Simulation And Analysis Of The Effect Of Atrial Cell Oxidative Stress On Action Potential Alternans

Cardiovascular diseases seriously threaten human health.As one of the most dangerous cardiovascular disease,atrial fibrillation may cause a variety of complications,the most serious of which is cerebral thromboembolism,commonly known as stroke.Therefore,it is very important to fully understand the underlying mechanism of atrial fibrillation.Action potential alternans,the successive beat-tobeat alternation in the profile of cardiac myocyte action potential observed in the clinic,is a precursor to the occurrence of atrial fibrillation.Many studies have shown that oxidative stress has a strong relationship with action potential alternans and atrial fibrillation.Therefore,this article explored the mechanism and prevention of atrial fibrillation with oxidative stress as the entry point.Based on an improved human atrial myocytes simulation model,this article explored the underlying mechanisms that led to action potential alternans and the effects of oxidative stress on action potential alternans.Firstly,we rebuilded the existing human atrial cell computaional model by using computer technology.Starting from the electrophysiological characteristics of the model and the pacing cycle length dependence of the cardiac alternans,we improved the deficiencies in the simulation results of the existing model,and obtained an ideal atrial cell computaional model that meets the physiological experiment results.Then,we simulated the action potential alternans of the improved model under different oxidative stress levels.Based on a typical action potential alternans phenomenon of the improved model,the characteristics of action potential alternans and the role of various electrophysiological variables in it are analyzed through different simulation experiments.We found that the alternation of sarcoplasmic reticulum(SR)calcium release under oxidative stress is a key factor driving the action potential alternans,while both the inhibition by reactive oxygen species(ROS)on the myocardial sarcoplasmic reticulum Ca2+-ATPase(SERCA)activity and the promotion of the release of SR calcium by ROS via calcium/calmodulin-dependent protein kinase II(Ca MKII)are the direct cause of the action potential alternans.In addition,we also demonstrated that when ROS-induced action potential alternans appear,the steepness of calcium-induced calcium release is increased.Based on the improved atrial cell computational model,we builded a onedimensional ideal atrial tissue model.designed a simulation protocol.Since the conduction of excitaion is limited when the model is paced under a rapid stimulation rate,we simulated the effect of oxidative stress on the action potential alternans of the atrial fibrillation model.The simulation results showed that the oxidative stress can increase the amplitude of the action potential alternans of the atrial tissue during rapid stimulation,which meets the conclutions in single cell model.Finally,based on the simulation experiments of reactive oxygen species,we developed an atrial cell model simulation software.Users can set parameters of the cell model and specify different simulation protocols in the software and visually observe various electrophysiological data and action potential characteristics in the simulation results,which can provides convenience for users to either learn about the cardiac electrophysiology and oxidative stress knowledge or do relatived researches.