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A study of early afterdepolarizations in a model for human ventricular tissue

Vandersickel, Nele ; Kazbanov, Ivan V ; Nuitermans, Anita ; Weise, Louis D ; Pandit, Rahul ; Panfilov, Alexander V Bondarenko, Vladimir E.

PloS one, 2014-01, Vol.9 (1), p.e84595 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
A study of early afterdepolarizations in a model for human ventricular tissue
Autor: Vandersickel, Nele ; Kazbanov, Ivan V ; Nuitermans, Anita ; Weise, Louis D ; Pandit, Rahul ; Panfilov, Alexander V
Bondarenko, Vladimir E.
Assuntos: Action potential ; Action Potentials ; Algorithms ; Analysis ; Arrhythmias, Cardiac ; Astronomy ; Biology ; Brugada Syndrome ; Calcium ; Calcium channels (L-type) ; Calcium channels (voltage-gated) ; Calcium conductance ; Calcium currents ; Calcium signalling ; Cardiac arrhythmia ; Cardiac Conduction System Disease ; Cell culture ; Cells ; Cells (Biology) ; Computer Science ; Computer simulation ; Conductance ; Depolarization ; Electrocardiography ; Fibrillation ; Fourier Analysis ; Gene mapping ; Heart ; Heart Conduction System - abnormalities ; Heart diseases ; Heart Ventricles - physiopathology ; Humans ; Mathematical models ; Mathematics ; Medicine ; Models, Cardiovascular ; Models, Theoretical ; Mutation ; Optical properties ; Physics ; Potassium ; Potassium currents ; Propagation ; Resistance ; Sodium ; Sodium currents ; Stem cells ; Studies ; Toxicity ; Ventricle ; Wave propagation
É parte de: PloS one, 2014-01, Vol.9 (1), p.e84595
Notas: Conceived and designed the experiments: NV IVK AVP. Performed the experiments: NV. Analyzed the data: NV IVK RP AVP. Contributed reagents/materials/analysis tools: NV IVK AN LDW AVP. Wrote the paper: NV LDW RP AVP.
Competing Interests: The authors have declared that no competing interests exist.
Descrição: Sudden cardiac death is often caused by cardiac arrhythmias. Recently, special attention has been given to a certain arrhythmogenic condition, the long-QT syndrome, which occurs as a result of genetic mutations or drug toxicity. The underlying mechanisms of arrhythmias, caused by the long-QT syndrome, are not fully understood. However, arrhythmias are often connected to special excitations of cardiac cells, called early afterdepolarizations (EADs), which are depolarizations during the repolarizing phase of the action potential. So far, EADs have been studied mainly in isolated cardiac cells. However, the question on how EADs at the single-cell level can result in fibrillation at the tissue level, especially in human cell models, has not been widely studied yet. In this paper, we study wave patterns that result from single-cell EAD dynamics in a mathematical model for human ventricular cardiac tissue. We induce EADs by modeling experimental conditions which have been shown to evoke EADs at a single-cell level: by an increase of L-type Ca currents and a decrease of the delayed rectifier potassium currents. We show that, at the tissue level and depending on these parameters, three types of abnormal wave patterns emerge. We classify them into two types of spiral fibrillation and one type of oscillatory dynamics. Moreover, we find that the emergent wave patterns can be driven by calcium or sodium currents and we find phase waves in the oscillatory excitation regime. From our simulations we predict that arrhythmias caused by EADs can occur during normal wave propagation and do not require tissue heterogeneities. Experimental verification of our results is possible for experiments at the cell-culture level, where EADs can be induced by an increase of the L-type calcium conductance and by the application of I[Formula: see text] blockers, and the properties of the emergent patterns can be studied by optical mapping of the voltage and calcium.
Editor: United States: Public Library of Science
Idioma: Inglês

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A study of early afterdepolarizations in a model for human ventricular tissue

Vandersickel, Nele ; Kazbanov, Ivan V ; Nuitermans, Anita ; Weise, Louis D ; Pandit, Rahul ; Panfilov, Alexander V Bondarenko, Vladimir E.

United States: Public Library of Science

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