Abstract Body: Introduction:
Approximately 1 in 4 people will develop heart failure in their lifetime, with more than half being diagnosed with heart failure with preserved ejection fraction and nearly all having some relaxation impairment, i.e. diastolic dysfunction. Mechanical Control of Relaxation (MCR), which is the strain rate dependence of relaxation studied in intact cardiac trabeculae, can accelerate relaxation. Our prior studies showed MCR is likely sarcomeric in source but is not differentially modified by myosin isoforms.
Goal:
To study the effect of thin filament activation on MCR using levosimendan, a compound that sensitizes cardiac troponin C to calcium. We hypothesize that levosimendan will increase the isometric tension of the cardiac trabeculae tested and decrease MCR because it would maintain activation.
Methods:
Intact cardiac trabeculae were obtained from rat hearts, mounted between a force transducer and length motor, and stretched to their optimal length. Trabeculae were studied under isometric and isotonic conditions to determine isometric tension and MCR at increasing concentrations of levosimendan.
Results/Discussion:
Preliminary results show that maximum isometric tension is stable and/or increases as levosimendan concentration increases, whereas MCR did not consistently increase as expected. This contrasts with our previously reported findings with Omecamtiv Mercarbil which does not increase isometric tension but does increase MCR. Since MCR and the isometric relaxation rate is constant, it appears that the thin filament is not deactivating slower with increasing Levosimendan. Thus, the binding of calcium may not be a modifier of MCR, but further studies to investigate thin filament deactivation may be warranted.