Stroke Volume Analog on a Chip - In Vitro Hydrodynamic Model of Cardiac Pumping Efficiency

Abstract

Stroke volume serves as a key metric of heart performance. Despite its central importance in diagnosing many cardiomyopathies, there exists limited in vitro models whose readouts can be directly mapped to this clinical indicator. To address this, as a simplified model of the heart’s left-ventricle, here we use two-dimensional Muscular Thin Films (2D-MTFs) as an assay for monitoring cardiac fluid-dynamics. Comprised of anisotropic cardiac microtissues which recapitulate the laminar architecture of the ventricular endocardium, we studied how differing tissue alignments can be used to form small-scale muscular pumps capable of driving local fluid-flows. Serving as an in vitro model of cardiac pumping efficiency, we show that in addition to determining diastolic and systolic contractile stresses, when patterned in an angled manner, MTFs can be used to model ventricular contraction and the resulting cardiac fluid-dynamics. This includes providing measurements of thrust generation and mass flux, which can be used to reconstruct a two-dimensional analog to stroke volume. Using experimental models combined with fluid-dynamics simulations, we find that tissue angles of ~20-30° produce maximal outputs, which is reminiscent of the helical wrapping angles observed in the left ventricle of the human heart. Additionally, we demonstrate in a preliminary study how MTFs can be used as hydrodynamic assays for determining therapeutic dose-response curves, testing the inotropic effects of isoproterenol for wild-type human stem cell derived cardiomyocytes. Overall, this work provides new experimental techniques for probing cardiac fluid-dynamics in vitro and can help map between laboratory experiments and clinical outcomes by providing more physiologically relevant metrics of cardiac performance in a scalable manner.