Fractionated Electrograms From a Computer Model of Heterogeneously Uncoupled Anisotropic Ventricular Myocardium

Ellis, Willard S.; Auslander, David M.; Lesh, Michael D.

doi:10.1161/01.cir.92.6.1619

Cited by 28 publications

(20 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well recognized that discontinuity in wavefront propagation may lead to complex polyphasic (fractionated) extracellular potential recordings. 9,26 To investigate the possibility of fractionation in extracellular recordings from ventricular tissue, we plotted extracellular potential waveforms at 28 sites throughout the rat tissue volume. The signals from the discontinuous and continuous models are shown in Figure 4 (top and bottom panels, respectively).…”

Section: Part Imentioning

confidence: 99%

Cardiac Microstructure

Hooks

Tomlinson

Marsden

et al. 2002

Circulation Research

222

View full text Add to dashboard Cite

Abstract-Our understanding of the electrophysiological properties of the heart is incomplete. We have investigated two issues that are fundamental to advancing that understanding. First, there has been widespread debate over the mechanisms by which an externally applied shock can influence a sufficient volume of heart tissue to terminate cardiac fibrillation. Second, it has been uncertain whether cardiac tissue should be viewed as an electrically orthotropic structure, or whether its electrical properties are, in fact, isotropic in the plane orthogonal to myofiber direction. In the present study, a computer model that incorporates a detailed three-dimensional representation of cardiac muscular architecture is used to investigate these issues. We describe a bidomain model of electrical propagation solved in a discontinuous domain that accurately represents the microstructure of a transmural block of rat left ventricle. From analysis of the model results, we conclude that (1) the laminar organization of myocytes determines unique electrical properties in three microstructurally defined directions at any point in the ventricular wall of the heart, and (2)

show abstract

Section: Part Imentioning

confidence: 99%

Cardiac Microstructure

Hooks

Tomlinson

Marsden

et al. 2002

Circulation Research

222

View full text Add to dashboard Cite

show abstract

“…An alternative approach to study the effect of tissue structure on electrogram morphology is to make use of computer simulation. To date, most studies have considered obstacles or inhomogeneity at the scale of 1–3 mm inside models with otherwise continuous properties 5,6,7,8 . Several studies have suggested that the spatial scale of heterogeneity is often much smaller (e.g.…”

Section: Introductionmentioning

confidence: 99%

Genesis of complex fractionated atrial electrograms in zones of slow conduction: A computer model of microfibrosis

2009

View full text Add to dashboard Cite

BACKGROUND Complex fractionated atrial electrograms are used as potential targets for catheter ablation therapy of atrial fibrillation. Although fibrosis has been associated with the presence of fractionated electrograms, characterizing the substrate through the inspection of electrograms is challenging. OBJECTIVE To determine how progression of microfibrosis and slow conduction affect electrogram morphology. METHODS A microstructure computer model representing a monolayer of cardiac cells was developed. Slow conduction was induced by (1) sodium channel blockade, (2) uniform reduction in cell-to-cell coupling, and (3) microfibrosis incorporated as a set of collagenous septa disconnecting transverse coupling. The density (0 to 30%) and length (30 to 945 μm) of these collagenous septa were varied. Unipolar and bipolar electrograms were computed during paced rhythm for a set of electrodes with different tip sizes. RESULTS The analysis of unipolar electrograms with realistic temporal and spatial filtering revealed that increasing the density and length of collagenous septa decreased conduction velocity by up to 75% and increased the amount of fractionation (up to 14 deflections) and asymmetry of the electrograms. In contrast, slow conduction induced by sodium channel blockade or uniformly-reduced coupling did not result in electrogram fractionation. When a larger electrode was used, electrogram amplitude was smaller and fractionation increased in a substrate-dependent way. CONCLUSION Microscale obstacles cause significant changes to electrogram waveforms. Conduction velocity and electrogram amplitude and degree of fractionation can be used to discriminate the nature of the substrate and characteristics of fibrosis giving rise to slow conduction.

show abstract

“…Computer simulations in a onedimensional (1-D) cable by Starmer et al (34,35) showed that reduced Na ϩ channel density or slowed recovery simulating electrical remodeling increased the vulnerable window (VW) for unidirectional conduction block. In addition, computer simulations investigating abnormal cell coupling on unidirectional block in 1-D cables (14, 31, 38) and conduction in two-dimensional (2-D) tissue (6,7,19,32) have demonstrated that abnormal coupling promotes unidirectional conduction block and irregular conduction. However, susceptibility to unidirectional conduction block in a 1-D cable is not equivalent to vulnerability to reentry in 2-D or three-dimensional (3-D) tissue, because, in addition to unidirectional conduction block, induction of reentry requires an alternate conduction pathway of adequate spatial dimension.…”

mentioning

confidence: 99%

Effects of Na⁺ channel and cell coupling abnormalities on vulnerability to reentry: a simulation study

