| Project/Area Number |
17590187
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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 physiology
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| Research Institution | Okayama University |
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Principal Investigator |
ANDO Motonori Okayama University, Faculty of Education, Associate Professor, 教育学部, 助教授 (20222789)
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| Co-Investigator(Kenkyū-buntansha) |
KATARE Rajesh G. Kochi Medical School, Faculty of Medicine, Research Associate, 医学部, 助手 (20380313)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | vagal nerve / electrical stimulation / arrhythmia / gap junction / connexin / acetylcholine |
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| Research Abstract |
Myocardial ischemia (MI) leads to derangements in cellular electrical stability and the generation of lethal arrhythmias. Vagal nerve stimulation has been postulated to contribute to the antifibrillatory effect. In this study, we demonstrate a novel mechanism for the antiarrhythmogenic properties of electrical vagal nerve stimulation during acute MI. Under anesthesia, Wistar rats underwent 30 minutes of left coronary artery (LCA) ligation with vagal stimulation (MI-VS group) and with sham stimulation (MI-SS group). Eight of the 12 rats in the MI-SS group had ventricular tachyarrhythmia (VT) during 30-minute LCA ligation; on the other hand, VT occurred in only 1 of the 11 rats in the MI-VS group (67% versus 9%, respectively). Atropine administration abolished the antiarrhythmogenic effect of vagal stimulation. Immunoblotting revealed that the MI-SS group showed a marked reduction in the amount of phosphorylated connexin43 (Cx43), whereas the MI-VS group showed only a slight reduction compared with the sham operation and sham stimulation group (37+/-20% versus 79+/-18%). Immunohistochemistry confirmed that the MI-induced loss of Cx43 from intercellular junctions was prevented by vagal stimulation. In addition, studies with rat primary-cultured cardiomyocytes demonstrated that acetylcholine (ACh) effectively prevented the hypoxia-induced loss of phosphorylated Cx43 and ameliorated the loss of cell-to-cell communication as determined by Lucifer Yellow dye transfer assay, which supports the in vivo results. Furthermore, in-vitro studies also revealed that ACh induced Akt phosphorylation, which was inhibited by wortmannin. These results suggest that ACh protects cardiomyocytes through the PI3K/Akt pathway. In conclusion, vagal nerve stimulation exerts both anti-arrhythmogenic and anti-apoptotic effects during acute MI and thus plays a critical role in improving ischemia-induced electrical instability and in activating cell-survival signals.
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