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Genesis of ectopic waves: role of coupling, automaticity, and heterogeneity.

ABSTRACT: Many arrhythmias are believed to be triggered by ectopic sources arising from the border of the ischemic tissue. However, the development of ectopic activity from individual sources to a larger mass of cardiac tissue remains poorly understood. To address this critical issue, we used monolayers of neonatal rat cardiomyocytes to create conditions that promoted progression of ectopic activity from single cells to the network that consisted of hundreds of cells. To explain complex spatiotemporal patterns observed in these experiments we introduced a new theoretical framework. The framework's main feature is a parameter space diagram, which uses cell automaticity and coupling as two coordinates. The diagram allows one to depict network behavior, quantitatively address the heterogeneity factor, and evaluate transitions between different regimes. The well-organized wave trains were observed at moderate and high cell coupling values and network heterogeneity was found to be qualitatively unimportant for these regimes. In contrast, at lower values of coupling, spontaneous ectopic activity led to the appearance of fragmented ectopic waves. For these regimes, network heterogeneity played an essential role. The ectopic waves occasionally gave rise to spiral activity in two different regions within the parameter space via two distinct mechanisms. Together, our results suggest that localized ectopic waves represent an essential step in the progression of ectopic activity. These studies add to the understanding of initiation and progression of arrhythmias and can be applied to other phenomena that deal with assemblies of coupled oscillators.

SUBMITTER: Pumir A

PROVIDER: S-EPMC1366734 | biostudies-literature | 2005 Oct

REPOSITORIES: biostudies-literature

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Genesis of ectopic waves: role of coupling, automaticity, and heterogeneity.

Pumir Alain A Arutunyan Ara A Krinsky Valentin V Sarvazyan Narine N

Biophysical journal 20050729 4

Many arrhythmias are believed to be triggered by ectopic sources arising from the border of the ischemic tissue. However, the development of ectopic activity from individual sources to a larger mass of cardiac tissue remains poorly understood. To address this critical issue, we used monolayers of neonatal rat cardiomyocytes to create conditions that promoted progression of ectopic activity from single cells to the network that consisted of hundreds of cells. To explain complex spatiotemporal pat ...[more]

PMID: 16055545

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Project description:Sleep spindles of non-REM sleep are transient, waxing-and-waning 10-16 Hz EEG oscillations, whose cortical synchronization depends on the engagement of thalamo-cortical loops. However, previous studies in animal models lacking the corpus callosum due to agenesis or total callosotomy and in humans with agenesis of the corpus callosum suggested that cortico-cortical connections may also have a relevant role in cortical (inter-hemispheric) spindle synchronization. Yet, most of these works did not provide direct quantitative analyses to support their observations. By studying a rare sample of callosotomized, split-brain patients, we recently demonstrated that the total resection of the corpus callosum is associated with a significant reduction in the inter-hemispheric propagation of non-REM slow waves. Interestingly, sleep spindles are often temporally and spatially grouped around slow waves (0.5-4 Hz), and this coordination is thought to have an important role in sleep-dependent learning and memory consolidation. Given these premises, here we set out to investigate whether total callosotomy may affect the generation and spreading of sleep spindles, as well as their coupling with sleep slow waves. To this aim, we analysed overnight high-density EEG recordings (256 electrodes) collected in five patients who underwent total callosotomy due to drug-resistant epilepsy (age 40-53, two females), three non-callosotomized neurological patients (age 44-66, two females), and in a sample of 24 healthy adult control subjects (age 20-47, 13 females). Individual sleep spindles were automatically detected using a validated algorithm and their properties and topographic distributions were computed. All analyses were performed with and without a regression-based adjustment accounting for inter-subject age differences. The comparison between callosotomized patients and healthy subjects did not reveal systematic variations in spindle density, amplitude or frequency. However, callosotomized patients were characterized by a reduced spindle duration, which could represent the result of a faster desynchronization of spindle activity across cortical areas of the two hemispheres. In contrast with our previous findings regarding sleep slow waves, we failed to detect in callosotomized patients any clear, systematic change in the inter-hemispheric synchronization of sleep spindles. In line with this, callosotomized patients were characterized by a reduced extension of the spatial association between temporally coupled spindles and slow waves. Our findings are consistent with a dependence of spindles on thalamo-cortical rather than cortico-cortical connections in humans, but also revealed that, despite their temporal association, slow waves and spindles are independently regulated in terms of topographic expression.

Dataset Information

Genesis of ectopic waves: role of coupling, automaticity, and heterogeneity.

Publications

Genesis of ectopic waves: role of coupling, automaticity, and heterogeneity.

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