Connexin43 as a determinant of arrhythmia inducibility in cardiac gap junction of infarct heart
| Project/Area Number |
14571286
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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, Department of Surgery, Fellow, 医学部, 助手 (20291718)
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| Co-Investigator(Kenkyū-buntansha) |
OHMORI Hiroya Nippon Medical School, Department of Surgery, Fellow, 医学部, 助手 (40343587)
MIYAGI Yasuo Nippon Medical School, Department of Surgery, Fellow, 医学部, 助手 (00350611)
NITTA Takashi Nippon Medical School, Department of Surgery, Assistant Professor, 医学部, 助教授 (40256954)
SASAKI Takashi Nippon Medical School, Department of Surgery, Fellow, 医学部, 助手 (80350065)
清水 一雄 日本医科大学, 医学部, 教授 (20133449)
田中 茂夫 日本医科大学, 医学部, 教授 (70089720)
石井 庸介 日本医科大学, 医学部, 助手 (10307895)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Gap Junction / Connexin43 / Isohemia / Arrhythmia |
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| Research Abstract |
Sudden cardiac death is common in patients who have survived myocardial infarction (MI), but the molecular mechanisms responsible are complex and poorly defined. To facilitate development of a mouse model to define gene products critical in lethal arrhythmia following MI, we created MI by LAD coronary occlusion in C57BL/6J mice heterozygous for a major gap junction protein Cx43 null allele and wildtype. To characterize structural consequences in MI, we used echocardiography. Left ventricular end-diastolic volume was increased as a function of infarct size at both 1 and 10 weeks after surgery. However, no differences in the relationship between left ventricular end-diastolic volume and infarct size were seen in wildtype and Cx43-deficient mice. Post-infarction remodeling as a function of infarct size was not affected by diminished Cx43 expression. Isolated hearts with healed MI were analyzed with extrastimulus protocol for inducing ventricular tachycardia (VT). VT was induced in both Cx
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43+/-and +/+ hearts with MI. Ventricular sections were examined histologically. Infarct size was smaller in Cx43+/-mice compared with +/+ mice. Specific morphological features were evaluated including whether infarcts were transmural or non-transmural, and the presence or absence of ventricular aneurysmal dilatation, patchy interstitial fibrosis at infarct border zones, and surviving subendocardial myocytes. A layer of surviving subendocardial myocytes was seen more frequently in hearts in which VT could be induced but the occurrence of this feature was similar in Cx43+/-and +/+ hearts. The other features of post-infarct remodeling pertinent to development of arrhythmias and contractile dysfunction in hearts with healed infarcts were also observed with equal frequency in Cx43 +/-and +/+ hearts. Reduced basal coupling does not by itself significantly alter infarct healing or post-MI remodeling. 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. Less
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Report
(3 results)
Research Products
(7 results)
