Genetic background dominates the susceptibility to ventricular arrhythmias in a murine model of β-adrenergic stimulation

Abstract In cardiovascular research, several mouse strains with differing genetic backgrounds are used to investigate mechanisms leading to and sustaining ventricular arrhythmias. The genetic background has been shown to affect the studied phenotype in other research fields. Surprisingly little is k...

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Autores principales:	Marisa Jelinek, Charlotte Wallach, Heimo Ehmke, Alexander Peter Schwoerer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/073b6d5462ee414dad74391ff2e26e17
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spelling	oai:doaj.org-article:073b6d5462ee414dad74391ff2e26e172021-12-02T15:08:57ZGenetic background dominates the susceptibility to ventricular arrhythmias in a murine model of β-adrenergic stimulation10.1038/s41598-018-20792-52045-2322https://doaj.org/article/073b6d5462ee414dad74391ff2e26e172018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-20792-5https://doaj.org/toc/2045-2322Abstract In cardiovascular research, several mouse strains with differing genetic backgrounds are used to investigate mechanisms leading to and sustaining ventricular arrhythmias. The genetic background has been shown to affect the studied phenotype in other research fields. Surprisingly little is known about potential strain-specific susceptibilities towards ventricular arrhythmias in vivo. Here, we hypothesized that inter-strain differences reported in the responsiveness of the β-adrenergic pathway, which is relevant for the development of arrhythmias, translate into a strain-specific vulnerability. To test this hypothesis, we characterized responses to β-adrenergic blockade (metoprolol) and β-adrenergic stimulation (isoproterenol) in 4 mouse strains commonly employed in cardiovascular research (Balb/c, BS, C57Bl/6 and FVB) using telemetric ECG recordings. We report pronounced differences in the electrical vulnerability following isoproterenol: Balb/c mice developed the highest number and the most complex arrhythmias while BS mice were protected. Balb/c mice, therefore, seem to be the background of choice for experiments requiring the occurrence of arrhythmias while BS mice may give insight into electrical stability. Arrhythmias did not correlate with the basal β-adrenergic tone, with the response to β-adrenergic stimulation or with the absolute heart rates during β-adrenergic stimulation. Thus, genetic factors dominate the susceptibility to ventricular arrhythmias in this model of β-adrenergic stimulation.Marisa JelinekCharlotte WallachHeimo EhmkeAlexander Peter SchwoererNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marisa Jelinek Charlotte Wallach Heimo Ehmke Alexander Peter Schwoerer Genetic background dominates the susceptibility to ventricular arrhythmias in a murine model of β-adrenergic stimulation
description	Abstract In cardiovascular research, several mouse strains with differing genetic backgrounds are used to investigate mechanisms leading to and sustaining ventricular arrhythmias. The genetic background has been shown to affect the studied phenotype in other research fields. Surprisingly little is known about potential strain-specific susceptibilities towards ventricular arrhythmias in vivo. Here, we hypothesized that inter-strain differences reported in the responsiveness of the β-adrenergic pathway, which is relevant for the development of arrhythmias, translate into a strain-specific vulnerability. To test this hypothesis, we characterized responses to β-adrenergic blockade (metoprolol) and β-adrenergic stimulation (isoproterenol) in 4 mouse strains commonly employed in cardiovascular research (Balb/c, BS, C57Bl/6 and FVB) using telemetric ECG recordings. We report pronounced differences in the electrical vulnerability following isoproterenol: Balb/c mice developed the highest number and the most complex arrhythmias while BS mice were protected. Balb/c mice, therefore, seem to be the background of choice for experiments requiring the occurrence of arrhythmias while BS mice may give insight into electrical stability. Arrhythmias did not correlate with the basal β-adrenergic tone, with the response to β-adrenergic stimulation or with the absolute heart rates during β-adrenergic stimulation. Thus, genetic factors dominate the susceptibility to ventricular arrhythmias in this model of β-adrenergic stimulation.
format	article
author	Marisa Jelinek Charlotte Wallach Heimo Ehmke Alexander Peter Schwoerer
author_facet	Marisa Jelinek Charlotte Wallach Heimo Ehmke Alexander Peter Schwoerer
author_sort	Marisa Jelinek
title	Genetic background dominates the susceptibility to ventricular arrhythmias in a murine model of β-adrenergic stimulation
title_short	Genetic background dominates the susceptibility to ventricular arrhythmias in a murine model of β-adrenergic stimulation
title_full	Genetic background dominates the susceptibility to ventricular arrhythmias in a murine model of β-adrenergic stimulation
title_fullStr	Genetic background dominates the susceptibility to ventricular arrhythmias in a murine model of β-adrenergic stimulation
title_full_unstemmed	Genetic background dominates the susceptibility to ventricular arrhythmias in a murine model of β-adrenergic stimulation
title_sort	genetic background dominates the susceptibility to ventricular arrhythmias in a murine model of β-adrenergic stimulation
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/073b6d5462ee414dad74391ff2e26e17
work_keys_str_mv	AT marisajelinek geneticbackgrounddominatesthesusceptibilitytoventriculararrhythmiasinamurinemodelofbadrenergicstimulation AT charlottewallach geneticbackgrounddominatesthesusceptibilitytoventriculararrhythmiasinamurinemodelofbadrenergicstimulation AT heimoehmke geneticbackgrounddominatesthesusceptibilitytoventriculararrhythmiasinamurinemodelofbadrenergicstimulation AT alexanderpeterschwoerer geneticbackgrounddominatesthesusceptibilitytoventriculararrhythmiasinamurinemodelofbadrenergicstimulation
_version_	1718387916759105536

Genetic background dominates the susceptibility to ventricular arrhythmias in a murine model of β-adrenergic stimulation

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