Improving Glucose Metabolism and/or Sarcoplasmic Reticulum Ca^<2+>-ATPase Function is Warranted for Immature Pressure Overload Hypertrophied Myocardium

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概要

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• The cellular mechanisms of abnormal calcium regulation and excitation-contraction coupling in relation to glucose metabolism in the hypertrophied heart are not well understood. The present study evaluated the myocardial mechanics of 6-7-week-old pressure overload hypertrophied rabbit hearts in response to dobutamine by(1)serial echocardiograms in vivo and(2)isolated Langendorff perfusion. Cytosolic Ca^<2+>([Ca^<2+>]i)and sarcoplasmic reticulum Ca^<2+>-ATPase(SERCA2)expression were measured by fluorescence spectroscopy and Western immunoblotting, respectively. The effect of glycolytic inhibition by 2-deoxy-D-glucose±pyruvate was also evaluated. Both systolic and diastolic[Ca^<2+>]i tended to be higher and diastolic calcium removal(τCa)significantly slower in the hypertrophied heart. The myocardial response to dobutamine was blunted and dobutamine insignificantly improved τCa. The SERCA2 protein level was higher in early hypertrophy, but was significantly reduced by 6 weeks of age, with progressive contractile failure. Inhibition of glycolysis or SERCA2 caused an increase in [Ca^<2+>]i as Well as a slower τCa. Pyruvate completely preserved myocardial function and [Ca^<2+>]i handling during glycolytic inhibition. It was concluded that in this model of advanced pressure overload hypertrophy, contractile failure and inotrope insensitivity are associated with increased [Ca^<2+>]i, slower τCa and reduced sensitivity of the contractile proteins to Ca^<2+>. These changes occur in association with downregulation of the SERCA2, probably caused by impaired glucose metabolism.

• 社団法人日本循環器学会の論文
• 2001-11-20

著者

• NAGASHIMA Mitsugi

  Department of Cardiovascular Surgery, Ehime University Hospital

• Nido Pedro

  Department Of Cardic Surgery Childern's Hospital Boston And Harvard Medical School

• Nido Pedro

  Departments Of Cardiac Surgery Children's Hospital Of Boston And Harvard Medical School

• MUNAKATA Mamoru

  First Department of Surgery, Hirosaki University School of Medicine

• FUKUI Kozo

  First Department of Surgery, Hirosaki University School of Medicine

• Takeuchi Koh

  First Department of Surgery, Hirosaki University School of Medicine

• ltoh Kazuo

  First Department of Surgery, Hirosaki University School of Medicine

• Minagawa Masahito

  First Department of Surgery, Hirosaki University School of Medicine

• Ichinoseki Ikko

  First Department of Surgery, Hirosaki University School of Medicine

• McGowan Jr

  Departments of Anesthesia, Children's Hospital of Boston and Harvard Medical School

• Mcgowan Jr

  Departments Of Anesthesia Children's Hospital Of Boston And Harvard Medical School

• Ltoh Kazuo

  First Department Of Surgery Hirosaki University School Of Medicine

• Takeuchi Koh

  First Department Of Surgery Hirosaki University School Of Medicine

• Ichinoseki Ikko

  First Department Of Surgery Hirosaki University School Of Medicine

• Minagawa Masahito

  First Department Of Surgery Hirosaki University School Of Medicine

• Fukui Kozo

  First Department Of Surgery Hirosaki University School Of Medicine

• Munakata Mamoru

  First Department Of Surgery Hirosaki University School Of Medicine

• Nagashima Mitsugi

  Department Of Cardiovascular Surgery Ehime University Hospital

• Nagashima Mitsugi

  Departments Of Cardiac Surgery Children's Hospital Of Boston And Harvard Medical School

• Nagashima Mitsugi

  Department Of Cardiovascular Surgery Ehime University Graduate School Of Medicine

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