Development Of Atrial Cell Oxidative Stress Model And Analysis Of Its Effect On Electrophysiology

Arrhythmia has become the important factor that causes heart disease,and its incidence rate is increasing year by year.Especially in the aggravating trend of aging population,exploring the pathogenesis of arrhythmia has important practical significance.The study of the virtual heart model provides a new approach to the investigation of heart-related diseases.It can simulate the physiological and pathological phenomena at the microscopic level of the heart,providing quantitative analysis of protein molecules,cells,tissues,and the whole,and deepening the microscopic field of the heart that cannot be noticed by clinical medicine.Oxidative stress is the main manifestation of cell metabolism disorders.Related experiments have shown that it can affect multiple ion channels and proteases in cells,causing abnormal action potentials and eventually triggering arrhythmias.We developed the atrial cell simulation model to explore the intrinsic mechanism of arrhythmia induced by oxidative stress.Firstly,we established a human atrial cell simulation computational model to simulate the atrial cell electrophysiological changes,including ion current,ion concentration,calcium cycle and excitation-contraction coupling mechanism.And Ca MKII activation model and the effect of Ca MKII on related proteins and ion channels was fused.Physiological experiments have shown that reactive oxygen species(ROS)participates in the activation of Ca MKII,so the model will use Ca MKII as the bridge between oxidative stress and electrophysiology of atrial cells.The simulation results show that oxidative stress leads to early after-depolarization(EAD)of action potentials by affecting the calcium circulation process.Oxidative stress gradually increases the concentration of calcium ions in the cytoplasm by enhancing L-type calcium currents and the feedback of calcium circulation mechanisms.The amplitude of sodium-calcium exchange current is increased by increasing calcium concentration,which raises the plateau potential of the action potential and indirectly slows down the inactivation of L-type calcium current.As a result,the plateau of the action potential is prolonged,and the L-type calcium current is reactivated due to excessive membrane potential after inactivation,resulting in an EAD phenomenon.Then based on the atrial cell simulation model,we established a two-dimensional ideal tissue model to explore the effect of oxidative stress on the electrical excitatory conduction process in cell tissue.Simulation experiments have shown that oxidative stress cells can hinder the conduction of electrical excitation and may initiate reentry.Meanwhile,oxidative stress causes rupture of the reentry wave,which causes the heart to beat rhythm and causes arrhythmia.Finally,we developed the atrial cell simulation model as a demonstration software.The user can set the environmental parameters of cell and related cell composition parameters,then can observe the simulation data and graphic display of the atrial cell model.This software is convenient for users to learn about the electrophysiological knowledge of atrial cells and related experimental research.