Peculiar mechanisms of graft recovery through anti-inflammatory responses after rat lung transplantation from donation after cardiac death

Sumiharu Yamamoto, Mikio Okazaki, Masaomi Yamane, Kentaro Miyoshi, Shinji Otani, Tomokazu Kakishita, Osamu Yoshida, Naohisa Waki, Shinichi Toyooka, Takahiro Oto, Yoshifumi Sano, Shinichiro Miyoshi

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Background: Although lung transplantation from donation after cardiac death (DCD), especially uncontrolled DCD, is limited by warm ischemic periods, the molecular mechanism of warm ischemia-reperfusion-injury (IRI) has not been well elucidated. The purpose of this study was to clarify the particular longitudinal mechanisms of molecular factors involved in warm IRI. Methods: Cold ischemic-time (CIT)-group lungs were retrieved and subjected to 3-h of cold preservation, whereas warm ischemic-time (WIT)-group lungs were retrieved after 3-h of warm ischemia. Orthotopic rat lung transplantation was performed and the grafts were reperfused for 1 or 4-h. The graft functions, gene expression, and activation of inflammatory molecules in the grafts were analyzed. Exhaled-carbon-monoxide-concentration (ExCO-C) was measured during reperfusion. Results: Only the WIT-group showed obvious primary graft dysfunction at 1-h reperfusion, but the graft function was recovered during 4-h reperfusion. Most of pro-inflammatory cytokines and stress-induced molecules showed different expression and activation patterns between CIT and WIT groups. In the WIT-group, the expressions of anti-inflammatory molecules, IL-10 and HO-1, were significantly increased at 1-h reperfusion compared to the CIT-group, and these high levels were maintained through 4-h reperfusion. Furthermore, ExCO-C levels in the WIT-group increased immediately after reperfusion compared to the CIT-group. Conclusions: This study indicates that warm IRI may involve a different mechanism than cold IRI and anti-inflammatory pathways may play important roles in the graft recovery after lung transplantation from uncontrolled DCD.

Original languageEnglish
Pages (from-to)133-139
Number of pages7
JournalTransplant Immunology
Issue number2-3
Publication statusPublished - Mar 2012


  • Donation after cardiac death
  • Ischemia reperfusion injury
  • Lung transplantation
  • Warm ischemia

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Transplantation


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