Human Myocardial Cell Model And Simulation Study Of The Brugada Syndrome

Computer modeling and simulation is one of important research methods for heart cell electrophysiological property investigation. But, most previous simulation studies for ventricular myocardium cell are based on animal models, not human models. These animal models provide good references for simulations studies for ventricular myocardium cell, whereas, as we know that animal hearts used for simulation studies may differ significantly from human hearts (heart size, heart rate, action potential(AP) shape, duration, and restitution, vulnerability to arrhythmias, etc.), But, these models can not really reflect the electrophysiological mechanism of human ventricular myocardium cell.In this article, we introduce a mathematical model of the action potential of human ventricular cells including a high level of electrophysiological detail, which is computationally cost-effective enough to be applied in simulation studies for ventricular myocardium cell. The model is based on Luo-Rudy2000 model (LR2000 model), and recent experimental data on most of the major ionic currents (L-type calcium, the fast sodium, transient outward, rapid and slow delayed rectifier, and inward rectifier current) is considered, moreover, the formulations of Tusscher et al. are used in our model. According to brugada syndrome physiological mechanism, simulations are conducted in isolated epicardial, endocardial, and midmyocardial (M) cells, which are simulated by varying the maximum conductance (density), G_Ks, of the slowly activating delayed-rectifier potassium current I_Ks. I_t0, the transient outward current and I_cal, L-type Ca current, are also incorporated into our model.The simulation results show that our model reproduces the physiological experiment of brugada syndrome observed data well. Comparedthe normal ventricular cell AP with the brugada syndrome ventricular cell AP, we find that endocardial and M cells AP have little changes, but, the epicardial AP changes apparently in two different ventricular cell, the brugada syndrome epicardial cell exhibits an accentuation of the spike and dome morphology of AP, resulting in a delay in the development of the dome, secondary to widening of the AP notch. A further shift in the balance of current leads to loss of the AP dome and marked abbreviation.Using our simulation model incorporated the temperature sensitivity coefficient Q,o, we can acquire the different ventricular cell AP due to body temperature increasing. The result just explains why some brugada patients are easy to sudden death during a febrile state. This simulation model also can illuminate the reason that brugada patients often break out during the night when they are sleeping. During sleeping, controlled by increased activity of pneumogastric nerve, heart rate decreases, and transient outward currents increase, which can induce the brugada syndrome. Despite decades of research their causes are still poorly understood, using our model, we can make good explanation about these reasons. Our simulation study suggests that the proposed model reproduce a variety of electrophysiological behaviors and provide a basis for studies of heart disease.