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.
Highlights
Electrical conduction abnormalities are common in heart failure and lead to cardiac arrhythmias and sudden cardiac death [1]
We present here a study of the structural and molecular changes in the rabbit atrioventricular junction (AVJ) associated with congestive heart failure
The PR interval was longer in heart failure both at baseline and after autonomic blockade
Summary
Electrical conduction abnormalities are common in heart failure and lead to cardiac arrhythmias and sudden cardiac death [1]. The electrocardiographic PR interval represents conduction from the sinus node to the Purkinje fibres. It primarily reflects atrioventricular conduction [2]. Both in ischaemic and non-ischaemic cardiomyopathy first degree heart block is common [3] and approximately half of arrhythmic deaths are bradycardic in origin, including those due to atrioventricular block [4]. First degree atrioventricular block is associated with worse outcomes in patients with heart failure [3,5] and in the general population [6]. Patients with first degree atrioventricular block derive greater benefit from CRT [5]
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