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Large animal experimental study on lung repair by hydrogen diffusion for lung transplantation from donation after cardiac death

Research Project

Project/Area Number 17H04295
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory surgery
Research InstitutionKyoto University

Principal Investigator

Date Hiroshi  京都大学, 医学研究科, 教授 (60252962)

Co-Investigator(Kenkyū-buntansha) 陳 豊史  京都大学, 医学研究科, 准教授 (00452334)
濱路 政嗣  京都大学, 医学研究科, 講師 (70782142)
本山 秀樹  京都大学, 医学研究科, 助教 (20762264)
青山 晃博  京都大学, 医学(系)研究科(研究院), その他 (60379047)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords水素水 / 肺移植 / 虚血再灌流障害 / 冷保存 / 心停止ドナー / 冷虚血障害 / 水素 / 肺障害
Outline of Final Research Achievements

Molecular hydrogen (H2) has protective effects against ischemia-reperfusion (I/R) injury in various organs. They are easier to transport and safer to use than inhaled H2. In this study, we examined the protective effects of an H2-rich solution for lung preservation in a canine left lung transplantation (LTx) model. Ten beagles underwent orthotopic left LTx after 23 h of cold ischemia followed by reperfusion for 4 h. The beagles were divided into two groups: control (CON group, n=5) and hydrogen (H2 group, n=5). Significantly higher partial pressure of arterial oxygen and significantly lower partial pressure of carbon dioxide were observed in the H2 group than in the CON group. The W/D ratio was significantly lower in the H2 group. Moreover, in histological examination, less lung injury and fewer apoptotic cells were observed in the H2 group.
Our results indicated that the H2-rich preservation solution attenuated I/R injury in a canine left LTx model.

Academic Significance and Societal Importance of the Research Achievements

水素ガス吸入法は、肺保存実験において報告されてきたが、取り扱いが難しく、爆発性があるなどの欠点があった。爆発性のない水素水が肺保存に有用であることを、小動物(ラット)の胸膜還流モデルを使って報告してきた。しかし、大動物では胸膜を通じての肺内への水素の拡散に限界があった。そこで本研究では、臨床肺移植に近い条件の大動物(ビーグル犬)を使用して、水素水を保存液と浸漬液に使用することの有用性を示し、23時間の冷保存を可能とした。
8-10時間が限界とされてきた安全保存時間を延長させる可能性を示した学術的意義は大きく、臓器移植数を増加せせる可能性があることは、ドナー不足の日本において社会的意義も大きい。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (31 results)

All 2020 2019 2018 2017 Other

All Journal Article (23 results) (of which Peer Reviewed: 22 results,  Open Access: 18 results) Presentation (7 results) (of which Int'l Joint Research: 6 results,  Invited: 4 results) Remarks (1 results)

  • [Journal Article] Protective effects of a hydrogen-rich solution during cold ischemia in rat lung transplantation.2020

    • Author(s)
      Saito M, Chen-Yoshikawa TF, Takahashi M, Kayawake H, Yokoyama Y, Kurokawa R, Hirano SI, Date H.
    • Journal Title

      J Thorac Cardiovasc Surg

      Volume: 159 Issue: 5 Pages: 2110-2118

    • DOI

      10.1016/j.jtcvs.2019.09.175

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intermediate outcomes of right-to-left inverted living-donor lobar lung transplantation.2019

    • Author(s)
      Chen-Yoshikawa TF, Tanaka S, Yamada Y, Yutaka Y, Nakajima D, Ohsumi A, Hamaji M, Menju T, Date H.
    • Journal Title

      Eur J Cardiothorac Surg

      Volume: 56 Issue: 6 Pages: 1046-1053

    • DOI

      10.1093/ejcts/ezz244

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Living-donor lobar lung transplants provide comparable pulmonary function to cadaveric lung transplants.2019

    • Author(s)
      Nakajima D, Chen-Yoshikawa TF, Ohsumi A, Date H.
    • Journal Title

      J Thorac Cardiovasc Surg

      Volume: - Issue: 1 Pages: e87-e90

    • DOI

      10.1016/j.jtcvs.2019.07.099

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acquired recipient pulmonary function is better than lost donor pulmonary function in living-donor lobar lung transplantation.2019

    • Author(s)
      Kayawake H, Chen-Yoshikawa TF, Hamaji M, Nakajima D, Ohsumi A, Aoyama A, Date H.
    • Journal Title

      J Thorac Cardiovasc Surg

      Volume: 158 Issue: 6 Pages: 1710-1716

    • DOI

      10.1016/j.jtcvs.2019.06.058

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gastrointestinal complications after lung transplantation in Japanese patients.2018

