title: A single intraperitoneal dose of carbon monoxide-saturated ringer's lactate solution ameliorates postoperative ileus in mice.
abstract: Treatment with inhaled carbon monoxide (CO) has been shown to ameliorate bowel dysmotility caused by surgical manipulation of the gut in experimental animals. We hypothesized that administration of CO dissolved in lactated Ringer's solution (CO-LR) might provide similar protection to that observed with the inhaled gas while obviating some of its inherent problems. Postoperative gut dysmotility (ileus) was induced in mice by surgical manipulation of the small intestine. Some mice were treated with a single intraperitoneal dose of CO-LR immediately after the surgical procedure, whereas other mice received only the LR vehicle. Twenty-four hours later, intestinal transit of a nonabsorbable marker (70-kDa fluorescein isothiocyanate-labeled dextran) was delayed in mice subjected to intestinal manipulation but not the sham procedure. Gut manipulation also was associated with increased expression within the muscularis propria of transcripts for interleukin-1beta, cyclooxygenase-2, inducible nitric-oxide synthase, intracellular adhesion molecule-1, and Toll-like receptor-4, as well as infiltration of the muscularis propria with polymorphonuclear leukocytes and activation of mitogen-activated protein kinases and nuclear factor-kappaB. All of these effects were attenuated by treatment with CO-LR. The salutary effect of CO-LR on gut motility, as well as many of the anti-inflammatory effects of CO-LR, was diminished by treatment with a soluble guanylyl cyclase (sGC) inhibitor, suggesting that the effects of CO are mediated via activation of sGC. These data support the view that a single intraperitoneal dose of CO-LR ameliorates postoperative ileus in mice by inhibiting the inflammatory response in the gut wall induced by surgical manipulation, possibly in a sGC-dependent fashion.
authors.affiliation: Thomas E. Starzl Transplantation Institute, Pennsylvania, USA.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nakao
authors.forename: Joachim
authors.initials: J
authors.lastname: Schmidt
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Harada
authors.forename: Allan
authors.initials: A
authors.lastname: Tsung
authors.forename: Burkhard
authors.initials: B
authors.lastname: Stoffels
authors.forename: Ruy J
authors.initials: RJ
authors.lastname: Cruz
authors.forename: Junichi
authors.initials: J
authors.lastname: Kohmoto
authors.forename: Ximei
authors.initials: X
authors.lastname: Peng
authors.forename: Koji
authors.initials: K
authors.lastname: Tomiyama
authors.forename: Noriko
authors.initials: N
authors.lastname: Murase
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bauer
authors.forename: Mitchell P
authors.initials: MP
authors.lastname: Fink
mesh_terms: D000818:Animals; D052160:Benzothiazoles; D015153:Blotting, Western; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002263:Carboxyhemoglobin / Q000378:metabolism; D003959:Diamines; D024202:Electrophoretic Mobility Shift Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D045823:Ileus / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007421:Intestine, Small / Q000187:drug effects / Q000503:physiopathology; D007552:Isotonic Solutions / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D020556:Neutrophil Infiltration / Q000502:physiology; D009930:Organic Chemicals; D009195:Peroxidase / Q000378:metabolism; D011183:Postoperative Complications / Q000503:physiopathology / Q000517:prevention & control*; D011804:Quinolines; D000077325:Ringer's Lactate
chemical_list: D052160:Benzothiazoles; D003959:Diamines; D018836:Inflammation Mediators; D007552:Isotonic Solutions; D016328:NF-kappa B; D009930:Organic Chemicals; D011804:Quinolines; D000077325:Ringer's Lactate; C098022:SYBR Green I; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin; D009195:Peroxidase; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases