Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit

• Published in: PloS one Vol. 10; no. 10; p. e0141452
• Main Authors: Nikolaidou, Theodora, Cai, Xue J, Stephenson, Robert S, Yanni, Joseph, Lowe, Tristan, Atkinson, Andrew J, Jones, Caroline B, Sardar, Rida, Corno, Antonio F, Dobrzynski, Halina, Withers, Philip J, Jarvis, Jonathan C, Hart, George, Boyett, Mark R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.10.2015; Public Library of Science (PLoS)
• Subjects: Animals; Aorta; Aortic valve; Atrial Remodeling; Atrioventricular node; Banding; Calcium channels (voltage-gated); Cardiomegaly - metabolism; Cardiomegaly - pathology; Cardiomegaly - physiopathology; Complications and side effects; Computed tomography; Congestive heart failure; Connexin 43; Connexin 43 - metabolism; Disease Models, Animal; Echocardiography; Electrocardiography; Elongation; Enlargement; Gene expression; Health aspects; Heart; Heart failure; Heart Failure - diagnosis; Heart Failure - metabolism; Heart Failure - pathology; Heart Failure - physiopathology; Ion channels; Ion channels (cyclic nucleotide-gated); Ion Channels - metabolism; Male; Myocardium - metabolism; Myocardium - pathology; Nerve conduction; Physiology; Polymerase chain reaction; Prolongation; Protein expression; Proteins; Rabbits; Remodeling; RNA, Messenger - genetics; Septum; Sodium channels (voltage-gated); Syncope; Tissues; Ventricle; Ventricular Remodeling; X-Ray Microtomography; United Kingdom > UK; Malaysia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0141452

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.