    • Author(s)
      Kayawake H, Chne-yoshikawa TF, Motoyama H, Hamaji M, Nakajima D, Aoyama A, Date H.
    • Journal Title

      Surg Today

      Volume: -

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nonntuberculous mycobacterial and Aspergillus infections among cadaveric lung transplant recipients in Japan.2018

    • Author(s)
      Tachibana K, Okada Y, Matsuda Y, Miyyoshi K, Oto T, Chen-Yoshikawa TF, Date H, Minami M, Okumura M, Iwasaki A, Shiraishi T, Maeda S, Matsumura Y, Nakajima T, Toshino I, Hayashi S.
    • Journal Title

      Respr Investig

      Volume: 56(3) Pages: 243-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of early tracheostomy on clinical outcomes in critically ill lung transplant recipients.2018

    • Author(s)
      Miyoshi R, Chen-Yoshikawa TF, Hamaji M, Kawaguchi A, Kayawake H, Hijiya K, Motoyama H, Aoyama A, Date H.
    • Journal Title

      Gen Thorac Cardiovasc Surg

      Volume: -

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Outcomes of various transplant procedures (single, sparing, inverted) in living-donor lobar lung transplantation.2017

    • Author(s)
      Date H, Aoyama A, Hijiya K, Motoyama H, Handa T, Kinoshita H, Baba S, Mizota T, Minakata K, Chen-Yoshikawa TF.
    • Journal Title

      J Thorac Cardiovasc Surg

      Volume: 153 Pages: 479-86

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immune function monitoring in lung transplantation using adenosine triphosphate production: time trends and relationship to postoperative infection.2017

    • Author(s)
      Takahashi M, Ohsumi A, Ohata K, Kondo T, Motoyama H, Hijiya K, Aoyama A, Date H, Chen-Yoshikawa TF.
    • Journal Title

      Surg Today

      Volume: 47(6) Pages: 762-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Can we kill 2 birds with 1 stone?2017

    • Author(s)
      Date H
    • Journal Title

      J Thorac Caridiovasc Surg

      Volume: 153(3) Pages: 725-725

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Right-to-left inverted living-donor lobar lung transplantation combined with sparing of native upper lobe.2017

    • Author(s)
      Goda Y, Motoyama H, Aoyama A, Hamaji M, Hijiya K, Chen-Yoshikawa TF, Date H.
    • Journal Title

      J Heart Lung Transplant

      Volume: 36(5) Pages: 483-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Excellent outcome of donor lobectomy with various surgical techniques for the interlobar artery.2017

    • Author(s)
      Kayawake H, Chen-Yoshikawa TF, Aoyama A, Motoyama H, Hijiya K, Menju T, Sato T, Sonobe M, Date H.
    • Journal Title

      Eur J Cardiothorac Surg

      Volume: 51(2) Pages: 279-83

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of local intrapulmonary production of antibodies specific to donor major histocompatibility complex class I with the progression of chronic rejection of lung allografts.2017

    • Author(s)
      Miyamoto E, Motoyama H, Sato M, Aoyama A, Menju T, Shikuma K, Sowa T, Yoshizawa A, Saito M, Takahagi A, Tanaka S, Takahashi M, Ohata K, Kondo T, Hijiya K, Chen-Yoshikawa TF, Date H.
    • Journal Title

      Transplantation

      Volume: 101(5)

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Living-donor lung transplantation after bone marrow transplantation for Chediac-Higashi syndrome.2017

    • Author(s)
      Yamada T, Chen-Yoshikawa TF, Oh S, Ito-Taniguchi R, Gochi F, Sato M, Aoyama A, Date H.
    • Journal Title

      Ann Thorac Surg

      Volume: 103(3)

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Late-onset chest wall abscess due to a biogradable rib pin infection after lung transplantation.2017

    • Author(s)
      Goda Y, Chen-Yoshikawa TF, Kusunose M, Hamaji M, Motoyama H, Hijiya K, Aoyama A, Date H.
    • Journal Title

      Gen Thorac Cardiovasc Surg

      Volume: -

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Superior mesenteric artery syndrome after lung transplantation: a rare early gastrointestinal complication of lung transplantation.2017

    • Author(s)
      Kayawake H, Chen-Yoshikawa TF, Aoyama A, Zhang J, Date H.
    • Journal Title

      Surg Today

      Volume: -

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Basiliximab for posterior reversible encephalopathy syndrome after lung transplantation.2017

    • Author(s)
      Yamagishi H, Chen-Yoshikawa TF, Date H.
    • Journal Title

      Eur J Cardiothorac Surg

      Volume: 52(4) Pages: 823-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pulmonary venoplasty with a pericardical conduit in living-donor lobar lung retransplantation.2017

