Research Project: Cardiac Monolayers as a Model System to Study Cardiac Remodeling

Principal Investigator: Dulciana Chan

Many cardiac therapy modalities alter the natural activation sequence of the heart, including pacemakers, internal cardioverter defibrillators, cardiac resynchronization therapy devices, and ablation of reentrant circuit pathways. It has been demonstrated that chronically altering the natural activation sequence of heart tissue can have deleterious effects including reduced cardiac output, and an increased susceptibility to cardiac arrhythmias. The goal of this research is to implement a disease and therapy model analogous to that in the heart when the natural activation sequence is altered and to use the model to characterize the deleterious effects of chronic dis-synchrony. We have implemented a simplified in-vitro 2D model of cardiac tissue in which mechanically stretched cultured cardiac myocyte monolayers are subjected to dis-synchronous electrical stimuli and mechanical stretch. We propose to investigate changes in cardiac electrodynamics induced by altering the natural activation sequence of the heart using optical mapping techniques. We will also quantify changes in protein expression of the cardiomyocyte.

(Top) Staining of relevant proteins in control rat cardiac monolayers (left) and isochrone map indicating centripetal wave propagation from a central pacing electrode (right).

(Bottom) Staining of relevant proteins in rat cardiac monolayers which were mechanically stretched during development (left) and isochrone map indicating an increase in propagation speed compared to control (right).