Qu¹,

Karagueuzian²,

Garfinkel³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

. Effects of Na ϩ channel and cell coupling abnormalities on vulnerability to reentry: a simulation study. Am J Physiol Heart Circ Physiol 286: H1310-H1321, 2004. First published November 20, 2003 10.1152/ajpheart.00561.2003.-The role of dynamic instabilities in the initiation of reentry in diseased (remodeled) hearts remains poorly explored. Using computer simulations, we studied the effects of altered Na ϩ channel and cell coupling properties on the vulnerable window (VW) for reentry in simulated two-dimensional cardiac tissue with and without dynamic instabilities. We related the VW for reentry to effects on conduction velocity, action potential duration (APD), effective refractory period dispersion and restitution, and concordant and discordant APD alternans. We found the following: 1) reduced Na ϩ current density and slowed recovery promoted postrepolarization refractoriness and enhanced concordant and discordant APD alternans, which increased the VW for reentry; 2) uniformly reduced cell coupling had little effect on cellular electrophysiological properties and the VW for reentry. However, randomly reduced cell coupling combined with decoupling promoted APD dispersion and alternans, which also increased the VW for reentry; 3) the combination of decreased Na ϩ channel conductance, slowed Na ϩ channel recovery, and cellular uncoupling synergistically increased the VW for reentry; and 4) the VW for reentry was greater when APD restitution slope was steep than when it was flat. In summary, altered Na ϩ channel and cellular coupling properties increase vulnerability to reentrant arrhythmias. In remodeled hearts with altered Na ϩ channel properties and cellular uncoupling, dynamic instabilities arising from electrical restitution exert important influences on the VW for reentry. vulnerable window; action potential duration alternans; remodeling; computer simulation IN THE NORMAL HEART, dynamic instability has been shown to have an important influence on the propensity for wavebreak during reentry (20,26,39). Dynamic instability is caused by factors such as restitution of the action potential duration (APD) or effective refractory period (ERP) (27, 29), restitution of conduction velocity (CV) (26, 41), intracellular calcium cycling (3), and other factors (8). Although dynamic instability in normal hearts promotes wavebreak during reentry, it is not well characterized as to whether it also increases vulnerability to the induction of reentry (the clinically relevant goal for therapeutic intervention). Moreover, the role of dynamic instabilities on cardiac vulnerability to reentry in diseased (remodeled) hearts received less attention. In diseased hearts, preexisting electroanatomic tissue heterogeneity is amplified considerably, which by itself increases vulnerability to reentrant arrhythmias. For example, in hearts with myocardial infarctions, electrical and structural remodeling in the epicardial border zone (EBZ) causes regional slowing of conduction, reduced excitability, and prolonged ERP compared with adjace...

show abstract

Fractionated Electrograms From a Computer Model of Heterogeneously Uncoupled Anisotropic Ventricular Myocardium

Abstract: These findings confirm our hypothesis that the spatial variation of morphology of electrograms recorded simultaneously from multiple sites increases with increasing heterogeneity of intercellular coupling.

Cited by 28 publications

References 28 publications

Cardiac Microstructure

Cardiac Microstructure

Genesis of complex fractionated atrial electrograms in zones of slow conduction: A computer model of microfibrosis

Effects of Na⁺ channel and cell coupling abnormalities on vulnerability to reentry: a simulation study

Contact Info

Product

Resources

About

Fractionated Electrograms From a Computer Model of Heterogeneously Uncoupled Anisotropic Ventricular Myocardium

Abstract: These findings confirm our hypothesis that the spatial variation of morphology of electrograms recorded simultaneously from multiple sites increases with increasing heterogeneity of intercellular coupling.

Cited by 28 publications

References 28 publications

Cardiac Microstructure

Cardiac Microstructure

Genesis of complex fractionated atrial electrograms in zones of slow conduction: A computer model of microfibrosis

Effects of Na+ channel and cell coupling abnormalities on vulnerability to reentry: a simulation study

Contact Info

Product

Resources

About

Effects of Na⁺ channel and cell coupling abnormalities on vulnerability to reentry: a simulation study