Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit.pdf (4.78 MB)
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Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit.

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posted on 24.10.2019, 14:46 by T Nikolaidou, XJ Cai, RS Stephenson, J Yanni, T Lowe, AJ Atkinson, CB Jones, R Sardar, AF Corno, H Dobrzynski, PJ Withers, JC Jarvis, G Hart, MR Boyett
Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ.

Funding

This work was funded by a programme grant from the British Heart Foundation RG/06/005. The Manchester X-ray Imaging Facility was funded in part by the EPSRC (grants EP/F007906/1, EP/F001452/1 and EP/I02249X/1). The Bioimaging Facility microscopes used in this study were purchased with grants from the Biotechnology and Biological Sciences Research Council, Wellcome Trust and the University of Manchester Strategic Fund. TN was funded by the Manchester Biomedical Research Centre. RSS was funded by the Alder Hey Children's NHS Foundation Trust. GH held the David A. Price Evans Chair of Medicine at the University of Liverpool during the course of this work.

History

Citation

PLoS ONE, 2015, 10(10): e0141452.

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

Version

VoR (Version of Record)

Published in

PLoS ONE

Publisher

Public Library of Science

eissn

1932-6203

Acceptance date

08/10/2015

Copyright date

2015

Available date

24/10/2019

Publisher version

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0141452

Language

en