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dc.contributor.authorAhmad, Shiraz
dc.contributor.authorValli, H
dc.contributor.authorEdling, C
dc.contributor.authorGrace, Andrew
dc.contributor.authorJeevaratnam, K
dc.contributor.authorHuang, Christopher
dc.date.accessioned2017-10-03T12:43:44Z
dc.date.accessioned2018-06-21T09:22:41Z
dc.date.available2017-10-03T12:43:44Z
dc.date.available2018-06-21T09:22:41Z
dc.date.issued2017-12
dc.identifier.issn0031-6768
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/277320
dc.description.abstractA range of chronic clinical conditions accompany cardiomyocyte energetic dysfunction and constitute independent risk factors for cardiac arrhythmia. We investigated pro-arrhythmic and arrhythmic phenotypes in energetically deficient C57BL mice with genetic ablation of the mitochondrial promoter peroxisome proliferator activated receptor-γ coactivator-1β (Pgc-1β), a known model of ventricular arrhythmia. Pro-arrhythmic and cellular action potential (AP) characteristics were compared in intact Langendorff-perfused hearts from young (12-16 week) and aged (>52 week), WT and Pgc-1β-/- mice. Simultaneous electrocardiographic and intracellular microelectrode recordings were made through successive trains of 100 regular stimuli at progressively incremented heart rates. Aged Pgc-1β-/- hearts displayed an increased incidence of arrhythmia compared to other groups. Young and aged Pgc-1β-/- hearts showed higher incidences of alternans in both AP activation (maximum AP upshoot velocity (dV/dt)max and latency), recovery (action potential duration (APD90) and resting membrane potential (RMP)) characteristics compared to WT hearts. This was particularly apparent at lower pacing frequencies. These findings accompanied reduced (dV/dt)max and increased AP latency values in the Pgc-1β-/- hearts. APs observed prior to termination of the protocol showed lower (dV/dt)max and longer AP latencies, but indistinguishable APD90 and RMPs in arrhythmic compared to non-arrhythmic hearts. APD restitution analysis showed that Pgc-1β-/- and WT hearts showed similar limiting gradients. However, Pgc-1β-/- hearts had shortened plateau AP wavelengths, particularly in aged Pgc-1β-/- hearts. Pgc-1β-/- hearts therefore show pro-arrhythmic instabilities attributable to altered AP conduction and activation rather than recovery characteristics.
dc.description.sponsorshipWe acknowledge the financial support from the Medical Research Council (MR/M001288/1); the Wellcome Trust (105727/Z/14/Z); the British Heart Foundation (PG/14/79/31102 and PG/15/12/31280), Sudden arrhythmic death syndrome (SADS) UK; The McVeigh Benefaction and by the Fundamental Research Grant Scheme (FRGS/2/2014/SKK01/PERDANA/02/1), Ministry of Education, Malaysia.
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.replaceshttps://www.repository.cam.ac.uk/handle/1810/267690
dc.relation.replaces1810/267690
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectPeroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1)
dc.subjectventricles
dc.subjectaction potential
dc.subjectwavelength
dc.subjectcardiac conduction
dc.subjectcardiac arrhythmias
dc.titleEffects of ageing on pro-arrhythmic ventricular phenotypes in incrementally paced murine Pgc1β-/- hearts
dc.typeArticle
prism.publicationNamePflugers Archiv European Journal of Physiology
dc.identifier.doi10.17863/CAM.13623
dc.identifier.doi10.17863/CAM.24610
dcterms.dateAccepted2017-08-02
rioxxterms.versionofrecord10.1007/s00424-017-2054-3
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.licenseref.startdate2017-08-02
dc.contributor.orcidHuang, Christopher [0000-0001-9553-6112]
dc.identifier.eissn1432-2013
rioxxterms.typeJournal Article/Review
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/G017565/1)
pubs.funder-project-idWellcome Trust (105727/Z/14/Z)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idMedical Research Council (MR/M001288/1)
pubs.funder-project-idBritish Heart Foundation (PG/15/12/31280)
cam.issuedOnline2017-08-18
cam.orpheus.successThu Jan 30 13:00:24 GMT 2020 - The item has an open VoR version.
rioxxterms.freetoread.startdate2100-01-01


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