title: Peculiar mechanisms of graft recovery through anti-inflammatory responses after rat lung transplantation from donation after cardiac death.
abstract: 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.
authors: Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors: Sumiharu
authors: S
authors: Yamamoto
authors: Mikio
authors: M
authors: Okazaki
authors: Masaomi
authors: M
authors: Yamane
authors: Kentaro
authors: K
authors: Miyoshi
authors: Shinji
authors: S
authors: Otani
authors: Tomokazu
authors: T
authors: Kakishita
authors: Osamu
authors: O
authors: Yoshida
authors: Naohisa
authors: N
authors: Waki
authors: Shinichi
authors: S
authors: Toyooka
authors: Takahiro
authors: T
authors: Oto
authors: Yoshifumi
authors: Y
authors: Sano
authors: Shinichiro
authors: S
authors: Miyoshi
mesh_terms: D000818:Animals; D003643:Death; D006085:Graft Survival / Q000276:immunology*; D051547:Heme Oxygenase-1 / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000276:immunology*; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D016753:Interleukin-10; D051547:Heme Oxygenase-1