title: Right ventricular inflammation following lung resection surgery
Creators: name: Murphy, Emma
Publisher: name: University of Glasgow
Year: 2023

description: Lung cancer is the third commonest cancer in the United Kingdom and the most common cancer overall in Scotland. Whilst the best chance of a cure is surgical resection, patients undergoing lung resection surgery are generally considered to be ‘high-risk’ surgical candidates and are at risk of major post-operative cardiac and respiratory complications following surgery. The literature has widely described a deterioration in right ventricular function following lung resection surgery; however, the mechanism of this dysfunction remains unclear. The first section of this thesis describes the complex geometry, structure and physiology of the right ventricle and reviews the available methods to assess the structure and function of the right ventricle, providing context for further investigations described later in this thesis (Chapter 1). An overview of the literature describing the right ventricular response to lung resection is described in Chapter 2. There is a complex interplay of aetiologies potentially responsible for the right ventricular dysfunction seen following lung resection including increases in afterload and altered contractility. Animal models of pulmonary embolism, which are functionally analogous to lung resection surgery and one lung ventilation with transient clamping of the lobar branches of the pulmonary artery, have widely described a right ventricular inflammatory injury leading to the hypothesis that a myocardial inflammatory injury may be a contributing factor in right ventricular dysfunction after lung resection. A review of the literature examining right ventricular inflammation after pulmonary embolism and animal models of acute afterload are described in Chapter 3. The literature demonstrates a consistent inflammatory response within the right ventricle which is associated with right ventricular dysfunction. Chapter 4 describes the methods available to measure myocardial inflammation with particular focus on cardiovascular magnetic resonance imaging given it is the gold standard imaging technique for assessment of the right ventricle. The following chapters describe the results of a prospective, observational cohort study, examining the role of right ventricular inflammation after lung resection using cardiovascular resonance imaging conducted by the author. The feasibility and reproducibility of T1 mapping (a marker of inflammation or oedema) and Extracellular Volume quantification (a marker of fibrosis or oedema) following lung resection are described in the first investigation in this thesis (Chapter 7). The excellent intra- and inter-observer reproducibility confirms T1 mapping is a suitable method for assessing the myocardial response to lung resection. The main finding of this work describes an increase in myocardial T1 and Extracellular Volume in the right ventricular insertion points and septum with no change in the left ventricle in the immediate peri-operative period following lung resection (Chapter 8). It is hypothesised that an increase in acute afterload results in an increase in right ventricular wall tension and paradoxical movement of the interventricular septum leading to an increase in mechanical stress in the ventricular insertion points. This triggers a discrete intrinsic myocardial inflammatory response (demonstrated with increases in myocardial T1) altering myocardial contractility which contributes to right ventricular dysfunction. On an exploratory basis, increases in T1 were associated with poorer RV function, poorer pre- and predicted post-operative lung function and poor patient reported post-operative outcomes. Biomarkers of myocardial dysfunction (B-type natriuretic peptide and N-terminal B-type natriuretic peptide) and systemic inflammation (C-reactive protein) were measured contemporaneously with the imaging study (Chapter 9). This investigation demonstrates a rise in all three biomarkers in the peri-operative period with an early peak rise in BNP at twelve hours compared with seventytwo hours for NT-proBNP. This suggests BNP has superiority in the peri-operative period as an early indicator of patients who have sustained injury potentially allowing identification, monitoring, and therapy with the aim to intervene early in those at higher risk of peri-operative complications and poorer long term outcomes following lung resection. This thesis provides further insight into the mechanisms of right ventricular dysfunction following lung resection. It provides validated methods for future work in this patient population, suggests an association between a myocardial inflammatory insult and post operative right ventricular function and highlights a potentially novel diagnostic pathway allowing targeted intervention ameliorating disabling postoperative functional limitation.