| Project/Area Number |
14207034
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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 | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Nagoya University |
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Principal Investigator |
KODAMA Itsuo Nagoya University, Research Institute of Environmental Medicine, Professor, 環境医学研究所, 教授 (30124720)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIYA Kaichiro Nagoya University, Research Institute of Environmental Medicine, Professor, 環境医学研究所, 教授 (50194973)
HONJO Haruo Nagoya University, Research Institute of Environmental Medicine, Associate Professor, 環境医学研究所, 助教授 (70262912)
SAKUMA Ichiro The University of Tokyo, Graduate School of Frontier Sciences, Professor, 大学院・新領域創成科学研究科, 教授 (50178597)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥39,260,000 (Direct Cost: ¥30,200,000、Indirect Cost: ¥9,060,000)
Fiscal Year 2004: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2003: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2002: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
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| Keywords | Arrhythmia / Reentry / Optical mapping / Action potential / Anisotropic conduction / Antiarrhythmic drug / スパイラルリエントリー / 心室細動 / 心室頻拍 / 坑不整脈薬 / amiodarone / nifekalant / 興奮間隙 |
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| Research Abstract |
Spiral-type reentrant excitation is a principal mechanism for the genesis of various life-threatening ventricular tachyarrhythmias including ventricular fibrillation and tachycardia. We have developed a new high-resolution optical mapping system equipped with a C-MOS-type digital high-speed video camera to investigate dynamics of spiral-type excitations during ventricular tachyarrhythmias in a two-dimensional thin myocardial layer (1 mm thick) of ventricles of isolated Langendorff-perfused rabbit hearts with endocardial cyoablation. Pharmacological modulation of spiral-type reentry by antiarrhythmic drugs was also investigated. During ventricular tachyarrhythmias induced by cross-field DC stimulation, spiral-type excitations rotating sound a line of functional block were often observed. Dynamics of spiral reentry was primarily determined by "leading-circle"-type electronic interactions of reentrant excitations and wave front curvature-dependent modulation of the safety margin for condu
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ction (curvature effect) as well as architecture of the myocardium showing uniform anisotropy. A decrease in myocardial excitability by Na channel blockade caused a prolongation of the functional line of block, a slowing of reentrant excitations. Spiral-type excitations were more organized with appreciable spatial and temporal excitable gaps after Na channel blockade. On the other hand, spiral-type excitations under K channel blockade was characterized by chaotic meandering with a prolonged line of functional block and frequent wave break-ups via wave front-to-tail interactions as well as early spontaneous termination. These effects of K channel blockade are expected to be effective in preventing formation of stable spiral reentry but may facilitate transition from ventricular tachycardia to fibrillation. These results obtained form this study may provide useful information for the development of new strategy in effective prevention and termination of life-threatening ventricular tachyarrhythmias. Less
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