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Combination of drinking behavior modulation with pharmacological vagal activation for treatment of chronic heart failure

Research Project

Project/Area Number 18K08091
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

Zheng Can  国立研究開発法人国立循環器病研究センター, 研究所, 特任研究員 (50443495)

Co-Investigator(Kenkyū-buntansha) 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, 上級研究員 (60443496)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords心不全 / 飲水制限 / 迷走神経刺激 / ドネペジル / 薬物治療 / 水分制限 / 飲水行動制御 / 飲水行動
Outline of Final Research Achievements

One of the fundamental problems facing developed countries with an aging society is lifestyle-related diseases and chronic heart failure that develops and progresses with aging. Despite advances in medical medication and the development of surgical treatments, including assisted circulatory devices, the prognosis for patients with heart failure is poor. Inadequate management of salt and water in patients with heart failure is one of the leading causes of readmission rates. Currently, it is recommended to limit daily water intake, but there is no evidence to support it. This study developed an automatic measure and control device that can control drinking behavior. We have verified whether the combination of fluid restriction and pharmaceutical vagal activation by donepezil, a cholinesterase inhibitor, is beneficial for chronic heart failure in a rat model.

Academic Significance and Societal Importance of the Research Achievements

心不全患者の塩分・水分管理の不徹底が再入院率の主な原因の一つである。現状では毎日の水摂取量制限を勧められるですが、その根拠となるエビデンスが示されてない。小まめに飲水パターンは、循環系に与える影響少ないために、生体内環境の恒常性維持有利の可能性があると考えられる。ドネペジルを慢性心不全の治療効果の機序は中枢経由で体内水バランスの調整にも役割することを示した。これらの成果は実験動物で初めでの報告ですので、心不全の水代謝の病態生理またドネペジルの作用機序に関する知識を深めるに役立つことと今後臨床応用研究への展開するために重要な実験的根拠になると考える。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (24 results)

All 2022 2021 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (20 results) (of which Int'l Joint Research: 6 results)

  • [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 Annual Research 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
      2021 Annual Research Report 2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chronic vagal nerve stimulation exerts additional beneficial effects on the beta-blocker-treated failing heart2018

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

      The Journal of Physiological Sciences

      Volume: 69 Issue: 2 Pages: 295-303

    • DOI

      10.1007/s12576-018-0646-0

    • NAID

      40021819001

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Low-Dose Landiolol Reduces Heart Rate and Cardiac Oxygen Consumption Without Compromising Initial Hemodynamic Resuscitation in a Canine Model of Endotoxin Shock2018

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

      Shock.

      Volume: Jul Issue: 1 Pages: 25-25

    • DOI

      10.1097/shk.0000000000001224

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] ドネペジルの投与によるSHR心筋梗塞ラットにおける心不全進行の抑制及び予後の改善作用2022

    • Author(s)
      李 梅花、鄭 燦、川田 徹、朔 啓太、杉町 勝
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Acetylcholinesterase Inhibition Prevents the Progression of Chronic Heart Failure in Obesity-induced Hypertensive Rats with Reperfused Myocardial Infarction2022

    • Author(s)
      Li M, Zheng C, Kawada T, Uemura K, Inagaki M, Saku K, Sugimachi M
    • Organizer
      第86回日本循環器学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Donepezil Treatment as a Novel Pharmacotherapy for Chronic Heart Failure with Renal Artery Stenosis-Induced Hypertension2022

    • Author(s)
      Li M, Zheng C, Kawada T, Uemura K, Inagaki M, Saku K, Sugimachi M
    • Organizer
      第86回日本循環器学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Abdominal Vagal Nerve Activation Markedly Contributes to Maintaining Hemodynamics After Acute Myocardial Infarction in Rats.2021

    • Author(s)
      Li M, Zheng C, Kawada T, Uemura K, Inagaki M, Sugimachi M
    • Organizer
      第85回日本循環器学会学術集会. 2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] Donepezil Markedly Suppresses the Progression of Cardiovascular Remodeling and Dysfunction in Obesity-induced Hypertensive Rats with Reperfused Myocardial Infarction2021

