A study of early afterdepolarizations in a model for human ventricular tissue.
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 syndrom...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2014-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3888406?pdf=render |
id |
doaj-c152f28370684a5597c6d9ad7795166d |
---|---|
record_format |
Article |
spelling |
doaj-c152f28370684a5597c6d9ad7795166d2020-11-25T01:25:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8459510.1371/journal.pone.0084595A study of early afterdepolarizations in a model for human ventricular tissue.Nele VandersickelIvan V KazbanovAnita NuitermansLouis D WeiseRahul PanditAlexander V PanfilovSudden 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.http://europepmc.org/articles/PMC3888406?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nele Vandersickel Ivan V Kazbanov Anita Nuitermans Louis D Weise Rahul Pandit Alexander V Panfilov |
spellingShingle |
Nele Vandersickel Ivan V Kazbanov Anita Nuitermans Louis D Weise Rahul Pandit Alexander V Panfilov A study of early afterdepolarizations in a model for human ventricular tissue. PLoS ONE |
author_facet |
Nele Vandersickel Ivan V Kazbanov Anita Nuitermans Louis D Weise Rahul Pandit Alexander V Panfilov |
author_sort |
Nele Vandersickel |
title |
A study of early afterdepolarizations in a model for human ventricular tissue. |
title_short |
A study of early afterdepolarizations in a model for human ventricular tissue. |
title_full |
A study of early afterdepolarizations in a model for human ventricular tissue. |
title_fullStr |
A study of early afterdepolarizations in a model for human ventricular tissue. |
title_full_unstemmed |
A study of early afterdepolarizations in a model for human ventricular tissue. |
title_sort |
study of early afterdepolarizations in a model for human ventricular tissue. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3888406?pdf=render |
work_keys_str_mv |
AT nelevandersickel astudyofearlyafterdepolarizationsinamodelforhumanventriculartissue AT ivanvkazbanov astudyofearlyafterdepolarizationsinamodelforhumanventriculartissue AT anitanuitermans astudyofearlyafterdepolarizationsinamodelforhumanventriculartissue AT louisdweise astudyofearlyafterdepolarizationsinamodelforhumanventriculartissue AT rahulpandit astudyofearlyafterdepolarizationsinamodelforhumanventriculartissue AT alexandervpanfilov astudyofearlyafterdepolarizationsinamodelforhumanventriculartissue AT nelevandersickel studyofearlyafterdepolarizationsinamodelforhumanventriculartissue AT ivanvkazbanov studyofearlyafterdepolarizationsinamodelforhumanventriculartissue AT anitanuitermans studyofearlyafterdepolarizationsinamodelforhumanventriculartissue AT louisdweise studyofearlyafterdepolarizationsinamodelforhumanventriculartissue AT rahulpandit studyofearlyafterdepolarizationsinamodelforhumanventriculartissue AT alexandervpanfilov studyofearlyafterdepolarizationsinamodelforhumanventriculartissue |
_version_ |
1725115001539133440 |