Effects of Alterations in Sarcomere Structure and Prestretch Timing on Cardiac Muscle Mechanics.

摘要

Changes in mechanical function in the heart have been shown to be associated with different mechanisms of heart failure. Mechanical function is disrupted in dyssynchronous heart failure, as the timing of contraction in altered in different regions of the heart, preventing a uniform contraction. This dyssynchrony can be simulated using regional ventricular pacing, which also alters mechanical function. One purpose of the work presented here was to determine the effects of the altered cardiac muscle mechanics that arise due to regional ventricular pacing. It was found that a prestretch associated with dyssynchronous contraction can affect tension and work production in isolated cardiac muscle. The timing and magnitude of this stretch was also found to be of importance. Ultimately, the results could mostly be explained by a few well known muscle mechanics mechanisms: time-varying stiffness, the force-velocity relation, and shortening deactivation. Dilated cardiomyopathy (DCM) is another cause of heart failure, which can be brought about by mechanical dysfunction. The work presented here proposes a novel mechanism for contractile dysfunction associated with cardiac vinculin deletion, which is a precursor to dilated cardiomyopathy. It was shown that an increase in lattice spacing due to vinculin deletion increased transverse systolic stiffness and explains the altered systolic wall strains associated with vinculin deficiency. A combination of experiments, model development, and model simulation was used to uncover how changes in mechanical function associated with heart failure can alter cardiac muscle mechanics.