TY - JOUR
T1 - Protective effect of carbon monoxide inhalation for cold-preserved small intestinal grafts
AU - Nakao, Atsunori
AU - Kimizuka, Kei
AU - Stolz, Donna B.
AU - Neto, Joao Seda
AU - Kaizu, Takashi
AU - Choi, Augustine M.K.
AU - Uchiyama, Takashi
AU - Zuckerbraun, Brian S.
AU - Bauer, Anthony J.
AU - Nalesnik, Michael A.
AU - Otterbein, Leo E.
AU - Geller, David A.
AU - Murase, Noriko
N1 - Funding Information:
Supported by NIH Grant DK54232 (Murase), CA76541 (Stolz), HL60234, AI42365, HL55330 (Choi), GM58241 and GM53789 (Bauer), and American Heart 160332U and Atorvastatin Pfizer Research Award (Otterbein)
PY - 2003/8/1
Y1 - 2003/8/1
N2 - 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. Conclusion. These results indicate a significant role for CO in protecting the intestine from cold I/R injury associating with small intestinal transplantation.
AB - 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. Conclusion. These results indicate a significant role for CO in protecting the intestine from cold I/R injury associating with small intestinal transplantation.
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U2 - 10.1067/msy.2003.238
DO - 10.1067/msy.2003.238
M3 - Article
C2 - 12947331
AN - SCOPUS:0041827066
SN - 0039-6060
VL - 134
SP - 285
EP - 292
JO - Surgery
JF - Surgery
IS - 2
ER -