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Delayed conduction and its implications in murine Scn5a(+/−) hearts: independent and interacting effects of genotype, age, and sex

We explored for relationships between SCN5A haploinsufficiency, implicated in clinical arrhythmogenicity, and right ventricular (RV) conduction disorders in Langendorff-perfused, male and female, and young (3 months) and old (>12 month old) Scn5a (+/−) and wild type (WT) hearts. The investigated...

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Autores principales: Jeevaratnam, Kamalan, Poh Tee, Sui, Zhang, Yanmin, Rewbury, Rebecca, Guzadhur, Laila, Duehmke, Rudolf, Grace, Andrew A., Lei, Ming, Huang, Christopher L.-H.
Formato: Texto
Lenguaje:English
Publicado: Springer-Verlag 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3016216/
https://www.ncbi.nlm.nih.gov/pubmed/21127902
http://dx.doi.org/10.1007/s00424-010-0906-1
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author Jeevaratnam, Kamalan
Poh Tee, Sui
Zhang, Yanmin
Rewbury, Rebecca
Guzadhur, Laila
Duehmke, Rudolf
Grace, Andrew A.
Lei, Ming
Huang, Christopher L.-H.
author_facet Jeevaratnam, Kamalan
Poh Tee, Sui
Zhang, Yanmin
Rewbury, Rebecca
Guzadhur, Laila
Duehmke, Rudolf
Grace, Andrew A.
Lei, Ming
Huang, Christopher L.-H.
author_sort Jeevaratnam, Kamalan
collection PubMed
description We explored for relationships between SCN5A haploinsufficiency, implicated in clinical arrhythmogenicity, and right ventricular (RV) conduction disorders in Langendorff-perfused, male and female, and young (3 months) and old (>12 month old) Scn5a (+/−) and wild type (WT) hearts. The investigated conditions of genotype, age, and sex affected latencies but not repolarization time courses of RV monophasic action potentials. This prompted examination of the patterns of RV epicardial activation, its dispersion, and their interrelationships as possible arrhythmic mechanisms using a 64-channel, multi-electrode array. Mean ventricular activation times (T*(MEAN)), spatial dispersions (D* (S)) between recording channels/cardiac cycle, and maximum activation times (T* (MAX)) representing the slowest possible conduction in any given heart were all higher in old male Scn5a (+/−) compared with young male and old female Scn5a (+/−) and old male WT. Temporal dispersions (D*(T)) of recording channels were similarly higher in old male Scn5a (+/−) compared with old male WT. All groupings of D*(T), D*(S), and T*(MAX) nevertheless linearly correlated with T*(MEAN), with indistinguishable slopes. The variates explored thus influence D*(T), D*(S), and T*(MAX) through actions on T*(MEAN). These findings in turn correlated with increased levels of fibrosis in young male, young female, and old male Scn5a (+/−) compared with the corresponding WTs. We thus demonstrate for the first time independent and interacting effects of genotype, age, and sex on epicardial conduction and its dispersions at least partially attributable to fibrotic change, resulting in the greatest effects in old male Scn5a (+/−) in an absence of alterations in repolarization time courses. This directly implicates altered depolarization in the clinical arrhythmogenicity associated with Scn5a (+/−).
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spelling pubmed-30162162011-02-04 Delayed conduction and its implications in murine Scn5a(+/−) hearts: independent and interacting effects of genotype, age, and sex Jeevaratnam, Kamalan Poh Tee, Sui Zhang, Yanmin Rewbury, Rebecca Guzadhur, Laila Duehmke, Rudolf Grace, Andrew A. Lei, Ming Huang, Christopher L.-H. Pflugers Arch Cardiovascular Physiology We explored for relationships between SCN5A haploinsufficiency, implicated in clinical arrhythmogenicity, and right ventricular (RV) conduction disorders in Langendorff-perfused, male and female, and young (3 months) and old (>12 month old) Scn5a (+/−) and wild type (WT) hearts. The investigated conditions of genotype, age, and sex affected latencies but not repolarization time courses of RV monophasic action potentials. This prompted examination of the patterns of RV epicardial activation, its dispersion, and their interrelationships as possible arrhythmic mechanisms using a 64-channel, multi-electrode array. Mean ventricular activation times (T*(MEAN)), spatial dispersions (D* (S)) between recording channels/cardiac cycle, and maximum activation times (T* (MAX)) representing the slowest possible conduction in any given heart were all higher in old male Scn5a (+/−) compared with young male and old female Scn5a (+/−) and old male WT. Temporal dispersions (D*(T)) of recording channels were similarly higher in old male Scn5a (+/−) compared with old male WT. All groupings of D*(T), D*(S), and T*(MAX) nevertheless linearly correlated with T*(MEAN), with indistinguishable slopes. The variates explored thus influence D*(T), D*(S), and T*(MAX) through actions on T*(MEAN). These findings in turn correlated with increased levels of fibrosis in young male, young female, and old male Scn5a (+/−) compared with the corresponding WTs. We thus demonstrate for the first time independent and interacting effects of genotype, age, and sex on epicardial conduction and its dispersions at least partially attributable to fibrotic change, resulting in the greatest effects in old male Scn5a (+/−) in an absence of alterations in repolarization time courses. This directly implicates altered depolarization in the clinical arrhythmogenicity associated with Scn5a (+/−). Springer-Verlag 2010-12-03 2011 /pmc/articles/PMC3016216/ /pubmed/21127902 http://dx.doi.org/10.1007/s00424-010-0906-1 Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Cardiovascular Physiology
Jeevaratnam, Kamalan
Poh Tee, Sui
Zhang, Yanmin
Rewbury, Rebecca
Guzadhur, Laila
Duehmke, Rudolf
Grace, Andrew A.
Lei, Ming
Huang, Christopher L.-H.
Delayed conduction and its implications in murine Scn5a(+/−) hearts: independent and interacting effects of genotype, age, and sex
title Delayed conduction and its implications in murine Scn5a(+/−) hearts: independent and interacting effects of genotype, age, and sex
title_full Delayed conduction and its implications in murine Scn5a(+/−) hearts: independent and interacting effects of genotype, age, and sex
title_fullStr Delayed conduction and its implications in murine Scn5a(+/−) hearts: independent and interacting effects of genotype, age, and sex
title_full_unstemmed Delayed conduction and its implications in murine Scn5a(+/−) hearts: independent and interacting effects of genotype, age, and sex
title_short Delayed conduction and its implications in murine Scn5a(+/−) hearts: independent and interacting effects of genotype, age, and sex
title_sort delayed conduction and its implications in murine scn5a(+/−) hearts: independent and interacting effects of genotype, age, and sex
topic Cardiovascular Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3016216/
https://www.ncbi.nlm.nih.gov/pubmed/21127902
http://dx.doi.org/10.1007/s00424-010-0906-1
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