H. Ying. Investigation of atrial fibrillation induced remodeling in human right atrium: a simulation study. Institute of Biomedical Engineering, Universität Karlsruhe (TH). . 2004
AF is a common arrhythmia, arising from the disturbance of initiation and propagation of excitation pattern in atrial tissue. AF itself causes progressive electrophysiological and/or structural changes, which promote the initiation or perpetuation of AF. The involvement of electrophysiological changes to accom- plish the pathological adaptation from SR to the fibrillatory rhythm is termed as electrophysiological remodeling. In the present work, we investigate the re- modeling effects in response to the restored SR by cardioversion in RA in order to provide insights for the maintenance and progression of AF.A schematic anatomical right atrial model was established to simulate the wave propagation. It is composed of the SA node, which is the initiator of the physiological electrical activation, and the main musculature in RA: the terminal crest, pectinate muscles and the working myocardium, among which CT and PM are anisotropic and fast-conducting. Heterogeneous electrical ac- tivities (APD and morphology) in the different regions of RA and SA node are taken into account through modification of the parameters in the Courte- manche cellular model, which can reproduce the action potential (AP) of human atrial myocytes. The cellular electrical interconnection was described by using a monodomain approach combined with a finite difference method. Various conductivities were assigned to the model of healthy tissue to achieve the con- duction velocity approximating the experimental data obtained from human atria.At first, the cellular model was modified by incorporating the chronic AF in- duced electrophysiological changes reported in  to acquire the AP adapted from the SR to the fibrillatory rhythm. The individual impact of each elec- trophysiological change on the remodeling effect was investigated. Then the excitation propagation was simulated adopting the same method mentioned above with the schematic RA model in the physiological and remodeling case, respectively. In both cases the activation sequences were evaluated by measur- ing ERP, APD90, the conduction velocity, the activation time of RA and the heart rate.The remarkably abbreviated APD90 and ERP, and the attenuated rate ac- commodation of APD90 and ERP are the critical components of the results, which are the important characteristic of chronic AF. These effects are as- sociated with the decreased ICaL, Ito and enhanced IK1. Attenuated ERP rate-adaptation and short ERP cause the considerably decreased wavelength of atrial refractoriness (product of conduction velocity and ERP), thus allowing more wavelets to coexist in a given tissue mass. The enhanced vulnerability to propagate the premature depolarization promotes to the maintenance and perpetuation of AF. Fast atrial rate has been proposed as a potential trigger of electrophysiological remodeling by preventing the completely depolarised rest- ing potential and by Ca2+ overload per cardiac cycle. Remodeling may be a cellular adapative response at high heart rate to keep the APD short, thus op- pose Ca2+ overload, but at the expense of re-entry promoting ERP-shortening.The principal features of remodeling AP are reconstructed in this model. They are consistent with the clinical and experimental measurements. The sim- ulated impulse wavefront underlying the Courtemanche model with remodeling conditions resembles excitation propagation in the patients with chronic AF af- ter cardioversion. The relations between the abnormal propagating properties in tissue model and the cellular electrophysiological changes are elucidated. We have sought an explanation for AF begets AF at the cellular electrophysiolog- ical level. The remodeled RA model presents a dysfunctional substrate, which is more probable to induce and perpetuate AF.In the further work, it can be extended to simulate the AF effect, e.g. initi- ation and maintenance of re-entry wavelets in both atria, as well as the whole heart, if the triggers of AF are involved. The anatomical features will be cap- tured more realistically in future models. New pharmacological approaches to stabilize the atrial rhythm can be validated utilizing this model. In the present work, we employed uniform conductivity in the working myocardium and a monodomain formulation. In future, anisotropic and more detailed descrip- tion of cellular connection will be included. The remodeling conditions can be incorporated in CT and PM to match the clinical experimental data more accurately.