Dataset Information

The Contribution of Ionic Currents to Rate-Dependent Action Potential Duration and Pattern of Reentry in a Mathematical Model of Human Atrial Fibrillation.

ABSTRACT: Persistent atrial fibrillation (PeAF) in humans is characterized by shortening of action potential duration (APD) and attenuation of APD rate-adaptation. However, the quantitative influences of particular ionic current alterations on rate-dependent APD changes, and effects on patterns of reentry in atrial tissue, have not been systematically investigated. Using mathematical models of human atrial cells and tissue and performing parameter sensitivity analysis, we evaluated the quantitative contributions to action potential (AP) shortening and APD rate-adaptation of ionic current remodeling seen with PeAF. Ionic remodeling in PeAF was simulated by reducing L-type Ca2+ channel current (ICaL), increasing inward rectifier K+ current (IK1) and modulating five other ionic currents. Parameter sensitivity analysis, which quantified how each ionic current influenced APD in control and PeAF conditions, identified interesting results, including a negative effect of Na+/Ca2+ exchange on APD only in the PeAF condition. At high pacing rate (2 Hz), electrical remodeling in IK1 alone accounts for the APD reduction of PeAF, but at slow pacing rate (0.5 Hz) both electrical remodeling in ICaL alone (-70%) and IK1 alone (+100%) contribute equally to the APD reduction. Furthermore, AP rate-adaptation was affected by IKur in control and by INaCa in the PeAF condition. In a 2D tissue model, a large reduction (-70%) of ICaL becomes a dominant factor leading to a stable spiral wave in PeAF. Our study provides a quantitative and unifying understanding of the roles of ionic current remodeling in determining rate-dependent APD changes at the cellular level and spatial reentry patterns in tissue.

SUBMITTER: Lee YS

PROVIDER: S-EPMC4795605 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Contribution of Ionic Currents to Rate-Dependent Action Potential Duration and Pattern of Reentry in a Mathematical Model of Human Atrial Fibrillation.

Lee Young-Seon YS Hwang Minki M Song Jun-Seop JS Li Changyong C Joung Boyoung B Sobie Eric A EA Pak Hui-Nam HN

PloS one 20160310 3

Persistent atrial fibrillation (PeAF) in humans is characterized by shortening of action potential duration (APD) and attenuation of APD rate-adaptation. However, the quantitative influences of particular ionic current alterations on rate-dependent APD changes, and effects on patterns of reentry in atrial tissue, have not been systematically investigated. Using mathematical models of human atrial cells and tissue and performing parameter sensitivity analysis, we evaluated the quantitative contri ...[more]

PMID: 26964092

Similar Datasets

Project description:BackgroundThere is debate whether human atrial fibrillation is driven by focal drivers or multiwavelet reentry. We propose that the changing activation sequences surrounding a focal driver can at times self-sustain in the absence of that driver. Further, the relationship between focal drivers and surrounding chaotic activation is bidirectional; focal drivers can generate chaotic activation, which may affect the dynamics of focal drivers.Methods and resultsIn a propagation model, we generated tissues that support structural micro-reentry and moving functional reentrant circuits. We qualitatively assessed (1) the tissue's ability to support self-sustaining fibrillation after elimination of the focal driver, (2) the impact that structural-reentrant substrate has on the duration of fibrillation, the impact that micro-reentrant (3) frequency, (4) excitable gap, and (5) exposure to surrounding fibrillation have on micro-reentry in the setting of chaotic activation, and finally the likelihood fibrillation will end in structural reentry based on (6) the distance between and (7) the relative lengths of an ablated tissue's inner and outer boundaries. We found (1) focal drivers produced chaotic activation when waves encountered heterogeneous refractoriness; chaotic activation could then repeatedly initiate and terminate micro-reentry. Perpetuation of fibrillation following elimination of micro-reentry was predicted by tissue properties. (2) Duration of fibrillation was increased by the presence of a structural micro-reentrant substrate only when surrounding tissue had a low propensity to support self-sustaining chaotic activation. Likelihood of micro-reentry around the structural reentrant substrate increased as (3) the frequency of structural reentry increased relative to the frequency of fibrillation in the surrounding tissue, (4) the excitable gap of micro-reentry increased, and (5) the exposure of the structural circuit to the surrounding tissue decreased. Likelihood of organized tachycardia following termination of fibrillation increased with (6) decreasing distance and (7) disparity of size between focal obstacle and external boundary.ConclusionFocal drivers such as structural micro-reentry and the chaotic activation they produce are continuously interacting with one another. In order to accurately describe cardiac tissue's propensity to support fibrillation, the relative characteristics of both stationary and moving drivers must be taken into account.

Project description:Background Atrial fibrillation (AF) driver mechanisms are obscured to clinical multielectrode mapping approaches that provide partial, surface-only visualization of unstable 3-dimensional atrial conduction. We hypothesized that transient modulation of refractoriness by pharmacologic challenge during multielectrode mapping improves visualization of hidden paths of reentrant AF drivers for targeted ablation. Methods and Results Pharmacologic challenge with adenosine was tested in ex vivo human hearts with a history of AF and cardiac diseases by multielectrode and high-resolution subsurface near-infrared optical mapping, integrated with 3-dimensional structural imaging and heart-specific computational simulations. Adenosine challenge was also studied on acutely terminated AF drivers in 10 patients with persistent AF. Ex vivo, adenosine stabilized reentrant driver paths within arrhythmogenic fibrotic hubs and improved visualization of reentrant paths, previously seen as focal or unstable breakthrough activation pattern, for targeted AF ablation. Computational simulations suggested that shortening of atrial refractoriness by adenosine may (1) improve driver stability by annihilating spatially unstable functional blocks and tightening reentrant circuits around fibrotic substrates, thus unmasking the common reentrant path; and (2) destabilize already stable reentrant drivers along fibrotic substrates by accelerating competing fibrillatory wavelets or secondary drivers. In patients with persistent AF, adenosine challenge unmasked hidden common reentry paths (9/15 AF drivers, 41±26% to 68±25% visualization), but worsened visualization of previously visible reentry paths (6/15, 74±14% to 34±12%). AF driver ablation led to acute termination of AF. Conclusions Our ex vivo to in vivo human translational study suggests that transiently altering atrial refractoriness can stabilize reentrant paths and unmask arrhythmogenic hubs to guide targeted AF driver ablation treatment.

Dataset Information

The Contribution of Ionic Currents to Rate-Dependent Action Potential Duration and Pattern of Reentry in a Mathematical Model of Human Atrial Fibrillation.

Publications

The Contribution of Ionic Currents to Rate-Dependent Action Potential Duration and Pattern of Reentry in a Mathematical Model of Human Atrial Fibrillation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets