| Project/Area Number |
07045051
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | University-to-University Cooperative Research |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | OSAKA UNIVERSITY |
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Principal Investigator |
KUSUOKA Hideo OSAKA UNIVERSITY,MEDICAL SCHOOL,ASSOCIATE PROFESSOR, 医学部, 助教授 (00112011)
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| Co-Investigator(Kenkyū-buntansha) |
LAWRENCE John THE JOHNS HOPKINS UNIVERSITY,SCHOOL OF MEDICINE,ASSISTANT PROFESSOR, ホプキンス大学・医学部, 助教授
MARBAN Eduardo THE JOHNS HOPKINS UNIVERSITY,SCHOOL OF MEDICINE,PROFESSOR, ホプキンス大学・医学部, 教授
MATSUMURA Yasushi OSAKA UNIVERSITY,MEDICAL HOSPITAL,RESEARCH ASSISTANT, 医学部・附属病院, 助手 (90252642)
井上 通敏 大阪大学, 医学部, 教授 (30028401)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | MYOCARDIUM / ION HOMEOSTASIS / ISCHEMIA / REPERFUSION / CALCIUM ION / SODIUM ION / STUNNING / NUCLEAR MAGNETIC RESONANCE / 糖尿病 / カルシウム・ホメオスタシス / カルシウム・チャネル遮断薬 / 核磁気共鳴法 |
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| Research Abstract |
This project aimed to reveal the relation between the abnormalities in ion homeostasis and contractile failure in the models of diseased hearts. The follwing points were clarified in this research project ;
1. The relation between the abnormalities in intracellular calcium ion homeostasis and contractile failure in the hearts reperfused after acute ischemia. The transient calcium overload during early phase of reperfusion after a brief period of ischemia activates calcium-dependent protease, and protease disappears myofilament-related skeletal proteins, resulting in contractile failure.
2. The mechanism of calcium channel blockers for protection against ischemia/reperfusion injury. Pretreatment of calcium channel blockers prevents calcium overload during ischemia, and protects myocardium against contractile failure induced by ischemia and/or reperfusion. It is clarified that calcium influx from the extracellular space is necessary for the calcium overload during ischemia.
3. The relation between the abnormalities in intracellular sodium ion homeostasis during ischemia and contractile failure after reperfusion. Sodium accumulation during ischemia is mediated by sodium influx via Na/H exchanger, and shows significant negative correlation with contractile recovery after reperfusion. Cardiac protection against ischemia in diabetic hearts is caused by the reduced activity of Na/H exchanger. These results indicate that the abnormalities in ion homeostasis is one of major mechanisms for contractile dysfunction in diseased hearts.
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