CARDIAC ELECTROPHYSIOLOGY

& TISSUE ENGINEERING  

 

Nima Badie, BS

I am working to help bridge the gap between the structure and function of 2D cardiomyocyte monolayers and that of an actual 3D heart. Using data obtained by from an intact heart with diffusion tensor magnetic resonance imaging (DTMRI), general fiber directions and patterns can be extracted for any cross-section. Using these same patterns to guide the growth and positioning of cultured cardiomyocytes, we hope to culture a 2D monolayer that resembles the projected cross-section of the native tissue in both structure and function. Ultimately, we wish to use optical mapping to provide insight into the complex dynamics of impulse propagation and structure-dependent arrhythmogenicity.

 

Fig. 1. Micropattern Development
(A) DTMRI-measured in-plane fiber directions of three murine ventricular cross-sections, shown using circular colormap from B. (B) Angle map of a transverse ventricular cross-section in MATLAB. For each pixel, the white line and pixel color denote fiber direction and angle relative to x-axis, respectively.

 

Fig. 2. Formation of realistic cardiac microstructure in anisotropic slice cultures.
(A-C) Plated cells were found to attach and align along the underlying fibronectin lines and spread to form confluent cardiac fibers by day 6. (D) Composite image of entire micropatterned slice culture. (E) Close-up of four adjacent pixels delineated by dashed line and underlying fibronectin pattern (green, inset). Note abrupt changes in cardiac fiber directions in neighboring pixels without loss of cell confluence. Red, sarcomeric a-actinin; green, connexin43; blue, nuclei.

 

 

Movie 1. Isopotential movie illustrating ramped rapid pacing-induced conduction block.
Conduction block occurs at the anterior edge of the junction between the septum and right ventricular free wall junction. Pacing was applied in the center of the right ventricular free wall (pacing times denoted by white flashes). Red indicates action potential peak, blue indicates rest.