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Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H764-74. Epub 2007 Nov 30.

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

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Department of Theoretical Biology, Utrecht University, Padualaan 8, Utrecht, 3584 CH, The Netherlands.


The onset of ventricular fibrillation (VF) has been associated with steep action potential duration 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 three-dimensional 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 anatomic 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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