Experimental study to repair non-heart beating donor lung using ex-vivo lung perfusion for clinical application

• Project/Area Number: 23390333
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic 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): 小池 薫 京都大学, 医学(系)研究科 (10267164) ; 板東 徹 京都大学, 医学(系)研究科 (20293954) ; 阪井 宏彰 京都大学, 医学(系)研究科 (50362489) ; 陳 豊史 京都大学, 医学(系)研究科 (00452334) ; 佐藤 寿彦 京都大学, 医学(系)研究科 (40388822) ; 庄司 剛 京都大学, 医学研究科, 助教 (80402840) ; 藤永 卓司 京都大学, 医学研究科, 助教 (00444456)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2013: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2011: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
• Keywords: 心停止ドナー肺 / 肺移植 / EVLP / 心臓死ドナー / 障害肺 / 心停止ドナー / 肺灌流 / 低温EVLP / 冷保存 / 肺潅流

Research Abstract

One of the main obstacles in performing cadaveric lung transplantation from brain dead donor is shortage of available donor, especially in Japan. The purpose of this experimental animal study was to establish a clinically applicable method for lung transplantation utilizing non-heart-beating donors. The donor lungs obtained after cardiac arrest without heparinization were repaired by ex-vivo lung perfusion (EVLP) and were implanted to the recipient animal. Three experimental studies were conducted during 2011-13. 1) EVLP provided better lung preservation than cold static preservation using a canine left lung transplantation model in 2011. 2) Hypothermic EVLP repaired warm ischemic lung injury in a rat perfusion model in 2012. 3) Short term hypothermic EVLP repaired warm ischemic lung injury in a canine left lung transplantation model in 2013.

