Modeling And Simulation Study Of Ventricular Arrhythmia In Post Acidosis

Heart disease is a serious threat to human life and health, therefore, the study of physiological and pathological heart get more and more attention. The method of using computer modeling to simulate the related physiological parameters of heart has become a hot topic of interdisciplinary, which can effectively overcome the risks and limitations of animal or human experiments and greatly improve the efficiency of researchers. Based on this, this paper used the advanced computer technology and mathematical modeling knowledge to establish a human ventricular acidotic model. In addition, we discussed the mechanism of Ventricular Arrhythmia induced by post acidosis based on the model.In a number of pathological conditions, myocardial cells become acidic. Acidosis affects the response of Ca2+ to muscle filaments and the process of excitation-contraction coupling, including muscle membrane and sarcoplasmic reticulum ion flows. These changes can reduce the contractility of myocardial cells, causing arrhythmias. Most importantly, at the early stage of the post acidosis, triggered activities induced in the cellular membrane potential could cause arrhythmias, which may cause malignant arrhythmia such as ventricular tachycardia or ventricular fibrillation. However, the studies for post-acidosis arrhythmogenic mechanisms mainly focused on the the micro level and most of them are based on animal experiments as a result of the limitation of experimental conditions. Therefore, the process of microscopic pathological changes leading to the macro cardiac arrhythmias is still unclear.In this paper, based on the CaMKII dynamic model developed by Decker et al, we impeoved the human ventricular acidosis model proposed by Lascano as well as built a series of multi-scale and multi-modal electrophysiological models. To analyze the functional influence of acidosis on cardiac electrical activity and ventricular arrhythmia,dynamic changes of cellular and tissue electrical activity were simulated and the acidosis-induced changes of electrocardiogram waveform were quantified. In addition, in order to clarify the intrinsic link between microscopic pathological changes of cells and macroscopic changes in ECG, we also quantitatively analyzed the impact of microscopic pathological changes on ECG during acidosis. Research can be divided into the following sections.Firstly, we create a virtual model of human ventricular acidosis cell and simulated the changes in ion concentration and action potential of single cell during acidosis(from normal to acidosis,and then to post acidosis). The results found that in the process of acidosis, CaMKII was highly activated, the concentration of sodium and calcium concentration within the cell elevated. Especially, at the early stage of the post acidosis,sarcoplasmic reticulum calcium load increased calcium leak, leading to delayedafterdepolarizations in the cellular membrane potential. In addition, acidosis also resulted in high resting membrane potential and reduced maximum upstroke velocity, leading to the generation of slow conduction and conduction block. The above experiment results are consistent with animal experiments and simulations.Secondly, the acidosis-induced changes of electrocardiogram waveform were quantified based on the one-dimensional tissue model. Results demonstrated that acidosis led to shortened action potential duration and decreased transmural dispersion of repolarization, resulting in reduced QT interval and shortened amplitude and width of T wave. And, the triggered activities induced in cells during post acidosis period caused ectopic depolarization and ectopic repolarization in the cardiac tissue. Meanwhile, the electrocardiogram showed premature ventricular contractions.Thirdly, Reentrant waves were simulated in the two-dimensional tissue model. The results show that: the acidosis region in tissue can spontaneously generate excitement. In addition, these electrical impulses enough to inspire surrounding tissue and make it excited, causing the conduction of the electrical impulses through the tissue. However,reentrant waves will produce when these electrical impulses meet with the the normal electrical impulses.In summary, this paper based on researches on post-acidosis arrhythmia and the powerful computing capability of computers constructed a series of electrophysiological models from ions to cell and then to tissue. Using the models we simulated the dynamic changes of cellular and tissue electrical activity and quantified the acidosis-induced changes of electrocardiogram waveform. Finally, we studied the mechanism of reentrant waves. All in all, we used computer technology to establish a set of complete ventricular electrophysiological system. The results have great clinical significance for the understanding of the mechanism of arrhythmia from micro to macro.