Integrative study on homeostasis and pathophysiology of cardiac metabolism-automaticity coupling

2024 Fiscal Year Final Research Report

• Project/Area Number: 23K24065
• Project/Area Number (Other): 22H02803 (2022-2023)
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Multi-year Fund (2024); Single-year Grants (2022-2023)
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: University of Fukui
• Principal Investigator: Matsuoka Satoshi 福井大学, 学術研究院医学系部門, 教授 (00263096)
• Co-Investigator(Kenkyū-buntansha): 竹田 有加里 福井大学, 学術研究院医学系部門, 助教 (20582159) ; 長谷川 奏恵 福井大学, 学術研究院医学系部門, 講師 (20770358)
• Project Period (FY): 2024-04-01 – 2025-03-31
• Keywords: 心臓 / 代謝 / グルコース / 自動能

Outline of Final Research Achievements

Effects of high glucose (25mM, HG) on the cardiac automaticity was investigated using mice hearts. In the analysis of cell contraction interval in isolated sinoatrial myocytes using Poincare plot, the HD application augmented both standard deviation along short axis which indicates short-term variation (SD1) and the one along long axis which indicates long-term variation (SD2). The HD application increased the amplitude of local Ca2+ release (LCR) and the frequency of LCR which appeared in early phase of cardiac cycle, and increased mitochondrial reactive oxygen species (ROS). In Langendorff heart experiments, the HD perfusion increased SD1 of RR interval. Taken together, it was suggested that the HD application to mouse heart increases ROS and alters LCR dynamics in sinoatrial myocytes, leading to impairment of automaticity and to heart rate variability.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

本研究はマウス心臓を用いて、高濃度グルコースが心臓自動能を障害し大きな心拍数変動を誘発することを初めて明らかにした。ヒトにおいては、食後に高血糖が起こることがあるが、本研究成果は、食後高血糖が心臓洞房結節自動能を直接障害し大きな心拍変動を引き起こす可能性を示す。