Abstract
BackgroundHigh-grade inflammation may play a pivotal role in the pathogenesis of left ventricular (LV) dysfunction. Evidence to support a role of systemic inflammation in mediating impaired LV function in experimental models of rheumatoid arthritis (RA) remains limited. The aim of the present study was to determine the effects of high-grade systemic inflammation on LV diastolic and systolic function in collagen-induced arthritis (CIA).MethodsTo induce CIA, bovine type-II collagen emulsified in incomplete Freund’s adjuvant was injected at the base of the tail into 21 three-month old Sprague Dawley rats. Nine-weeks after the first immunisation, LV function was assessed by pulsed Doppler, tissue Doppler imaging and Speckle tracking echocardiography. Cardiac collagen content was determined by picrosirius red staining; circulating inflammatory markers were measured using ELISA.ResultsCompared to controls (n = 12), CIA rats had reduced myocardial relaxation as indexed by lateral e’ (early diastolic mitral annular velocity) and e’/a’ (early-to-late diastolic mitral annular velocity) and increased filling pressures as indexed by E/e’. No differences in ejection fraction and LV endocardial fractional shortening between the groups were recorded. LV global radial and circumferential strain and strain rate were reduced in CIA rats compared to controls. Higher concentrations of circulating inflammatory markers were associated with reduced lateral e’, e’/a’, radial and circumferential strain and strain rate. Greater collagen content was associated with increased concentrations of circulating inflammatory markers and E/e’.ConclusionHigh-grade inflammation is associated with impaired LV diastolic function and greater myocardial deformation independent of haemodynamic load in CIA rats.
Highlights
Heart failure with a preserved ejection fraction (HFpEF) accounts for more than 50% of all heart failure cases and is associated with an increased morbidity and mortality [1]
left ventricular (LV) global radial and circumferential strain and strain rate were reduced in collagen-induced arthritis (CIA) rats compared to controls
High-grade inflammation is associated with impaired LV diastolic function and greater myocardial deformation independent of haemodynamic load in CIA rats
Summary
Heart failure with a preserved ejection fraction (HFpEF) accounts for more than 50% of all heart failure cases and is associated with an increased morbidity and mortality [1]. Hypertension, diabetes mellitus and obesity comprise traditional cardiovascular risk factors that are associated with diastolic dysfunction [6] These metabolic abnormalities fail to account for all changes in diastolic function [7]. A systemic pro-inflammatory state has been proposed as a mediator for the causal molecular or biochemical mechanisms of diastolic dysfunction in persons exposed to metabolic risk factors [8]. In this regard, diseases that are associated with chronic high-grade inflammation including rheumatoid arthritis (RA), markedly exacerbate the risk for developing diastolic dysfunction and HFpEF compared to the general population [9, 10]. The aim of the present study was to determine the effects of high-grade systemic inflammation on LV diastolic and systolic function in collagen-induced arthritis (CIA).
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