Reentry via high-frequency pacing in a mathematical model for human-ventricular cardiac tissue with a localized fibrotic region

Zimik, Soling; Pandit, Rahul

doi:10.1038/s41598-017-15735-5

Cited by 12 publications

(14 citation statements)

References 61 publications

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“…We used a very simple model of diffuse fibrosis. Different models could be considered to describe compact, interstitial or patchy fibrosis or to include myocyte-fibroblast connections 22 , 31 , 45 . Nevertheless, it is worth mentioning that we obtained similar results, in terms of micro-reentry and the generation of ectopic beats, in a previous work that used a more detailed and realistic model of diffuse fibrosis by considering a fine sub-cellular spatial resolution of 8 μm 26 .…”

Section: Discussionmentioning

confidence: 99%

“…This block roughly represented a pack of 25 cardiac myocytes (each approximately 100 × 20 × 20 μm ). This approach has been extensively employed to study reentries in cardiac tissue 16 , 17 , 21 , 22 , 25 . The maze of conducting tissue co-located within an inert fibrotic structure produced a fractionation of the AP propagation on active cardiac tissue, Ω A .…”

Section: Methodsmentioning

confidence: 99%

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Ectopic beats arise from micro-reentries near infarct regions in simulations of a patient-specific heart model

Oliveira

Alonso

Campos

et al. 2018

Sci Rep

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Ectopic beats are known to be involved in the initiation of a variety of cardiac arrhythmias. Although their location may vary, ectopic excitations have been found to originate from infarct areas, regions of micro-fibrosis and other heterogeneous tissues. However, the underlying mechanisms that link ectopic foci to heterogeneous tissues have yet to be fully understood. In this work, we investigate the mechanism of micro-reentry that leads to the generation of ectopic beats near infarct areas using a patient-specific heart model. The patient-specific geometrical model of the heart, including scar and peri-infarct zones, is obtained through magnetic resonance imaging (MRI). The infarct region is composed of ischemic myocytes and non-conducting cells (fibrosis, for instance). Electrophysiology is captured using an established cardiac myocyte model of the human ventricle modified to describe ischemia. The simulation results clearly reveal that ectopic beats emerge from micro-reentries that are sustained by the heterogeneous structure of the infarct regions. Because microscopic information about the heterogeneous structure of the infarct regions is not available, Monte-Carlo simulations are used to identify the probabilities of an infarct region to behave as an ectopic focus for different levels of ischemia and different percentages of non-conducting cells. From the proposed model, it is observed that ectopic beats are generated when a percentage of non-conducting cells is near a topological metric known as the percolation threshold. Although the mechanism for micro-reentries was proposed half a century ago to be a source of ectopic beats or premature ventricular contractions during myocardial infarction, the present study is the first to reproduce this mechanism in-silico using patient-specific data.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Ectopic beats arise from micro-reentries near infarct regions in simulations of a patient-specific heart model

Oliveira

Alonso

Campos

et al. 2018

Sci Rep

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“…Spiral-wave dynamics in the MM2 WT model depends on the time τ S2 at which we initiate the S2 pulse. It behooves us, therefore, to examine whether obstacles (or conduction inhomogeneities) affect spiral-wave activity in the MM1 WT and MM2 WT models, for it has been shown, for HH-type models for cardiac tissue, that spiral-wave dynamics depends sensitively on the position, size, and shape of such obstacles [3,4,23,24]. Our obstacles consist of inexcitable points that are distributed randomly within a circular region of radius R; P f is the percentage of the area of the circle that has inexcitable obstacles.…”

Section: Wild-type Na Channelmentioning

confidence: 99%

“…Although there are several studies of the effects of different types of inhomogeneities on spiral-wave dynamics in mathematical models for cardiac tissue (see, e.g., Refs. [3,4,23,24] and references therein), to the best of our knowledge there has been no study, based on Markov-state models, of an inhomogeneity comprising mutant myocytes in a background of wild-type myocytes. Therefore we present a representative study of spiral-wave dynamics in the presence of a clump of only mutant cells, of radius R = 1.125 cm, embedded in a background of wild-type cells.…”

