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New insights on the cardiac safety factor: Unraveling the relationship between conduction velocity and robustness of propagation
| hal.structure.identifier | Johns Hopkins University [JHU] | |
| dc.contributor.author | BOYLE, Patrick | |
| hal.structure.identifier | Johns Hopkins University [JHU] | |
| dc.contributor.author | FRANCESCHI, William | |
| hal.structure.identifier | Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] [CRCTB] | |
| dc.contributor.author | CONSTANTIN, Marion | |
| hal.structure.identifier | Universidad de Navarra [Pamplona] [UNAV] | |
| dc.contributor.author | HAWKS, Claudia | |
| hal.structure.identifier | IHU-LIRYC | |
| dc.contributor.author | DESPLANTEZ, Thomas | |
| hal.structure.identifier | Johns Hopkins University [JHU] | |
| dc.contributor.author | TRAYANOVA, Natalia | |
| hal.structure.identifier | Modélisation et calculs pour l'électrophysiologie cardiaque [CARMEN] | |
| dc.contributor.author | VIGMOND, Edward | |
| dc.date.accessioned | 2024-04-04T02:51:43Z | |
| dc.date.available | 2024-04-04T02:51:43Z | |
| dc.date.issued | 2019-03 | |
| dc.identifier.issn | 0022-2828 | |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/192002 | |
| dc.description.abstractEn | Cardiac conduction disturbances are linked with arrhythmia development. The concept of safety factor (SF) has been derived to describe the robustness of conduction, but the usefulness of this metric has been constrained by several limitations. For example, due to the difficulty of measuring the necessary input variables, SF calculations have only been applied to synthetic data. Moreover, quantitative validation of SF is lacking; specifically, the practical meaning of particular SF values is unclear, aside from the fact that propagation failure (i.e., conduction block) is characterized by SF < 1. This study aims to resolve these limitations for our previously published SF formulation and explore its relationship to relevant electrophysiological properties of cardiac tissue. First, HL-1 cardiomyocyte monolayers were grown on multi-electrode arrays and the robustness of propagation was estimated using extracellular potential recordings. SF values reconstructed purely from experimental data were largely between 1 and 5 (up to 89.1% of sites characterized). This range is consistent with values derived from synthetic data, proving that the formulation is sound and its applicability is not limited to analysis of computational models. Second, for simulations conducted in 1-, 2-, and 3-dimensional tissue blocks, we calculated true SF values at locations surrounding the site of current injection for sub- and supra-threshold stimuli and found that they differed from values estimated by our SF formulation by <10%. Finally, we examined SF dynamics under conditions relevant to arrhythmia development in order to provide physiological insight. Our analysis shows that reduced conduction velocity (Θ) caused by impaired intrinsic cell-scale excitability (e.g., due to sodium current a loss-of-function mutation) is associated with less robust conduction (i.e., lower SF); however, intriguingly, Θ variability resulting from modulation of tissue scale conductivity has no effect on SF. These findings are supported by analytic derivation of the relevant relationships from first principles. We conclude that our SF formulation, which can be applied to both experimental and synthetic data, produces values that vary linearly with the excess charge needed for propagation. SF calculations can provide insights helpful in understanding the initiation and perpetuation of cardiac arrhythmia. | |
| dc.language.iso | en | |
| dc.publisher | Elsevier | |
| dc.subject.en | Cardiac electrophysiology | |
| dc.subject.en | Cardiac excitability | |
| dc.subject.en | Cardiac safety factor | |
| dc.subject.en | Conduction velocity | |
| dc.subject.en | Fibrosis | |
| dc.subject.en | Sodium channel | |
| dc.subject.en | Source-sink mismatch | |
| dc.title.en | New insights on the cardiac safety factor: Unraveling the relationship between conduction velocity and robustness of propagation | |
| dc.type | Article de revue | |
| dc.identifier.doi | 10.1016/j.yjmcc.2019.01.010 | |
| dc.subject.hal | Sciences du Vivant [q-bio] | |
| dc.subject.hal | Sciences du Vivant [q-bio]/Ingénierie biomédicale | |
| dc.subject.hal | Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Cardiologie et système cardiovasculaire | |
| bordeaux.journal | Journal of Molecular and Cellular Cardiology | |
| bordeaux.page | 117-128 | |
| bordeaux.volume | 128 | |
| bordeaux.hal.laboratories | Institut de Mathématiques de Bordeaux (IMB) - UMR 5251 | * |
| bordeaux.institution | Université de Bordeaux | |
| bordeaux.institution | Bordeaux INP | |
| bordeaux.institution | CNRS | |
| bordeaux.peerReviewed | oui | |
| hal.identifier | hal-02885622 | |
| hal.version | 1 | |
| hal.popular | non | |
| hal.audience | Internationale | |
| hal.origin.link | https://hal.archives-ouvertes.fr//hal-02885622v1 | |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal%20of%20Molecular%20and%20Cellular%20Cardiology&rft.date=2019-03&rft.volume=128&rft.spage=117-128&rft.epage=117-128&rft.eissn=0022-2828&rft.issn=0022-2828&rft.au=BOYLE,%20Patrick&FRANCESCHI,%20William&CONSTANTIN,%20Marion&HAWKS,%20Claudia&DESPLANTEZ,%20Thomas&rft.genre=article |
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