| Project/Area Number |
13670702
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Research Institute of Environmental Medicine, Nagoya University |
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Principal Investigator |
HONJO Haruo Nagoya University, Research Institute of Environmental Medicine, Associate Professor, 環境医学研究所, 助教授 (70262912)
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| Co-Investigator(Kenkyū-buntansha) |
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)
KODAMA Itsuo Nagoya University, Research Institute of Environmental Medicine, Professor, 環境医学研究所, 教授 (30124720)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | spiral reentry / optical mapping / ventricular tachycardia / antiarrhythmic drug / anisotropic conduction / curvature effect / excitable gap / 活動電位 / 坑不整脈薬 / スパイラルリエントリー / ブロックライン |
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| Research Abstract |
It is widely accepted that functional reentry plays an important role in the initiation and maintenance of ventricular tachycardia/fibrillation (VT/VF). Various concepts including "leading circle", anisotropic reentry and spiral-type excitation have been proposed to explain the functional reentry in the heart but its precise mechanisms remain to be elucidated. We investigated dynamics and pharmacological modulation cf VT by high-resolution optical mapping. Two-dimensional subepicardial ventricular myocardial sheet (〜1 mm in thickness) of the Langendorff-perfused rabbit heart was made by cryoablation of the endocardial side of the left ventricle. The heart was stained with di-4-ANEPPS (2 μM), and fluorescence images of theventricular myocardium were obtained via a high-speed video camera (temporal and spatial resolutions of〜1.3 ms and 〜0.1 mm, respectively). VT induced by cross-field stimulation was often the result of single reentry around a "Z"-shaped functional line of block. The cen
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tral segment of the block line, which was independent of the myocardial fiber direction, was associated with an abrupt phase-shift of the action potential. Small amplitude double potentials without electrical diastole were obtained at the central block line suggesting "leading circle"-type electrotonic interaction. The two terminal segments were caused by localized conduction delay around pivot points of the rotation and these lines were always parallel to the myocardial fiber direction. Source-to-sink imbalance created by wavefront curvature combined with tissue anisotropy may be responsible for the localized conduction delay around the pivot paints. Blockade of Na^+ channels by pilsicainide, disopyramide and cibenzoline extended the terminal block lines through the enhancement of the localized local conduction delay and caused appreciable electrical diastole (excitable gap) in the circuit except around pivot points. These results suggest that functional reentry in the two-dimensional ventricular myocardium is determined by wavefront-tail interaction and source-sink imbalance caused by wavefront curvature and tissue anisotropy. Less
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