| Project/Area Number |
24591076
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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 |
Circulatory organs internal medicine
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Research Collaborator |
AI Tomohiko Indiana University School of Medicine, IN, USA, Krannert Institute of Cardiology
LIN Shien-Fong Indiana University School of Medicine, IN, USA, Krannert Institute of Cardiology
CHEN Peng-Sheng Indiana University School of Medicine, IN, USA, Krannert Institute of Cardiology
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
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| Keywords | 心室細動 / 除細動 / 細胞内カルシウム / ATP感受性カリウムチャネル / 電気的ストーム |
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| Outline of Final Research Achievements |
This study tested the hypothesis that late phase 3 early afterdepolarization(EAD)induced by IKATP activation underlies the mechanisms of electrical storm (ES). Intracellular Ca(Cai) and membrane voltage were optically mapped in 32 Langendorff-perfused normalrabbit hearts. Repeated episodes of electrically induced ventricular fibrillation (VF) at baseline did not result in spontaneousVF (SVF). During isoproterenolinfusion, SVF occurred in 1 of 15 hearts studied in normal extracellular K([K+]o, 4.5M), 3 of 8 hearts in 2.0M[K+]o, 9 of 10 hearts in 1.5M [K+]o, and 7 of 7 hearts in 1.0M[K+]o (P<.001). Optical mapping showed that isoproterenol and hypokalemia enhanced Cai transient duration(CaiTD) and heterogeneously shortened action potential duration (APD) after defibrillation, leading to late phase 3 EAD and SVF. IKATP blocker glibenclamide reversed the post-defibrillation APD shortening and suppressed recurrent SVF in all hearts studied despite no evidence of ischemia.
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