Experimental and computational modeling of cardiac electrical propagation in bio-engineered sinoatrial node tissue.

The sinoatrial node (SAN) is a collection of auto-oscillatory cells in the heart that constitutes the pacemaker, sending rhythmic electrical stimulation to the myocardium to initiate contraction. Current arrhythmic or dysfunctional SAN treatments include ablation, pharmacological therapies, and implanted electronic pacing devices. Pediatric patients with congenital heart defects, treatment requires repeated procedures over the course of a lifetime. A proposed solution is bioengineered pacemaker cells that replicate healthy SAN behavior and control the heart’s rhythm. To manufacture a successful bioengineered pacemaker, it is critical we understand the electrical connection between the SAN and the surrounding tissue. In monolayer cultures of induced pacemaker cells, fluorescence signals of intracellular calcium concentrations show the action potential propagation on the cellular level. In this talk, I will discuss a minimal ionic cell model we constructed to replicate the observed SAN dynamics. Model parameters were estimated from experimental data using a genetic algorithm. The model was then coupled in complicated tissue geometries that resemble the SAN. furthermore, this model was implemented in full atrial simulations to determine the optimal geometries for robust pacemaking.