In silico study of multicellular automaticity of heterogeneous cardiac cell monolayers: Effects of automaticity strength and structural linear anisotropy

摘要

Author summary Implantation of electronic pacemakers is a standard treatment to pathologically slow heart rhythm. Despite improving quality of life, those devices display many shortcomings. Bioengineered tissue pacemakers may be a therapeutic alternative, but associated design methods usually lack control of the way cells with spontaneous activity are scattered throughout the tissue. Our study is the first to use a mathematical model to rigorously define and thoroughly characterize how pacemaker cells scattering at the microscopic level may affect macroscopic behaviors of the bioengineered tissue pacemaker. Automaticity strength (ability of pacemaker cell to drive its non-pacemaker neighbors) and anisotropy (preferential orientation of cell shape) are also implemented and give unparalleled insights on how effects of uncontrollable scattered pacemaker cells may be modulated by available experimental techniques. Our model is a powerful tool to aid in optimized bioengineered pacemaker therapies.