| Project/Area Number |
11357020
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Yamanashi Medical University |
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Principal Investigator |
HASHIMOTO Keitaro Yamannashi Medical University, Faculty of Medicine Professor, 医学部, 教授 (10004665)
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| Co-Investigator(Kenkyū-buntansha) |
NISHI Katuhide kumamoto University, Faculty of Medicne, Professor, 医学部, 教授 (00040220)
KIMURA Junko Fukushima Medical University, Faculty of Medicine, Professor, 医学部, 教授 (10186322)
NAKAYA Haruaki Chiba University, Faculty of Medicine, Professor, 医学部, 教授 (60113594)
TSUJIMOTO Gozoh National Center for Child Health and Develepment Research Institute Department of Molecular Cell Pharmacology, Direcotr, 薬剤治療研究部, 部長(研究職) (80172013)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥36,040,000 (Direct Cost: ¥33,400,000、Indirect Cost: ¥2,640,000)
Fiscal Year 2001: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
Fiscal Year 2000: ¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 1999: ¥14,100,000 (Direct Cost: ¥14,100,000)
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| Keywords | arhvthmia / sudden death / cardioprotective drugs / Na / H exchanger / Ca exchange / K_<ATP> channel / AVブロック / 心室細動 / Kチャネル / イオンチャネル / 不整脈モデル / トランスポーター / 心筋梗塞 / イヌ / 心室性不整脈 |
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| Research Abstract |
Sudden cardiac death (SCD) is a serious problem in cardiovascular patients, but the animal models for studying prevention of SCD have not yet establishd. We used coronary ligation/reperfusion induced and halothane-adrenaline arrhythmias to evaluate various cardioprotective drugs not including classical antiarrhythmic drugs, which have been shown to increase SCD. In these 3 years, we have demonstrated that Na/H exchange inhibitors are effective in decreasing arrhythmia death in in vivo animals, however Na/Ca exchange inhibitors and KATP channel openers or blockers have shown variable and mariginal protective effects.
However electophysiological characteristics of these drugs have been clarified in more detail using voltage clamp and genetically modified ion channel proteins. We also evaluated transgeneic mice models which lacks sympathetic alpha or beta receptors and found shorter lives in some of these models, but partly due to the problems of evaluating mice long term ECG recordig we have not yet demonstrated whether these animals can be used to study preention of SCD.
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