Elucidation of the pathogenesis of severe heat stroke and exploration of novel therapeutic approaches for vascular endothelial dysfunction

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09033
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Kurume University
• Principal Investigator: Hirayu Nobuhisa 久留米大学, 医学部, 助教 (00647745)
• Co-Investigator(Kenkyū-buntansha): 高須 修 久留米大学, 医学部, 教授 (90236216)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 重症熱中症 / 血管内皮障害 / 細胞外小胞 / ミトコンドリア

Outline of Final Research Achievements

Heatstroke has been increasing in recent years, but there are still many unknown aspects about the pathophysiology of severe cases leading to organ failure and death. Currently, cooling is the only established treatment. This study involved creating a heatstroke mouse model, investigating the direct effects of high temperatures, and exploring potential new treatments. We created a high temperature and high humidity environment to induce heatstroke in mice, causing an increase in intraperitoneal temperature. In cultured HUVEC cells, increasing the incubator temperature resulted in vascular endothelial injury. Heating blood samples indicated coagulation disorders as suggested by blood viscoelasticity tests. For new treatments, we focused on mitochondria and evaluated Mito-EVs from plasma using Nanosight and flow cytometry. In heated EVs samples, the mean fluorescence intensity decreased, indicating mitochondrial dysfunction due to heating.

Free Research Field

熱中症、救急集中治療、血管内皮障害

Academic Significance and Societal Importance of the Research Achievements

本研究は、重症熱中症における臓器障害の病態解明と新規治療法の探索について行った。高温環境が凝固障害、血小板の活性化、血管内皮障害を引き起こすことが示唆された。現在の重症熱中症診療における治療の根幹は、素早く体温を下げることにあるがそれを裏付ける病態と考えられる。さらに、加温によるmitochondriaの機能不全を示唆する結果を得て、新規治療の可能性を探る基礎を築いた。これにより、冷却以外の新規治療法探索の一助となり、今後の熱中症治療の進展が期待され、社会的にも有益な成果といえる。