| Project/Area Number |
16591417
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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 |
Thoracic surgery
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| Research Institution | Nippon Medical School |
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Principal Investigator |
KANNO Shigeto Nippon Medical School, Faculty of Medicine, Assistant Professor, 医学部, 講師 (20291718)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Kazuo Nippon Medical School, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (20133449)
NITTA Takashi Nippon Medical School, Faculty of Medicine, Professor, 医学部, 教授 (40256954)
MIYAGI Yasuo Nippon Medical School, Faculty of Medicine, Research Associate, 医学部, 助手 (00350116)
OHMORI Hiroya Nippon Medical School, Faculty of Medicine, Research Associate, 医学部, 助手 (40343587)
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| Project Period (FY) |
2004 – 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: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Gap Junction / Connexin43 / Ischemia / Arrhythmia |
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| Research Abstract |
In Japan sudden cardiac death is common in patients who have survived myocardial infarction. Also many patients who have cardiac dysfunction have the high risk of sudden arrhythmic death. But the molecular mechanisms responsible for the lethal arrhythmia in such patients have not defined yet In order to gain insights about the role of critical arrhythmia we created the ischemia model in mice heterozygous for a major gap junction protein Cx43 null allele and wild type. The structural consequences following myocardial infarction (MI) were examined by echocardiography and histopathological study. Although post-infarction remodeling was not affected by diminished Cx43 expression in cardiac gap junctions, infarct size was smaller it C×43-deficient (C×43+/-) mice compared with wild type (C×43+/+). Implanted telemetry system revealed spontaneous ventricular arrhythmias occurred only in C×43+/-mice with infarction. Isolated hearts with healed myocardial infarction were analyzed by the arrhythm
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ia induction study. Ventricular tachycardia was induced in both Cx43+/-and +/+ hearts with MI. But the inducibility of ventricular arrhythmia was higher in C×43+/-in acute phase in mice with ischemia. Interestingly the electrica recovery was rather quick compared with morphological wound healing. Reduced basal coupling was observed as the distribution of Cx43 in gap junction channel which was visualized by immunohistochemical study. Gap junction remodeling was considered as an essential factor of arrhythmogenesis in heart with ischemic injury. Perioperative patients in human cardiac surgery are considered as being in the similar condition of these ischemic model. Analysis of arrhythmias following MI in mouse lines with defined genetic defects will shed light on the roles of these proteins in sudden cardiac death in patients with healed MI or post operative patients. Alterations in cell-cell communication occur as a fundamental response to myocyte injury which contributes to arrhythmogenesis. Human disease models in genetically altered mice are invaluable for mechanistic understanding of sudder cardiac death and to prevent it at its source instead of terminating a lethal arrhythmia once it occurred. Less
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