2022 Fiscal Year Final Research Report

Functional assessment and cardio-protective post-conditioning strategies of the donor heart following circulatory death

Research Project

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Project/Area Number	20H03763
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 55030:Cardiovascular surgery-related
Research Institution	Chiba University
Principal Investigator	MATSUMIYA GORO 千葉大学, 大学院医学研究院, 教授 (20314312)
Co-Investigator(Kenkyū-buntansha)	黄野皓木千葉大学, 医学部附属病院, 講師 (40375803) 松浦馨千葉大学, 医学部附属病院, 助教 (50436375) 渡邉倫子千葉大学, 医学部附属病院, 助教 (20766274) 乾友彦千葉大学, 医学部附属病院, 助教 (70816503) 上田秀樹千葉大学, 医学部附属病院, 講師 (50738987)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	虚血再灌流障害 / 心臓移植 / 心停止ドナー / IL-11 / post conditioning
Outline of Final Research Achievements	This study aimed to determine the cardioprotective effect of interleukin-11 (IL-11) against warm ischemia-reperfusion injury, which is a key for successful donor after circulatory death heart transplantation. Rat hearts were procured, subjected to 25-minute warm ischemia, and re-perfused. IL-11 was administered before procurement and during reperfusion in the IL-11 group. Hemodynamic analyses demonstrated significantly favorable data in the IL-11 group throughout the reperfusion time. Although no apoptosis was observed in both groups, severely damaged mitochondria was observed in the control group while the mitochondrial structure was relatively preserved in the IL-11 group. Immunoblot analysis using cultured cardiomyocytes revealed phosphorylation of STAT3 at Ser727, which is known to act for mitochondrial protection. IL-11 may have a beneficial effect on the functional recovery after warm ischemia-reperfusion injury through protective effect of STAT3 against mitochondrial damage.
Free Research Field	心臓血管外科学
Academic Significance and Societal Importance of the Research Achievements	先進諸国の中で最も脳死下臓器提供が少なくドナー不足が深刻な問題であるわが国においては、近年欧米で臨床応用されるようになってきた心停止下ドナー（Donation after Circulatory death; DCD）からの心臓移植は進めるべき重要な課題である。本研究により、心停止から再灌流までの温阻血および虚血再灌流障害によるグラフト不全に対する対策として、IL-11を用いたpost-conditioning法が有用であることが示された。DCD心移植を実現するうえで、最も大きな懸念である移植後のグラフト不全を防止するために重要な知見と考えられ、臨床応用されれば社会的意義は大きい。