Cargando…

Action potential wavelength restitution predicts alternans and arrhythmia in murine Scn5a(+/−) hearts

Reductions in cardiac action potential wavelength, and the consequent wavebreak, have been implicated in arrhythmogenesis. Tachyarrhythmias are more common in the Brugada syndrome, particularly following pharmacological challenge, previously modelled using Scn5a(+/−) murine hearts. Propagation laten...

Descripción completa

Detalles Bibliográficos
Autores principales: Matthews, Gareth D K, Guzadhur, Laila, Sabir, Ian N, Grace, Andrew A, Huang, Christopher L-H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Science Inc 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779110/
https://www.ncbi.nlm.nih.gov/pubmed/23836691
http://dx.doi.org/10.1113/jphysiol.2013.254938
_version_ 1782285199024848896
author Matthews, Gareth D K
Guzadhur, Laila
Sabir, Ian N
Grace, Andrew A
Huang, Christopher L-H
author_facet Matthews, Gareth D K
Guzadhur, Laila
Sabir, Ian N
Grace, Andrew A
Huang, Christopher L-H
author_sort Matthews, Gareth D K
collection PubMed
description Reductions in cardiac action potential wavelength, and the consequent wavebreak, have been implicated in arrhythmogenesis. Tachyarrhythmias are more common in the Brugada syndrome, particularly following pharmacological challenge, previously modelled using Scn5a(+/−) murine hearts. Propagation latencies and action potential durations (APDs) from monophasic action potential recordings were used to assess wavelength changes with heart rate in Langendorff-perfused wild-type (WT) and Scn5a(+/−) hearts. Recordings were obtained from right (RV) and left (LV) ventricular, epicardial and endocardial surfaces during incremental pacing, before and following flecainide or quinidine challenge. Conduction velocities (θ′), action potential wavelengths (λ′= APD ×θ′), and their corresponding alternans depended non-linearly upon diastolic interval (DI). Maximum θ′ was lower in Scn5a(+/−) RV epicardium than endocardium. Flecainide further reduced θ′, accentuating this RV conduction block. Quinidine reduced maximum θ′ in WT and caused earlier conduction failure in the RV of both Scn5a(+/−) and WT. Use of recovery wavelengths (λ′(0)= DI ×θ′) rather than DI, provided novel λ restitution plots of λ′ against λ′(0), which sum to a basic cycle distance permitting feedback analysis. λ′ restitution gradient better correlated with alternans magnitude than either APD or θ restitution gradient. The large differences in θ′ and APD restitution contrasted with minor differences in maximum λ′ between epi- and endocardia of untreated hearts, and quinidine-treated WT hearts. Strikingly, all regions and conditions converged to a common instability point, implying a conserved relationship. Flecainide or quinidine decreased the pacing rates at which this occurred, through reducing basic cycle distance, in the Scn5a(+/−) RV epicardium, directly predictive of its arrhythmic phenotype.
format Online
Article
Text
id pubmed-3779110
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Blackwell Science Inc
record_format MEDLINE/PubMed
spelling pubmed-37791102014-02-21 Action potential wavelength restitution predicts alternans and arrhythmia in murine Scn5a(+/−) hearts Matthews, Gareth D K Guzadhur, Laila Sabir, Ian N Grace, Andrew A Huang, Christopher L-H J Physiol Research Papers Reductions in cardiac action potential wavelength, and the consequent wavebreak, have been implicated in arrhythmogenesis. Tachyarrhythmias are more common in the Brugada syndrome, particularly following pharmacological challenge, previously modelled using Scn5a(+/−) murine hearts. Propagation latencies and action potential durations (APDs) from monophasic action potential recordings were used to assess wavelength changes with heart rate in Langendorff-perfused wild-type (WT) and Scn5a(+/−) hearts. Recordings were obtained from right (RV) and left (LV) ventricular, epicardial and endocardial surfaces during incremental pacing, before and following flecainide or quinidine challenge. Conduction velocities (θ′), action potential wavelengths (λ′= APD ×θ′), and their corresponding alternans depended non-linearly upon diastolic interval (DI). Maximum θ′ was lower in Scn5a(+/−) RV epicardium than endocardium. Flecainide further reduced θ′, accentuating this RV conduction block. Quinidine reduced maximum θ′ in WT and caused earlier conduction failure in the RV of both Scn5a(+/−) and WT. Use of recovery wavelengths (λ′(0)= DI ×θ′) rather than DI, provided novel λ restitution plots of λ′ against λ′(0), which sum to a basic cycle distance permitting feedback analysis. λ′ restitution gradient better correlated with alternans magnitude than either APD or θ restitution gradient. The large differences in θ′ and APD restitution contrasted with minor differences in maximum λ′ between epi- and endocardia of untreated hearts, and quinidine-treated WT hearts. Strikingly, all regions and conditions converged to a common instability point, implying a conserved relationship. Flecainide or quinidine decreased the pacing rates at which this occurred, through reducing basic cycle distance, in the Scn5a(+/−) RV epicardium, directly predictive of its arrhythmic phenotype. Blackwell Science Inc 2013-09-01 2013-07-08 /pmc/articles/PMC3779110/ /pubmed/23836691 http://dx.doi.org/10.1113/jphysiol.2013.254938 Text en © 2013 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ © 2013 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Papers
Matthews, Gareth D K
Guzadhur, Laila
Sabir, Ian N
Grace, Andrew A
Huang, Christopher L-H
Action potential wavelength restitution predicts alternans and arrhythmia in murine Scn5a(+/−) hearts
title Action potential wavelength restitution predicts alternans and arrhythmia in murine Scn5a(+/−) hearts
title_full Action potential wavelength restitution predicts alternans and arrhythmia in murine Scn5a(+/−) hearts
title_fullStr Action potential wavelength restitution predicts alternans and arrhythmia in murine Scn5a(+/−) hearts
title_full_unstemmed Action potential wavelength restitution predicts alternans and arrhythmia in murine Scn5a(+/−) hearts
title_short Action potential wavelength restitution predicts alternans and arrhythmia in murine Scn5a(+/−) hearts
title_sort action potential wavelength restitution predicts alternans and arrhythmia in murine scn5a(+/−) hearts
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779110/
https://www.ncbi.nlm.nih.gov/pubmed/23836691
http://dx.doi.org/10.1113/jphysiol.2013.254938
work_keys_str_mv AT matthewsgarethdk actionpotentialwavelengthrestitutionpredictsalternansandarrhythmiainmurinescn5ahearts
AT guzadhurlaila actionpotentialwavelengthrestitutionpredictsalternansandarrhythmiainmurinescn5ahearts
AT sabiriann actionpotentialwavelengthrestitutionpredictsalternansandarrhythmiainmurinescn5ahearts
AT graceandrewa actionpotentialwavelengthrestitutionpredictsalternansandarrhythmiainmurinescn5ahearts
AT huangchristopherlh actionpotentialwavelengthrestitutionpredictsalternansandarrhythmiainmurinescn5ahearts