    • Author(s)
      Kayawake H, Chen-Yoshikawa TF, Motoyama H, Date H.
    • Journal Title

      Interact Cardiovasc Thorac Surg

      Volume: 25(5) Pages: 830-31

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful conservative management of an anastomotic airway dehiscence at the left main bronchus following bilateral cadaveric lung transplantation.2017

    • Author(s)
      Miyata R, Chen-Yoshikawa TF, Hamaji M, Gochi F, Motoyama H, Menju T, Aoyama A, Sato T, Sonobe M, Date H.
    • Journal Title

      Gen Thorac Cardiovasc Surg

      Volume: -

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pulmonary function and exercise capacity in patients with flat chests after lung transplantation.2017

    • Author(s)
      Miyoshi R, Chen-Yoshikawa TF, Takahagi A, Oshima Y, Hjiya K, Motoyama H, Aoyama A, Date H.
    • Journal Title

      Ann Thorac Surg

      Volume: 104(5) Pages: 1695-1701

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytomegalovirus infection in living-donor and cadaveric lung transplantations.2017

    • Author(s)
      Ohata K, Chen-Yoshikawa TF, Takahashi K, Aoyama A, Motoyama H, Hijiya K, Hamaji M, Menju T, Sonobe M, Takakura S, Date H.
    • Journal Title

      Interact Cardiovasc Thorac Surg

      Volume: 25(5): Pages: 710-15

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Living-related lung transplantation.2017

    • Author(s)
      Date H.
    • Journal Title

      J Thorac Dis

      Volume: 9(9) Pages: 3362-71

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inverted lobes have satisfactory functions compared with noninverted lobes in lung transplantation.2017

    • Author(s)
      Kayawake H, Chen-Yoshikawa TF, Motoyama H, Hamaji M, Hijiya K, Aoyama A, Goda Y, Oda H, Ueda S, Date H.
    • Journal Title

      Ann Thorac Surg

      Volume: -

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Hydrogen-rich preservation solution attenuates lung ischemia-reperfusion injury after prolonged cold ischemia in a canine left lung transplant model.2019

    • Author(s)
      Hidenao Kayawake, Toyofumi F. Chen-Yoshikawa, Masao Saito, Shin-ichi Hirano, Hiroya Yamagishi, Fumiaki Gochi, Ryo Okabe, Junko Tokuno, Satoshi Ueda, Yuhei Yokoyama, Masaki Ikeda, Hiromi Oda, Yoshito Yamada, Yojiro Yutaka, Daisuke Nakajima, Akihiro Ohsumi, Masatsugu Hamaji, Hiroshi Date
    • Organizer
      ISHLT 2019 Annual Meeting and Scientific Sessions
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 水素含有臓器保存液は肺移植後の虚血再灌流障害を抑制する2019

    • Author(s)
      栢分秀直、陳豊史、齊藤正男、平野伸一、黒川亮介、山岸弘哉、岡部亮、合地史明、徳野純子、上田聡司、横山雄平、池田政樹、尾田博美、山田義人、豊洋次郎、中島大輔、大角明宏、濱路政嗣、伊達洋至
    • Organizer
      第36回日本呼吸器外科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Hydrogen-Rich Preservation Solution Attenuates Lung Ischemia-Reperfusion Injury after Prolonged Cold Ischemia in a Canine Left Lung Transplant Model2019

    • Author(s)
      栢分秀直、芳川豊史(陳)、齊藤正男、平野伸一、黒川亮介、山岸弘哉、岡部亮、合地史明、徳野純子、上田聡司、横山雄平、池田政樹、尾田博美、山田義人、豊洋次郎、中島大輔、大角明宏、濱路政嗣、伊達洋至
    • Organizer
      39TH ANNUAL MEETING of International Society for Heart and Lung Transplantation
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Living-donor lobar lung transplantation2017

    • Author(s)
      Hiroshi Date
    • Organizer
      The 25th Annual Meeting of Asian Society for Cardiovascular and Thoracic Surgery
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Surgery for N2 lung cancer2017

    • Author(s)
      Hiroshi Date
    • Organizer
      The 25th Annual Meeting of Asian Society for Cardiovascular and Thoracic Surgery
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Particle therpay for lung cancer – Is it as effective as surgery2017

    • Author(s)
      Hiroshi Date
    • Organizer
      The 56th Annual Conference of the Particle Therapy Co-Operative Group
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] New techstratgies in living-donor lobar lung transplantation Comparison of diseased donor and living donor lung transplantation Current concepts in lung preservation2017

    • Author(s)
      Hiroshi Date
    • Organizer
      The 15th Congress of the Asian Society of Transplantation
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 京都大学呼吸器外科

    • URL

      https://www.thoracic-kyoto-u.gr.jp

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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