Section: Mutant Na Channelmentioning

confidence: 99%

Comparisons of wave dynamics in Hodgkin-Huxley and Markov-state formalisms for the sodium (Na) channel in some mathematical models for human cardiac tissue

Mulimani

Nayak

Pandit

2020

Phys. Rev. Research

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We compare and contrast the excitation properties of cardiac myocytes and cardiac tissue modeled by (a) a Hodgkin-Huxley-model (HHM) and (b) Markov-chain-model (MM) formalisms for the sodium (Na) ion channel. Specifically, we bring out the differences between HHM and MM formalisms, for both wild-type (WT) and mutant (MUT) models, for ion-channel kinetics, single-myocyte action potentials, and the spatiotemporal evolutions of spiral and scroll waves in different mathematical models of cardiac tissue. We show that the kinetic properties of Na ion channels are not the same for HHM and MM models; in particular, the range of values of the trans-membrane potential V m , in which there is a significant window current, depends significantly on these models, so there are marked differences in the opening times of the Na ion channels, the maximal amplitude of the Na current, and the presence or absence of a late Na current. Furthermore, these changes lead to different excitation behaviors in cardiac tissue; specifically, two of the WT models show stable spiral waves, but the other one shows meandering and transiently breaking spiral waves. Our results are based on extensive direct numerical simulations of waves of electrical activation in these models, in two-and three-dimensional (2D and 3D) homogeneous simulation domains and also in domains with localized heterogeneities, either obstacles with randomly distributed inexcitable regions or mutant cells in a wild-type background. Our study brings out the sensitive dependence of spiral-and scroll-wave dynamics on these five models and the parameters that define them. We list desiderata for a good model for the Na wild-type ion channel; we use these desired properties to select one of the MM models that we study.

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“…This normal rhythm in a heart can be disturbed by the formation of a spiral wave, which can override the function of the SAN as the primary source of waves and entrain the heart to follow the spiral-rotation frequency. There are multiple mechanisms through which spiral waves can occur in cardiac tissue [12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

An In Silico Study of Electrophysiological Parameters That Affect the Spiral-Wave Frequency in Mathematical Models for Cardiac Tissue

2022

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Spiral waves of excitation in cardiac tissue are associated with life-threatening cardiac arrhythmias. It is, therefore, important to study the electrophysiological factors that affect the dynamics of these spiral waves. By using an electrophysiologically detailed mathematical model of a myocyte (cardiac cell), we study the effects of cellular parameters, such as membrane-ion-channel conductances, on the properties of the action-potential (AP) of a myocyte. We then investigate how changes in these properties, specifically the upstroke velocity and the AP duration (APD), affect the frequency ω of a spiral wave in the mathematical model that we use for human-ventricular tissue. We find that an increase (decrease) in this upstroke-velocity or a decrease (increase) in the AP duration increases (decreases) ω. We also study how other intercellular factors, such as the fibroblast-myocyte coupling, diffusive coupling strength, and the effective number of neighboring myocytes and fibroblasts, modulate ω. Finally, we demonstrate how a spiral wave can drift to a region with a high density of fibroblasts. Our results provide a natural explanation for the anchoring of spiral waves in highly fibrotic regions in fibrotic hearts.

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Reentry via high-frequency pacing in a mathematical model for human-ventricular cardiac tissue with a localized fibrotic region

Cited by 12 publications

References 61 publications

Ectopic beats arise from micro-reentries near infarct regions in simulations of a patient-specific heart model

Ectopic beats arise from micro-reentries near infarct regions in simulations of a patient-specific heart model

Comparisons of wave dynamics in Hodgkin-Huxley and Markov-state formalisms for the sodium (Na) channel in some mathematical models for human cardiac tissue

An In Silico Study of Electrophysiological Parameters That Affect the Spiral-Wave Frequency in Mathematical Models for Cardiac Tissue

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