Abstract 1698: Micropatterned Heart Slice Cultures for Studies of Intramural Cardiac Electrophysiology
Current cardiac structure-function studies lack the ability to simultaneously assess local electrical activity and underlying tissue architecture inside the heart wall. We have developed a novel cardiac cell culture model (Fig. A⇓) that replicates the realistic chamber geometry and local myofiber directions of a cross-sectional tissue slice from a mouse ventricle. Local cardiac fiber directions in the ventricle were determined with 78 μm resolution using Diffusion tensor MRI (DTMRI). Photomasks were designed for select longitudinal and transverse cross-sectional planes, where each measured fiber direction was translated into a 210 μm pixel of parallel lines. Fibronectin micropatterns were printed based on the photomasks (Fig. B⇓, insert), on which neonatal rat cardiomyocytes were plated. By culture day 5, cardiomyocytes aligned along the fibronectin lines and interconnected locally and across neighboring pixels to reconstitute the native cardiac microarchitecture (Fig. B⇓). Average errors in local angle and gradient of cellular alignment compared to corresponding DTMRI values were only 4.7±4.0° and 3.2±4.2°/pixel, respectively, as measured for entire slices (~4000 pixels) by custom image analysis software. Optical mapping of membrane potentials at 504 sites revealed impulse propagation with an average velocity of 18±4 cm/s (Fig. C⇓). An example of anatomical reentry around the right ventricle is shown in Fig. D⇓. Future studies in this model system will elucidate the roles of the realistic intramural fiber directions and fiber direction gradients in the formation, maintenance, and termination of reentrant cardiac arrhythmias in healthy and hypertrophied hearts.