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

Research Project

Project/Area Number 20H03763
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 55030:Cardiovascular surgery-related
Research InstitutionChiba 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
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2022: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2020: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywords虚血再灌流障害 / 心臓移植 / 心停止ドナー / IL-11 / post conditioning / 心停止下ドナー / 虚血再灌流 / Ex vivo perfusion
Outline of Research at the Start

ブタを用いて心停止下ドナーからの同所性心臓移植を行い、移植後の心機能の経時的変化および病理組織学的変化をIL-11投与群と非投与群で比較する。ドナー心が使用可能かどうかを判定する評価法を確立するために、生化学的指標の妥当性について検討する。ROSやMitochondrial permeability transition (MPT) poreの活性化、アポトーシスといった虚血再灌流障害にかかわる因子を網羅的に解析し、臨床で使用可能で感度、特異性の高い指標を確立する。

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.

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。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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