Impact of Mechanically-Induced Fibrosis on Atrial Electromechanical Function

Atrial fibrillation is accompanied by remodelling processes on the structural, electrophysiological, and contractile levels.These alterations result at least in part from mechanical overload.In order to investigate the effects of mechanical forces on atrial cell and tissue mechano-electric functions, we established two human invitro models, one at cell and the other at tissue level.The cellular model consists of functional atrial-and ventricular-like cardiomyocyte populations from human induced pluripotent stem cells, to characterize their electrical and mechanical functions in various mechanical environments.The tissue-based model consists of slices that are electrically and mechanically stimulated in biomimetic chambers for up to 7 days.We hypothesize that mechanical overload induces fibrosis, mimicking the condition of atrial tissue from patients having sustained atrial fibrillation.We aim to use this model for an indepth characterization of the effects of mechanical.By compiling all data into a computational model, we propose to establish a digital slice model, in which parameters such as collagen distribution, tissue and extracellular matrix stiffness, as well as excitation can be changed independently to assess their contribution to passive and active mechanics and their effects on electrophysiological properties of atrial tissue slices over time.