Simulating cardiac electrical function is an example of successful integrative multi-scale modeling approach directly relevant to human disease. Today we stand at the threshold of a new era: anatomically-detailed tomographically-reconstructed models that integrate from the ion channel to the electromechanical interactions in the intact heart are being developed. Such models hold high promise for interpretation of clinical and physiological measurements; for improving the basic understanding of the mechanisms of dysfunction in disease, such as arrhythmias, myocardial ischemia, and heart failure; and for the development and performance optimization of medical devices. The goal of this article is to present an overview of current state-of-art advances towards predictive computational modeling of the heart as developed recently by the authors of this article. We first outline the methodology for constructing electrophysiological models of the heart. We then provide three different examples that demonstrate the use of these models, focusing specifically on the mechanisms for arrhythmogenesis and defibrillation in the heart. These include: 1) uncovering the role of ventricular structure in defibrillation; 2) examining the contribution of Purkinje fibers to the failure of the shock; and 3) using MRI reconstructed heart models to investigate the reentrant circuits formed in the presence of an infarct scar. 10.1113/expphysiol.2008.044073
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