Colonic postoperative inflammatory ileus in the rat.
OBJECTIVE
To investigate local inflammatory events within the colonic muscularis as a causative factor of postoperative ileus.


BACKGROUND
Surgically 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.


METHODS
Rats 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.


RESULTS
Colonic 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.


CONCLUSIONS
The results provide evidence for a surgically initiated local inflammatory cascade within the colonic muscularis that mediates smooth muscle dysfunction, which contributes to postoperative ileus.
Türler
Andreas
A
Department of Medicine, Division of Gastroenterology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Moore
Beverly A
BA
Pezzone
Michael A
MA
Overhaus
Marcus
M
Kalff
Jörg C
JC
Bauer
Anthony J
AJ
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D003106:Colon / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000276:immunology* / Q000502:physiology; D018836:Inflammation Mediators / Q000276:immunology*; D007418:Intestinal Pseudo-Obstruction / Q000276:immunology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D009130:Muscle, Smooth / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D010088:Oxidoreductases / Q000235:genetics / Q000276:immunology; D011183:Postoperative Complications / Q000276:immunology*; D011451:Prostaglandin-Endoperoxide Synthases; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley
D015815:Cell Adhesion Molecules; D018925:Chemokines; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D007527:Isoenzymes; D012333:RNA, Messenger; D010088:Oxidoreductases; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases