Low-dose carbon monoxide inhalation prevents ischemia/reperfusion injury of transplanted rat lung grafts

Junichi Kohmoto, Atsunori Nakao, Takashi Kaizu, Allan Tsung, Atsushi Ikeda, Koji Tomiyama, Timothy R. Billiar, Augustine M K Choi, Noriko Murase, Kenneth R. McCurry

Research output: Contribution to journalArticle

67 Citations (Scopus)

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°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-α, 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.

Original languageEnglish
Pages (from-to)179-185
Number of pages7
JournalSurgery
Volume140
Issue number2
DOIs
Publication statusPublished - Aug 2006
Externally publishedYes

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Carbon Monoxide
Reperfusion Injury
Inhalation
Transplants
Lung
Air
Transplantation
Cold Ischemia
Heme Oxygenase (Decyclizing)
Mitogen-Activated Protein Kinase 3
Lung Transplantation
Pulmonary Veins
Partial Pressure
Nitric Oxide Synthase Type II
Catalysis
Heme
Protein Kinases
Interleukin-6
Coloring Agents
Endothelial Cells

ASJC Scopus subject areas

  • Surgery

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Low-dose carbon monoxide inhalation prevents ischemia/reperfusion injury of transplanted rat lung grafts. / Kohmoto, Junichi; Nakao, Atsunori; Kaizu, Takashi; Tsung, Allan; Ikeda, Atsushi; Tomiyama, Koji; Billiar, Timothy R.; Choi, Augustine M K; Murase, Noriko; McCurry, Kenneth R.

In: Surgery, Vol. 140, No. 2, 08.2006, p. 179-185.

Research output: Contribution to journalArticle

Kohmoto, J, Nakao, A, Kaizu, T, Tsung, A, Ikeda, A, Tomiyama, K, Billiar, TR, Choi, AMK, Murase, N & McCurry, KR 2006, 'Low-dose carbon monoxide inhalation prevents ischemia/reperfusion injury of transplanted rat lung grafts', Surgery, vol. 140, no. 2, pp. 179-185. https://doi.org/10.1016/j.surg.2006.03.004
Kohmoto, Junichi ; Nakao, Atsunori ; Kaizu, Takashi ; Tsung, Allan ; Ikeda, Atsushi ; Tomiyama, Koji ; Billiar, Timothy R. ; Choi, Augustine M K ; Murase, Noriko ; McCurry, Kenneth R. / Low-dose carbon monoxide inhalation prevents ischemia/reperfusion injury of transplanted rat lung grafts. In: Surgery. 2006 ; Vol. 140, No. 2. pp. 179-185.
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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°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-α, 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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AU - Ikeda, Atsushi

AU - Tomiyama, Koji

AU - Billiar, Timothy R.

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