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1 Department of Theoretical Biology, Utrecht University, Utrecht, The Netherlands
2 University Laboratory of Physiology, University of Oxford, Oxford, United Kingdom
3 Department of Theoretical Biology, Utrecht University, Utrecht, The Netherlands; Division of Mathematics, University of Dundee, Dundee, United Kingdom
* To whom correspondence should be addressed. E-mail: khwjtuss{at}hotmail.com.
The experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. In this article we introduce a mathematical model of the action potential of human ventricular cells which, while including a high level of electrophysiological detail, is computationally cost effective enough to be applied in large scale spatial simulations for the study of reentrant arrhythmias. The model is based on recent experimental data on most of the major ionic currents: the fast sodium, L-type calcium, transient outward, rapid and slow delayed rectifier, and inward rectifier current. The model includes a basic calcium dynamics, allowing for the realistic modeling of calcium transients, calcium current inactivation, and the contraction staircase. We are able to reproduce epicardial, endocardial and M cell human action potentials, and show that differences can be explained by differences in the transient outward and slow delayed rectifier currents. Our model reproduces the experimentally observed data on APD restitution, which is an important characteristic for reentrant arrhythmias. The conduction velocity restitution of our model is broader than in other models and agrees better with available data. Finally, we model the dynamics of spiral wave rotation in a 2D sheet of human ventricular tissue and show that the spiral wave follows a complex meandering pattern and has a period of 265ms. We conclude that the proposed model reproduces a variety of electrophysiological behaviors and provides a basis for studies of reentrant arrhythmias in human ventricular tissue.
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