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2009 Fiscal Year Final Research Report

Development of CO inhalation therapy for acute lung injury

Research Project

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Project/Area Number 19591795
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionOkayama University

Principal Investigator

TAKAHASHI Toru  Okayama University, 岡山大学病院, 准教授 (40252952)

Co-Investigator(Kenkyū-buntansha) MORIMATSU Hiroshi  岡山大学, 岡山大学病院, 助教 (30379797)
MORITA Kiyoshi  岡山大学, 大学院・医歯薬学総合研究科, 教授 (40108171)
Project Period (FY) 2007 – 2009
Keywords周術期管理学 / 炎症 / 出血性ショック / 急性肺障害 / 一酸化炭素
Research Abstract

Hemorrhagic shock and resuscitation (HSR) induces pulmonary inflammation that leads to acute lung injury. Carbon monoxide (CO), a by-product of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. The aim of the present study was to examine the effects of CO inhalation at low concentration on lung injury induced by HSR in rats. Rats were subjected to HSR by bleeding to achieve mean arterial pressure of 30mmHg for 60min followed by resuscitation with shed blood and saline as needed to restore blood pressure. HSR animals were maintained either in room air, or exposed to CO at 250ppm for 1 hour before and 3 hours after HSR. HSR caused an increase in the DNA binding activity of nuclear factor (NF)-κB and activator protein 1 (AP-1) in the lung followed by the upregulation of pulmonary gene expression of tumor necrosis factor-α, inducible nitric oxide synthase and interleukin (IL)-10. HSR also resulted in an increase in myeloperoxidase activity and wet-weight to dry-weight ratio in the lung, and more prominent histopathological changes including congestion, edema, cellular infiltration and hemorrhage. In contrast, CO inhalation significantly ameliorated these inflammatory events as judged by fewer histological changes, less upregulation of inflammatory mediators and less activation of NF-κB and AP-1. Interestingly, the protective effects against lung injury afforded by CO were associated with further increases of mRNA expression of IL-10 in the lung. These findings suggest that inhaled CO at a low concentration ameliorated HSR-induced lung injury and attenuated inflammatory cascades by upregulation of anti-inflammatory IL-10.

  • Research Products

    (8 results)

All 2009 2008 2007 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (3 results) Book (1 results) Remarks (1 results)

  • [Journal Article] (1th author, other 7 authors): Heme Oxygenase-1 is an Essential Cytoprotective Component in Oxidative Tissue Injury Induced by Hemorrhagic Shock.2009

    • Author(s)
      Takahashi T, Morimatsu H, Morita K, et. al.
    • Journal Title

      J Clin Biochem Nutr Vol.44

      Pages: 28-40

    • Peer Reviewed
  • [Journal Article] (2nd author, other 6 authors): Protective effect of carbon monoxide inhalation on lung injury after hemorrhagic shock/resuscitation in rats.2009

    • Author(s)
      Kanagawa F, Takahashi T, Morimatsu H, Morita K, et. al.
    • Journal Title

      J Trauma (In press)

    • Peer Reviewed
  • [Journal Article] (2nd author, other 6 authors) Prevention of hemorrhagicshock-induced intestinal tissue injury by glutamine via heme oxygenase-1 induction.2009

    • Author(s)
      Umeda K, Takahashi T, Morimatsu H, Morita K, et. al.
    • Journal Title

      Shock Vol.31

      Pages: 40-49

    • Peer Reviewed
  • [Presentation] PROTECTIVE ROLE OF HEME OXYGENASE-1/CARBON MONOXIDE SYSTEM IN PULMONARY INJURY AND INFLAMMATION2008

    • Author(s)
      Toru Takahashi
    • Organizer
      The 11th International Symposium on Molecular Medicine
    • Place of Presentation
      Crete, Greece
    • Year and Date
      2008-10-11
  • [Presentation] HEME OXYGENASE-1/CARBON MONOXIDE SYSTEM: A NOVEL MOLECULAR TARGET AGAINST OXIDAITVE TISSUE INJURIES2007

    • Author(s)
      Toru Takahashi
    • Organizer
      The 10th International Symposium on Molecular Medicine
    • Place of Presentation
      Crete, Greece
    • Year and Date
      2007-10-10
  • [Presentation] Protective Role Played by HO-1 Gene Expression and CO in Critically Ill Conditions2007

    • Author(s)
      Toru Takahashi
    • Organizer
      The 5th International Congress Heme Oxygenases 2007
    • Place of Presentation
      Krakow, Poland
    • Year and Date
      2007-09-09
  • [Book] 全身性炎症反応における呼気中一酸化炭素(CO)濃度の上昇, (分担)「エンドトキシン研究10基礎と臨床の最新知見(上西紀夫, 小川利久, 小玉正智, 横地高志, 谷徹編)2007

    • Author(s)
      高橋徹, 森松博史, 松崎孝, 清水裕子, 井上一由, 井戸佳奈, 松三昌樹, 片山浩, 森田潔
    • Total Pages
      65-68
    • Publisher
      医学図書出版株式会社
  • [Remarks]

    • URL

      http://www.okadaimasui.com/

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Published: 2011-06-18   Modified: 2016-04-21  

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