Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury following heart transplantation in rats

• Project/Area Number: 15K20354
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Hyogo Medical University
• Principal Investigator: FUJISAKI NORITOMO 兵庫医科大学, 医学部, 助教 (90732644)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 虚血再灌流障害 / 一酸化炭素 / 心臓移植 / 心移植 / ドナー

Outline of Final Research Achievements

We hypothesized that the pretreatment with carbon monoxide (CO) gas before organ procurement effectively protected cardiac grafts from ischemia reperfusion (I/R)-induced injury in a rat heterotopic cardiac transplantation. CO-inhaled group improved serum troponin I, CPK, and reanimation time after I/R. Inflammatory cytokines mRNAs and migration of neutrophils and macrophages on the graft were decreased. VEGF, a potent growth factor that promotes differentiation and proliferation of endothelium and mediates vasodilatation, was increased by CO-inhalation. Our study showed CO-inhalation of donors was highly effective to provide potent anti-inflammatory effects against I/R injury. But the mechanisms by which CO potentiated the protective effects were unclear because we could not find the meaningful data from gene array analysis. CO treatment of potential organ donors can increase the future pool of organs suitable for transplantation, which could have a substantial clinical impact.

Research Products

• [Journal Article] Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury following heart transplantation in rats (2016)
  • Author(s): Noritomo Fujisaki, Keisuke Kohama, Takeshi Nishimura, Hayato Yamashita, Michiko Ishikawa, Akihiro Kanematsu, Taihei Yamada, Sungsoo Lee, Tetsuya Yumoto, Kohei Tsukahara, Joji Kotani, Atsunori Nakao
  • Journal Title: Medical Gas Research Volume: volume6 Issue: 3 Pages: 122-129
  • DOI: 10.4103/2045-9912.191357
  • Peer Reviewed / Open Access
• [Presentation] 一酸化炭素によるドナー前処置が及ぼすラット心臓移植後虚血再環流障害の予防効果 (2017)
  • Author(s): 藤崎宣友
  • Organizer: 日本救急医学会
• [Presentation] Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury following heart transplantation in rats (2016)
  • Author(s): Noritomo Fujisaki, Keisuke Kohama, Takeshi Nishimura, Hayato Yamashita, Michiko Ishikawa, Akihiro Kanematsu, Taihei Yamada, Sungsoo Lee, Tetsuya Yumoto, Kohei Tsukahara, Joji Kotani, Atsunori Nakao
  • Organizer: The 26th International Congress of The Transplantation Society
  • Place of Presentation: Hong Kong
  • Year and Date: 2016-08-20
  • Int'l Joint Research