A computationally efficient dynamic model of human epicardial tissue

Abstract

We present a new phenomenological model of human ventricular epicardial cells and we test its reentry dynamics. The model is derived from the Rogers-McCulloch formulation of the FitzHugh-Nagumo equations and represents the total ionic current divided into three contributions corresponding to the excitatory, recovery and transient outward currents. Our model reproduces the main characteristics of human epicardial tissue, including action potential amplitude and morphology, upstroke velocity, and action potential duration and conduction velocity restitution curves. The reentry dynamics is stable, and the dominant period is about 270 ms, which is comparable to clinical values. The proposed model is the first phenomenological model able to accurately resemble human experimental data by using only 3 state variables and 17 parameters. Indeed, it is more computationally efficient than existing models (i.e., almost two times faster than the minimal ventricular model). Beyond the computational efficiency, the low number of parameters facilitates the process of fitting the model to the experimental data.

Diffuse fibrosis and repolarization disorders explain ventricular arrhythmias in Brugada syndrome: a computational study

“…As a result, the time between two consequent extra stimulations of the healthy tissue is increased. Note that, when both the percentage of fibrotic tissue and are low, the high frequency of stimulation may induce spiral waves with large wavelength in the healthy tissue, similar to spiral waves described in our previous work 24 . Moreover, the average frequency of APs in the healthy tissue achieved with low values of and is similar to the dominant frequency of spiral waves in healthy tissue 24 .…”

“…We conceived the model to reproduce the characteristics of BrS action potentials, such as lost or delayed dome and low upstroke velocity. To develop the myocyte model we extended the phenomenological model of epicardial tissue described in our previous work 24 . The model represents the total transmembrane current divided into three contributions corresponding to the excitatory, recovery, and transient outward currents.…”

“…The model represents the total transmembrane current divided into three contributions corresponding to the excitatory, recovery, and transient outward currents. To more accurately represent the AP dome associated with BrS, we modified the original formulation 24 by introducing a quadratic dependency between the parameter A and the variable u : where we added the parameter . Note that, by setting , this formulation is equivalent to the original model (i.e., was used for the healthy myocyte in this work).…”

“…Note that, by setting , this formulation is equivalent to the original model (i.e., was used for the healthy myocyte in this work). Furthermore, we modified the parameters of the original formulation 24 to simulate the AP associated with BrS. First, we reduced the values of and to reproduce the slower upstroke dynamics.…”

“…In particular, we studied the insurgence of sustained reentry as a function of electrophysiological and structural alterations of the ROVT. To describe the electrophysiological alterations we adapted our previously published phenomenological model of ventricular epicardial cells 24 to reproduce the characteristics commonly associated to BrS action potentials, such as loss of AP dome, delayed dome, and low upstroke velocity, which is related to conduction slowing in Brugada patients 16 , 17 . The simple formulation of the model (i.e.…”