Development of a new pharmacotherapy for heart failure using alpha-2 adrenergic agonists

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09110
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: SHIMIZU Shuji 国立研究開発法人国立循環器病研究センター, 研究所, 研究員 (80443498)
• Co-Investigator(Renkei-kenkyūsha): KAWADA Toru 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (30243752) ; AKIYAMA Tsuyoshi 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 (70202554)
• Research Collaborator: FUKUMITSU Masafumi
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 心不全 / α２アドレナリン受容体作動薬 / デクスメデトミジン / 心臓交感神経 / 心臓迷走神経

Outline of Final Research Achievements

Animal experiments were performed to investigate therapeutic effects of alpha-2 adrenergic agonist-induced cardiac vagal activation on chronic heart failure. Ninety days survival was observed in doxorubicin-induced cardiomyopathy mice treated with dexmedetomidine or guanfacine. Because both alpha-2 adrenergic agonists did not improve 90 days survival in mice, several acute experimental studies using normal rats were added. These studies revealed that alpha-2 adrenergic agonists centrally suppressed cardiac sympathetic nerve activity but increased peripheral vascular resistance. Therefore, therapeutic benefits of alpha-2 adrenergic agonists on chronic heart failure may be dependent on the balance between sympatholytic effect and increased ventricular afterload in addition to cardiac vagal enhancement.

Free Research Field

循環生理学