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 journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)133-139
Number of pages7
JournalTransplant Immunology
Volume26
Issue number2-3
DOIs
Publication statusPublished - Mar 2012

Fingerprint

Warm Ischemia
Lung Transplantation
Anti-Inflammatory Agents
Cold Ischemia
Transplants
Reperfusion
Reperfusion Injury
Carbon Monoxide
Primary Graft Dysfunction
Lung
Interleukin-10
Transcriptional Activation
Cytokines
Gene Expression

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Transplantation

Cite this

Peculiar mechanisms of graft recovery through anti-inflammatory responses after rat lung transplantation from donation after cardiac death. / Yamamoto, Sumiharu; Okazaki, Mikio; Yamane, Masaomi; Miyoshi, Kentaro; Otani, Shinji; Kakishita, Tomokazu; Yoshida, Osamu; Waki, Naohisa; Toyooka, Shinichi; Oto, Takahiro; Sano, Yoshifumi; Miyoshi, Shinichiro.

In: Transplant Immunology, Vol. 26, No. 2-3, 03.2012, p. 133-139.

Research output: Contribution to journalArticle

@article{559895bc4b0c43e1ad54a43e1b500979,
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.",
keywords = "Donation after cardiac death, Ischemia reperfusion injury, Lung transplantation, Warm ischemia",
author = "Sumiharu Yamamoto and Mikio Okazaki and Masaomi Yamane and Kentaro Miyoshi and Shinji Otani and Tomokazu Kakishita and Osamu Yoshida and Naohisa Waki and Shinichi Toyooka and Takahiro Oto and Yoshifumi Sano and Shinichiro Miyoshi",
year = "2012",
month = "3",
doi = "10.1016/j.trim.2011.11.002",
language = "English",
volume = "26",
pages = "133--139",
journal = "Transplant Immunology",
issn = "0966-3274",
publisher = "Elsevier",
number = "2-3",

}

TY - JOUR

T1 - Peculiar mechanisms of graft recovery through anti-inflammatory responses after rat lung transplantation from donation after cardiac death

AU - Yamamoto, Sumiharu

AU - Okazaki, Mikio

AU - Yamane, Masaomi

AU - Miyoshi, Kentaro

AU - Otani, Shinji

AU - Kakishita, Tomokazu

AU - Yoshida, Osamu

AU - Waki, Naohisa

AU - Toyooka, Shinichi

AU - Oto, Takahiro

AU - Sano, Yoshifumi

AU - Miyoshi, Shinichiro

PY - 2012/3

Y1 - 2012/3

N2 - 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.

AB - 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.

KW - Donation after cardiac death

KW - Ischemia reperfusion injury

KW - Lung transplantation

KW - Warm ischemia

UR - http://www.scopus.com/inward/record.url?scp=84856521117&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856521117&partnerID=8YFLogxK

U2 - 10.1016/j.trim.2011.11.002

DO - 10.1016/j.trim.2011.11.002

M3 - Article

C2 - 22108534

AN - SCOPUS:84856521117

VL - 26

SP - 133

EP - 139

JO - Transplant Immunology

JF - Transplant Immunology

SN - 0966-3274

IS - 2-3

ER -