The effect of systemic autoimmunity on post myocardial infarction electrophysiological remodelling
File(s)
Author(s)
Jenkins, Catherine
Type
Thesis
Abstract
The work described in this thesis was to investigate the effects of underlying systemic autoimmunity on post-myocardial infarction electrophysiological remodelling. Systemic autoimmune conditions can predispose patients to cardiovascular damage, with patients being highly susceptible to myocardial infarction (MI). Underlying systemic autoimmunity has been shown to lead to worsened outcomes post-MI, however this exacerbation of the immune response to MI under systemic autoimmune conditions has not yet been investigated in relation to its effect on post-MI electrophysiology. In order to test the hypothesis that systemic autoimmunity exacerbates adverse electrophysiological remodelling after type 2 MI (T2MI), models for both T2MI and systemic autoimmunity had to be established. A method of inducing T2MI was chosen based on previous research using a single high dose of isoproterenol to elicit an ischemic cardiac injury comparable to that of T2MI. A chemically induced model of systemic autoimmunity was chosen for this study by testing two mouse strains for their susceptibility to acquiring a systemic autoimmune phenotype with cardiac involvement by treatment with TLR-7 agonist R848. Using the established models, the effects of acute R848 treatment on cardiac electrophysiology were assessed in order to fully understand the influence of R848-induced systemic autoimmunity on the heart, followed by assessment of our principal hypothesis by carrying out Langendorff perfusion and optical mapping. Our results indicated malignant arrhythmias in both T2MI and R848+T2MI groups, with more severe arrhythmias in the R848+T2MI group indicating an exacerbated phenotype compared to T2MI. The presence of elevated anti-cardiac autoantibodies, increased fibrosis, and increased cell infiltration in this model provide possible explanation for these arrhythmias. However, arrhythmias were so severe that optical mapping recordings could not be completed. Overall, this thesis supports the hypothesis that post-MI electrophysiological remodelling is adversely exacerbated in systemic autoimmunity, although the exact mechanisms behind this remain to be fully elucidated.
Version
Open Access
Date Issued
2023-09-28
Date Awarded
2024-03-01
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Ng, Fu Siong
Sattler, Susanne
Rosenthal, Nadia
Sponsor
British Heart Foundation
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)