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dc.contributor.authorAhmad, Shiraz
dc.contributor.authorValli, Haseeb
dc.contributor.authorSalvage, Samantha C
dc.contributor.authorGrace, Andrew A
dc.contributor.authorJeevaratnam, Kamalan
dc.contributor.authorHuang, Christopher L-H
dc.date.accessioned2018-04-18T10:06:15Z
dc.date.available2018-04-18T10:06:15Z
dc.date.issued2018-02
dc.identifier.issn0305-1870
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/274967
dc.description.abstractIncreasing evidence implicates chronic energetic dysfunction in human cardiac arrhythmias. Mitochondrial impairment through Pgc-1β knockout is known to produce a murine arrhythmic phenotype. However, the cumulative effect of this with advancing age and its electrocardiographic basis have not been previously studied. Young (12-16 weeks) and aged (>52 weeks), wild type (WT) (n = 5 and 8) and Pgc-1β-/- (n = 9 and 6), mice were anaesthetised and used for electrocardiographic (ECG) recordings. Time intervals separating successive ECG deflections were analysed for differences between groups before and after β1-adrenergic (intraperitoneal dobutamine 3 mg/kg) challenge. Heart rates before dobutamine challenge were indistinguishable between groups. The Pgc-1β-/- genotype however displayed compromised nodal function in response to adrenergic challenge. This manifested as an impaired heart rate response suggesting a functional defect at the level of the sino-atrial node, and a negative dromotropic response suggesting an atrioventricular conduction defect. Incidences of the latter were most pronounced in the aged Pgc-1β-/- mice. Moreover, Pgc-1β-/- mice displayed electrocardiographic features consistent with the existence of a pro-arrhythmic substrate. Firstly, ventricular activation was prolonged in these mice consistent with slowed action potential conduction and is reported here for the first time. Additionally, Pgc-1β-/- mice had shorter repolarisation intervals. These were likely attributable to altered K+ conductance properties, ultimately resulting in a shortened QTc interval, which is also known to be associated with increased arrhythmic risk. ECG analysis thus yielded electrophysiological findings bearing on potential arrhythmogenicity in intact Pgc-1β-/- systems in widespread cardiac regions.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherWiley
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAnimals
dc.subjectMice, Knockout
dc.subjectMice
dc.subjectElectrocardiography
dc.subjectGene Expression Regulation
dc.subjectAging
dc.subjectPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
dc.titleAge-dependent electrocardiographic changes in Pgc-1β deficient murine hearts.
dc.typeArticle
prism.endingPage186
prism.issueIdentifier2
prism.publicationDate2018
prism.publicationNameClin Exp Pharmacol Physiol
prism.startingPage174
prism.volume45
dc.identifier.doi10.17863/CAM.22118
dcterms.dateAccepted2017-09-19
rioxxterms.versionofrecord10.1111/1440-1681.12863
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.licenseref.startdate2018-02
dc.contributor.orcidJeevaratnam, Kamalan [0000-0002-6232-388X]
dc.contributor.orcidHuang, Christopher L-H [0000-0001-9553-6112]
dc.identifier.eissn1440-1681
rioxxterms.typeJournal Article/Review
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idWellcome Trust (105727/Z/14/Z)
pubs.funder-project-idMedical Research Council (MR/M001288/1)
cam.issuedOnline2017-11-29
cam.orpheus.successThu Jan 30 13:00:25 GMT 2020 - The item has an open VoR version.
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International