| Project/Area Number |
16K08682
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Showa University (2017-2019)
Kyoto Prefectural University of Medicine (2016) |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | 刺激伝導系 / 不整脈原性器質 / プルキンエ線維 / 心室性不整脈 / カルシウム動態 / 虚血 / 病理形態 / 不整脈器質 / 病理組織学 / 異常伝導路 / 右室流出路 / 心筋配列 / 再分極異常 / 異常興奮 / 組織学 / 病理学 / 循環器 / 不整脈 |
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| Outline of Final Research Achievements |
Recently, the region of right ventricular outflow tract (RVOT) has been highlighted as an arrhythmogenic substrate, however, its morphologic characteristics for arrhythmogenesis still remains unclear. In the present study, we assumed that the endocardial Purkinje fiber network is a crucial arrhythmogenic structure in the ventricle, and visualized electrical excitation patterns and intracellular calcium dynamics using fluorescent imaging in mouse heart myocardial infarct model. Irregular and slower impulse propagations were observed at the bordr of the infarction, and Purkinje fibers in the peri-infarct zone exhibited non-uniform intracellular calcium dynamics (beat-to-beat alternans of the calcium transient). This electrical vulnerability of the Purkinje fiber network under ischemic condition was observed as the unstable intracellular calcium dynamics at the border of the infarcted area. This phenomenon might be associated with the genesis of lethal ventricular arrhythmia.
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| Academic Significance and Societal Importance of the Research Achievements |
致死性不整脈の発生源の一つとして心室内の特殊な構造で刺激伝導系の末梢にあるプルキンエ線維の存在が臨床的にも注目されているが、実際にどのように機能障害を生じて不整脈源性を発揮しているのは明らかではない。本研究では心室性不整脈の発生につながる可能性のある電気生理学的異常がどのような形態学的基盤を基にして生じているのかを肉眼的かつ組織学的にも視覚的に示すことができた。心室の致死性不整脈の発生機序を解明する上で、このような生きた心臓の電気生理学的現象の視覚的情報はその病態の理解を深め、さらにそれに対するより有効な治療方法の開発の一助となる可能性を秘めている。
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