Overdrive pacing of spiral waves in a model of human ventricular tissue.
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ABSTRACT:
SUBMITTER: Pravdin SF
PROVIDER: S-EPMC7691998 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:For prevention of lethal arrhythmias, patients at risk receive implantable cardioverter-defibrillators, which use high-frequency antitachycardia pacing (ATP) to convert tachycardias to a normal rhythm. One of the suggested ATP mechanisms involves paced-induced drift of rotating waves followed by their collision with the boundary of excitable tissue. This study provides direct experimental evidence of this mechanism. In monolayers of neonatal rat cardiomyocytes in which rotating waves of activity were initiated by premature stimuli, we used the Ca(2+)-sensitive indicator fluo 4 to observe propagating wave patterns. The interaction of the spiral tip with a paced wave was then monitored at a high spatial resolution. In the course of the experiments, we observed spiral wave pinning to local heterogeneities within the myocyte layer. High-frequency pacing led, in a majority of cases, to successful termination of spiral activity. Our data show that 1) stable spiral waves in cardiac monolayers tend to be pinned to local heterogeneities or areas of altered conduction, 2) overdrive pacing can shift a rotating wave from its original site, and 3) the wave break, formed as a result of interaction between the spiral tip and a paced wave front, moves by a paced-induced drift mechanism to an area where it may become unstable or collide with a boundary. The data were complemented by numerical simulations, which was used to further analyze experimentally observed behavior.
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Project description:Localized heterogeneities, caused by the regional proliferation of fibroblasts, occur in mammalian hearts because of diseases like myocardial infarction. Such fibroblast clumps can become sources of pathological reentrant activities, e.g., spiral or scroll waves of electrical activation in cardiac tissue. The occurrence of reentry in cardiac tissue with heterogeneities, such as fibroblast clumps, can depend on the frequency at which the medium is paced. Therefore, it is important to study the reentry-initiating potential of such fibroblast clumps at different frequencies of pacing. We investigate the arrhythmogenic effects of fibroblast clumps at high- and low-frequency pacing. We find that reentrant waves are induced in the medium more prominently at high-frequency pacing than with low-frequency pacing. We also study the other factors that affect the potential of fibroblast clumps to induce reentry in cardiac tissue. In particular, we show that the ability of a fibroblast clump to induce reentry depends on the size of the clump, the distribution and percentage of fibroblasts in the clump, and the excitability of the medium. We study the process of reentry in two-dimensional and a three-dimensional mathematical models for cardiac tissue.
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Project description:Sleep apnea is one of the most common conditions around the world. This disorder can significantly impact cardiovascular morbidity and mortality. Atrial overdrive pacing (AOP) is a treatment modality that can potentially decrease respiratory events. There is currently a lack of evidence to confirm the benefits of AOP. We aimed to assess the impact of AOP in patients with obstructive sleep apnea (OSA), central sleep apnea (CSA), and mixed type. A literature search for studies that reported the impact on apnea-hypopnea index (AHI) by cardiac implantable electronic devices with different pacing modes was conducted using MEDLINE, Embase, and Cochrane Database from inception through July 2020. Pooled standard mean difference with 95%CI was calculated using a random-effects model. Fifteen studies, including thirteen randomized studies and two observational studies containing 440 patients, were identified. The standard mean difference in apnea-hypopnea index of atrial overdrive pacing demonstrated less duration of apnea/hypopnea in patients with atrial overdrive pacing (AOP) (SMD -0.29, 95%CI: -0.48, -0.10, I2 = 57%). Additional analysis was performed to assess the effect of atrial overdrive pacing in patients with or without severe sleep apnea syndrome (mean AHI < 30 defined as non-severe). There was no statistically significant difference in standardized mean in AHI in both subgroups between AOP and control groups (SMD -0.25, severe sleep apnea syndrome SMD -0.03, I2 = 0.00%). AOP was associated with a statistically significant reduction in AHI, but the magnitude of reduction was small. AOP may potentially be used as an adjunctive treatment with other modalities in treating patients with sleep apnea.
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Project description:We carry out an extensive numerical study of the dynamics of spiral waves of electrical activation, in the presence of periodic deformation (PD) in two-dimensional simulation domains, in the biophysically realistic mathematical models of human ventricular tissue due to (a) ten-Tusscher and Panfilov (the TP06 model) and (b) ten-Tusscher, Noble, Noble, and Panfilov (the TNNP04 model). We first consider simulations in cable-type domains, in which we calculate the conduction velocity θ and the wavelength λ of a plane wave; we show that PD leads to a periodic, spatial modulation of θ and a temporally periodic modulation of λ; both these modulations depend on the amplitude and frequency of the PD. We then examine three types of initial conditions for both TP06 and TNNP04 models and show that the imposition of PD leads to a rich variety of spatiotemporal patterns in the transmembrane potential including states with a single rotating spiral (RS) wave, a spiral-turbulence (ST) state with a single meandering spiral, an ST state with multiple broken spirals, and a state SA in which all spirals are absorbed at the boundaries of our simulation domain. We find, for both TP06 and TNNP04 models, that spiral-wave dynamics depends sensitively on the amplitude and frequency of PD and the initial condition. We examine how these different types of spiral-wave states can be eliminated in the presence of PD by the application of low-amplitude pulses by square- and rectangular-mesh suppression techniques. We suggest specific experiments that can test the results of our simulations.
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Project description:Spiral waves are a basic feature of excitable systems. Although such waves have been observed in a variety of biological systems, they have not been observed in the mammalian cortex during neuronal activity. Here, we report stable rotating spiral waves in rat neocortical slices visualized by voltage-sensitive dye imaging. Tissue from the occipital cortex (visual) was sectioned parallel to cortical lamina to preserve horizontal connections in layers III-V (500-mum-thick, approximately 4 x 6 mm(2)). In such tangential slices, excitation waves propagated in two dimensions during cholinergic oscillations. Spiral waves occurred spontaneously and alternated with plane, ring, and irregular waves. The rotation rate of the spirals was approximately 10 turns per second, and the rotation was linked to the oscillations in a one-cycle- one-rotation manner. A small (<128 mum) phase singularity occurred at the center of the spirals, about which were observed oscillations of widely distributed phases. The phase singularity drifted slowly across the tissue ( approximately 1 mm/10 turns). We introduced a computational model of a cortical layer that predicted and replicated many of the features of our experimental findings. We speculate that rotating spiral waves may provide a spatial framework to organize cortical oscillations.
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Project description:BACKGROUND:Spiral waves are considered to be one of the potential mechanisms that maintain complex arrhythmias such as atrial and ventricular fibrillation. The aim of the present study was to quantify the complex dynamics of spiral waves as the organizing manifolds of information flow at multiple scales. METHOD:We simulated spiral waves using a numerical model of cardiac excitation in a two-dimensional (2-D) lattice. We created a renormalization group by coarse graining and re-scaling the original time series in multiple spatiotemporal scales, and quantified the Lagrangian coherent structures (LCS) of the information flow underlying the spiral waves. To quantify the scale-invariant structures, we compared the value of the finite-time Lyapunov exponent between the corresponding components of the 2-D lattice in each spatiotemporal scale of the renormalization group with that of the original scale. RESULTS:Both the repelling and the attracting LCS changed across the different spatial and temporal scales of the renormalization group. However, despite the change across the scales, some LCS were scale-invariant. The patterns of those scale-invariant structures were not obvious from the trajectory of the spiral waves based on voltage mapping of the lattice. CONCLUSIONS:Some Lagrangian coherent structures of information flow underlying spiral waves are preserved across multiple spatiotemporal scales.
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