Increased Passive Stiffness of Cardiomyocytes in the Transverse Direction and Residual Actin and Myosin Cross-Bridge Formation in Hypertrophied Rat Hearts Induced by Chronic β-Adrenergic Stimulation

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  • Donato Martín
    Institute of Cardiovascular Physiopathology, Department of Pathology, School of Medicine, University of Buenos Aires
  • Gelpi Ricardo J.
    Institute of Cardiovascular Physiopathology, Department of Pathology, School of Medicine, University of Buenos Aires

書誌事項

タイトル別名
  • Assessment of Longitudinal Myocardial Stiffness Is Not Enough to Evaluate Diastolic Function
  • – What Is the Relevance of the Stiffness of Cardiomyocytes in the Transverse Direction? –

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説明

Background: Left ventricular (LV) hypertrophy is often present in patients with diastolic heart failure. However, stiffness of hypertrophied cardiomyocytes in the transverse direction has not been fully elucidated. The aim of this study was to assess passive cardiomyocyte stiffness of hypertrophied hearts in the transverse direction and the influence of actin-myosin cross-bridge formation on the stiffness. Methods and Results: Wistar rats received a vehicle (control) or isoproterenol (ISO) subcutaneously. After 7 days, compared with the controls, ISO administration had significantly increased heart weight and LV wall thickness and had decreased peak early annular relaxation velocity (e’) assessed by echocardiography. Elastic modulus of living cardiomyocytes in the transverse direction assessed by an atomic force microscope was significantly higher in the ISO group than in controls. We added butanedione monoxime (BDM), an inhibitor of actin-myosin interaction, and blebbistatin, a specific myosin II inhibitor, to the medium. BDM and blebbistatin significantly reduced the elastic modulus of cardiomyocytes in the ISO group. X-ray diffraction analysis showed that the reflection intensity ratio (I(1,0)/I(1,1)) at diastole was not different before and after treatment with BDM, which induces complete relaxation, in control hearts, but that I(1,0)/I(1,1) was significantly increased after BDM treatment in the ISO group, indicating residual cross-bridge formation in hypertrophied hearts. Conclusions: Passive cardiomyocyte stiffness in the transverse direction is increased in hearts with ISO-induced hypertrophy and this is caused by residual actin-myosin cross-bridge formation.  (Circ J 2013; 77: 741–748)<br>

収録刊行物

  • Circulation Journal

    Circulation Journal 77 (3), 608-609, 2013

    一般社団法人 日本循環器学会

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