Mathematical modeling of cardiac electrophysiology is an insightful method to investigate the underlying mechanisms responsible for arrhythmias such as atrial fibrillation. In past years, five models of human atrial electrophysiology with different formulations of ionic currents, and consequently diverging properties, have been published. The aim of this work is to give an overview of strengths and weaknesses of these models depending on the purpose and the general requirements of simulations. Therefore, these models were systematically benchmarked with respect to general mathematical properties and their ability to reproduce certain electrophysiological phenomena, such as action potential alternans. To assess the models ability to replicate modified properties of human myocytes and tissue in cardiac disease, electrical remodeling in chronic atrial fibrillation was chosen as test case. The healthy and remodeled model variants were compared with experimental results in single-cell, 1D and 2D tissue simulations to investigate action potential and restitution properties, as well as the initiation of reentrant circuits.
Student Theses (1)
H. Hettmann. Benchmarking electrophysiological models of human atrial myocytes. Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT). Bachelorarbeit. 2012
Investigating remedies for atrial fibrillation and the mechanisms underlying this tachycardia, the opportunities to operate directly on human atrial myocytes are limited since it is not easy to get experimental data of human atrial tissue in satisfactory quality. The results obtained with experiments on animals are also of limited validity and have to be adjusted because of the differences to human cell physiology. In silico studies, as a further possibility of scientific research, enable the computer based examination of physiological processes during atrial fibrillation as well as the supporting and inhibiting effects the respective drugs hypothetically have on them.In recent years, several mathematical cell models were published, which are a helpful device for the improved comprehension of atrial electrophysiology by computer simulations. Especially the atrial cell model developed by Courtemanche et al. was investigated in previous studies and reveals weaknesses is some aspects, as for instance the intracellular calcium handling.The aim of the current work is the comparison of the model of Courtemanche et al. with the four other mathematical cell models developed by Nygren et al., Maleckar et al., Koivumäki et al., and Bueno-Orovio et al. in order to determine the model, which is best suitable for simulations of healthy and also pathologically altered tissue. For this purpose, various simulations of single cells, as well as of one- and two-dimensional tissue patches are carried out using the five cell models. Aside from the examination of the physiological correctness and accordance to experimental data of human atrial myocytes, the results obtained by simulations are also compared among each other with regard to stability and velocity of the computation.