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Elucidation of the mechanism and optimization of the infarct size reduction effect of vagus nerve stimulation after reperfusion in acute myocardial infarction

Research Project

Project/Area Number 19K08504
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Inagaki Masashi  国立研究開発法人国立循環器病研究センター, 病院, 客員研究員 (80359273)

Co-Investigator(Kenkyū-buntansha) 杉町 勝  国立研究開発法人国立循環器病研究センター, 研究所, 客員研究員 (40250261)
李 梅花  国立研究開発法人国立循環器病研究センター, 研究所, 非常勤研究員 (60443496)
Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords臨床心臓病学 / 心筋梗塞 / 迷走神経 / 心不全 / 神経刺激
Outline of Research at the Start

本研究では、急性心筋梗塞に対する新しい治療法として再灌流後の短期的迷走神経刺激治療を確立して臨床応用に結び付けるために、迷走神経刺激による内在性心筋幹/前駆細胞の賦活化を介した心筋再生効果に着目して、治療機序の検討を行います。また、神経刺激刺激条件が心筋梗塞後の初期リモデリング抑制効果や不整脈抑制効果に及ぼす影響と、刺激条件が過度の心拍数・血圧低下、疼痛、咳嗽等の有害事象の発生に及ぼす影響を調査し、有効性・安全性の両視点からの最適な神経刺激条件の検討を行います。

Outline of Final Research Achievements

In this study, we established short-term vagus nerve stimulation therapy after reperfusion as a new treatment for acute myocardial infarction and aimed to link it to clinical application. We investigated (1) the therapeutic mechanism focusing on the anti-inflammatory and anti-apoptotic effects of vagus nerve stimulation, and (2) the optimal nerve stimulation conditions from the standpoints of both efficacy and safety.
(1) Vagus nerve stimulation therapy suppressed the infiltration of inflammatory macrophages, and suppressed apoptosis after myocardial infarction.
(2) Nerve stimulation for three days reduced infarct size. No significant effect on infarct size reduction was observed with nerve stimulation for 24 hours. No significant difference was observed in the effect on infarct size reduction between stimulation intensities that reduced heart rate by 10% and those that reduced heart rate by 5%.

Academic Significance and Societal Importance of the Research Achievements

心不全の患者数およびコストは世界的に増加の一途をたどっている(心不全パンデミック)。心不全患者の基礎疾患は心筋梗塞などの冠動脈疾患が最も多いことが報告されており、心筋梗塞後の心不全発症を防止する治療法の開発は急務である。急性心筋梗塞の再灌流障害や初期リモデリングを抑制して梗塞サイズを縮小するために様々な薬剤や遺伝子導入療法・再生医療が研究されてきたが、有効な治療法は確立されておらず、心筋梗塞後の心不全発症を十分に抑制できていない。このような状況に対して、「経皮経管的に行う短期的迷走神経刺激による急性心筋梗塞サイズの縮小」という新規治療法の確立は、心不全患者数の低減に大きく貢献する。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (10 results)

All 2024 2022 2021 2020 2019

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (6 results)

  • [Journal Article] Donepezil attenuates progression of cardiovascular remodeling and improves prognosis in spontaneously hypertensive rats with chronic myocardial infarction2024

    • Author(s)
      Li Meihua、Zheng Can、Kawada Toru、Uemura Kazunori、Yokota Shohei、Matsushita Hiroki、Saku Keita
    • Journal Title

      Hypertension Research

      Volume: 47 Issue: 5 Pages: 1298-1308

    • DOI

      10.1038/s41440-024-01629-3

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Early donepezil monotherapy or combination with metoprolol significantly prevents subsequent chronic heart failure in rats with reperfused myocardial infarction2022

    • Author(s)
      Meihua Li, Can Zheng, Toru Kawada, Kazunori Uemura, Masashi Inagaki, Keita Saku, Masaru Sugimachi
    • Journal Title

      The Journal of Physiological Sciences

      Volume: 72 Issue: 1 Pages: 12-12

    • DOI

      10.1186/s12576-022-00836-2

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of Peripheral α7-Nicotinic Acetylcholine Receptors on Cardioprotective Effects of Donepezil in Chronic Heart Failure Rats2021

    • Author(s)
      Li Meihua、Zheng Can、Kawada Toru、Inagaki Masashi、Uemura Kazunori、Akiyama Tsuyoshi、Sugimachi Masaru
    • Journal Title

      Cardiovascular Drugs and Therapy

      Volume: 35 Issue: 5 Pages: 877-888

    • DOI

      10.1007/s10557-020-07062-1

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 1.Intracerebroventricular infusion of donepezil prevents cardiac remodeling and improves the prognosis of chronic heart failure rats.2020

    • Author(s)
      i M, Zheng C, Kawada T, Inagaki M, Uemura K, Sugimachi M.
    • Journal Title

      J Physiol Sci

      Volume: 70 Issue: 1 Pages: 1-12

    • DOI

      10.1186/s12576-020-00739-0

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Donepezil Markedly Attenuates the Progression of Cardiac/Renal Remodeling in Rats with Renal Artery Stenosis-Induced Hypertension.2020

    • Author(s)
      Li M, Zheng C, Kawada T, Uemura K, Inagaki M, Hayama Y, Nishikawa T, Sugimachi M.
    • Organizer
      JCS 2020
    • Related Report
      2019 Research-status Report
  • [Presentation] Development of a Chronic Heart Failure Model by Renal Artery Stenosis-Induced Hypertension in Rats.2020

    • Author(s)
      Li M, Zheng C, Kawada T, Uemura K, Hayama Y, Nishikawa T, Inagaki M, Sugimachi M.
    • Organizer
      JCS 2020
    • Related Report
      2019 Research-status Report
  • [Presentation] Donepezil Treatment Prevents the Progression of Chronic Heart Failure and Improves the Prognosis in Spontaneously Hypertensive Rats with Myocardial Infarction.2020

    • Author(s)
      Li M, Zheng C, Kawada T, Uemura K, Inagaki M, Sugimachi M.
    • Organizer
      第97回日本生理学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 迷走神経刺激は心筋梗塞ラットにおける間葉系幹細胞移植の治療効果を増強する2020

    • Author(s)
      李 梅花、稲垣 正司、鄭 燦、川田 徹、上村 和紀、杉町 勝
    • Organizer
      第58回生体医工学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Oral Administration of Donepezil Markedly Prevents the Progression of Chronic Heart Failure in Renal Artery Stenosis-Induced Hypertensive Rats.2019

    • Author(s)
      Li M, Zheng C, Kawada T, Inagaki M, Uemura K, Sugimachi M.
    • Organizer
      ESC 2019
    • Related Report
      2019 Research-status Report
  • [Presentation] Chronic vagal nerve stimulation suppress thirst through decreasing vasopressin secretion in the rats with chronic heart failure2019

    • Author(s)
      C. Zheng, M. Li, K. Uemura, T. Kawada, M. Inagaki, M. Sugimachi
    • Organizer
      ESC Asia
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2025-01-30  

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