| Project/Area Number |
12480256
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KAWAHARA Koichi Hokkaido Univ., Res. Inst. For Electr. Sci., Prof., 電子科学研究所, 教授 (20125397)
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| Co-Investigator(Kenkyū-buntansha) |
TOUSE Noritsugu Sapporo Medical Univ., Fac. Of Medicine., Prof., 医学部, 教授 (80192657)
NISHIURA Yasumasa Hokkaido Univ., Res. Inst. For Electr. Sci., Prof., 電子科学研究所, 教授 (00131277)
YAMAUCHI Yoshiko Hokkaido Univ., Res. Inst. For Electr. Sci., Res. Assoc., 電子科学研究所, 助手 (50230313)
NAIKI Takeru Hokkaido Univ., Res. Inst. For Electr. Sci., Asso. Prof., 電子科学研究所, 助教授 (40241385)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥16,400,000 (Direct Cost: ¥16,400,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥11,300,000 (Direct Cost: ¥11,300,000)
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| Keywords | ischemia / apoptosis / remodeling / ventricular fibrillation / ventricular tachycardia / mitochondria / nitric oxide / 心筋細胞 / 拍動リズム / 細胞死 / 再灌流 |
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| Research Abstract |
Cardiac ischemia results in the increased vulnerability to lethal arrhythmias such as ventricular tachycardia and fibrillation. Cardiac ischemia also produces the death of cardiac myocytes by either necrosis or apoptosis. The present study aims at elucidating the mechanisms responsible for remodeling in the post-infarcted heart, and for conversion between ventricular tachycardia(VT) and fibrillation(VF). The results are summarized as follows :
1. Ligation of the left coronary artery of rat hearts resulted in the acute death of ventricular cardiac myocytes. Post-infarction left ventricular remodeling occurred at 2-3 weeks after the coronary artery ligation. TUNEL staining or immunohistochemical analysis using an anti-activated caspase-3 antibody revealed that apoptotic death of myocytes was observed almost coinciding with the morphological changes of the heart, suggesting that apoptosis of cardiac myocytes contributed to the process of post-infarction left ventricular remodeling.
2. In Langendorff-perfused rat hearts, treatment with either L-NMMA, an inhibitor of nitric oxide synthase (NOS), or 5-HD, a specific blocker of mitochondrial ATP-sensitive potassium (mitoK__<ATP>) channels, during reperfusion attenuated the vulnerability to ischemia/reperfusion-induced VT/VF, suggesting that the increased production of nitric oxide (NO) and the resultant activation of mitoK__<ATP> channels during reperfusion were involved in the increased vulnerability to ischemia/reperfusion-induced VT/VF.
3. In Langendorff-perfused rat hearts, perfusion with either ruthenium red (RR) or Ru 360, blockers of calcium uptake by mitochondria, resulted in the reversible conversion of VF to VT. Perfusion with spermine, an activator of mitochondrial calcium uptake, produced reversible conversion of VT to VF. These results suggested that changes in the calcium uptake by mitochondria contributed to the macro-dynamical transition between VT and VF.
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