Effect of acute global ischemia on the upper limit of vulnerability: a simulation study

Abstract

. 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...

Arrhythmogenesis in the heart: Multiscale modeling of the effects of defibrillation shocks and the role of electrophysiological heterogeneity

“…Similar to previous studies, 10,20 our results demonstrate that the midmyocardium exhibits a complex shock-induced VEP, which is not predictable from the epicardial VEP. Furthermore, the effect of varying shock timing on VEP differs significantly in the bulk of the midmyocardium and on the epicardial surface.…”

“…The waveforms used in our vulnerability study are (truncated exponential) monophasic shocks of 8 ms duration and 65% tilt. 10,20,21 Shock polarity is referred to as RV − when the RV was the cathode, and the one near the LV was a grounding electrode. The opposite polarity is referred to as LV − .…”

Using a Cell-to-ECG model to evaluate ischemia detection from different lead sets

“…Different from the definition in [11] which associates the ischemia stages with the time after acute global ischemia, the stages in this study are assigned with decreasing gradients at plateau of action potential and increasing gradients in resting potentials. The major parameter setting is shown in Table 1.…”

“…With this alteration, CVODE integrator is used to calculate the action potential. Moreover, the ATP-dependent K + current (I K,ATP ) was incorporated into this model using ShawRudy's formulation [10,11] for ischemia and infarction simulation. Figure 1.…”

Effects of electrical heterogeneity on transmural reentry during acute global ischemia

“…Up to now most of the simulation researches have not yet taken transmural heterogeneity into consideration (Xie et al 2001;Clayton et al 2002;Blanca et al 2004;Zhang et al 2006;Trenor et al 2007). However, it has been demonstrated that there are regional differences in electrical activities in the ventricular wall of the guinea pig, canine, and human (Akar et al 2002;Henry et al 2004).…”