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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 and release alter alternans onset and conduction block. The stimulus period for alternans onset (A, TAlt) and conduction block (B, TCB) is shown as a function of SR Ca uptake rate v and release parameter λ. The alternans window (TAlt − TCB) is shown in C.
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f8-cmc-suppl.1-2016-001: Reduced SR Ca uptake and release alter alternans onset and conduction block. The stimulus period for alternans onset (A, TAlt) and conduction block (B, TCB) is shown as a function of SR Ca uptake rate v and release parameter λ. The alternans window (TAlt − TCB) is shown in C.

Mentions: We next measure how both SR Ca parameter ν and λ alter the stimulus period for alternans onset (TAlt, defined as APD alternans greater than 10 ms) and conduction block (TCB). We find that both TAlt and TCB decrease as ν decreases, and in general, TAlt and TCB decrease as λ decreases, although this dependence is weaker (Fig. 8A and B). Thus, reduced SR Ca uptake and release decrease both the onset of alternans and conduction block, which would appear to be antiarrhythmogenic. Since both the onset of alternans and conduction block are functions of ν and λ, we can define an alternans window, ie, the size of the stimulus period range for which alternans is induced, given by TAlt – TCB.40 We find that the alternans window is largest for larger λ and ν ≈ 0.55 (Fig. 8C), while the alternans window is smaller for reduced SR Ca uptake and release.


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 and release alter alternans onset and conduction block. The stimulus period for alternans onset (A, TAlt) and conduction block (B, TCB) is shown as a function of SR Ca uptake rate v and release parameter λ. The alternans window (TAlt − TCB) is shown in C.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f8-cmc-suppl.1-2016-001: Reduced SR Ca uptake and release alter alternans onset and conduction block. The stimulus period for alternans onset (A, TAlt) and conduction block (B, TCB) is shown as a function of SR Ca uptake rate v and release parameter λ. The alternans window (TAlt − TCB) is shown in C.
Mentions: We next measure how both SR Ca parameter ν and λ alter the stimulus period for alternans onset (TAlt, defined as APD alternans greater than 10 ms) and conduction block (TCB). We find that both TAlt and TCB decrease as ν decreases, and in general, TAlt and TCB decrease as λ decreases, although this dependence is weaker (Fig. 8A and B). Thus, reduced SR Ca uptake and release decrease both the onset of alternans and conduction block, which would appear to be antiarrhythmogenic. Since both the onset of alternans and conduction block are functions of ν and λ, we can define an alternans window, ie, the size of the stimulus period range for which alternans is induced, given by TAlt – TCB.40 We find that the alternans window is largest for larger λ and ν ≈ 0.55 (Fig. 8C), while the alternans window is smaller for reduced SR Ca uptake and release.

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