Dataset Information

Cardiac inflammation and diastolic dysfunction in hypercholesterolemic rabbits.

ABSTRACT: BACKGROUND:Left ventricular diastolic dysfunction (LVDD) is present in more than 50% of patients suffering from heart failure. LVDD animal models are limited and its underlying mechanisms remain largely unknown. Aortic valve stenosis (AVS) may cause LVDD, and we recently reported LVDD in an AVS rabbit model. Here we aimed to develop a rabbit model of LVDD without AVS. METHODS:Rabbits were fed with a 0.5% cholesterol-enriched diet (n = 9) or normal diet (n = 8) until they developed LVDD defined by a value of the echocardiographic parameter E/Em ratio higher than the mean at baseline + 2SD. Rabbits were then fed a 0.2% cholesterol-enriched diet for 4 weeks (average total diet duration: 20 weeks). Detailed cardiac structure and function measurements were assessed by echocardiography at baseline, weeks 8, 12 and 14 to 20, when applicable. Histological analyses and RT-qPCR were performed on LV samples. RESULTS:The hypercholesterolemic diet induced LVDD without systolic dysfunction or AVS, as shown by multiple echocardiographic parameters, including early filling mitral peak velocity and deceleration rate, Em/Am ratio and E/Em ratio (all p<0.05), and by increased cardiac mRNA expression of brain natriuretic peptide (Bnp). Cardiac expression of mRNA for Nox2, Vcam1, Mmp12, Mmp12/Timp1, Il1b and Col1/Col3 ratios was also higher in these rabbits (p<0.05). In contrast, cardiac Sod2 mRNA expression was reduced in hypercholesterolemic rabbits compared to controls. CONCLUSION:Rabbits fed with a cholesterol-enriched diet develop LVDD with preserved systolic function and evidence of cardiac inflammation and oxidative stress. This rabbit model may be used in future studies to test treatment strategies against LVDD.

SUBMITTER: Nachar W

PROVIDER: S-EPMC6687122 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Cardiac inflammation and diastolic dysfunction in hypercholesterolemic rabbits.

Nachar Walid W Merlet Nolwenn N Maafi Foued F Shi Yanfen Y Mihalache-Avram Teodora T Mecteau Mélanie M Ferron Marine M Rhéaume Eric E Tardif Jean-Claude JC

PloS one 20190808 8

<h4>Background</h4>Left ventricular diastolic dysfunction (LVDD) is present in more than 50% of patients suffering from heart failure. LVDD animal models are limited and its underlying mechanisms remain largely unknown. Aortic valve stenosis (AVS) may cause LVDD, and we recently reported LVDD in an AVS rabbit model. Here we aimed to develop a rabbit model of LVDD without AVS.<h4>Methods</h4>Rabbits were fed with a 0.5% cholesterol-enriched diet (n = 9) or normal diet (n = 8) until they developed ...[more]

PMID: 31393963

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Project description:AimsDiastolic dysfunction is common in geriatric heart failure. A reliable parameter to predict myocardium stiffness and relaxation under similar end-diastolic pressure is being developed. We propose a material and mathematical model for calculating myocardium stiffness based on the concept of linear correlation between [Formula: see text] and wedge pressure.Methods and resultsWe enrolled 919 patients (male: [Formula: see text][Formula: see text]). Compared with the younger population of controls (mean age: [Formula: see text] years; [Formula: see text]; male: [Formula: see text] [Formula: see text]), the elderly (mean age: [Formula: see text]; [Formula: see text]; male: [Formula: see text] [Formula: see text]) had a greater prevalence of hypertension, diabetes mellitus, and coronary artery disease (all [Formula: see text]). We collected their M-mode and 2-D echocardiographic volumetric parameters, intraventricular filling pressure, and speckle tracking images to establish a mathematical model. The feasibility of this model was validated. The average early diastolic velocity of the mitral annulus assessed using tissue Doppler imaging was significantly attenuated in the elderly ([Formula: see text]: [Formula: see text] vs. [Formula: see text]; [Formula: see text]) and corresponded to the higher estimated wedge ([Formula: see text]) pressure ([Formula: see text] vs. [Formula: see text]; [Formula: see text]) in that cohort. E (Young's modulus) was calculated to describe the tensile elasticity of the myocardium. With the same intraventricular filling pressure, E was significantly higher in the elderly, especially those with [Formula: see text] values [Formula: see text]. Compared with diastolic dysfunction parameters, E also presented sentinel characteristics more sensitive for detecting early myocardial relaxation impairment, which indicates stiffer myocardium in aging hearts.ConclusionOur material and geometric mathematical model successfully described the stiffer myocardium in aging hearts with higher intraventricular pressure. Additional studies that compare individual differences, especially in health status, are needed to validate its application for detecting diastolic heart failure.

Dataset Information

Cardiac inflammation and diastolic dysfunction in hypercholesterolemic rabbits.

Publications

Cardiac inflammation and diastolic dysfunction in hypercholesterolemic rabbits.

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