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1992 Fiscal Year Final Research Report Summary

A Study on the Excitation-Contraction Coupling of Myocardium ---Analysis on Isolated, perfused Hearts using Multi-Nuclear NMR Methods.

Research Project

Project/Area Number 02045021
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionUniversity-to-University Cooperative Research
Research InstitutionOsaka University

Principal Investigator

INOUE Michitoshi  Osaka University Medical Hospital, 医学部附属病院, 教授 (30028401)

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
Project Period (FY) 1990 – 1992
KeywordsIsolated perfused heart / Ischemia / Reperfusion injury / Intracellular calcium / Nuclear magnetic resonance / Sodium calcium exchange / Calcium channel / Glycolysis
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

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] KUSUKA H: "Excitation-contraction coupling in postischemic myocardium" Circulation Research. 66. 1268-1276 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Marban E: "Quantification of[Ca^2+] in perfused hearts" Cirulation Research. 66. 1255-1267 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] KUSUOKA H: "Pathophysiology and pathogenesis of contratile failure in stunned myocardium" Japanese Circulation Journal. 55. 878-884 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Marban E: "Myocardial stunning and hibernation" Circulation. 83. 681-688 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Marban E: "Pathogenetic role for calcium in stunning?" Cardiovascular Drugs & Therapy. 5. 891-894 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] KUSUOKA H: "Cellular mechanisms of myocardial stunning" Annual Review Physiology. 54. 243-256 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] KUSUOKA H: "Myocardial energetics during ventriculal fibrillation investigated by magnetization transfer NMR spectroscopy" Circulation Research. 71. 1111-1122 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] KUSUOKA H: "Role of Sodium/Calcium exchange in the mechanism of myocardial stunning" Journal of American College of Cardiology. 21. 240-248 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kusuoka H: "Excitation-contraction coupling in postischemic mvocardium" Circulation Research. 66. 1268-1276 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Marban E: "Quantification of [Ca^<2+>]_i in perfused hearts" Circulation Research. 66. 1255-1267 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kusuoka H: "Pathophysiology and pathogenesis of contractile failure in stunned myocardium" japanese Circulation Journal. 55. 878-884 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Marban E: "Myocardial stunning and hibernation" Circulation. 83. 681-688 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Marban E: "Pathogenetic role for calcium in stunning?" Cardiovascular Drugs & Therapy. 5. 891-894 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kusuoka H: "Cellular mechanisms of myocardial stunning" Annual Review of Physiology. 54. 243-256 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kusuoka H: "Myocardial energetics during ventricular fibrillation investigated by magnetization transfer NMR spectroscopy" Circulation Research. 71. 1111-1122 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kusuoka H: "Role of Sodium/Calcium exchange in the mechanism of myocardial stunning" Journal of American College of Cardiology. 21. 240-248 (1993)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1994-03-24  

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