Abstract 13933: Increased Cardiomyocyte Stiffness in the Transverse Direction and Incomplete Relaxation in Hypertrophied Rat Hearts Induced by Chronic β-adrenergic Stimulation
Background: Passive stiffness of left ventricle is influenced by cardiomyocyte stiffness in the transverse direction, however their relationship remains unknown. We measured the elastic modulus of the transverse direction of a single cardiomyocyte obtained from rat hypertrophic hearts. We also performed X-ray diffraction analysis of heart muscles in order to observe actin-myosin interaction, because the extent of cross-bridge formation at end-diastole may influence the transverse stiffness.
Methods and Results: Male Wistar rats received a vehicle (control), ISO or ISO + β1-blocker metoprolol (MET) subcutaneously. After 7 days, compared with those in control and ISO+MET groups, ISO administration had increased left ventricular (LV) wall thickness (P<0.05) and decreased LV diastolic function as assessed by increased LV end-diastolic pressure (P<0.05). Elastic modulus of living cardiomyocytes from the LV free wall was measured by an atomic force microscope (AFM). Stiffness of cardiomyocytes was significantly higher in the ISO group than in control and ISO + MET groups (P<0.005). We added butanedione monoxime (BDM), an inhibitor of actin-myosin interaction, and blebbistatin, a specific myosin II inhibitor, to the culture medium. BDM and blebbistatin significantly reduced the elastic modulus of cardiomyocytes in the ISO group (P<0.01). X-ray diffraction analysis revealed that intensity ratio ((1,0)/(1,1)) at diastole was significantly increased after addition of BDM in the ISO group (P<0.005) (Figure), indicating that the proportion of myosin heads in proximity to actin was reduced by BDM.
Conclusions: Cardiomyocyte stiffness in the transverse direction is increased in hearts with ISO-induced hypertrophy with diastolic dysfunction. This is caused by incomplete relaxation.
- © 2010 by American Heart Association, Inc.