| Project/Area Number |
26461074
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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 |
Cardiovascular medicine
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| Research Institution | Nagasaki University |
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Principal Investigator |
TSUJI Yukiomi 長崎大学, 医歯薬学総合研究科(医学系), 講師 (60432217)
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| Co-Investigator(Kenkyū-buntansha) |
本荘 晴朗 名古屋大学, 環境医学研究所, 准教授 (70262912)
山崎 正俊 東京大学, 大学院工学系研究科, 特任助教 (30627328)
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| Co-Investigator(Renkei-kenkyūsha) |
MAKITA Naomasa 長崎大学, 医歯薬学総合研究科(医学系), 教授 (00312356)
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| Research Collaborator |
DOBREV Dobromir
NATTEL Stanley
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 心室細動 / トルサード・ド・ポアンツ / CaMKII / 遅延ナトリウム電流 / 電気的ストーム / 植込み型除細動器 / 心臓電気生理学 / 心室細動ストーム / カルモジュリンキナーゼ |
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| Outline of Final Research Achievements |
To elucidate mechanisms of ventricular tachycardia and fibrillation (VT/VF), we studied a rabbit model of electrical storm featuring multiple defibrillator-firings for repetitive VT/VF by electrical remodeling (QT-prolongation) due to chronic atrioventricular block. Optical mapping revealed that although a vortex-like reentrant activity called a rotor underlies both VT and VF, they have the rotor frequency and dynamics particular to themselves. VT resulted from a rotor in the distinctive manner, possibly explaining the ECG pattern of Torsades de Pointes (TdP), and VF was sustained by a high frequency stable rotor. Late Na-current was a major contributor to the substrate favoring TdP-related rotor, based on our findings that Na-channel Nav1.5 was hyperphosphorylated by Ca/calmodulin-dependent protein kinase II and that late Na-current blockade with lidocaine suppressed TdP. Conversion to a rapidly stationary rotor from a disease-specific rotor may be essential for VT-transition to VF.
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