A multiscale investigation of repolarization variability and its role in cardiac arrhythmogenesis.
Enhanced temporal and spatial variability in cardiac repolarization has been related to increased arrhythmic risk both clinically and experimentally. Causes and modulators of variability in repolarization and their implications in arrhythmogenesis are however not well understood. At the ionic level,...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2011
|
| _version_ | 1826265950973853696 |
|---|---|
| author | Pueyo, E Corrias, A Virág, L Jost, N Szél, T Varró, A Szentandrássy, N Nánási, P Burrage, K Rodríguez, B |
| author_facet | Pueyo, E Corrias, A Virág, L Jost, N Szél, T Varró, A Szentandrássy, N Nánási, P Burrage, K Rodríguez, B |
| author_sort | Pueyo, E |
| collection | OXFORD |
| description | Enhanced temporal and spatial variability in cardiac repolarization has been related to increased arrhythmic risk both clinically and experimentally. Causes and modulators of variability in repolarization and their implications in arrhythmogenesis are however not well understood. At the ionic level, the slow component of the delayed rectifier potassium current (I(Ks)) is an important determinant of ventricular repolarization. In this study, a combination of experimental and computational multiscale studies is used to investigate the role of intrinsic and extrinsic noise in I(Ks) in modulating temporal and spatial variability in ventricular repolarization in human and guinea pig. Results show that under physiological conditions: i), stochastic fluctuations in I(Ks) gating properties (i.e., intrinsic noise) cause significant beat-to-beat variability in action potential duration (APD) in isolated cells, whereas cell-to-cell differences in channel numbers (i.e., extrinsic noise) also contribute to cell-to-cell APD differences; ii), in tissue, electrotonic interactions mask the effect of I(Ks) noise, resulting in a significant decrease in APD temporal and spatial variability compared to isolated cells. Pathological conditions resulting in gap junctional uncoupling or a decrease in repolarization reserve uncover the manifestation of I(Ks) noise at cellular and tissue level, resulting in enhanced ventricular variability and abnormalities in repolarization such as afterdepolarizations and alternans. |
| first_indexed | 2024-03-06T20:31:35Z |
| format | Journal article |
| id | oxford-uuid:313a504d-0eb5-42f3-8032-fb863c1fd9e6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:31:35Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:313a504d-0eb5-42f3-8032-fb863c1fd9e62022-03-26T13:06:38ZA multiscale investigation of repolarization variability and its role in cardiac arrhythmogenesis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:313a504d-0eb5-42f3-8032-fb863c1fd9e6EnglishSymplectic Elements at Oxford2011Pueyo, ECorrias, AVirág, LJost, NSzél, TVarró, ASzentandrássy, NNánási, PBurrage, KRodríguez, BEnhanced temporal and spatial variability in cardiac repolarization has been related to increased arrhythmic risk both clinically and experimentally. Causes and modulators of variability in repolarization and their implications in arrhythmogenesis are however not well understood. At the ionic level, the slow component of the delayed rectifier potassium current (I(Ks)) is an important determinant of ventricular repolarization. In this study, a combination of experimental and computational multiscale studies is used to investigate the role of intrinsic and extrinsic noise in I(Ks) in modulating temporal and spatial variability in ventricular repolarization in human and guinea pig. Results show that under physiological conditions: i), stochastic fluctuations in I(Ks) gating properties (i.e., intrinsic noise) cause significant beat-to-beat variability in action potential duration (APD) in isolated cells, whereas cell-to-cell differences in channel numbers (i.e., extrinsic noise) also contribute to cell-to-cell APD differences; ii), in tissue, electrotonic interactions mask the effect of I(Ks) noise, resulting in a significant decrease in APD temporal and spatial variability compared to isolated cells. Pathological conditions resulting in gap junctional uncoupling or a decrease in repolarization reserve uncover the manifestation of I(Ks) noise at cellular and tissue level, resulting in enhanced ventricular variability and abnormalities in repolarization such as afterdepolarizations and alternans. |
| spellingShingle | Pueyo, E Corrias, A Virág, L Jost, N Szél, T Varró, A Szentandrássy, N Nánási, P Burrage, K Rodríguez, B A multiscale investigation of repolarization variability and its role in cardiac arrhythmogenesis. |
| title | A multiscale investigation of repolarization variability and its role in cardiac arrhythmogenesis. |
| title_full | A multiscale investigation of repolarization variability and its role in cardiac arrhythmogenesis. |
| title_fullStr | A multiscale investigation of repolarization variability and its role in cardiac arrhythmogenesis. |
| title_full_unstemmed | A multiscale investigation of repolarization variability and its role in cardiac arrhythmogenesis. |
| title_short | A multiscale investigation of repolarization variability and its role in cardiac arrhythmogenesis. |
| title_sort | multiscale investigation of repolarization variability and its role in cardiac arrhythmogenesis |
| work_keys_str_mv | AT pueyoe amultiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT corriasa amultiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT viragl amultiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT jostn amultiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT szelt amultiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT varroa amultiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT szentandrassyn amultiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT nanasip amultiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT burragek amultiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT rodriguezb amultiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT pueyoe multiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT corriasa multiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT viragl multiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT jostn multiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT szelt multiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT varroa multiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT szentandrassyn multiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT nanasip multiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT burragek multiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis AT rodriguezb multiscaleinvestigationofrepolarizationvariabilityanditsroleincardiacarrhythmogenesis |