| Project/Area Number |
63570393
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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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 Assistant Professor, 医学部, 助手 (00112011)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Hiroshi Osaka University Hospital Clinical Fellow, 医学部附属病院, 医員
HORI Masatsugu Osaka University Medical School Assistant Professor, 医学部, 助手 (20124779)
INOUE Michitoshi Osaka University Hospital Professor, 医学部附属病院, 教授 (30028401)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1988: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Ischemia / Reperfusion / Isolated, perfused heart / Intracellular free Ca^<2+> / Fluorine Nuclear Magnetic Resonance / 5F-BAPTA / Calcium Overload / 5FーBAPTA / 摘出灌流心標本 / カルシウム・オーバーロード |
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| Research Abstract |
This project aimed on the study of excitation-contraction coupling, especially dynamics of Intracellular free ion Ca^<2+>, in myocardium of ischemlc or reperfused hearts. The intracellular concentration of activator Ca^<2+> ([Ca^<2+>]_i) was measured in Isolated, perfused whole heart using fluorine nuclear magnetic resonance spectroscopy (^<19>F-NMR) coupled with Ca^<2+> chelator, 5F-BAPTA. The amounts of Ca^<2+> bounded and Ca^<2+> free 5F-BAPTA in myocardium were obtained from the signals of them in F-NMR spectrum, and [Ca^<2+>]_i was determined by the ratio of them. The following results were obtained in this project.
1. The changes in [Ca^<2+>]_i during ischemia and after reperfusion were investigated. The intracellular Ca^<2+> concentration significantly increased after 10 minutes of global ischemia at 37ﾟC compared with control, but rapidly came back to the control level during early phase of reperfusion after 15 minutes of ischemia.
2. We also focused on the pathophysiology of "stunned myocardium", i.e., myocardium reperfused after a brief period of ischemia. Such a brief ischemia is not enough to make necrosis but produces prolonged contractile failure. Developed pressure in the hearts reperfused after 15 minute of global ischemia at 37ﾟC showed only 70% of control (stunned myocardium) even the hearts were loaded with 5F-BAPTA. The amplitude of calcium translent, i.e., cyclical changes in [Ca^<2+>]_i, was significantly increased in stunned myocardium compared with that before ischemia. Coupled with our previous study, theses results revealed that this contractile dysfunction is due to the decrease in maximal Ca^<2+>-activated force in myofildment and the shift of myofilament Ca^<2+>-sensitivity to higher Ca with paradoxical increase in amplitude of calcium transients.
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