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Am J Physiol Heart Circ Physiol (November 30, 2007). doi:10.1152/ajpheart.00906.2007
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Submitted on August 6, 2007
Accepted on November 22, 2007

Effect of heterogeneous APD restitution on VF organization in a model of the human ventricles

Rikkert H. Keldermann1*, Kirsten H. W. J. ten Tusscher1, Martyn P. Nash2, Rok Hren3, Peter Taggart4, and Alexander V. Panfilov1

1 Theoretical Biology, Utrecht University, Utrecht, Utrecht, Netherlands
2 Engineering Science, University of Auckland
3 Department of Physics, University of Ljubljana, Ljubljana, Slovenia
4 Departments of Cardiology and Cardiothoracic Surgery, University College Hospital, London, United Kingdom

* To whom correspondence should be addressed. E-mail: R.H.Keldermann{at}uu.nl.

The onset of ventricular fibrillation (VF) has been associated with steep action potential duration (APD) restitution in both clinical and computational studies. Recently, detailed clinical restitution properties in cardiac patients were reported showing a substantial degree of heterogeneity in restitution slopes at the epicardium of the ventricles. The aim of the present study was to investigate the effect of heterogeneous restitution properties in a 3D model of the ventricles using these clinically measured restitution data. We used a realistic model of the human ventricles, including detailed descriptions of cell electrophysiology, ventricular anatomy, and fiber direction anisotropy. We extended this model by mapping the clinically observed epicardial restitution data to our anatomical representation using a diffusion based algorithm. Restitution properties were then fitted by regionally varying parameters of the electrophysiological model. We studied the effects of restitution heterogeneity on the organization of VF by analyzing filaments and the distributions of excitation periods. We found that the number of filaments and the excitation periods were both dependent on the extent of heterogeneity. An increased level of heterogeneity leads to a greater number of filaments and a broader distribution of excitation periods, thereby increasing the complexity and dynamics of VF. Restitution heterogeneity may play an important role in providing a substrate for cardiac arrhythmias.







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