Mathematical modeling and spectral simulation of genetic diseases in the human heart

Mathematical modeling and spectral simulation of genetic diseases in the human heart

Model Status

This CellML model is known to run in both COR and OpenCell to recreate the results of the original model. The units have been checked and they are consistent.

Model Structure

The applicability and usefulness of the new model have been proved by addressing the study of the Brugada syndrome, an important hereditary genetic disease able to cause sudden cardiac death in human patients even without identifiable structural abnormalities. Despite not incorporating independent descriptions for each of the known currents measured through the cell membrane, the model is however capable to correctly reproduce both the healthy and pathological conditions of the epicardial tissue layer, the latter being characterized by the presence of a much deeper notch in the cardiac action potential as a result of a loss of functionality of sodium channels which leaves unopposed the transient outward potassium current.

Despite being able of reproducing a great amount of available experimental data, one important limitation of the proposed minimal model is that it lacks of a complete description of intracellular calcium dynamics. Hence, the model cannot be used to study particular conditions of importance in the generation and development of arrhythmias, such as calcium overload, spontaneous calcium release or calcium-induced alternans. This limitation could be overcome however by coupling our simplified model of the cardiac transmembrane potential to a reduced model of the intracellular calcium cycling of the ventricular myocyte, such as the one suggested by Shiferaw et al. (2003), therefore yielding the first implementation of a second-generation simplified ionic model of the cardiac myocyte.

This model was taken from the PhD thesis of Alfonso Bueno:

Mathematical modeling and spectral simulation of genetic diseases in the human heart, Alfonso Bueno, Department of Mathematics, University of Castilla-La Mancha, Ciudad Real, May 2007.