The Electrophysiological Model And Simulation Study Of The Canine Right Ventricular Myocyte Cell During Heart Failure

Heart failure (HF) is one of the largest threats to the public health, which is a primary cardiac disease characterized by decreased myocardial contractility, reduced cardiac output and arrhythmia. During HF, the electrophysioiogy of heart will have some special changes, EAD as one of the typical symptoms during HF is meaningful for the research of mechanisms of HF.In this thesis, our work is based on the canine right ventricular myocyte cell model developed by the group of Winslow in 2006 and incorporated with the experimental data describing myocyte responses to theβ-AR agonist ISO. And we simulate the changes of AP especially for the early after-depolarization (EADs). The way we simulates the heart failure is through the modification of switch rate parameter in the Ca²⁺ mode switch model, reflecting the increased open possibility of L-type calcium channel (LCCs) because of its phosphorylation, as the result, the EADs happen.The simulation result shows: EADs appear to be random and do not occur at regular time intervals, the rate of EADs increases as the fraction of LCC gating in mode 2 increases; and when the fraction of LCC gating in mode 2 is greater than zero, EADs occur randomly as a consequence of the underlying nature of stochastic, long duration openings of LCC gating in mode 2. It reproduces experimentally observed alterations of the ventricular myocyte in response toβ-AR agonists ISO. So the model indicates that the shape and duration of cardiac AP are directly influenced by the dynamic properties of the underlying L-type Ca²⁺ currents, promote mode 2 gating of LCC, the probability of occurrence of EADs will increase, which provide us a new hypothesis to analysis the mechanism of HF.