Hydrogen Perfusion & Inhalation in Liver Transplantation: When, Where, and How?

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04271
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Kyoto University
• Principal Investigator: Hata Koichiro 京都大学, 医学研究科, 准教授 (90523118)
• Co-Investigator(Kenkyū-buntansha): 上本 伸二 京都大学, 医学研究科, 教授 (40252449)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 水素 / 臓器保存 / 肝移植 / 虚血再灌流障害 / 単純冷保存 / HyFACS / 水素ガス

Outline of Final Research Achievements

Molecular hydrogen (H2) has the remarkable potential to selectively neutralize harmful reactive oxygen species, just leaving harmless H2O. Towards its clinical application, however, there are multiple obstacles including flammability, high diffusivity/permeability, and low solubility. Thus we developed a simple ex vivo conditioning, HyFACS (Hydrogen Flush After Cold Storage), that involves injecting unsaturated H2 solution directly into the blood vessels of cold-stored organs just before implantation. Moreover, we tested the additive effect combined with HyIAR (Hydrogen Inhalation After Reperfusion), the most common method of H2 application.
HyFACS provides the additive protection to cold-stored livers, combined with HyIAR. HyFACS seems to be useful as a simple end-ischemic preconditioning for solid organ transplantation.

Free Research Field

臓器保存、臓器移植

Academic Significance and Societal Importance of the Research Achievements

虚血再灌流障害（IRI）は固形臓器移植における宿命的課題である。IRIでは、虚血後の再酸素化による活性酸素種（ROS）の発生が種々の組織障害を惹起する。分子状水素（H2）には、組織障害性の強いROSを選択的に中和し、その最終産物は水であるという利点がある一方で、その臨床応用に向けては、可燃性、高拡散性/透過性、低溶解度など解決すべき複数の障壁がある。そこで我々は、H2の新たなDelivery SystemとしてHyFACS法を考案した。この新たな水素の応用法は “利点を生かし難点を減ずる”革新的なDDSであり、その保護効果、水素ガス吸入法との相加的保護効果を実証した。