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Estimating the probabilities of rare arrhythmic events in multiscale computational models of cardiac cells and tissue.

ABSTRACT: Ectopic heartbeats can trigger reentrant arrhythmias, leading to ventricular fibrillation and sudden cardiac death. Such events have been attributed to perturbed Ca2+ handling in cardiac myocytes leading to spontaneous Ca2+ release and delayed afterdepolarizations (DADs). However, the ways in which perturbation of specific molecular mechanisms alters the probability of ectopic beats is not understood. We present a multiscale model of cardiac tissue incorporating a biophysically detailed three-dimensional model of the ventricular myocyte. This model reproduces realistic Ca2+ waves and DADs driven by stochastic Ca2+ release channel (RyR) gating and is used to study mechanisms of DAD variability. In agreement with previous experimental and modeling studies, key factors influencing the distribution of DAD amplitude and timing include cytosolic and sarcoplasmic reticulum Ca2+ concentrations, inwardly rectifying potassium current (IK1) density, and gap junction conductance. The cardiac tissue model is used to investigate how random RyR gating gives rise to probabilistic triggered activity in a one-dimensional myocyte tissue model. A novel spatial-average filtering method for estimating the probability of extreme (i.e. rare, high-amplitude) stochastic events from a limited set of spontaneous Ca2+ release profiles is presented. These events occur when randomly organized clusters of cells exhibit synchronized, high amplitude Ca2+ release flux. It is shown how reduced IK1 density and gap junction coupling, as observed in heart failure, increase the probability of extreme DADs by multiple orders of magnitude. This method enables prediction of arrhythmia likelihood and its modulation by alterations of other cellular mechanisms.

SUBMITTER: Walker MA

PROVIDER: S-EPMC5689829 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Estimating the probabilities of rare arrhythmic events in multiscale computational models of cardiac cells and tissue.

Walker Mark A MA Gurev Viatcheslav V Rice John J JJ Greenstein Joseph L JL Winslow Raimond L RL

PLoS computational biology 20171116 11

Ectopic heartbeats can trigger reentrant arrhythmias, leading to ventricular fibrillation and sudden cardiac death. Such events have been attributed to perturbed Ca2+ handling in cardiac myocytes leading to spontaneous Ca2+ release and delayed afterdepolarizations (DADs). However, the ways in which perturbation of specific molecular mechanisms alters the probability of ectopic beats is not understood. We present a multiscale model of cardiac tissue incorporating a biophysically detailed three-di ...[more]

PMID: 29145393

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Project description:The global rise in nature-based recreation increases the need for research on visitor activity use and interaction especially for multi-use trail systems. Conflict often arises during negatively perceived physical encounters (i.e., direct observation) of different user groups. Our study addresses these encounters on a winter multi-use refuge in Fairbanks, Alaska. Our goal was to develop a method that generates spatially and temporally explicit estimates of trail occupancy and encounter probabilities among different user groups. We used trail cameras with optic alteration to protect individual identity. We monitored winter recreational activity from November 2019 to April 2020 (n = 133 days) and sorted users into three user groups: 1) motor-powered, 2) dog-powered, and 3) human-powered. We calculated the total number of occurrences and proportion of activity across all user groups at each camera location. We identified hotspots of activity overlap (e.g., near trail access points), and peak times (14:01-15:00), days (Saturdays and Sundays), and months (December, February, and March) that may have had higher potential for physical encounters and conflict. We used multiplication and addition probability rules to estimate two probabilities: 1) the probability of user groups occupying individual trail segments, and 2) the probability of encounter between different user groups. We scaled up these probability estimates both temporally (hourly and daily) and spatially (refuge quadrant and refuge-wide). Researchers can adapt our novel method to any recreational trail system to identify locations with potential for congestion and conflict. This method can help inform management that improves visitor experience and overall trail user satisfaction.Management implicationsWe provide managers of recreational trail systems with a quantitative, objective, and noninvasive method to monitor activity among trail user groups. This method can be altered both spatially and temporally to fit any recreational trail system's research questions. These questions may involve congestion, trail carrying capacity, or user group and wildlife encounters. Our method advances current knowledge of trail use dynamics by quantifying the extent of activity overlap between different user groups that may be prone to conflict. Managers can use this information to incorporate relevant management strategies to mitigate congestion and conflict for their own recreational trail system.

Dataset Information

Estimating the probabilities of rare arrhythmic events in multiscale computational models of cardiac cells and tissue.

Publications

Estimating the probabilities of rare arrhythmic events in multiscale computational models of cardiac cells and tissue.

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