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From the Department of Theoretical Biology (K.H.W.J.T.T., A.V.P.), Utrecht University, The Netherlands; and Institute of Mathematics (R.H.), Physics Mechanics, University of Ljubljana, Slovenia.
Correspondence to K.H.W.J. Ten Tusscher, Utrecht University, Department of Theoretical Biology, Padualaan 8, 3584 CH Utrecht, The Netherlands. E-mail khwjtuss{at}hotmail.com
Sudden cardiac death is a major cause of death in the industrialized world, claiming approximately 300 000 victims annually in the United States alone. In most cases, sudden cardiac death is caused by ventricular fibrillation (VF). Experimental studies in large animal hearts have shown that the uncoordinated contractions during VF are caused by large numbers of chaotically wandering reentrant waves of electrical activity. However, recent clinical data on VF in the human heart seem to suggest that human VF may have a markedly different organization. Here, we use a detailed model of the human ventricles, including a detailed description of cell electrophysiology, ventricular anatomy, and fiber direction anisotropy, to study the organization of human VF. We show that characteristics of our simulated VF are qualitatively similar to the clinical data. Furthermore, we find that human VF is driven by only approximately 10 reentrant sources and thus is much more organized than VF in animal hearts of comparable size, where VF is driven by approximately 50 sources. We investigate the influence of anisotropy ratio, tissue excitability, and restitution properties on the number of reentrant sources driving VF. We find that the number of rotors depends strongest on minimum action potential duration, a property that differs significantly between human and large animal hearts. Based on these findings, we suggest that the simpler spatial organization of human VF relative to VF in large animal hearts may be caused by differences in minimum action potential duration. Both the simpler spatial organization of human VF and its suggested cause may have important implications for treating and preventing this dangerous arrhythmia in humans.
Key Words: ventricular fibrillation computer simulation spatial organization
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