Autonomic Modulation in a Rabbit Model of Heart Failure
thesisposted on 2017-06-12, 14:24 authored by Shui Hao Chin
In this thesis, autonomic modulation of atrial and ventricular electrophysiology was studied in both normal and diseased models of rabbit hearts using isolated, dual-innervated, Langendorff-perfused heart preparation. In normal hearts, accentuated antagonism was present in heart rate changes during sympatho-vagal interaction, with a dominant vagal effect of heart rate reduction observed. At the ventricular level, sympathetic effect prevailed with the resultant lowering of ventricular fibrillation threshold (VFT) and steepening of action potential duration restitution (APD-RT) despite concurrent vagal stimulation, suggesting a different pre-synaptic neuro-cardiac interaction at the ventricular level. No sympatho-vagal interaction was demonstrated for ventricular refractoriness (ERP). Beta-blockade during sympatho-vagal interaction abolished the prevailing sympathetic effect in ventricular electrophysiology in addition to raising overall VFT. An infarct-driven heart failure model was created by surgical ligation of circumflex artery whilst sham model underwent open-chest surgeries with no coronary ligation. A learning curve was encountered with post-operative mortality improved by various refinements. Six weeks following coronary ligation, transthoracic echocardiography revealed cardiac remodelling evident as left atrial and ventricular dilatation correlating with impaired systolic function. Ex-vivo cardiac magnetic resonance imaging confirmed apical myocardial scarring in heart failure rabbits. Systemic remodelling manifested as increased weights of heart, lungs and liver, all correlating with impaired systolic function. At baseline, heart failure rabbits exhibited longer atrio-ventricular delay, lower VFT, steeper APD-RT, greater apico-basal restitution dispersion and shorter ERP when compared to the shams. There was exaggerated sympathetic response in heart failure animals with significantly greater heart rate increment and atrio-ventricular delay shortening, VFT lowering, ERP shortening, APD-RT steepening, and greater apico-basal restitution dispersion. Simultaneously, the opposing effects of vagal stimulation were attenuated. Infarctdriven heart failure in rabbits following coronary ligation resulted in adverse structural and electrical remodelling which promotes ventricular fibrillation in response to autonomic dysfunction characterised by sympathetic overdrive and vagal attenuation.
Supervisor(s)Ng, G. André; Brack, Kieran
Date of award2017-06-07
Author affiliationDepartment of Cardiovascular Sciences
Awarding institutionUniversity of Leicester