| Project/Area Number |
62045020
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| Research Category |
Grant-in-Aid for Overseas Scientific Survey.
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| Allocation Type | Single-year Grants |
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| Section | University-to-University Cooperative Research |
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| Research Institution | Osaka University |
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Principal Investigator |
INOUE Michitoshi Osaka University Hospital Professor, 医学部・附属病院, 教授 (30028401)
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| Co-Investigator(Kenkyū-buntansha) |
EDUARDO Marb ジョンズ. ホプキンス大学, 医学部, 准教授
MYRON.L Weis ジョンズ. ホプキンス大学, 医学部, 教授
KUSUOKA Hideo Osaka University Medical School Assistant Professor, 医学部, 助手 (00112011)
MARBAN Eduardo The Johns Hopkins University School of Medicine Associate Professor
WEISFELDT Myron L. The Johns Hopkins University School of Medicare Professor
EDUARDO MARB ジョンズホプキンス大学, 医学部, 助教授
MYRON L WEIS ジョンズホプキンス大学, 医学部, 教授
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1989: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1988: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1987: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Myocardial Excitation-Contraction Coupling / Isolated, Perfused Heart / Intracellular Calcium Ion / Maximal Calcium-activated Force / Calcium Sensitivity / Ischemia / Reperfusion / Calcium Overload |
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| Research Abstract |
This project aimed on the assessment of excitation-contraction (E-C) coupling in myocardium of isolated, perfused hearts.
The following results were obtained in this University-to-University Cooperative Research. (1)Development of the methods to assess the endpoints in E-C coupling: The intracellular concentration of activator Ca^<2+> ([Ca^<2+>]_i) was measured in perfused heart using fluorine nuclear magnetic resonance spectroscopy (^<19>F-NMR) coupled with Ca^<2+> chelator, 5F-BAPTA. Calcium transients could be evaluated by this F-NMR technique with gating. Maximal Ca^<2+>-activated pressure (MCAP), the index of maximal Ca^<2+>-activated force in myofilament was evaluated by left ventricular isovolumic pressure during tetani elicited by the rapid pacing after exposure to ryanodine. (2)Mechanism of early contractile failure during ischemia: It was revealed that inorganic phosphate (Pi) decreases MCAP and proton (H^+) induces both the decrease in MCAP and the shift of Ca^<2+>-sensitivit
… More
y to higher Ca. Thus, these results indicate that the increase of Pi and H^+ during ischemia causes early contractile failure. (3)Pathophysiology of stunned myocardium: Reperfusion after a brief period of ischemia produces prolonged contractile failure without necrosis ("stunned myocardium"). In stunned myocardium, MCAP decreased and the amplitude of calcium transient increased compared with the control. Thus, these results indicate that this contractile dysfunction is due to the decrease in maximal Ca^<2+>-activated force and the shift of Ca^<2+>-sensitivity to higher Ca with paradoxical increase in amplitude of calcium transients. (4)Pathogenesis of stunned myocardium: Our data suggested that a transient calcium overload during ischemia and reperfusion causes the contractile failure in stunned myocardium. The changes in [Ca^<2+>]_i during ischemia and after reperfusion were also directly measured and the exist of calcium overload was confirmed. (5)Effect of non-ischemic calcium overload on contractility: Doxorubicin increased [Ca^<2+>]_i without ischemic changes and caused contractile disorder. Thus, these results indicate that calcium overload itself deteriorates the cardiac function. Less
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