Underling mechanisms of atrial fibrillation induced by atrial pressure/ volume overload, and new therapeutic approach for the management of atrial fibrillation
| Project/Area Number |
18590769
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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 | Nagoya University |
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Principal Investigator |
YAMAMOTO Mitsuru Nagoya University, Graduated Scinol of Medicine, Researcher (10422768)
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| Co-Investigator(Kenkyū-buntansha) |
SOKABE Masahiro Nagoya University, Graduated School of Meclicine, Professor (10093428)
KODAMA Itsuo Nagoya University, Research Institute of Environmental Medicine, Professor (30124720)
HONJO Haruo Nagoya University, Research Institute of Envitonmental Medicine, Asscoiate Professor (70262912)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | atrial fibrillation / pressure / volume overload / stretch activated channel / optical mapping |
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| Research Abstract |
Atrial fibrillation (AF) is a common and troublesome arrhythmia among aged population. Prevention and management of AF is one of the most urgent and worldwide task amid increasing morbidity and modality of AF. Several factors underlie the promotion of AF, one of well-known factors is the pressure and/or volume overload in atria. Recently, prevention of Al' by using a spider venom derivative (GsMtx-4), which inhibits stretch activated channels, has been reported and drawing attention in the management of AF. This project was designed to elucidate the underlying mechanisms of the stretch-induced AF and develop a new therapeutic approach to treat AF
Several findings in this project have been obtained as below :
1) AF model, in which atria were acutely inflated in excised coronary-perfused rabbit hearts, was developed in our laboratory.
2) Short amino peptides (TVP 003, 017), which was developed based on GsMtx-4, were investigated to assess the efficacy on stretch-induced Al'. But data resulted in no obvious reduction of vulnerability to AF induced by a burst of pacing.
3)Statins and TRP channel inhibitors (SKF-96365, BTP-2), which were enrolled as an alternative candidates, were subsequently examined in the present study. These agents were revealed to reduce the vulnerability to AF and this effect was at least, in part, brought by reducing abbreviation of stretch-induced AERP (atrial effective refractory period) shortening.
4) Fluorescence-based optical imaging system, which was designed to observe transmembrane potentials dynamics, demonstrated that inhomogeneous activation pattern, leading to reentrant activities was evoked by atrial premature stimulation or high-frequency stimulation during atrial inflation. Abbreviation of APD (action potential duration) was reduced by application of TRP channel inhibitors, this result was in line with the change in AERP due to atrial inflation.
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Report
(3 results)
Research Products
(11 results)
