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Impaired Sarcoplasmic Reticulum Calcium Uptake and Release Promote Electromechanically and Spatially Discordant Alternans: A Computational Study.

Weinberg SH - Clin Med Insights Cardiol (2016)

Bottom Line: Cardiac electrical dynamics are governed by cellular-level properties, such as action potential duration (APD) restitution and intracellular calcium (Ca) handling, and tissue-level properties, including conduction velocity restitution and cell-cell coupling.Irregular dynamics at the cellular level can lead to instabilities in cardiac tissue, including alternans, a beat-to-beat alternation in the action potential and/or the intracellular Ca transient.We find that an intermediate SR Ca uptake rate and larger SR Ca release resulted in the widest range of stimulus periods that promoted alternans.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA.

ABSTRACT
Cardiac electrical dynamics are governed by cellular-level properties, such as action potential duration (APD) restitution and intracellular calcium (Ca) handling, and tissue-level properties, including conduction velocity restitution and cell-cell coupling. Irregular dynamics at the cellular level can lead to instabilities in cardiac tissue, including alternans, a beat-to-beat alternation in the action potential and/or the intracellular Ca transient. In this study, we incorporate a detailed single cell coupled map model of Ca cycling and bidirectional APD-Ca coupling into a spatially extended tissue model to investigate the influence of sarcoplasmic reticulum (SR) Ca uptake and release properties on alternans and conduction block. We find that an intermediate SR Ca uptake rate and larger SR Ca release resulted in the widest range of stimulus periods that promoted alternans. However, both reduced SR Ca uptake and release promote arrhythmogenic spatially and electromechanically discordant alternans, suggesting a complex interaction between SR Ca handling and alternans characteristics at the cellular and tissue level.

No MeSH data available.


Related in: MedlinePlus

Reduced SR Ca uptake can promote EMD alternans. APD, peak intracellular Ca, and SR Ca load are shown as a function of stimulus period T on even (black) and odd (red) beats, for SR Ca uptake rate v = (A) 0.7, (B) 0.4, (C) 0.28, and (D) 0.1. Other parameters: λ = 1.
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Related In: Results  -  Collection


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f2-cmc-suppl.1-2016-001: Reduced SR Ca uptake can promote EMD alternans. APD, peak intracellular Ca, and SR Ca load are shown as a function of stimulus period T on even (black) and odd (red) beats, for SR Ca uptake rate v = (A) 0.7, (B) 0.4, (C) 0.28, and (D) 0.1. Other parameters: λ = 1.

Mentions: We iterate the single cell map for 1000 beats and plot APD, peak intracellular Ca, and SR Ca as a function of the stimulus period T (Fig. 2). For SR uptake rate ν = 0.7, APD and Ca alternans are present at faster stimulus rates, between T of 265 and 320 ms, below which there is a loss of capture (Fig. 2A). Further, alternans is EMC, ie, a long APD corresponds with a large peak Ca, and vice versa. SR Ca is out of phase with the peak intracellular Ca, consistent with a high SR Ca load leading to a larger SR Ca release on the subsequent beat. For a smaller uptake rate, ν = 0.4, both the peak intracellular Ca and SR Ca load are reduced (Fig. 2B). EMC alternans is present at a longer stimulus period, while loss of capture occurs at a shorter stimulus period.


Impaired Sarcoplasmic Reticulum Calcium Uptake and Release Promote Electromechanically and Spatially Discordant Alternans: A Computational Study.

Weinberg SH - Clin Med Insights Cardiol (2016)

Reduced SR Ca uptake can promote EMD alternans. APD, peak intracellular Ca, and SR Ca load are shown as a function of stimulus period T on even (black) and odd (red) beats, for SR Ca uptake rate v = (A) 0.7, (B) 0.4, (C) 0.28, and (D) 0.1. Other parameters: λ = 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4920205&req=5

f2-cmc-suppl.1-2016-001: Reduced SR Ca uptake can promote EMD alternans. APD, peak intracellular Ca, and SR Ca load are shown as a function of stimulus period T on even (black) and odd (red) beats, for SR Ca uptake rate v = (A) 0.7, (B) 0.4, (C) 0.28, and (D) 0.1. Other parameters: λ = 1.
Mentions: We iterate the single cell map for 1000 beats and plot APD, peak intracellular Ca, and SR Ca as a function of the stimulus period T (Fig. 2). For SR uptake rate ν = 0.7, APD and Ca alternans are present at faster stimulus rates, between T of 265 and 320 ms, below which there is a loss of capture (Fig. 2A). Further, alternans is EMC, ie, a long APD corresponds with a large peak Ca, and vice versa. SR Ca is out of phase with the peak intracellular Ca, consistent with a high SR Ca load leading to a larger SR Ca release on the subsequent beat. For a smaller uptake rate, ν = 0.4, both the peak intracellular Ca and SR Ca load are reduced (Fig. 2B). EMC alternans is present at a longer stimulus period, while loss of capture occurs at a shorter stimulus period.

Bottom Line: Cardiac electrical dynamics are governed by cellular-level properties, such as action potential duration (APD) restitution and intracellular calcium (Ca) handling, and tissue-level properties, including conduction velocity restitution and cell-cell coupling.Irregular dynamics at the cellular level can lead to instabilities in cardiac tissue, including alternans, a beat-to-beat alternation in the action potential and/or the intracellular Ca transient.We find that an intermediate SR Ca uptake rate and larger SR Ca release resulted in the widest range of stimulus periods that promoted alternans.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA.

ABSTRACT
Cardiac electrical dynamics are governed by cellular-level properties, such as action potential duration (APD) restitution and intracellular calcium (Ca) handling, and tissue-level properties, including conduction velocity restitution and cell-cell coupling. Irregular dynamics at the cellular level can lead to instabilities in cardiac tissue, including alternans, a beat-to-beat alternation in the action potential and/or the intracellular Ca transient. In this study, we incorporate a detailed single cell coupled map model of Ca cycling and bidirectional APD-Ca coupling into a spatially extended tissue model to investigate the influence of sarcoplasmic reticulum (SR) Ca uptake and release properties on alternans and conduction block. We find that an intermediate SR Ca uptake rate and larger SR Ca release resulted in the widest range of stimulus periods that promoted alternans. However, both reduced SR Ca uptake and release promote arrhythmogenic spatially and electromechanically discordant alternans, suggesting a complex interaction between SR Ca handling and alternans characteristics at the cellular and tissue level.

No MeSH data available.


Related in: MedlinePlus