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

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 early-after-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

Stigmergy-based, Dual-Layer Coverage of Unknown Indoor Regions

We present algorithms for uniformly covering an unknown indoor region with a swarm of simple, anonymous and autonomous mobile agents. The exploration of such regions is made difficult by the lack of a common global reference frame, severe degradation of radio-frequency communication, and numerous ground obstacles. We propose addressing these challenges by using airborne agents, such as Micro Air Vehicles, in dual capacity, both as mobile explorers and (once they land) as beacons that help other agents navigate the region. The algorithms we propose are designed for a swarm of simple, identical, ant-like agents with local sensing capabilities. The agents enter the region, which is discretized as a graph, over time from one or more entry points and are tasked with occupying all of its vertices. Unlike many works in this area, we consider the requirement of informing an outside operator with limited information that the coverage mission is complete. Even with this additional requirement we show, both through simulations and mathematical proofs, that the dual role concept results in linear-time termination, while also besting many well-known algorithms in the literature in terms of energy use

Dynamics of conduction blocks in a model of paced cardiac tissue

We study numerically the dynamics of conduction blocks using a detailed electrophysiological model. We find that this dynamics depends critically on the size of the paced region. Small pacing regions lead to stationary conduction blocks while larger pacing regions can lead to conduction blocks that travel periodically towards the pacing region. We show that this size-dependence dynamics can lead to a novel arrhythmogenic mechanism. Furthermore, we show that the essential phenomena can be captured in a much simpler coupled-map model.Comment: 8 pages 6 figure

A probabilistic peridynamic framework with an application to the study of the statistical size effect

This is the final version. Available from Elsevier via the DOI in this record. Data availability: No data was used for the research described in the article.The high computational expense of peridynamic models remains a major limitation, hindering ‘outer-loop’ applications that require a large number of simulations, for example, uncertainty quantification. This contribution presents a framework that makes such computations feasible. By employing a Multilevel Monte Carlo framework, where the majority of simulations are performed using a coarse mesh, and performing relatively few simulations using a fine mesh, a significant reduction in computational cost can be realised, and statistics of structural failure can be estimated. The maximum observed speed-up factor is 16 when compared to a standard Monte Carlo estimator, thus enabling the efficient forward propagation of uncertain parameters in a computationally expensive peridynamic model. Furthermore, the multilevel method provides an estimate of both the discretisation error and sampling error, thereby improving confidence in numerical predictions. The performance of the approach is demonstrated through an examination of the statistical size effect in quasi-brittle materials.Turing Fellowshi

Noise Induced Coherence in Neural Networks

We investigate numerically the dynamics of large networks of $N$ globally pulse-coupled integrate and fire neurons in a noise-induced synchronized state. The powerspectrum of an individual element within the network is shown to exhibit in the thermodynamic limit ($N\to \infty$) a broadband peak and an additional delta-function peak that is absent from the powerspectrum of an isolated element. The powerspectrum of the mean output signal only exhibits the delta-function peak. These results are explained analytically in an exactly soluble oscillator model with global phase coupling.Comment: 4 pages ReVTeX and 3 postscript figure

Predicting acute termination and non-termination during ablation of human atrial fibrillation using quantitative indices

Background: Termination of atrial fibrillation (AF), the most common arrhythmia in the United States, during catheter ablation is an attractive procedural endpoint, which has been associated with improved long-term outcome in some studies. It is not clear, however, whether it is possible to predict termination using clinical data. We developed and applied three quantitative indices in global multielectrode recordings of AF prior to ablation: average dominant frequency (ADF), spectral power index (SPI), and electrogram quality index (EQI). Methods: In N = 42 persistent AF patients (65 ± 9 years, 14% female) we collected unipolar electrograms from 64-pole baskets (Abbott, CA). We studied N = 17 patients in whom AF terminated during ablation ('Term') and N = 25 in whom it did not ('Non-term'). For each index, we determined its ability to predict ablation by computing receiver operating characteristic (ROC) and calculated the area under the curve (AUC). Results: The ADF did not differ for Term and Non-term patients at 5.28 ± 0.82 Hz and 5.51 ± 0.81 Hz, respectively (p = 0.34). Conversely, the SPI for these two groups was. 0.85 (0.80-0.92) and 0.97 (0.93-0.98) and the EQI was 0.61 (0.58-0.64) and 0.56 (0.55-0.59) (p < 0.0001). The AUC for predicting AF termination for the SPI was 0.85 ([0.68, 0.95] 95% CI), and for the EQI, 0.86 ([0.72, 0.95] 95% CI). Conclusion: Both the EQI and the SPI may provide a useful clinical tool to predict procedural ablation outcome in persistent AF patients. Future studies are required to identify which physiological features of AF are revealed by these indices and hence linked to AF termination or non-termination

Coherence Resonance and Noise-Induced Synchronization in Globally Coupled Hodgkin-Huxley Neurons

The coherence resonance (CR) of globally coupled Hodgkin-Huxley neurons is studied. When the neurons are set in the subthreshold regime near the firing threshold, the additive noise induces limit cycles. The coherence of the system is optimized by the noise. A bell-shaped curve is found for the peak height of power spectra of the spike train, being significantly different from a monotonic behavior for the single neuron. The coupling of the network can enhance CR in two different ways. In particular, when the coupling is strong enough, the synchronization of the system is induced and optimized by the noise. This synchronization leads to a high and wide plateau in the local measure of coherence curve. The local-noise-induced limit cycle can evolve to a refined spatiotemporal order through the dynamical optimization among the autonomous oscillation of an individual neuron, the coupling of the network, and the local noise.Comment: five pages, five figure

Coexisting Pulses in a Model for Binary-Mixture Convection

We address the striking coexistence of localized waves (`pulses') of different lengths which was observed in recent experiments and full numerical simulations of binary-mixture convection. Using a set of extended Ginzburg-Landau equations, we show that this multiplicity finds a natural explanation in terms of the competition of two distinct, physical localization mechanisms; one arises from dispersion and the other from a concentration mode. This competition is absent in the standard Ginzburg-Landau equation. It may also be relevant in other waves coupled to a large-scale field.Comment: 5 pages revtex with 4 postscript figures (everything uuencoded