Cardiac vulnerability to electric shocks during phase 1A of acute global ischemia
Introduction
Understanding cardiac vulnerability to electric shocks has long been considered a route to understanding arrhythmogenesis by failed defibrillation shocks.1, 2, 3, 4, 5 Although the majority of patients who undergo defibrillation suffer from coronary disease, research on shock-induced arrhythmogenesis has focused mostly on normal hearts (see, for instance, references 1, 2, 3) and rarely on hearts with ischemic disease.4, 5 This is due to the fact that during ischemia, myocardial electrophysiologic properties change rapidly.6 This renders experimental evaluation of arrhythmogenesis difficult: tissue state varies from shock to shock in during the course of a single experiment.4, 5 Therefore, changes in cardiac vulnerability to electric shocks over the course of ischemia phase 1A remain poorly understood.
Simulations of postshock electrical events in a realistic model of the normal ventricles have afforded significant insights into the mechanisms of shock-induced arrhythmogenesis2, 7 by providing information, with a high spatiotemporal resolution, regarding shock-induced electrical behavior within the myocardial depth not currently accessible by experimental techniques. The present study extends this approach to arrhythmogenesis in the acutely ischemic ventricles. The goal is to characterize the changes in vulnerability to electric shocks during phase 1A of global ischemia and to determine the mechanisms responsible for these changes. This study focuses on global ischemia as an important step4, 5 in understanding the mechanisms that underlie vulnerability to electric shocks following an ischemic event associated with coronary heart disease.
Because break-excitations secondary to shock-induced virtual electrode polarization underlie postshock activity in the myocardium,1, 2, 3, 8, 9, 10 we hypothesize that dynamic changes in ionic currents and concentrations over the course of ischemia phase 1A affect the characteristics of break-excitation wavefronts and their propagation, thus altering the vulnerable window and the upper limit of vulnerability (ULV) to electric shocks. The present research tests this hypothesis.
Section snippets
Computational model
We used the anatomically accurate finite-element bidomain rabbit ventricular model (Figure 1) described previously.2, 7 Numerical aspects regarding ventricular discretization and finite-element solver can be found in previous publications by our group.11, 12
Global ischemia was implemented by assigning the same (ischemic) membrane dynamics to every cell in the rabbit ventricles. Ionic currents were represented by an ischemic version8 of the Luo-Rudy dynamic model13, 14 modified for
Electrical activity in acute global ischemia
Figure 2 illustrates the effect of increasing ischemia severity on action potential morphology (panel A), APD and Vrest (panel B), ERP and postrepolarization refractoriness period (panel C), and on the maps of activation and repolarization times (panel D). Note that because action potential morphology and ERP are the same for each cell (per our implementation of global ischemia), changes in the parameters shown in panels A, B, and C over the course of acute ischemia refer to any ventricular
Discussion
This study uses for the first time a sophisticated computer model of ventricular electrophysiology to provide mechanistic insight into the dynamic changes in cardiac vulnerability to electric shocks during phase 1A of acute global ischemia. Our results demonstrate that ULV diminishes as ischemia progresses, whereas the range of CIs comprising the vulnerable window shifts as a function of ischemia severity. Altogether the ventricles become less vulnerable to electric shocks as global ischemia
Acknowledgment
The authors thank Dr. J.M. Ferrero Jr. (Universidad Politécnica de Valencia, Spain) for helpful comments and suggestions.
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Cited by (47)
Multiscale numerical simulation of heart electrophysiology
2019, Advances in Biomechanics and Tissue RegenerationVulnerability in regionally ischemic human heart. Effect of the extracellular potassium concentration
2018, Journal of Computational ScienceCitation Excerpt :However, these and subsequent simulations were limited to two dimensional tissue preparations [7,32], providing only a partial view of the problem. Three dimensional simulations have been limited to the globally ischemic heart [25], with limited work performed in modeling the human heart subjected to acute ischemic conditions [5,13,33]. In this regard, Weiss et al. [33], account for heterogeneities caused by ischemia, as well as AP duration (APD) differences, both transmurally and apex to base.
Computational rabbit models to investigate the initiation, perpetuation, and termination of ventricular arrhythmia
2016, Progress in Biophysics and Molecular BiologyCitation Excerpt :The VEPs elicited the formation of wavefronts that propagated through excitable gaps and led to successful defibrillation (Bishop et al., 2012). Rabbit ventricular models have also been used to elucidate the mechanisms of defibrillation in ischemic and infarcted hearts (Rantner et al., 2012; Rodriguez et al., 2004b, 2004c). Rodriguez et al. used the UCSD rabbit ventricle model to examine the role of electrophysiological remodeling during different phases of global acute ischemia in determining success or failure of defibrillation shocks (Rodriguez et al., 2004a, 2004b; Rodriguez and Trayanova, 2003).
Rabbit-specific computational modelling of ventricular cell electrophysiology: Using populations of models to explore variability in the response to ischemia
2016, Progress in Biophysics and Molecular BiologyCitation Excerpt :Finally, it has been inserted into a model of the rabbit right ventricular wall to elucidate mechanisms of low-voltage cardioversion (Rantner et al., 2013) and into a rabbit ventricular slice model to investigate the role of the coronary vasculature in defibrillation (Bishop et al., 2010, 2012). The study of electrophysiological disturbances leading to arrhythmias due to heterogeneity caused by acute ischemia is one area in particular where rabbit-specific computational modelling has provided valuable insight (although in some cases, while rabbit-specific geometries were used, the underlying cellular models were in fact developed for other species) (Jie et al., 2010; Jie and Trayanova, 2010; Li et al., 2006; Michailova et al., 2007; Rodriguez et al., 2006a, 2004, 2006b; Tice et al., 2007). Acute ischemia is a major cause of sudden cardiac death (Rubart and Zipes, 2005), thought to account for 80% of all sudden deaths without a prior history of heart disease (Myerburg et al., 1997).
Defibrillation
2014, Comprehensive Biomedical Physics
This work was supported by AHA Established Investigator Award to Dr. Trayanova, National Institutes of Health (NIH) Grant HL063195 to Dr. Trayanova, Pre-NPEBC NIH grant P20EB001432 (Tulane Center for Computational Sciences), and grants from the Whitaker and Keck Foundations to Dr. Eason. For this work, Dr. Rodríguez was awarded first prize in the Young Investigator Award Competition at the NASPE–Heart Rhythm Society Meeting in 2004; thus, a portion of this work was published previously in abstract form.23