Research Products

• [Journal Article] Prognostic factors for patients in postoperative brain metastases from surgically resected non-small cell lung cancer. (2014)
  • Author(s): Sakamoto J, Sonobe M, Kobayashi M, Ishikawa M, Kikuchi R, Nakajima D, Yamada T, Nakayama E, Takahashi T, Sato T, Chen F, Bando T, Date H.
  • Journal Title: Int J Clin Oncol Volume: 19 Pages: 50-6
  • Peer Reviewed
• [Journal Article] Protective effect of surfactant inhalation against warm ischemic injury in an isolated rat lung ventilation model (2013)
  • Author(s): Ohsumi A, Chen F, Sakamoto J, Nakajima D, Kobayashi M, Bando T, Date H
  • Journal Title: PLoS One Volume: 8(8) Issue: 8 Pages: e72574-e72574
  • DOI: 10.1371/journal.pone.0072574
  • NAID: 120005324900
  • Peer Reviewed
• [Journal Article] Protective effect of plasmin in marginal donor lungs in an ex vivo lung perfusion model (2013)
  • Author(s): Motoyama H, Chen F, Ohsumi A, Hijiya K, Okita K, Nakajima D, Sakamoto J, Yamada T, Sato M, Aoyama A, Bando T, Date H
  • Journal Title: J Heart Lung Transplant Volume: 32(5) Issue: 5 Pages: 505-10
  • DOI: 10.1016/j.healun.2013.02.007
  • Peer Reviewed
• [Journal Article] Incidence and pattern of hemolytic anemia after minor ABO-mismatch living-donor lobar lung transplantation. (2013)
  • Author(s): Ohsumi A, Chen F, Yurugi K, Maekawa T, Shoji T, Sato M, Aoyama A, Bando T, Date H.
  • Journal Title: Surg Today Volume: 43 Pages: 1250-3
  • NAID: 120005526704
  • Peer Reviewed
• [Journal Article] Adaptation over a wide range of donor graft lung size discrepancies in living-donor lobar lung transplantation. (2013)
  • Author(s): Chen F, Kubo T, Yamada T, sato M, Aoyama A, Bando T, Date H.
  • Journal Title: Am J Transplant Volume: 13 Pages: 1336-42
  • Peer Reviewed
• [Journal Article] Postoperative respiratory management in living-donor lobar lung transplantation. (2013)
  • Author(s): Chen F, Chin K, Sato M, Aoyama A, Murase k, Azuma M, Bando T, Date H.
  • Journal Title: Clin Transplant. Volume: 27
  • Peer Reviewed
• [Journal Article] Protective effect of surfactant inhalation against warm ischemic injury in an isolated rat lung ventilation model. (2013)
  • Author(s): Ohsumi A, Chen F, Sakamoto J, Nakajima D, Kobayashi M, Bando T, Date H.
  • Journal Title: J Heart Lung Transplant Volume: 32 Pages: 505-10
  • NAID: 120005324900
  • Peer Reviewed
• [Journal Article] Reconditioning lungs donated after cardiac death using short-term hypothermic machine perfusion (2012)
  • Author(s): Nakajima D, Chen F, Okita K, Motoyama H, Hijiya K, Ohsumi A, Sakamoto J, Yamada T, Sato M, Aoyama A, Bando T, Date H
  • Journal Title: Transplantation 2012 Volume: 94(10) Issue: 10 Pages: 999-1004
  • DOI: 10.1097/tp.0b013e31826f632e
  • NAID: 120005398546
  • Peer Reviewed
• [Journal Article] Therapeutic Effect of Surfactant Inhalation during Warm Ischemia in an Isolated Rat Lung Perfusion Model (2012)
  • Author(s): Ohsumi A, Chen F, Nakajima D, Sakamoto J, Yamada T, Fujinaga T, Shoji T, Sakai H, Bando T, Date H
  • Journal Title: Transpl Int Volume: 25(10) Issue: 10 Pages: 1096-105
  • DOI: 10.1111/j.1432-2277.2012.01532.x
• [Journal Article] The effect of beta-2 adrenoreceptor agonist inhalation on lungs donated after cardiac death in a canine lung transplantation model (2012)
  • Author(s): Sakamoto J, Chen F, Nakajima D, Yamada T, Ohsumi A, Zhao X, Sakai H, Bando T, Date H
  • Journal Title: J Heart Lung Transplant Volume: 31(7) Pages: 773-9
• [Journal Article] Reconditioning of The Lungs from Non-Heart-Beating Donors with Normothermic Ex Vivo Lung Perfusion (2012)
  • Author(s): Nakajima D, Chen F, Yamada T, Sakamoto J, Ohsumi A, Bando T, Date H
  • Journal Title: J Heart Lung Transplant Volume: 31(2) Pages: 187-93
• [Journal Article] Reconditioning of lungs donated after circulatory death with normothermic ex vivo lung perfusion (2012)
  • Author(s): Nakajima D, et al
  • Journal Title: The Journal of Heart and Lung Transplantation Volume: 31 Issue: 2 Pages: 187-93
  • DOI: 10.1016/j.healun.2011.11.007
  • Peer Reviewed
• [Journal Article] Effect of pre-procurement ventilation on lungs donated after cardiac death in a canine lung transplantation model (2011)
  • Author(s): Sakamoto J, Chen F, Yamada T, Nakajima D, Ohsumi A, Kikuchi R, Zhao X, Fujinaga T, Shoji T, Sakai H, Bando T, Date H
  • Journal Title: Transplantation Volume: 92(8) Pages: 864-70
  • NAID: 120004995874
• [Journal Article] Hypothermic machine perfusion ameliorates ischemia-reperfusion injury in rat lungs from non-heart-beating donors (2011)
  • Author(s): Nakajima D, Chen F, Yamada T, Sakamoto J, Osumi A, Fujinaga T, Shoji T, Sakai H, Bando T, Date H
  • Journal Title: Transplantation Volume: 92(8) Pages: 858-63
• [Presentation] Reconditioning of lungs donated after cardiac deathwith short-term hypothermic machine perfusion (2012)
  • Author(s): Nakajima D, Chen F, Okita K, Motoyama H, Hijiya K, Ohsumi A, Sakamoto J, Yamada T, Sato M, Aoyama A, Bando T, Date H
  • Organizer: CO10.02 XXIV International Congress of The Transplantation Society Berlin
  • Place of Presentation: Germany
• [Presentation] Protective effect of plasmin for the non-heparinized donor lungs after cardiac death (2012)
  • Author(s): Motoyama H, Chen F, Ohsumi A, Hijiya K, Okita K, Nakajima D, Sakamoto J, Yamada T, Sato M, Aoyama A, Bando T, Date H
  • Organizer: PO10.36 XXIV International Congress of The Transplantation Society Berlin
  • Place of Presentation: Germany
• [Presentation] Prophylactic Surfactant Inhalation Attenuates Warm Ischemic Injury in Rat Lungs from Donation after Cardiac Death Donors (2012)
  • Author(s): Ohsumi A, Chen F, Nakajima D, Sakamoto J, Kobayashi M, Yamada T, Fujinaga T, Shoji T, Sakai H, Bando T, Date H
  • Organizer: CO33.08 XXIV International Congress of The Transplantation Society Berlin
  • Place of Presentation: Germany
• [Presentation] Beta2-ADRENORECEPTOR AGONIST INHALATION AMELIORATES ISCHEMIA REPERFUSION INJURY FOLLOWING LUNG TRANSPLANTATION FROM NON-HEART-BEATING DONORS IN A CANINE MODEL. PB 5-2 (2011)
  • Author(s): Jin Sakamoto, Fengshi Chen, Daisuke Nakajima, Tetsu Yamada, Akihiro Ohsumi, Takuji Fujinaga, Tsuyoshi Shoji, Hiroaki Sakai, Toru Bando, Hiroshi Date
  • Organizer: The 12th Congress of the Asian Society of Transplantation
  • Place of Presentation: Seoul
• [Presentation] Prophylactic surfactant inhalation ameliorates ischemia-reperfusion injury in rat lungs from donation after cardiac death donors. OB 5-3 (2011)
  • Author(s): Akihiro Ohsumi, Fengshi Chen, Daisuke Nakajima, Jin Sakamoto, Tetsu Yamada, Takuji Fujinaga, Tsuyoshi Shoji, Hiroaki Sakai, Toru Bando, Hiroshi Date
  • Organizer: The 12th Congress of the Asian Society of Transplantation
  • Place of Presentation: Seoul
• [Remarks]
  • URL: http://www.thoracic-kyoto-u.gr.jp/