Congestive heart failure leads to prolongation of the PR interval and atrioventricular junction enlargement and ion channel remodelling in the rabbit

Theodora Nikolaidou; Xue J Cai; Robert Stephenson; Joseph Yanni; Tristan Lowe; Andrew J Atkinson; Caroline B Jones; Rida Sardar; Antonio F Corno; Halina Dobrzynski; Philip J Withers; Jonathan C Jarvis; George Hart; Mark R Boyett

doi:10.1371/journal.pone.0141452

Congestive heart failure leads to prolongation of the PR interval and atrioventricular junction enlargement and ion channel remodelling in the rabbit

Theodora Nikolaidou, Xue J Cai, Robert Stephenson, Joseph Yanni, Tristan Lowe, Andrew J Atkinson, Caroline B Jones, Rida Sardar, Antonio F Corno, Halina Dobrzynski, Philip J Withers, Jonathan C Jarvis, George Hart, Mark R Boyett

Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

84 Downloads (Pure)

Abstract

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 Ca_v1.3 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 Na_vβ1 was increased with heart failure; Na_v1.1 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, Ca_v1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ.

Original language	English
Article number	e0141452
Number of pages	18
Journal	PLoS ONE
Volume	10
Issue number	10
DOIs	https://doi.org/10.1371/journal.pone.0141452
Publication status	Published - 28 Oct 2015

Keywords

Animals
Atrial Remodeling
Cardiomegaly/metabolism
Connexin 43/metabolism
Disease Models, Animal
Echocardiography
Electrocardiography
Heart Failure/diagnosis
Ion Channels/metabolism
Male
Myocardium/metabolism
RNA, Messenger/genetics
Rabbits
Ventricular Remodeling
X-Ray Microtomography

Access to Document

10.1371/journal.pone.0141452Licence: Creative Commons: Attribution (CC BY)

NikolaidouT2015CongestiveFinal published version, 4.78 MBLicence: Creative Commons: Attribution (CC BY)

https://doi.org/10.1371/journal.pone.0141452Licence: Creative Commons: Attribution (CC BY)

Cite this

Nikolaidou, T., Cai, X. J., Stephenson, R., Yanni, J., Lowe, T., Atkinson, A. J., Jones, C. B., Sardar, R., Corno, A. F., Dobrzynski, H., Withers, P. J., Jarvis, J. C., Hart, G., & Boyett, M. R. (2015). Congestive heart failure leads to prolongation of the PR interval and atrioventricular junction enlargement and ion channel remodelling in the rabbit. PLoS ONE, 10(10), Article e0141452. https://doi.org/10.1371/journal.pone.0141452

@article{5300df51e96a4c798e0b99b5018ce840,

title = "Congestive heart failure leads to prolongation of the PR interval and atrioventricular junction enlargement and ion channel remodelling in the rabbit",

abstract = "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. ",

keywords = "Animals, Atrial Remodeling, Cardiomegaly/metabolism, Connexin 43/metabolism, Disease Models, Animal, Echocardiography, Electrocardiography, Heart Failure/diagnosis, Ion Channels/metabolism, Male, Myocardium/metabolism, RNA, Messenger/genetics, Rabbits, Ventricular Remodeling, X-Ray Microtomography",

author = "Theodora Nikolaidou and Cai, {Xue J} and Robert Stephenson and Joseph Yanni and Tristan Lowe and Atkinson, {Andrew J} and Jones, {Caroline B} and Rida Sardar and Corno, {Antonio F} and Halina Dobrzynski and Withers, {Philip J} and Jarvis, {Jonathan C} and George Hart and Boyett, {Mark R}",

year = "2015",

month = oct,

day = "28",

doi = "10.1371/journal.pone.0141452",

language = "English",

volume = "10",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science (PLOS)",

number = "10",

}

Nikolaidou, T, Cai, XJ, Stephenson, R, Yanni, J, Lowe, T, Atkinson, AJ, Jones, CB, Sardar, R, Corno, AF, Dobrzynski, H, Withers, PJ, Jarvis, JC, Hart, G & Boyett, MR 2015, 'Congestive heart failure leads to prolongation of the PR interval and atrioventricular junction enlargement and ion channel remodelling in the rabbit', PLoS ONE, vol. 10, no. 10, e0141452. https://doi.org/10.1371/journal.pone.0141452

TY - JOUR

T1 - Congestive heart failure leads to prolongation of the PR interval and atrioventricular junction enlargement and ion channel remodelling in the rabbit

AU - Nikolaidou, Theodora

AU - Cai, Xue J

AU - Stephenson, Robert

AU - Yanni, Joseph

AU - Lowe, Tristan

AU - Atkinson, Andrew J

AU - Jones, Caroline B

AU - Sardar, Rida

AU - Corno, Antonio F

AU - Dobrzynski, Halina

AU - Withers, Philip J

AU - Jarvis, Jonathan C

AU - Hart, George

AU - Boyett, Mark R

PY - 2015/10/28

Y1 - 2015/10/28

N2 - 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.

AB - 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.

KW - Animals

KW - Atrial Remodeling

KW - Cardiomegaly/metabolism

KW - Connexin 43/metabolism

KW - Disease Models, Animal

KW - Echocardiography

KW - Electrocardiography

KW - Heart Failure/diagnosis

KW - Ion Channels/metabolism

KW - Male

KW - Myocardium/metabolism

KW - RNA, Messenger/genetics

KW - Rabbits

KW - Ventricular Remodeling

KW - X-Ray Microtomography

U2 - 10.1371/journal.pone.0141452

DO - 10.1371/journal.pone.0141452

M3 - Article

C2 - 26509807

SN - 1932-6203

VL - 10

JO - PLoS ONE

JF - PLoS ONE

IS - 10

M1 - e0141452

ER -

Congestive heart failure leads to prolongation of the PR interval and atrioventricular junction enlargement and ion channel remodelling in the rabbit

Abstract

Keywords

Access to Document

Fingerprint

Cite this