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

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08091
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: National 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
• 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

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.

Free Research Field

循環生理学

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。