Effects of coupling heterogeneity on fractionated electrograms in a model of nonuniformly anisotropic ventricular myocardium

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

doi:10.1016/s0022-0736(94)80087-1

Cited by 11 publications

(5 citation statements)

References 22 publications

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“…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

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. 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...

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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

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“…Because cell coupling determines conduction velocity (CV) and is key to action potential propagation, it is considered to be critical for cardiac arrhythmogenesis. Computer simulations investigating abnormalities of cell coupling on unidirectional block in one-dimensional (1D) cables (23,45,53) and conduction in two-dimensional (2D) tissue (12,13,40,49) have demonstrated that abnormal coupling promotes unidirectional conduction block and irregular conduction. In addition to the effects of cell coupling on conduction block, the effects of cell coupling on nonlinear dynamics have also been studied (7,32,40).…”

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confidence: 99%

Dynamical effects of diffusive cell coupling on cardiac excitation and propagation: a simulation study

Qu¹

2004

American Journal of Physiology-Heart and Circulatory Physiology

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Cell coupling is considered to be important for cardiac action potential propagation and arrhythmogenesis. We carried out computer simulations to investigate the effects of stimulation strength and cell-to-cell coupling on action potential duration (APD) restitution, APD alternans, and stability of reentry in models of isolated cell, one-dimensional cable, and two-dimensional tissue. Phase I formulation of the Luo and Rudy action potential model was used. We found that stronger stimulation resulted in a shallower APD restitution curve and onset of APD alternans at a faster pacing rate. Reducing diffusive coupling between cells prolonged APD. Weaker diffusive currents along the direction of propagation steepened APD restitution and caused APD alternans to occur at a slower pacing rate in tissue. Diffusive current due to curvature changed APD but had little effect on APD restitution slope and onset of instability. Heterogeneous cell coupling caused APD inhomogeneities in space. Reduction in coupling strength either uniformly or randomly had little effect on the rotation period and stability of a reentry, but random cell decoupling slowed the rotation period and, thus, stabilized the reentry, preventing it from breaking up into multiple waves. Therefore, in addition to its effects on action potential conduction velocity, diffusive cell coupling also affects APD in a rate-dependent manner, causes electrophysiological heterogeneities, and thus modulates the dynamics of cardiac excitation. These effects are brought about by the modulation of ionic current activation and inactivation.

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“…The model was a standard, monodomain resistive network, 11–14 representing a single cell layer, in which the extracellular space was grounded, so removing variations in extracellular resistive connections between cells 15 . Fibrous tissue was represented as barrier 10 times the length and diameter of a cardiomyocyte with an infinite resistance (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Anisotropic propagation 13–15 was modeled by using an intracellular resistivity along the long axis of the cells ( y ‐axis) of 500 Ω cm and 3500 Ω cm in the transverse direction. The tissue sheet was formed by an array of 201 by 201 elements, each 100 μm square, with defined AP properties and electrical resistance between its neighbors.…”

Section: Methodsmentioning

confidence: 99%

Numerical Simulation of Paced Electrogram Fractionation: Relating Clinical Observations to Changes in Fibrosis and Action Potential Duration

Turner

Huang

Saumarez

2005

Cardiovasc electrophysiol

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Effects of coupling heterogeneity on fractionated electrograms in a model of nonuniformly anisotropic ventricular myocardium

Cited by 11 publications

References 22 publications

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

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

Dynamical effects of diffusive cell coupling on cardiac excitation and propagation: a simulation study

Numerical Simulation of Paced Electrogram Fractionation: Relating Clinical Observations to Changes in Fibrosis and Action Potential Duration

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Effects of coupling heterogeneity on fractionated electrograms in a model of nonuniformly anisotropic ventricular myocardium

Cited by 11 publications

References 22 publications

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

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

Dynamical effects of diffusive cell coupling on cardiac excitation and propagation: a simulation study

Numerical Simulation of Paced Electrogram Fractionation: Relating Clinical Observations to Changes in Fibrosis and Action Potential Duration

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

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

Numerical Simulation of Paced Electrogram Fractionation: Relating Clinical Observations to Changes in Fibrosis and Action Potential Duration