Abstract | BACKGROUND:
Carbon monoxide (CO), a byproduct of heme catalysis by heme oxygenases, has been shown to provide protection against ischemia/reperfusion (I/R) injury. We examined the cytoprotective effect of CO at a low concentration on cold I/R injury of transplanted lung grafts. METHODS: Orthotopic left lung transplantation was performed in syngenic Lewis to Lewis rat combination. Grafts were preserved in University of Wisconsin solution at 4 degrees C for 6 hours. Donors and/or recipients were exposed to CO (250 ppm) in air for 1 hour before surgery and then continuously post- transplantation. RESULTS: Blood oxygen partial pressure of graft pulmonary veins in the CO-treated group versus the air-treated group was significantly higher. The increase of messenger RNA of inflammatory mediators such as interleukin-6, tumor necrosis factor-alpha, inducible nitric oxide synthase, and cycloooxygenase-2 was markedly inhibited in the CO-treated group. The expression of phosphorylated-extracellular signal-regulated protein kinase 1/2 was significantly reduced in the CO-treated group. CO treatment reduced the number of infiltrating macrophages into the lung grafts. Vascular endothelial cells detected by CD31 stain were well preserved in CO-treated grafts, while those in air-treated grafts were faint and interrupted. CONCLUSIONS: These results demonstrate that exogenous low-dose CO treatment of donors and recipients can prevent lung I/R injury and significantly improve function of lung grafts after extended cold preservation and transplantation.
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Authors | Junichi Kohmoto, Atsunori Nakao, Takashi Kaizu, Allan Tsung, Atsushi Ikeda, Koji Tomiyama, Timothy R Billiar, Augustine M K Choi, Noriko Murase, Kenneth R McCurry |
Journal | Surgery
(Surgery)
Vol. 140
Issue 2
Pg. 179-85
(Aug 2006)
ISSN: 0039-6060 [Print] United States |
PMID | 16904967
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Inflammation Mediators
- Carbon Monoxide
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Topics |
- Administration, Inhalation
- Animals
- Blood Gas Analysis
- Carbon Monoxide
(administration & dosage)
- Drug Administration Schedule
- Graft Survival
- Inflammation Mediators
(blood)
- Lung Transplantation
(adverse effects)
- Male
- Rats
- Rats, Inbred Lew
- Reperfusion Injury
(etiology, prevention & control)
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