| Project/Area Number |
02045021
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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 Institution | Osaka University |
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Principal Investigator |
INOUE Michitoshi Osaka University Medical Hospital, 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, 教授
KUSUOKA Hideo Osaka University Medical School, 医学部, 助教授 (00112011)
MARBAN Eduardo The Johns Hopkins University School of Medicine
EDUARD Marba ジョンズ, ホプキンス大学・医学部, 準教授
WEISFELDT My ジョンズ, ホプキンス大学・医学部, 教授
武田 裕 大阪大学, 医学部附属病院, 助教授 (20127252)
MARBAN Edupr ジョンズ, ホプキンス大学・医学部, 准教授
WEISFELDT.MY マイロン ジョンズ, ホプキンス大学・医学部, 教授
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1992: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1991: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Isolated perfused heart / Ischemia / Reperfusion injury / Intracellular calcium / Nuclear magnetic resonance / Sodium calcium exchange / Calcium channel / Glycolysis / 心筋 / フッ素核磁気共鳴法 |
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| Research Abstract |
This research program focused on the mechanism for the disruption of intracellular calcium homeostasis induced by ischemia and reperfusion. Intracellular ionic calcium concentration ([Ca^<2+>]_i) was measured with fluorine-19 NMR (F-NMR) coupled with a calcium indicator, 5F-BAPTA. The results obtained in this program are as follows.
1)[Ca^<2+>]_i significantly increased at the end of ischemia and during the early phase of reperfusion when hearts were subjected into 30-min ischemia at30ﾟC. The increase of [Ca^<2+>]_i was attenuated by pretreatment ofCa^<2+> channel blocker, indicating that opening of Ca^<2+> channel is one of the mechanism of Ca^<2+> increase during ischemia. 2)Hearts reperfused after 15-min global ischemia at 37ﾟshowed myocardial stunning. In contrast, hearts reperfused with high-[Na]_o. solution showed significantly better recovery. Nevertheless, reperfusion with solutions in which the additional Na was substituted either by sucrose or by choline chloride did not impro
… More
ve functional recovery, indicating that the beneficial effects of high-[Na]_o. reperfusion are not due either to high ionic strength or to high osmolarity. These results indicate that high-[Na]_o. reperfusion protects against stunning, supporting the idea that the Na^+/Ca^+ exchange plays an important role in the mechanism of stunned myocardium. 3)Myocardial content of sugar phosphates ([SP]) and [Ca^<2+>]_i were measured to elucidate the contribution of glycolysis to intracellular Ca^<2+> homeostasis. After the depletion of glycogen, the perfusion without substrate of glycolysis showed no significant changes in end-diastolic LV pressure (EDP) and [SP]. Even after the blockage of glycolysis, omission of glucose from the perfusate increased neither [SP] nor EDP. Nevertheless, addition of glucose to perfusate consistently increased EDP with accumulation of SP. F-NMR revealed that EDP correlates significantly with [Ca^<2+>]_i. These results indicate that disruption of intracellular Ca^<2+> homeostasis is caused by the accumulation of SP, rather than the inhibition of glycolysis. Less
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