Parameter sensitivity analysis of the myocardial cell models in ischemia and screening of drug targets

Previous studies have shown that coronary artery occlusion can cause myocardial ischemia, which can induce ventricular tachycardia or fibrillation. According to the time sequence, myocardial ischemia can be divided into different pathological stages: the ischemia 1a stage (0-15 minutes), the ischemia 1b stage (15-45 minutes), the short-term myocardial infarction (MI) (within a few days) and the long-term MI (within a few weeks). However, few studies give attention to antiarrhythmic drugs directly acting on ion channels for the treatment of myocardial ischemia. The main reason is that the effective targets in myocardial ischemia are unclear. Therefore, based on the technology of electrophysiological simulation, the paper modeled the human ventricular cell model in myocardial ischemia. On this basis, the parameter sensitivity of the model was analyzed and the effective drug targets are selected. Firstly, human ventricular cell models were modeled in ischemia 1a, ischemia 1b, short-term MI and long-term MI based on the experimental data. Then, the sensitivity analysis of output parameters (APA, APD and RP) of the cell model in ischemia was analyzed based on the Sobol method. The results of parameter sensitivity analysis in this paper showed that APD of cell models in ischemia 1a, ischemia 1b and short-term MI was the most sensitive to the change of I_KATP, and APA and RP of cells were the most sensitive to the change of [K⁺]_o. The parameter sensitivity analysis of the cell model in long-term MI showed that APD of cell models was sensitive to I_Ks and I_CaL, and APA was most sensitive to I_Na.