Protective effect of carbon monoxide inhalation for cold-preserved small intestinal grafts.
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.
Nakao
Atsunori
A
University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Kimizuka
Kei
K
Stolz
Donna B
DB
Seda Neto
Joao
J
Kaizu
Takashi
T
Choi
Augustine M K
AM
Uchiyama
Takashi
T
Zuckerbraun
Brian S
BS
Bauer
Anthony J
AJ
Nalesnik
Michael A
MA
Otterbein
Leo E
LE
Geller
David A
DA
Murase
Noriko
N
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*
D005740:Gases; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1