2007
DOI: 10.1152/ajpheart.01309.2006
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Effects of early afterdepolarizations on reentry in cardiac tissue: a simulation study

Abstract: Early afterdepolarizations (EADs) are classically generated at slow heart rates when repolarization reserve is reduced by genetic diseases or drugs. However, EADs may also occur at rapid heart rates if repolarization reserve is sufficiently reduced. In this setting, spontaneous diastolic sarcoplasmic reticulum (SR) Ca release can facilitate cellular EAD formation by augmenting inward currents during the action potential plateau, allowing reactivation of the window L-type Ca current to reverse repolarization. H… Show more

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Cited by 30 publications
(34 citation statements)
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“…However, the principles of partial chaos synchronization delineated here also apply to chaotic behavior at rapid heart rates, as shown by our previous study (28). It is known that EADs can also occur at faster heart rates, often in association with delayed afterdepolarizations (32,33); our analysis should apply as well as to this situation. These phenomena will be exacerbated by preexisting tissue heterogeneity in the diseased heart, which is therefore likely to accelerate the development of electrophysiological dispersion by partial chaos synchronization, because the temporal evolution is sensitive to the size of the initial perturbation (Fig.…”
Section: Discussionmentioning
confidence: 63%
See 1 more Smart Citation
“…However, the principles of partial chaos synchronization delineated here also apply to chaotic behavior at rapid heart rates, as shown by our previous study (28). It is known that EADs can also occur at faster heart rates, often in association with delayed afterdepolarizations (32,33); our analysis should apply as well as to this situation. These phenomena will be exacerbated by preexisting tissue heterogeneity in the diseased heart, which is therefore likely to accelerate the development of electrophysiological dispersion by partial chaos synchronization, because the temporal evolution is sensitive to the size of the initial perturbation (Fig.…”
Section: Discussionmentioning
confidence: 63%
“…EADs have been observed to occur over a wide range of takeoff potentials during AP repolarization (15,16,(32)(33)(34). EAD propagation is favored when the takeoff potential is more negative than in the AP model used in Figs.…”
Section: Partial Regional Synchronization Of Chaotic Eads Generates Lmentioning
confidence: 99%
“…It is well known that Cadependent signaling pathways, such as CaMKII signaling, can affect many ionic currents as well as Ca cycling properties (70), which can have much more complex effects on EADs and DADs. Our AP model does not include some of the Ca-dependent ionic currents, such as I ns(Ca) (71,72) and the small conductance Ca-activated K channel (60) (38). Therefore, a dynamic [Na] i may have additional effects on EADs and DADs.…”
Section: Limitationsmentioning
confidence: 99%
“…The underlying cellular mechanisms that produce EADs are clearly important, and further work with biophysically detailed cell models [4,29] would enable the parameters that are important for determining EAD waveform shape to be identified. Detailed cell models combined with anatomically detailed models of 3D ventricular anatomy [30,31] also have the potential to identify new therapeutic targets to suppress EAD activity.…”
Section: Further Workmentioning
confidence: 99%
“…It is possible that EAD activity may underlie sustained arrhythmias; this question was not addressed in the present study because EAD behaviour was 'switched off' following the first EAD. However, the findings of recent computational studies indicate that EADs are capable of destabilising re-entrant arrhythmias [29], and this idea has important implications for our understanding of ventricular fibrillation mechanisms.…”
Section: Further Workmentioning
confidence: 99%