A simulation study on the effect of antiarrhythmic drugs during myocardial infarction

Cuiping Liang1, Qince Li2, Jun Liu2
1Beijing Institute of Computer Technology and Application, 2Harbin Institute of Technology


Abstract

Cardiovascular diseases can lead to sudden cardiac death, most of which were caused by arrhythmias induced by myocardial infarction. The damaged cardiomyocytes in myocardial infarction can restore their electrophysiological function at the action of drugs. However, current simulation researches mainly focus on the effect of myocardial fibrosis on wave propagation in tissues, and few studies gave attention to antiarrhythmic drugs for the treatment of myocardial infarction. Therefore, the aim of this study is to simulate the therapeutic effect of common antiarrhythmic drugs. Firstly, this paper constructed the human ventricular cell model in myocardial infarction based on the TP06 model according to the experimental data. Then, the single-cell model was remodeled by adding the change of ion currents after drug action. We simulated the therapeutic effects of the two drugs (telmisartan and nifedipine) at different concentrations on the single cell model in myocardial infarction, and compared the changes of parameters (APA, APD, RP, dV/dtmax) before and after the drug action. At the same time, the co-action of the two drugs were simulated on the cell model in myocardial infarction. The simulation results showed INa agonist telmisartan could increase the maximum depolarization rate of cells in myocardial infarction, but the drug had no effect on APD of action potential. On the contrary, ICaL blocker nifedipine mainly affected the APD of myocardial cells and had no effect on the depolarization stage. Under the combined action of the two drugs, APA, RP and APD of myocardial cells in myocardial infarction basically returned to normal values, and dV/dtmax returned to 85% of the normal value. Although at present, there are no drugs that only act on these two targets (INa and ICaL), new antiarrhythmic drugs acting on these two targets can be designed to treat myocardial infarction diseases in the future.