The transition process, aggravating factor and therapeutic strategies from volume overload to heart failure

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H07135
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Applied pharmacology
• Research Institution: Toho University
• Principal Investigator: CAO Xin 東邦大学, 薬学部, 博士研究員 (40805652)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: 容量負荷 / 拡張不全

Outline of Final Research Achievements

The aims of this study were to evaluate the progression from creation of aorto-venocaval shunt (AVS) to diastolic heart failure (DHF), investigate the impact of chronic infusion of aldosterone on the development of DHF and find the potential therapeutic strategies. The time course of changes in cardiac function and structure were evaluated by echocardiography before surgery at 4, 12 and 24 weeks. Cardiopathy was characterized by atrial natriuretic peptide analysis, electrophysiologic and hemodynamic tests, morphometric and histological examinations at 24 weeks. AVS tended to gradually reduced ejection fraction, and impaired diatolic function acutely in 4 weeks and then kept them at a steady state until 24 weeks. Aldosterone decreased systolic function and accelerated the transition from diastolic dysfunction to systolic heart failure in the AVS rats. Amiroride suppressed inducibility of ventricular tachycardia.

Free Research Field

薬物治療学

Academic Significance and Societal Importance of the Research Achievements

本研究成果では、容量負荷がどのようにして生体内で拡張と収縮能に影響を与え、心不全を起こすのか、その進展過程を初めて証明した。また、アルドステロンによる圧負荷を介さない作用は心不全の収縮能に影響し、拡張障害から収縮障害への移行を促進したことを証明した。非選択制伸展活性化チャネル阻害剤は容量負荷による心室頻拍の誘発率を減少することができたことから、有効な、新しいタイプの心不全の治療薬開発の戦略構築が期待できる。