| Project/Area Number |
06670705
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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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 |
HAYASHI Hideharu Hamamatsu University School of Medicine Photon Medical Research Center Associate Professor, 光量子医学研究センター, 助教授 (50135258)
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| Co-Investigator(Kenkyū-buntansha) |
TERADA Hajime Hamamatsu University School of Medicine Department of Medicine Assistant, 医学部, 助手 (50252177)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | metabolic inhibition / simulated ischemia / reperfusion / [Na^+]i / [Ca^<2+>]i / hexamethylene amiloride / Na^+ / H^+ exchange / Ca^<2+> exchange / ヘキサメチロンアミロライド / 心筋虚血 / カルシウム過負荷 / 細胞内カルシウム濃度 / 細胞内ナトリウム濃度 / 細胞内pH / Na / Ca交換 / 細胞拘縮 / ストロファンチジン / H交換 |
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| Research Abstract |
Na^+i increased during the first 20 min of metabolic inhibition (MI : 3.3 mM amytal and 5muM CCCP), while [Ca^<2+>]i was low. [Ca^<2+>]i increased after cells had contracted in the following 30 min, and was 167<plus-minus>14% of the control (mean<plus-minus>SE ; p<0.01). [Ca^2]i when cells contracted during MI was much lower than that during digitalis perfusion, whereas [Na^+]i increased further. However, addition of 10 mM glucose after 20 min of MI (energy repletion) led to a dramatic increase in [Ca^<2+>]i to 442<plus-minus>72% (p<0.01). The increase in [Ca^<2+>]i after energy repletion was suppressed by hexamethylene amiloride (HMA) or Ca^<2+> free solution. It was suggested that Na^<2+>/Ca^<2+> exchange was inhibited during MI,causing the dissociation between [Na^<2+>]i and [Ca^<2+>]i. Na^<2+>/Ca^<2+> exchange could be reactivated by energy repletion, resulting in Ca^<2+> overload. Next, myocardial ischemia was simulated by MI with pH 6.6, and reperfusion was achieved by washout with pH 7.4 [Na^+]i increased from 9.8<plus-minus>1.3 mM to 16.2<plus-minus>2.1 mM (p<0.01) during 7.5 min of simulated ischemia and increased further to 25.0<plus-minus>2.6 mM (p<0.01) after reperfusion. [Ca^<2+>]i increased to 133<plus-minus>9% (p<0.01) during simulated ischemia and gradually returned to control after reperfusion. Intracellular pH decreased from 7.53<plus-minus>0.04 to 6.30<plus-minus>0.01 (p<0.01) and recovered quickly after reperfusion. HMA prevented the reperfusioninduced increase in [Na^+]i, and Ca^<2+> free solution prevented the increase in [Ca^<2+>]i. It was suggested that Na^+/H^+ exchange was active during reperfusion, resulting in the additional [Na^+]i elevation, and that there was a Ca^<2+> influx via Na^+/Ca^<2+> exchange after reperfusion.
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