Abstract 5782: Increased Cardiomyocyte Elasticity in the Transverse Direction in Hypertrophied Rat Hearts Induced by Chronic β-adrenergic Stimulation
Background: Cardiomyocyte stiffness in longitudinal direction is increased in patients with diastolic heart failure. However, stiffness in transverse direction has not been elucidated. We hypothesized that cardiomyocyte elasticity in transverse direction is also increased in hypertrophied hearts. We measured the elasticity of a single cardiomyocyte by use of an atomic force microscope (AFM) in isoproterenol (ISO)-induced hypertrophied rat hearts.
Methods and Results: Male Wistar rats (9 weeks old) received a vehicle (control), ISO (2.4 mg · kg−1 · day−1) or ISO + β1-blocker metoprolol (MET) (24 mg · kg−1 · day−1) subcutaneously (n=5 in each group). 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 (ISO: 15.3±2.0 vs control: 4.8±0.5 or ISO + MET: 6.6±0.8 mmHg, P<0.05). Elasticity of 10 living cardiomyocytes from LV free wall was measured by parabolic force curves of cantilever deflection/indentation obtained by AFM (Fig A⇓). Elasticity of cardiomyocytes was significantly higher in ISO group than in control and ISO + MET groups (Fig B⇓). Next, we added butanedione monoxime (BDM) (20 mM), an inhibitor of actin-myosin interaction, and blebbistatin (10 μM), a specific myosin II inhibitor, to culture medium. BDM and blebbistatin significantly reduced the elasticity of cardiomyocytes in ISO group (Fig B⇓).
Conclusions: Cardiomyocyte elasticity in transverse direction was increased in hearts with ISO-induced hypertrophy along with diastolic dysfunction. This may be caused by incomplete relaxation.