| Project/Area Number |
05670602
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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 | Hamamatsu University School of Medicine |
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Principal Investigator |
KANEKO Masanori Hamamatsu University School of Medicine Assistante, 医学部, 助手 (70191989)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1993: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Oxygen Free Radicals / Hydrogen Peroxide / Ischemia-Reperfusion Injury / Calcium Overload / Nuclear Magnetic Resonance / Diabetes / Glycolytic Inhibition / 活性酸素ラジカル / カルシウム / NMR / 虚血-再潅流障害 |
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| Research Abstract |
Oxygen free radicals (OFR) has been suggested as a mechanism of the myocardial injury during ischemia and reperfusion. The purpose of this study is 1) to elucidate the mechanism of the myocardial injury induced by OFR concerning the high-energy phosphate metabolism with ^<31>P-NMR method and the intracellular Ca^<2+> changes with ^<19>F-NMR method, and 2) to clarify the response of diabetic hearts to OFR as well. The exposure of an isolated perfused heart to hydrogen peroxide (H_2O_2) for a short duration (8 min) provoked the biphasic cardiac dysfunction which is characterized by a transient depression of left ventricular developed pressure and a progressive elevation of left ventricular end-diastolic pressure. We defined the former as the early component (EC) of cardiac dysfunction and the latter as its late component (LC). According to the ^<31>P-NMR study, EC was associated with the glycolytic inhibition, and LC was related to the depletion of total ATP content. According to the ^<1
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9>F-HMR study, the intracellular Ca^<2+> concentration ([Ca^<2+>]_i) increaed from 315(]SY.+-.])23 nM to 701(]SY.+-.])58 nM through the exposure to H_2O_2. The alteration of [Ca^<2+>]_i was in good agreement with the time course of LC.These suggest that OFR produced during myocardial ischemia and reperfusion induce the abnormal energy metabolism due to glycolytic inhibition and intracellular Ca^<2+> overload, and these changes may be responsible for cardiac dysfunction in the reperfused myocardium. The injuring mechanism of OFR may be the disturbed membrane function due to peroxidation of membrane lipids and the enzymatic inactivation due to denaturation of proteins. Recent reports have suggested that diabetic myocardium was resistant to the ischemia-reperfusion injury. We also studied the response of streptozotocin-induced diabetic hearts and insulin-treated diabetic hearts to H_2O_2. We observed that the diabetic hearts were resistant to the exogeneous H_2O_2, and the chronic insulin treatment attenuated the tolerance to OFR.Our results indicated that its tolerance might be attributed to the attenuation of glycolytic inhibition and the suppression of intracellular Ca^<2+> overload. The resistance of diabetic hearts to ischemia-reperfusion injury might be, at least in part, associated with its tolerance to OFR. Less
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