Lung repair by inhalation therapy during ex-vivo lung perfusion for lung transplantation from donation after circulatory death

• Project/Area Number: 26293315
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Kyoto University
• Principal Investigator: Date Hiroshi 京都大学, 医学(系)研究科(研究院), 教授 (60252962)
• Co-Investigator(Kenkyū-buntansha): 陳 豊史 京都大学, 医学(系)研究科(研究院), 講師 (00452334) ; 小池 薫 京都大学, 医学(系)研究科(研究院), 教授 (10267164) ; 佐藤 寿彦 京都大学, 医学(系)研究科(研究院), 准教授 (40388822) ; 青山 晃博 京都大学, 医学(系)研究科(研究院), 助教 (60379047) ; 佐藤 雅昭 京都大学, 医学(系)研究科(研究院), 助教 (00623109) ; 山田 徹 京都大学, 医学(系)研究科(研究院), 助教 (90534347)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000); Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2015: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2014: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
• Keywords: lung transplantation / ex-vivo lung perfusion / inhalation therapy / circulatory death / surfactant / 心停止ドナー / 肺移植 / サーファクタント / Ex vivo lung perfusion / 肺傷害

Outline of Final Research Achievements

Severe shortage of brain dead donor is unsolved problem in Japan. Lung transplantation from donation after circulatory arrest (DCD) may increase the donor pool. Ex-vivo lung perfusion (EVLP) is a potential modality to repair lung injury caused by warm ischemic change. Beagle lungs were harvested 150 minutes after circulatory arrest and perfused by EVLP for 4 hours and these lungs were implanted to the recipient animal. Inhalation with β2 adrenoreceptor agonist and surfactant during EVLP significantly improved lung function after transplantation. These results suggested that lung transplantation for DCD donor is possible.

