Ectopic Activity in Ventricular Cells Induced by Early Afterdepolarizations Developed in Purkinje Cells

Monserrat, M.; Sáiz, Javier; Ferrero, J.M.; Thakor, Nitish V.

doi:10.1114/1.1326032

Cited by 17 publications

(15 citation statements)

References 37 publications

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“…This can be thought of as a premature stimulus coming from the Purkinje fiber. 31 Our main result is summarized in Fig. 9 where we show the length of reentry, measured in seconds, as a function of the two geometry parameters, w and r, for fixed long QT syndrome strength µ = 0.08.…”

Section: Two Dimensionsmentioning

confidence: 98%

“…42 Under this condition, numerical simulations have revealed that the inclusion of a large resistive barrier between the Purkinje fibers and the ventricular cells can lead to early after depolarizations in the Purkinje fibers that are able to generate extra stimuli in the ventricular domain. 31 Our numerical simulations were carried out using a simplified transmural geometry of the ventricular wall that consisted of a centrally located M cell domain, sandwiched between two electrophysiologically equal domains representing the endo-and epicardium. Incorporating more realistic geometries and endo-and epicardial cells with different electrophysiological properties, however, will most likely not change the qualitative conclusions of this study.…”

Section: Discussionmentioning

confidence: 99%

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The role of M cells and the long QT syndrome in cardiac arrhythmias: Simulation studies of reentrant excitations using a detailed electrophysiological model

Henry

Rappel

2004

Chaos: An Interdisciplinary Journal of Nonlinear Science

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In this numerical study, we investigate the role of intrinsic heterogeneities of cardiac tissue due to M cells in the generation and maintenance of reentrant excitations using the detailed Luo-Rudy dynamic model. This model has been extended to include a description of the long QT 3 syndrome, and is studied in both one dimension, corresponding to a cable traversing the ventricular wall, and two dimensions, representing a transmural slice. We focus on two possible mechanisms for the generation of reentrant events. We first investigate if early-after-depolarizations occurring in M cells can initiate reentry. We find that, even for large values of the long QT strength, the electrotonic coupling between neighboring cells prevents earlyafter-depolarizations from creating a reentry. We then study whether M cell domains, with their slow repolarization, can function as wave blocks for premature stimuli. We find that the inclusion of an M cell domain can result in some cases in reentrant excitations and we determine the lifetime of the reentry as a function of the size and geometry of the domain and of the strength of the long QT syndrome. 1Spatial heterogeneity of cardiac tissue causes cells to repolarize at different rates, leading to a dispersion of repolarization time. Dispersion of repolarization has been postulated to function as a substrate for reentry phenomena which occur when the propagation of the electric wave is blocked in one direction causing the wave front to curl and reenter the previously excited tissue. The ensuing incoherent electrical activity of the heart is thought to subsequently lead to ventricular fibrillation, the leading cause of sudden death in the industrialized world. In this numerical study, we investigate the role of intrinsic heterogeneities due to M cells in the generation and maintenance of reentrant excitations. These cells, located in the midmyocardium, exhibit a prolonged action potential duration and the resulting dispersion of repolarization is exacerbated in patients with the long QT syndrome. Using a detailed electrophysiological model, two previously postulated mechanisms are investigated: one in which the M cells create premature stimuli that lead to reentrant events and one in which the M cell domains function as wave blocks for electrically propagating waves originating, as usually, from the endocardium. We find that the first mechanism is unlikely to happen under the conditions we study, due to the strong electrotonic coupling that is normally present between neighboring cells. The second mechanism, on the other hand, can result in reentrant excitations. We determine the lifetime of the reentry as a function of the size and geometry of the domain, and of the strength of the long QT syndrome.

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Section: Two Dimensionsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

The role of M cells and the long QT syndrome in cardiac arrhythmias: Simulation studies of reentrant excitations using a detailed electrophysiological model

Henry

Rappel

2004

Chaos: An Interdisciplinary Journal of Nonlinear Science

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“…NS was kept under normal physiological conditions while AS was set under conditions that favor the induction of EADs (figure 1). The generation of EADs is favored by conditions that lengthen action potential duration (APD), such as conditions that increase an inward current or decrease an outward current [8]. We blocked the components of the delayed rectifier K + current, I Kr and I Ks, in the range from 0% to 100% while the L-type Ca 2+ current (I caL ) was incremented to 100% in order to probe different EAD conditions.…”

Section: Methodsmentioning

confidence: 99%

“…Early afterdepolarizations (EADs) are subthreshold depolarizations that occur in phases 2 and 3 of the action potential (AP), causing interruption or delay in repolarization [6][7][8]. January et al suggested that induction of EADs require the prolongation of the action potential plateu and the recovery of the L-type calcium current (I CaL ) [9].…”

Section: Introductionmentioning

confidence: 99%

“…January et al suggested that induction of EADs require the prolongation of the action potential plateu and the recovery of the L-type calcium current (I CaL ) [9]. Some experimental studies have shown that EADs generated in Purkinje fibers propagate to ventricular cells, inducing ectopic activity [8]. On the other hand, in vitro studies suggested that EADs may be responsible for some arrhythmias by prolonging the action potential, generating injury currents and inducing triggered activity [10].…”

Section: Introductionmentioning

confidence: 99%

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A computer model of reflection induced by early afterdepolarizations in ventricular tissue

Ramirez¹,

Sáiz²,

Monserrat³

et al. 2005

Computers in Cardiology, 2005

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Ectopic Activity

Sáiz

Monserrat

Ferrero

et al. 2006

Wiley Encyclopedia of Biomedical Engineering

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The term ectopic activity is used to indicate situations in which the electrical stimulus responsible for the contraction of the heart originates in a zone of the cardiac tissue (ectopic focus) different from the normal one (the sinoatrial node). Two main mechanisms exist that may induce ectopic activity: automaticity (generally subdivided into normal and abnormal) and triggered activity. Ectopic activity caused by normal automaticity appears in cardiac cells in which the automaticity (spontaneous generation of electrical impulses) is an intrinsic property. In normal situations, the potential pacemaker activity in cells different from those in the sinoatrial node is inactive because the spontaneous frequency of impulse generation is higher in the sinoatrial node. However, when the frequency of the sinoatrial node decreases below the spontaneous frequency of a subsidiary pacemaker, this pacemaker takes the control of the heart rate and becomes an ectopic focus. Under several pathological situations, any cell in the heart, even those that normally have no spontaneous activity, could become abnormally automatic. Another mechanism for ectopic activity is known as triggered activity, which consists of an impulse (or a train of impulses) provoked by after‐depolarizations, which are abnormal oscillations of the action potential. Two types of after‐depolarizations exist: early (EADs), which appear during the repolarization phase of action potential, and delayed (DADs), which occur when the repolarization phase of the action potential is completed. The main characteristic of the ectopic activity induced by after‐depolarizations is that a previous electrical impulse is necessary to trigger one or more ectopic beats.

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Ectopic Activity in Ventricular Cells Induced by Early Afterdepolarizations Developed in Purkinje Cells

Cited by 17 publications

References 37 publications

The role of M cells and the long QT syndrome in cardiac arrhythmias: Simulation studies of reentrant excitations using a detailed electrophysiological model

The role of M cells and the long QT syndrome in cardiac arrhythmias: Simulation studies of reentrant excitations using a detailed electrophysiological model

A computer model of reflection induced by early afterdepolarizations in ventricular tissue

Ectopic Activity

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