injection of fluorescently labeled LPS and microspheres. Mediator mRNA induction was quantified by real-time RT-PCR. Muscularis leukocytic infiltrates were characterized. In vitro circular muscle contractility was assessed in a standard organ bath. RESULTS: Ileostomy rats presented with a significant delay in small intestinal transit after colonic manipulation. This was associated with leukocyte recruitment and inflammatory mediator mRNA induction within the small intestinal muscularis. Colonic manipulation caused the transference of intracolonic LPS and microspheres into the intestinal muscularis. Postoperative in vitro small intestinal circular muscle contractility was impaired by 42% compared with controls. Gut decontamination and TLR-4 deletion significantly alleviated the small intestinal muscularis inflammation and prevented intestinal muscle dysfunction. CONCLUSIONS: Selective colonic manipulation initiates a distant inflammatory response in the small intestinal muscularis that contributes to postoperative ileus. The data provide evidence that gut-derived bacterial products are mechanistically involved in the initiation of this remote inflammatory cascade.

Original languageEnglish
Pages (from-to)734-744
Number of pages11
JournalAnnals of Surgery
Volume245
Issue number5
DOIs
Publication statusPublished - May 2007
Externally publishedYes

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Ileus
Endotoxins
Gastrointestinal Transit
Ileostomy
Colon
Inflammation
Microspheres
Muscles
Messenger RNA
Decontamination
Emigration and Immigration
Baths
Real-Time Polymerase Chain Reaction
Leukocytes
Injections
In Vitro Techniques

ASJC Scopus subject areas

  • Surgery

Cite this

Endogenous endotoxin participates in causing a panenteric inflammatory ileus after colonic surgery. / Türler, Andreas; Schnurr, Christoph; Nakao, Atsunori; Tögel, Sandra; Moore, Beverley A.; Murase, Noriko; Kalff, Jörg C.; Bauer, Anthony J.

In: Annals of Surgery, Vol. 245, No. 5, 05.2007, p. 734-744.

Research output: Contribution to journalArticle

Türler, A, Schnurr, C, Nakao, A, Tögel, S, Moore, BA, Murase, N, Kalff, JC & Bauer, AJ 2007, 'Endogenous endotoxin participates in causing a panenteric inflammatory ileus after colonic surgery', Annals of Surgery, vol. 245, no. 5, pp. 734-744. https://doi.org/10.1097/01.sla.0000255595.98041.6b
Türler, Andreas ; Schnurr, Christoph ; Nakao, Atsunori ; Tögel, Sandra ; Moore, Beverley A. ; Murase, Noriko ; Kalff, Jörg C. ; Bauer, Anthony J. / Endogenous endotoxin participates in causing a panenteric inflammatory ileus after colonic surgery. In: Annals of Surgery. 2007 ; Vol. 245, No. 5. pp. 734-744.
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abstract = "OBJECTIVE: To investigate muscularis inflammation and endogenous endotoxin as causes of postoperative ileus. BACKGROUND: Postoperative inflammatory ileus of the colon is associated with a significant delay in gastrointestinal transit. We investigated whether these changes are caused by the downstream obstructive barrier of the surgically altered colon or by small intestinal muscularis inflammation itself. Furthermore, we evaluated the mechanistic role of gut derived endotoxin in the development of postoperative intestinal dysfunction. METHODS: Rats underwent surgical manipulation of the colon. Isolated gastrointestinal transit was analyzed in animals with ileostomy. The perioperative emigration of intracolonic particles was investigated by colonic luminal injection of fluorescently labeled LPS and microspheres. Mediator mRNA induction was quantified by real-time RT-PCR. Muscularis leukocytic infiltrates were characterized. In vitro circular muscle contractility was assessed in a standard organ bath. RESULTS: Ileostomy rats presented with a significant delay in small intestinal transit after colonic manipulation. This was associated with leukocyte recruitment and inflammatory mediator mRNA induction within the small intestinal muscularis. Colonic manipulation caused the transference of intracolonic LPS and microspheres into the intestinal muscularis. Postoperative in vitro small intestinal circular muscle contractility was impaired by 42{\%} compared with controls. Gut decontamination and TLR-4 deletion significantly alleviated the small intestinal muscularis inflammation and prevented intestinal muscle dysfunction. CONCLUSIONS: Selective colonic manipulation initiates a distant inflammatory response in the small intestinal muscularis that contributes to postoperative ileus. The data provide evidence that gut-derived bacterial products are mechanistically involved in the initiation of this remote inflammatory cascade.",
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