title: Protective effect of carbon monoxide inhalation for cold-preserved small intestinal grafts.
abstract: BACKGROUND
  Heme oxygenase (HO)-1 system has been shown to provide protection against oxidative stress through the degradation of heme to biliverdin, free iron, and carbon monoxide (CO). This study investigated cytoprotective efficacy of CO at a low concentration on cold ischemia/reperfusion (I/R) injury of transplanted intestine.
  
  
  METHODS
  Lewis rat recipients of syngenic orthotopic small intestinal transplantation with 6 hours UW cold preservation were either kept in room air (air-treated control) or exposed to CO (250 ppm) for 1 hour before and 24 hours after surgery.
  
  
  RESULTS
  In air-treated grafts, mRNA levels for interleukin-6, intracellular adhesion molecule-1, cyclooxygenase-2, and inducible nitric oxide synthase promptly increased. Sequential histopathologic analysis of untreated grafts revealed initial rapid epithelial loss, subsequent recruitment of inflammatory infiltrates, and local hemorrhage in the lamina propria, which extended downward to the epithelial crypt and muscle layer with time. CO effectively blocked proinflammatory cascade during I/R injury, inhibited upregulation of inflammatory molecules and ameliorated intestinal tissue injuries. Beneficial effects of CO were associated with improved graft blood flow without inhibiting endogenous HO-1 activity. Recipient animal survival was significantly improved with CO to 100% versus 58% in air-treated controls.
  
  
  CONCLUSIONS
  These results indicate a significant role for CO in protecting the intestine from cold I/R injury associating with small intestinal transplantation.
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nakao
authors.forename: Kei
authors.initials: K
authors.lastname: Kimizuka
authors.forename: Donna B
authors.initials: DB
authors.lastname: Stolz
authors.forename: Joao
authors.initials: J
authors.lastname: Seda Neto
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaizu
authors.forename: Augustine M K
authors.initials: AM
authors.lastname: Choi
authors.forename: Takashi
authors.initials: T
authors.lastname: Uchiyama
authors.forename: Brian S
authors.initials: BS
authors.lastname: Zuckerbraun
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Bauer
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nalesnik
authors.forename: Leo E
authors.initials: LE
authors.lastname: Otterbein
authors.forename: David A
authors.initials: DA
authors.lastname: Geller
authors.forename: Noriko
authors.initials: N
authors.lastname: Murase
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002248:Carbon Monoxide / Q000008:administration & dosage*; D002263:Carboxyhemoglobin / Q000032:analysis; D015925:Cryopreservation; D004790:Enzyme Induction; D005740:Gases / Q000097:blood; D005772:Gastrointestinal Transit; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D007421:Intestine, Small / Q000098:blood supply / Q000473:pathology / Q000637:transplantation*; D008297:Male; D009994:Osmolar Concentration; D011182:Postoperative Care; D011300:Preoperative Care; D051381:Rats; D011917:Rats, Inbred Lew; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*
chemical_list: D005740:Gases; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1