The objective of this article is to present a set of methods for constructing realistic computational models of cardiac structure from high-resolution structural and diffusion tensor magnetic resonance images and to demonstrate the applicability of the models in simulation studies. The structural image is segmented to identify various regions such as normal myocardium, ventricles, and infarct. A finite element mesh is generated from the processed structural data, and fiber orientations are assigned to the elements. The Purkinje system, when visible, is modeled using linear elements that interconnect a set of manually identified points. The methods were applied to construct 2 different models; and 2 simulation studies, which demonstrate the applicability of the models in the analysis of arrhythmia and defibrillation, were performed. The models represent cardiac structure with unprecedented detail for simulation studies.

Background Low-voltage termination of VT and atrial fibrillation has shown promising results, however the mechanisms and full range of applications remain unexplored. Objective This study aimed to elucidate the mechanisms for low-voltage cardioversion and defibrillation, and to develop an optimal low-voltage defibrillation protocol. Methods We developed a detailed MRI-based computational model of the rabbit right ventricular wall. We applied multiple low-voltage far-field stimuli of various strengths (≤1 V/cm) and stimulation rates in VT and VF. Results Out of the five stimulation rates tested, stimuli applied at 16 or 88% of VT cycle length (CL) were most effective in cardioverting VT, the mechanism being consecutive excitable gap decreases. Stimuli given at 88% of VF CL defibrillated successfully, whereas a faster stimulation rate (16%) often failed because the fast stimuli did not capture enough tissue. In this model, defibrillation threshold (DFT) energy for multiple low-voltage stimuli at 88% VF CL was 0.58% of the DFT energy for a single strong biphasic shock. Based on the simulation results, a novel two-stage defibrillation protocol was proposed. The first stage converted VF into VT by applying low-voltage stimuli at times of maximal excitable gap, capturing large tissue volume and synchronizing depolarization; the second stage terminated VT. The energy required for successful defibrillation using this protocol was 57.42% of the energy for low-voltage defibrillation when stimulating at 88% CL. Conclusion A novel two-stage low-voltage defibrillation protocol using the excitable gap extent to time multiple stimuli defibrillated VF with the least energy by first converting VF into VT, then terminating VT.

. Effect of acute global ischemia on the upper limit of vulnerability: a simulation study. Am J Physiol Heart Circ Physiol 286: H2078 -H2088, 2004. First published January 29, 2004 10.1152/ajpheart.01175.2003The goal of this modeling research is to provide mechanistic insight into the effect of altered membrane kinetics associated with 5-12 min of acute global ischemia on the upper limit of cardiac vulnerability (ULV) to electric shocks. We simulate electrical activity in a finiteelement bidomain model of a 4-mm-thick slice through the canine ventricles that incorporates realistic geometry and fiber architecture. Global acute ischemia is represented by changes in membrane dynamics due to hyperkalemia, acidosis, and hypoxia. Two stages of acute ischemia are simulated corresponding to 5-7 min (stage 1) and 10 -12 min (stage 2) after the onset of ischemia. Monophasic shocks are delivered in normoxia and ischemia over a range of coupling intervals, and their outcomes are examined to determine the highest shock strength that resulted in induction of reentrant arrhythmia. Our results demonstrate that acute ischemia stage 1 results in ULV reduction to 0.8A from its normoxic value of 1.4A. In contrast, no arrhythmia is induced regardless of shock strength in acute ischemia stage 2. An investigation of mechanisms underlying this behavior revealed that decreased postshock refractoriness resulting mainly from 1) ischemic electrophysiological substrate and 2) decrease in the extent of areas positively-polarized by the shock is responsible for the change in ULV during stage 1. In contrast, conduction failure is the main cause for the lack of vulnerability in acute ischemia stage 2. The insight provided by this study furthers our understanding of mechanisms by which acute ischemia-induced changes at the ionic level modulate cardiac vulnerability to electric shocks. ionic channels; computer simulations; arrhythmias ELECTRICAL DEFIBRILLATION is recognized as the most effective therapy against the malignant arrhythmias that lead to sudden cardiac death. However, although the majority of the patients that undergo defibrillation typically suffer from some form of coronary disease, little is known about the effect of acute ischemia on defibrillation efficacy. Experimental studies provide conflicting evidence: some report an increase in defibrillation threshold (DFT) (3,29,38,43), whereas others find no change (5,20,22,32) or even a decrease (2) in DFT during acute ischemia.Numerous studies (5,7,18) have demonstrated that the DFT is strongly linked to the upper limit of vulnerability (ULV) of cardiac tissue to electric shocks. Much research has focused on investigating the mechanisms of cardiac vulnerability in an attempt to better understand how failed defibrillation shocks reinitiate cardiac arrhythmias. During the past decade, experiments using optical mapping techniques (8,12,13,46) and computer simulation studies (25,30,37,41) have significantly improved the understanding of the mechanisms of shockinduced arrhythmogenesis, cul...

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Knowledge of the mechanism by which specific electrophysiological heterogeneities underlie arrhythmogenesis during acute ischaemia could be useful in developing preventative treatments for patients at risk of coronary vascular disease.

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Simulation of cardiac electrical function, and specifically, simulation aimed at understanding the mechanisms of cardiac rhythm disorders, represents an example of a successful integrative multiscale modeling approach, uncovering emergent behavior at the successive scales in the hierarchy of structural complexity. The goal of this article is to present a review of the integrative multiscale models of realistic ventricular structure used in the quest to understand and treat ventricular arrhythmias. It concludes with the new advances in image-based modeling of the heart and the promise it holds for the development of individualized models of ventricular function in health and disease.

Although the majority of patients undergoing defibrillation suffer from coronary heart disease, little is known about defibrillation in the setting of ischemic disease. The goal of this study is to aid understanding of defibrillation failure in ischemic hearts by studying changes in cardiac vulnerability to electric shocks the first 10 min following LAD occlusion. To do so, a 3D anatomically-accurate electrophysiologically-detailed bidomain model of the regionally ischemic ventricles following LAD occlusion was developed based on experimental data. The ventricles were paced at the apex and truncated exponential monophasic shocks were applied over a range of coupling intervals to determine the upper limit of vulnerability (ULV) and the vulnerable window (VW) in normoxia and 10 min post-occlusion. Simulation results demonstrate that, despite the profound electrophysiological changes in the ischemic region, the ULV remains unchanged 10 min post-occlusion because following high shock strengths gesULV virtual electrode polarization and postshock behavior remain unaffected by ischemia. However, the range of coupling intervals comprising the VW increases from spanning 60 ms in normoxia to 90 ms at 10 min post-occlusion. The increased in vulnerability in regional ischemia stems from the fact that slow conduction and increased dispersion of refractoriness in the ischemic region increase the likelihood of the establishment of a reentrant circuit following shocks of strength