2002 Fiscal Year Final Research Report Summary
Effects of atrial muscle structure on the initiation mechanism of atrial fibrillation and its drug therapy
| Project/Area Number |
13670083
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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 |
General pharmacology
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| Research Institution | Shinshu University |
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Principal Investigator |
HIROSE Masamichi Shinshu University School of Medicine, Assistant Professor, 医学部, 講師 (40273081)
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| Project Period (FY) |
2001 – 2002
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| Keywords | PACAP / Atrial muscle structure / Atriai fibrillation / Action potential / E-4031 / Zatebradine / Autonomic nervous system |
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| Research Abstract |
In isolated arterially perfused canine atria, transmural repolarization gradients were observed using high resolution optical mapping techniques to measure action potentials from the epicardial and endocardial surface on the right at rial free wall. These are performed during control conditions, during electrical stimulation of the fat pad at the right pulmonary vein-atrial junction (i.e. intracardiac parasympathetic stimulations) and during acetylcholine (ACh) infusion. Transmural repolarization gradients did not increase during intracardiac parasympathetic stimulation and during ACh infusion compared to during control. During ACh infusion, at rial tachyarrhythmia (AT) was initiated with a single premature stimulus and was associated with a focal pattern of activation (84 %). Importantly, AT initiation during intracardiac parasympathetic stimulations was also associated with the focal pattern of activity (36 %) without conduction block when repolarization gradients were small. During
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intracardiac parasympathetic stimulations, however, when repolarization gradients were large, patterns of conduction block and incomplete macroreentry were often observed (64 %). During pituitary adenylate activating polypeptide injection, repolarization gradients were small across the atrial surface and transmirally and a single premature stimulus initiated AT which was associated with a focal pattern of activation (100 %) without conduction block. These results suggest that the complicated tissue structure of atrial tissue has an important role for initiating focal pattern of AT. We examined the spatial variation in ionic current density us ing E-4031, the rapidly activating component of delayed rectifier potassium current blocker, and Zatebradine, hyperpolarization activated-current blocker. E-4031 increased action potential duration (APD) greater in the right atrial free wall than in the pulmonary vein area of left atrium. In contrast, Zatebradine equally increased APD between them. These results suggest the regional variation in atrial ionic currents. Less
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