    • Author(s)
      Li M, Zheng C, Kawada T, Uemura K, Inagaki M, Sugimachi M
    • Organizer
      第85回日本循環器学会学術集会. 2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] Acetylcholinesterase Inhibition Prevents the Progression of Chronic Heart Failure and Renal Dysfunction in Renal Artery Stenosis-Induced Hypertensive Rats2021

    • Author(s)
      Li M, Zheng C, Kawada T, Uemura K, Inagaki M, Sugimachi M
    • Organizer
      第85回日本循環器学会学術集会. 2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] 急性心筋梗塞ラットの血行動態に対する腹部迷走神経活性化の影響2021

    • Author(s)
      李 梅花、鄭 燦、川田 徹、杉町 勝
    • Organizer
      第98回日本生理学会大会. 2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] ドネペジル投与による自然発症高血圧ラットにおける心筋梗塞後重症心不全の心機能・生存率の改善作用2021

    • Author(s)
      李 梅花、鄭 燦、川田 徹、上村 和紀、稲垣 正司、杉町 勝
    • Organizer
      第41回日本循環制御学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Daily fluid restriction improves survival rate in rats with chronic heart failure.2021

    • Author(s)
      Can Zheng, Meihua Li, Toru Kawada, Kazunori Uemura and Masashi Inagaki
    • Organizer
      第85回日本循環器学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Abdominal Vagal Nerve Activation Markedly Contributes to Maintaining Hemodynamics After Acute Myocardial Infarction in Rats2021

    • Author(s)
      Li M, Zheng C, Kawada T, Uemura K, Inagaki M, Nishikawa T, Sugimachi M.
    • Organizer
      第85回日本循環器学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Donepezil Markedly Suppresses the Progression of Cardiovascular Remodeling and Dysfunction in Obesity-induced Hypertensive Rats with Reperfused Myocardial Infarction.2021

    • Author(s)
      Li M, Zheng C, Kawada T, Uemura K, Inagaki M, Nishikawa T, Sugimachi M.
    • Organizer
      第85回日本循環器学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Acetylcholinesterase Inhibition Prevents the Progression of Chronic Heart Failure and Renal Dysfunction in Renal Artery Stenosis-Induced Hypertensive Rats.2021

    • Author(s)
      Li M, Zheng C, Kawada T, Uemura K, Inagaki M, Sugimachi M.
    • Organizer
      第85回日本循環器学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 急性心筋梗塞ラットの血行動態に対する腹部迷走神経活性化の影響.2021

    • Author(s)
      李 梅花,鄭 燦,川田 徹,杉町 勝.
    • Organizer
      第98回日本生理学会 (OP-12-2)
    • Related Report
      2020 Research-status Report
  • [Presentation] ドネペジル投与による自然発症高血圧ラットにおける心筋梗塞後重症心不全の心機能・生存率の改善作用.2021

    • Author(s)
      李 梅花,鄭 燦,川田 徹,上村 和紀,稲垣 正司,杉町 勝.
    • Organizer
      第41回日本循環制御医学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Donepezil as a novel therapy for suppressing the progression of cardiovascular remodeling in obesity-induced hypertensive rats with reperfused myocardial infarction.2020

    • Author(s)
      Li M, Zheng C, Kawada T, Inagaki M, Uemura K, Sugimachi M.
    • Organizer
      ESC 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Donepezil Markedly Prevents the Progression of Chronic Heart Failure and Renal Dysfunction in Renal Artery Stenosis-Induced Hypertensive Rats2020

    • Author(s)
      Li M, Zheng C, Kawada T, Uemura K, Inagaki M, Nishikawa T, Sugimachi M.
    • Organizer
      ESC 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [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 with APSC & AFC
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [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, Toshiaki Shishido, Sugimachi M.
    • Organizer
      ESC
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pericardiectomy decreases exercise capacity through elimination respiratory suction2018

    • Author(s)
      Can Zheng, Meihua Li, Toru Kawada, Masashi Inagaki, Kazunori Uemura, Masaru Sugimachi
    • Organizer
      欧州心臓病学会総会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Feasibility and Efficacy of Early Donepezil with or Without Metoprolol in Reperfused Myocardial Infarction Rats2018

    • Author(s)
      Meihua Li, Can Zheng, Toru Kawada, Masashi Inagaki, Kazunori Uemura, Masaru Sugimachi
    • Organizer
      欧州心臓病学会総会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2023-01-30  

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