2022 Fiscal Year Final Research Report

Development of a novel strategy of circulatory management of septic shock with modulation of splanchnic hemodynamics.

Research Project

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Project/Area Number	20K09317
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	Kansai Medical University
Principal Investigator	KUWAGATA Yasuyuki 関西医科大学, 医学部, 教授 (50273678)
Co-Investigator(Kenkyū-buntansha)	室谷卓関西医科大学, 医学部, 講師 (20528434) 池側均関西医科大学, 医学部, 准教授 (80379198)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	敗血症性ショック / エンドトキシン / 恐怖臭物質 / 上腸間膜静脈血流 / 空腸粘膜組織血流
Outline of Final Research Achievements	This study aimed to explore a novel strategy of circulatory management of septic shock with modulation of splanchnic hemodynamics. We focused on 2-methyl-2thiazoline (2MT), which has been reported to inhibit inflammatory cytokines in septic animals. 2MT is one of the thiazoline-related fear odors, which were developed as a group of artificial odor molecules that induce innate fear-related behaviors in animals. A single i.v. dose of 2MT at 80mg increased arterial pressure without changes in cardiac output in intact rabbits, indicating that 2MT acts as a simple vasoconstrictor. 2MT at the same dosage significantly inhibited LPS-induced hemodynamic derrangement as indicated by restoration of MAP and improvement of blood flow both in superior mesenteric vein and jejunal mucosal tissue. 2MT may play a significant role in the development of a novel circulatory management against septic shock.
Free Research Field	救急医学
Academic Significance and Societal Importance of the Research Achievements	敗血症性ショックは、現在集中治療室内における死因の１位をしめる病態である。その理想的な治療法は、病的な血管運動姓メディエータの制御であるが、いまだ成し遂げられていない。国際診療ガイドラインにおいてもnoradrenalineなどの血管収縮薬投与による対症療法に終始しているのが現実である。本研究は人工臭気物質の一つである2MTが、現行の血管収縮薬投与でもっとも虚血の生じやすい部位である腸管粘膜血流を維持しながら腸管循環の病的血管抵抗減弱を制御し、体循環のショックを改善することを明らかにした。臓器虚血の発生を阻止しながら敗血症性ショックを治療する可能性を示唆しており、学術的・社会的意義は大きい。