Limits...
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 can promote EMD alternans. Parameter regimes for no alternans, EMC alternans, EMD alternans, and loss of capture are shown as a function of stimulus period T and SR Ca release parameter λ, for SR Ca uptake rate v = (A) 0.7, (B) 0.4, (C) 0.28, and (D) 0.1.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4920205&req=5

f4-cmc-suppl.1-2016-001: Reduced SR Ca uptake and release can promote EMD alternans. Parameter regimes for no alternans, EMC alternans, EMD alternans, and loss of capture are shown as a function of stimulus period T and SR Ca release parameter λ, for SR Ca uptake rate v = (A) 0.7, (B) 0.4, (C) 0.28, and (D) 0.1.

Mentions: We next investigate to what extent SR Ca release parameter λ alters the incidence of EMC and discordant alternans. For large ν = 0.7, we find that, for all values of λ, there is a transition from regimes of no alternans, EMC alternans, and loss of capture as T decreases (Fig. 4A). Decreasing λ leads to alternans and loss of capture at slightly shorter stimulus periods T. For a smaller ν = 0.4, decreasing λ leads to a more pronounced decrease in the onset of alternans, with a smaller decrease in the period for loss of capture (Fig. 4B). Critically, there is a transition from EMC to EMD alternans as λ decreases. For a slightly smaller ν = 0.28, the transition from EMC to EMD alternans occurs as λ or T decreases (Fig. 4C), while for ν = 0.1, only EMD alternans is present (Fig. 4D).


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 can promote EMD alternans. Parameter regimes for no alternans, EMC alternans, EMD alternans, and loss of capture are shown as a function of stimulus period T and SR Ca release parameter λ, for SR Ca uptake rate v = (A) 0.7, (B) 0.4, (C) 0.28, and (D) 0.1.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-cmc-suppl.1-2016-001: Reduced SR Ca uptake and release can promote EMD alternans. Parameter regimes for no alternans, EMC alternans, EMD alternans, and loss of capture are shown as a function of stimulus period T and SR Ca release parameter λ, for SR Ca uptake rate v = (A) 0.7, (B) 0.4, (C) 0.28, and (D) 0.1.
Mentions: We next investigate to what extent SR Ca release parameter λ alters the incidence of EMC and discordant alternans. For large ν = 0.7, we find that, for all values of λ, there is a transition from regimes of no alternans, EMC alternans, and loss of capture as T decreases (Fig. 4A). Decreasing λ leads to alternans and loss of capture at slightly shorter stimulus periods T. For a smaller ν = 0.4, decreasing λ leads to a more pronounced decrease in the onset of alternans, with a smaller decrease in the period for loss of capture (Fig. 4B). Critically, there is a transition from EMC to EMD alternans as λ decreases. For a slightly smaller ν = 0.28, the transition from EMC to EMD alternans occurs as λ or T decreases (Fig. 4C), while for ν = 0.1, only EMD alternans is present (Fig. 4D).

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