Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607026
Title: Mammalian atrioventricular junction anatomy, electrophysiology and ion channel remodelling in health and disease
Author: Nikolaidou, Theodora
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2013
Availability of Full Text:
Access through EThOS:
Access through Institution:
Abstract:
The atrioventricular junction (AVJ) is a complex anatomical structure. It has an important role in maintaining synchronised atrioventricular conduction and protects from ventricular tachycardia, as well as bradycardia. Its embryological development and function is under tight transcription factor control. Heart failure is a chronic systemic condition, affecting one million people in the UK alone. Slowing of atrioventricular conduction in heart failure is associated with increased morbidity and mortality. The molecular and anatomical basis of abnormal atrioventricular conduction was studied in a rabbit model of heart failure due to aortic insufficiency and abdominal aortic constriction. The PR interval was significantly prolonged in heart failure animals. Using laser-assisted microdissection, the tiny tissues of the AVJ were collected for RT-PCR analysis. HCN1, Cav1.3, Cx40 and Cx43 transcripts were significantly downregulated by heart failure, with a compensatory increase in CLCN2, Nav1.1, Navβ1, SUR2A and PAK1. Immunolabelling for Cx43 showed reduction in protein level and longitudinal dissociation not only in the inferior nodal extension but also in the His bundle in heart failure animals. Anatomical studies of the AVJ have previously been limited by its small size and inaccessible location. Contrast-enhanced micro-CT scanning allowed non-destructive imaging of the AVJ anatomy. AVJ length and volume were increased in the rabbit model of heart failure, which is expected to contribute to atrioventricular conduction abnormalities. Micro-CT additionally resolved the anatomy of the canine AVJ and atria, including fibre orientation in the pulmonary vein sleeves and Bachmann’s bundle. The physiological effects of loss of T-box transcription factor 5 (Tbx5) in the AVJ were studied in a transgenic inducible Tbx5 knockout mouse model using optical mapping. Tbx5-deficient mice had a prolonged PR interval in vivo and a higher incidence of atrioventricular block and ventricular conduction abnormalities in Langendorff-perfused hearts.
Supervisor: Neyses, Ludwig; Oceandy, Delvac; Boyett, Mark Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.607026  DOI: Not available
Keywords: atrioventricular junction ; atrioventricular node ; heart failure ; laser microdissection ; ion channels ; Tbx5
Share: