Arrhythmogenesis in calcium-overloaded human cardiomyocytes in isolation and within cardiac tissue. Simulation study

Calcium overload of cardiomyocytes is fraught with rhythm disturbances. We are being involving mathematical modeling to study this phenomenon. Here we implemented our recently developed mathematical model of the human ventricular cardiomyocyte electromechanical activity 'TP+M' and one-dimensional virtual myocardial strand in which both electrical and mechanical interactions between the cells are accounted for. Each cell in the strand is represented by the TP+M model. Mechano-electric feedback loops in the model are provided by the intracellular mechanisms of cooperativity between regulatory and contractile proteins. Numerical experiments in the onedimensional strand revealed that mechanical interaction between the cells provoked rhythm disturbances in the multicellular myocardium locally overloaded with calcium. Subcellular excitation-contraction coupling including mechano-electric feedback mechanisms underlay vulnerability to the arrhythmia. Electrotonic interaction of the calciumoverloaded myocytes with fibroblasts revealed clear albeit moderate antiarrhythmic effects both in the single cell model and in the one-dimensional strand.