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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 promote complex alternans patterns. Parameter regimes for no alternans, SC, SD, EMC, and EMD alternans, and conduction block 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) 0.5, (C) 0.4, (D) 0.35, (E) 0.3, and (F) 0.2. The regime boundary between SC and SD alternans regimes is indicated by a thick black line, and between EMC and EMD alternans, regime is indicated by a thin black line. The parameter regimes for cable simulations are bounded by black lines. Parameter regimes are identified as SC-EMC (blue), SD-EMC (red), SC-EMD (yellow), and SD-EMD (green). The boundaries for the single cell simulation regimes are shown in gray, for comparison.
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f7-cmc-suppl.1-2016-001: Reduced SR Ca uptake and release promote complex alternans patterns. Parameter regimes for no alternans, SC, SD, EMC, and EMD alternans, and conduction block 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) 0.5, (C) 0.4, (D) 0.35, (E) 0.3, and (F) 0.2. The regime boundary between SC and SD alternans regimes is indicated by a thick black line, and between EMC and EMD alternans, regime is indicated by a thin black line. The parameter regimes for cable simulations are bounded by black lines. Parameter regimes are identified as SC-EMC (blue), SD-EMC (red), SC-EMD (yellow), and SD-EMD (green). The boundaries for the single cell simulation regimes are shown in gray, for comparison.

Mentions: In Figure 7, we plot the parameter regimes for spatial and electromechanical concordance and discordance for different stimulus rates T, and SR Ca uptake and release parameters ν and λ. For ν = 0.7, as in the single myocyte model, alternans is EMC, for all values of λ (Fig. 7A). Further, as T decreases, there is a transition from SC to SD alternans. There is a small difference between the onsets of alternans and conduction block stimulus period in the cable simulations (black lines), in comparison with the single cell simulations (gray lines).


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 promote complex alternans patterns. Parameter regimes for no alternans, SC, SD, EMC, and EMD alternans, and conduction block 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) 0.5, (C) 0.4, (D) 0.35, (E) 0.3, and (F) 0.2. The regime boundary between SC and SD alternans regimes is indicated by a thick black line, and between EMC and EMD alternans, regime is indicated by a thin black line. The parameter regimes for cable simulations are bounded by black lines. Parameter regimes are identified as SC-EMC (blue), SD-EMC (red), SC-EMD (yellow), and SD-EMD (green). The boundaries for the single cell simulation regimes are shown in gray, for comparison.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7-cmc-suppl.1-2016-001: Reduced SR Ca uptake and release promote complex alternans patterns. Parameter regimes for no alternans, SC, SD, EMC, and EMD alternans, and conduction block 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) 0.5, (C) 0.4, (D) 0.35, (E) 0.3, and (F) 0.2. The regime boundary between SC and SD alternans regimes is indicated by a thick black line, and between EMC and EMD alternans, regime is indicated by a thin black line. The parameter regimes for cable simulations are bounded by black lines. Parameter regimes are identified as SC-EMC (blue), SD-EMC (red), SC-EMD (yellow), and SD-EMD (green). The boundaries for the single cell simulation regimes are shown in gray, for comparison.
Mentions: In Figure 7, we plot the parameter regimes for spatial and electromechanical concordance and discordance for different stimulus rates T, and SR Ca uptake and release parameters ν and λ. For ν = 0.7, as in the single myocyte model, alternans is EMC, for all values of λ (Fig. 7A). Further, as T decreases, there is a transition from SC to SD alternans. There is a small difference between the onsets of alternans and conduction block stimulus period in the cable simulations (black lines), in comparison with the single cell simulations (gray lines).

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