Research Products

• [Journal Article] Stenosis of the segmental bronchus is a characteristic airway complication in living-donor lobar lung transplantation. (2016)
  • Author(s): Miyamoto E. Chen-Yoshikawa TF, Higuchi H, Aoyama A, Date H.
  • Journal Title: J Heart Lung Transplant Volume: 35(3) Pages: 389-92
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhibition of Toll-like recetor 4 signaling ameliorates lung ischemia-reperfusion injury in acute hyperglycemic conditions. (2016)
  • Author(s): Takahashi M, Chen-Yoshikawa TF, Menju T, Ohata K, Kondo T, Motoyama H, Hijiya K, Aoyama A, Date H.
  • Journal Title: J Heart Lung Transplant 35(6):815-22 Volume: J35(6) Pages: 815-22
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Vascular endothelial-cadherin expression after reperfusion correlates with lung injury in rat lung transplantation. (2016)
  • Author(s): Tanaka S, Chen-Yoshikawa TF, Miyamoto E, Takahashi M, Ohata K, Kondo T, Hijiya K, Motoyama H, Aoyama A, Date H.
  • Journal Title: Ann Thorac Surg Volume: 101(6) Pages: 2161-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Bronchodilator inhalation during ex vivo lung perfusion improves posttransplant graft function after warm ischemia. (2016)
  • Author(s): Hijiya K, Chen-Yoshikawa TF, Kondo T, Motoyama H, Ohsumi A, Nakajima D, Sakamoto J, Ohata K, Takahashi M, Tanaka S, Miyamoto E, Aoyama A, Date H.
  • Journal Title: Ann Thorac Surg Volume: -
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Protective effect of inhaled Rho-kinase inhibitor on lung ischemia-reperfusion injury. (2016)
  • Author(s): Ohata K, Chen-Yoshikawa TF, Menju T, Miyamoto E, Tanaka S, Takahashi M, Motoyama H, Hijiya K, Aoyama A, Date H.
  • Journal Title: Ann Thorac Surg Volume: -
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Protective effects of Imatinib on ischemia/reperfusion injury in rat lung. (2016)
  • Author(s): Tanaka S, Chen-Yoshikawa TF, Kajiwara M, Menju T, Ohata K, Takahashi M, Kondo T, Hijiya K, Motoyama H, Aoyama A, Masuda S, Date H.
  • Journal Title: Ann Thorac Surg Volume: 102(5) Pages: 1717-1724
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Malignancies after living-donor and cadaveric lung transplantation in Japanease patients. (2016)
  • Author(s): Tanaka S, Chen-Yoshikawa TF, Yamada T, Hijiya K, Motoyama H, Aoyama A, Date H.
  • Journal Title: Surg Today Volume: 46(12) Pages: 1415-19
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Outcomes of various transplant prodedures (single, sparing, inverted) in living-donor lobar lung transplantation. (2016)
  • 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: -
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Immune function monitoring in lung transplantation using adenosine triphosphate production: time trends and relationship to postoperative infection. (2016)
  • 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: -
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel thermographic detection of regional malperfusion caused by a thrombosis during ex vivo lung perfusion. (2015)
  • Author(s): Motoyama H, Chen F, Hijiya K, Kondo T, Ohata K, Takahashi M, Yamada T, Sato M, Aoyama A, Date H.
  • Journal Title: Interact Cardiovasc Thorac Surg Volume: 20(2) Pages: 242-7
  • Peer Reviewed / Open Access
• [Journal Article] Unilateral chronic lung allograft dysfunction is a characteristic of bilateral living-donor lobar lung transplantation. (2015)
  • Author(s): Miyamoto E, Chen F, Aoyama A, Sato M, Yamada T, Date H.
  • Journal Title: Eur J Cardiovasc Surg Volume: 48(3) Pages: 463-9
  • Peer Reviewed / Open Access
• [Journal Article] β2-adrenoreceptor agonist inhalation during ex vivo lung perfusion attenuates lung injury. (2015)
  • Author(s): Kondo T, Chen F, Ohsumi A, Hijiya K, Motoyama H, Sowa T, Ohata K, Takahashi M, Yamada T, Sato M, Aoyama A, Date H.
  • Journal Title: Ann Thorac Surg Volume: 100(2) Pages: 480-6
  • Peer Reviewed / Open Access
• [Journal Article] Living-donor lobar lung transplantation provides similar survival to cadaveric lung transplantation even for very ill patients. (2014)
  • Author(s): Date H, Sato M, Aoyama A, Yamada T, Mizota T, Kinoshita H, Handa T, Tanizawa K, Chin K, Minakata K, Chen F.
  • Journal Title: Eur J Cardiovasc Surg Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] Effect of hypogammaglobulinemia after lung transplantation: a single-institutional study. (2014)
  • Author(s): Ohsumi A, Chen F, Yamada T, Sato M, Aoyama A, Bando T, Date H.
  • Journal Title: Eur J Cardiovasc Surg Volume: 45(3)
  • Peer Reviewed / Open Access
• [Journal Article] Qwantitative evaluation of native lung hyperinflation after single lung transplantation for emphysema using three-dimensional computed tomography volumetry. (2014)
  • Author(s): Motoyama H, Chen F, Ohsumi A, Hijiya K, takahashi M, Ohata K, Yamada T, Sato M, Aoyama A, bando T, Date H.
  • Journal Title: Transplant Proc Volume: 46(3) Pages: 941-3
  • Peer Reviewed / Open Access
• [Journal Article] Plasmin administration during ex vivo lung perfusion ameliorates lung ischemia-reperfusion injury. (2014)
  • Author(s): Motoyama H, Chen F, Hijiya K, Kondo T, Ohsumi A, Yamada T, Sato M, Aoyama A, Bando T, Date H.
  • Journal Title: J Heart Lung Transplant Volume: 33(10) Pages: 1093-9
  • Peer Reviewed / Open Access
• [Journal Article] Unilateral chronic lung allograft dysfunction is a characteristic of bilateral living-donor lobar lung transplantation. (2014)
  • Author(s): Miyamoto E, Chen F, Aoyama A, Sato M, Yamada T, Date H.
  • Journal Title: Eur J Cardiovasc Surg Volume: -
  • Peer Reviewed / Open Access
• [Presentation] Current topics in lung transplantation (2016)
  • Author(s): Hiroshi Date
  • Organizer: The 24th Annual Meeting of Asian Society for Cardiovascular and Thoracic Surgery
  • Place of Presentation: Taipei,Taiwan
  • Year and Date: 2016-04-07
  • Int'l Joint Research
• [Presentation] Living-donor lobar lung transplantation provides similar survival to cadaveric lung transplantation even for sicker patients. (2014)
  • Author(s): Hiroshi Date, Akihiro Aoyama, Masaaki Sato, Tetsu Yamada, Kyoko Hijiya, takeshi Kondo, Hideki Motoyama, Mamoru Takahashi, Keiji Ohata, Fegshi Chen
  • Organizer: 22nd European Conference on General Thoracic Surgery
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2014-06-15 – 2015-06-18
• [Presentation] Long-term results after surgical treatment for 1,763 lung cancer patients with interstitial lung diseases – should it be done? (2014)
  • Author(s): Hiroshi Date, Toshihiko Sato, Satoshi Teramukai, Atsushi Watanabe, Kazuma Kishi, Masahito Ebina, Yukihiko Sugiyama, Haruhiko Kondo,
  • Organizer: 94th Annual Meeting of American Association for Thoracic Surgery
  • Place of Presentation: Canada,Toronto
  • Year and Date: 2014-04-26 – 2014-04-30
• [Book] 肺移植、弦間昭彦（編）呼吸器疾患診療最新ガイドライン (2014)
  • Author(s): 伊達洋至
  • Total Pages: 15
  • Publisher: 総合医学社
• [Remarks] 京都大学呼吸器外科
  • URL: http://www.thoracic-kyoto-u.gr.jp