Carbon monoxide reduces pulmonary ischemia-reperfusion injury in miniature swine

Hisashi Sahara, Akira Shimizu, Kentaro Setoyama, Masayoshi Okumi, Manei Oku, Emma Samelson-Jones, Kazuhiko Yamada

Research output: Contribution to journalArticlepeer-review


Objectives: Carbon monoxide is produced endogenously as a by-product of heme catalysis and has been shown to reduce ischemia-reperfusion injury in a variety of organs in murine models. The aims of this translational research were to establish an in situ porcine lung model of warm ischemia-reperfusion injury and to evaluate the cytoprotective effects of low-dose inhaled carbon monoxide in this model. Methods: Warm ischemia was induced for 90 minutes by clamping the left pulmonary artery and veins in 8 Clawn miniature swine (Japan Farm CLAWN Institute, Kagoshima, Japan). The left main bronchus was also dissected and reanastomosed just before reperfusion. Four animals were treated with inhaled carbon monoxide at a concentration of approximately 250 ppm throughout the procedure. Lung function and structure were serially accessed via lung biopsy, chest x-ray films, and blood gas analysis. Results: Carbon monoxide inhalation dramatically decreased the lung injury associated with ischemia and reperfusion. Two hours after reperfusion, the arterial oxygen tension of the carbon monoxide-treated group was 454 ± 34 mm Hg, almost double the arterial oxygen tension of the control group (227 ± 57 mm Hg). There were fewer pathologic changes seen on chest x-ray films and in biopsy samples from animals in the carbon monoxide-treated group. Animals in the carbon monoxide-treated group also had fewer inflammatory cell infiltrates and a markedly smaller increase in serum concentrations of the proinflammatory cytokines interleukin 1β, interleukin 6, and high-mobility group box 1 after ischemia-reperfusion injury. Conclusions: The perioperative administration of low-dose inhaled carbon monoxide decreases warm ischemia-reperfusion injury in lungs in miniature swine. This protective effect is mediated in part by the downregulation of proinflammatory mediators.

Original languageEnglish (US)
Pages (from-to)1594-1601
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Issue number6
StatePublished - Jun 2010
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine


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