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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
- Source :
- Circulation journal : official journal of the Japanese Circulation Society. 77(3)
- Publication Year :
- 2012
-
Abstract
- 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)
- Subjects :
- Male
medicine.medical_specialty
Diastole
Cardiomegaly
macromolecular substances
Diacetyl
Myosins
Microscopy, Atomic Force
Heterocyclic Compounds, 4 or More Rings
Muscle hypertrophy
Internal medicine
Myosin
medicine
Myocyte
Animals
Myocytes, Cardiac
Enzyme Inhibitors
Rats, Wistar
Elastic modulus
Transverse direction
Cells, Cultured
Ultrasonography
business.industry
Diastolic heart failure
Isoproterenol
General Medicine
Organ Size
Adrenergic beta-Agonists
Papillary Muscles
medicine.disease
Actins
Elasticity
Rats
Radiography
Disease Models, Animal
Heart failure
Cardiology
Hypertrophy, Left Ventricular
Cardiology and Cardiovascular Medicine
business
Subjects
Details
- ISSN :
- 13474820
- Volume :
- 77
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Circulation journal : official journal of the Japanese Circulation Society
- Accession number :
- edsair.doi.dedup.....0d992e17346441ba214f39609e515c8a