| Project/Area Number |
10480240
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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) |
TAKAHASHI Eiji Yamagata Univ., Fac. Of Medicine, Asso. Prof., 医学部, 助教授 (30206792)
YAMAUCHI Yoshiko Hokkaido Univ., Res. Inst. For Electr. Sci., Res. Assoc., 電子科学研究所, 助手 (50230313)
NAKAMURA Takao Hokkaido Univ., Res. Inst. For Electr. Sci., Asso. Prof., 電子科学研究所, 助教授 (00142654)
YONEYAMA Mitsuru Yokohama Res. Cent., Senior Res. Sci., 横浜総合研究所, 主任研究員
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥10,100,000 (Direct Cost: ¥10,100,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1998: ¥8,400,000 (Direct Cost: ¥8,400,000)
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| Keywords | ischemia / reperfusion / cardiac myocyte / beating rhythm / myocyte death |
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| Research Abstract |
Cardiomyocyte apoptosis has been demonstrated in animal models of ischemia/reperfusion injury as well as patients with congestive heart failure or acute myocardial infarction. However, the mechanism responsible for cardiomyocyte apoptosis remains largely unknown. The present study aimed at elucidating the mechanisms responsible for the induction of cardiac arrhythmia associated with ischemia/reperfusion cardiac injury. The results obtained from this study are summarized as follows:
(1) In the cultured dissociated myocytes from neonatal rats, inhibition of de novo protein synthesis itself by cycloheximide (CHX) evoked myocyte-specific apoptosis-like cell death. CHX-induced myocyte death was reduced by a treatment with a cell-permeable, specific inhibitor of caspase-3 (CPP32). Reactive oxygen Species (ROS) appeared to be involved in the CHX-induced myocyte death, because such cell death was prevented by co-treatment of Mn(III) tetrakis(benzoic acid) porphyrin (MnTBAP), a cell-permeable superoxide dismutase mimic. Our results suggest a possibility that cardiomyocyte apoptosis would not require de novo protein synthesis, and that protein synthesis inhibition itself would result in the myocyte apoptosis.
(2) In the cultured dissociated myocytes from neonatal rats, hypoxia and glucose deprivation (in vitro ischemia) resulted in the increase of the contraction interval and of the fluctuation of the beating rhythm. However, synchronization between myocytes remained unchanged during in vitro ischemia. This result suggests a possibility that gap-junction among myocytes remained open during hypoxia/ischemla.
(3) In the Langendorff-perfused heart from adult rats, global ischemia resulted in the elongation of heart periods, and the heart eventually stopped beating in about 10 min. However, heart beat rhythm recovered to the control one after reperfusion in most of the Langendorff preparations. In some cases, reperfusion induced arrhythmia-like irregular beat.
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