Mavacamten preserved length-dependent contractility and improved diastolic function in human engineered heart tissue.

Mavacamten preserved length-dependent contractility and improved diastolic function in human engineered heart tissue. Am J Physiol Heart Circ Physiol. 2021 Jan 15;: Authors: Sewanan LR, Shen S, Campbell SG Abstract Comprehensive functional characterization of cardiac tissue includes investigation of length and load dependence. Such measurements have been slow to develop in engineered heart tissues (EHTs), whose mechanical characterizations have been limited primarily to isometric and near-isometric behaviors. A more realistic assessment of myocardial function would include force-velocity curves to characterize power output and force-length loops mimicking the cardiac cycle to characterize work output. We developed a system that produces force-velocity curves and work loops in human EHTs using an adaptive iterative control scheme. We used human EHTs in this system to perform a detailed characterization of the cardiac beta-myosin specific inhibitor, mavacamten. Consistent with the clinically proposed application of this drug to treat hypertrophic cardiomyopathy, our data support the premise that mavacamten improves diastolic function through reduction of diastolic stiffness and isometric relaxation time. Meanwhile, the effects of mavacamten on length- and load-dependent muscle performance were mixed. The drug attenuated the length-dependent response at small stretch values but showed normal length dependency at longer lengths. Peak pow...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research