2022 Fiscal Year Final Research Report

Development of the machine perfusion and non-invasive assessement of marginal cardiac grafts

Research Project

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Project/Area Number	20K08974
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55010:General surgery and pediatric surgery-related
Research Institution	Hokkaido University
Principal Investigator	Fukai Moto 北海道大学, 医学研究院, 特任講師 (60374344)
Co-Investigator(Kenkyū-buntansha)	新宮康栄北海道大学, 医学研究院, 講師 (30617064) 暮地本宙己東京慈恵会医科大学, 医学部, 講師 (60632841) 木村太一北海道大学, 医学研究院, 客員研究員 (90435959) 藤好真人北海道大学, 医学研究院, 客員研究員 (90844720)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	心移植 / 臓器灌流 / 虚血再灌流傷害 / 重水 / 心臓
Outline of Final Research Achievements	We found that heavy water containing orginal preservation solution improved the graft survival rate in an extended cold preservation and subsequent heterotopic heart transplantation in rats. The metabolome analysis revealed the similar profiles in grafts preservaed in the new prervation solution at the end of cold presservation and that of normal heart without preservation. Only in the UW-preserved group, the metabolomics profile was quite different. However, in Langendorff perfusion model, the superiority of the new preservation solution was abolished. To explain the discrepncy, we established the methods of osmium maceration SEM to observe the ultrastructure, flavonoids (Ribflavin, FMN, FAD) measuremetn by HPLC with fluorescent detector, and metabolome with NMR detection were established. Furthermore, reduction of cold preservation injury was shown in water-soluble polyphenol "X" together with the direct scavenging of radicals and the activation od Nrf2.
Free Research Field	臓器移植
Academic Significance and Societal Importance of the Research Achievements	新規臓器保存液や新規抗酸化物を用いた心臓の冷保存障害軽減法を提示し、ミトコンドリアが保護されることを代謝物profileや超微形態変化によって明らかにした。不可能とされた長時間冷保存の可能性を示し、空輸から陸送への転換、コスト削減、安全性向上が見込まれる。学術的には、重水の生物活性、オスミウム浸軟SEM法による超微形態評価、新規抗酸化物の効果などの新規性がある。今後、proteomics解析が進めば、ミトコンドリア、小胞体、ゴルジ装置に特異的なたんぱく質の変化が見いだされる可能性があり、免疫電顕法との組み合わせにより、新たな臓器障害の様式、修復の標的が明らかになる可能性がある。