Anticytokine therapy alleviates oxidative stress and attenuates left ventricular remodeling in experimental heart failure

Abstract Heart failure is a clinical syndrome that appears as a consequence of a structural disease, and the most common cause of left ventricular systolic dysfunction results from myocardial ischemia. Cardiac remodeling and neuroendocrine activation are the major compensatory mechanisms in heart failure. The main objective of the study is to identify the association between serum biomarkers illustrating the extent of myocardial necrosis (highly sensitive troponin as-says), left ventricular dysfunction (NT-proBNP), and systemic inflammatory response (illustrated via serum levels of hsCRP and interleukins) during the acute phase of a myocardial infarction, and the left ventricular remodeling process at 6 months following the acute event, quantified via speckle tracking echocardiography. The study will include 400 patients diagnosed with acute myocardial infarction without signs and symptoms of heart failure at the time of enrollment that will undergo a complex clinical examination and speckle tracking echocardiography. Serum samples from the peripheral blood will be collected in order to determine the inflammatory serum biomarkers. After 6 months, patients will be divided into 2 groups according to the development of ventricular remodeling, quantified by speckle tracking echocardiography: group 1 will consist of patients with a remodeling index lower than 15%, and group 2 will consist of patients with a remodeling index higher than 15%. All clinical and imaging data obtained at the baseline will be compared between these two groups in order to determine the features associated with a higher risk of deleterious ventricular remodeling and heart failure.

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The Pattern of Ventricular Remodeling Influences the Level of Oxidative Stress in Heart Failure Patients

Revista de Chimie ◽

10.37358/rc.17.7.5705 ◽

2017 ◽

Vol 68 (7) ◽

pp. 1506-1511

Author(s):

Cerasela Mihaela Goidescu ◽

Anca Daniela Farcas ◽

Florin Petru Anton ◽

Luminita Animarie Vida Simiti

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Ventricular Remodeling ◽

Clinical Laboratory ◽

Left Ventricular ◽

Control Group ◽

Reactive Protein ◽

Lv Mass ◽

Few Data

Oxidative stress (OS) is increased in chronic diseases, including cardiovascular (CV), but there are few data on its effects on the heart and vessels. The isoprostanes (IsoP) are bioactive compounds, with 8-iso-PGF25a being the most representative in vivo marker of OS. They correlate with the severity of heart failure (HF), but because data regarding OS levels in different types of HF are scarce, our study was aimed to evaluate it by assessing the urinary levels of 8-iso-PGF2aand its correlations with various biomarkers and parameters. Our prospective study included 53 consecutive patients with HF secondary to ischemic heart disease or dilative cardiomyopathy, divided according to the type of HF (acute, chronic decompensated or chronic compensated HF). The control group included 13 hypertensive patients, effectively treated. They underwent clinical, laboratory - serum NT-proBNP, creatinine, uric acid, lipids, C reactive protein (CRP) and urinary 8-iso-PGF2a and echocardiographic assessment. HF patients, regardless the type of HF, had higher 8-iso-PGF2a than controls (267.32pg/�mol vs. 19.82pg/�mol, p[0.001). The IsoP level was directly correlated with ejection fraction (EF) (r=-0.31, p=0.01) and NT-proBNP level (r=0.29, p=0.019). The relative wall thickness (RWT) was negatively correlated with IsoP (r=-0.55, p[0.001). Also 8-iso-PGF25a was higher by 213.59pg/�mol in the eccentric left ventricular (LV) hypertrophy subgroup comparing with the concentric subgroup (p=0.014), and the subgroups with severe mitral regurgitation (MR) and moderate/severe pulmonary hypertension (PAH) had the highest 8-iso-PGF2a levels. Male sex, severe MR, moderate/severe PAH, high LV mass and low RWT values were predictive for high OS level in HF patients.Eccentric cardiac remodeling, MR severity and PAH severity are independent predictors of OS in HF patients.

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Severity of left ventricular remodeling defines outcomes and response to therapy in heart failure

ACC Current Journal Review ◽

10.1016/j.accreview.2004.08.034 ◽

2004 ◽

Vol 13 (9) ◽

pp. 26

Author(s):

M. Wong ◽

Staszewsky ◽

R. Latini

Keyword(s):

Heart Failure ◽

Ventricular Remodeling ◽

Left Ventricular Remodeling ◽

Left Ventricular ◽

Response To Therapy

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Importance of antioxidant and antiapoptotic effects of β-receptor blockers in heart failure therapy

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00797.2003 ◽

2004 ◽

Vol 287 (3) ◽

pp. H1003-H1012 ◽

Cited By ~ 55

Author(s):

Keisuke Kawai ◽

Fuzhong Qin ◽

Junya Shite ◽

Weike Mao ◽

Shuji Fukuoka ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Ventricular Remodeling ◽

Diastolic Pressure ◽

Cardiac Pacing ◽

Left Ventricular ◽

Beneficial Effects ◽

Myocyte Apoptosis ◽

Adrenergic Blocking ◽

Fractional Shortening

The present study was carried out to determine whether beneficial effects of carvedilol in congestive heart failure (CHF) are mediated via its β-adrenergic blocking, antioxidant, and/or α-adrenergic blocking action. Rabbits with heart failure induced by rapid cardiac pacing were randomized to receive subcutaneous carvedilol, metoprolol, propranolol plus doxazosin, or placebo pellets for 8 wk and compared with sham-operated rabbits without pacing. We found rapid cardiac pacing produced clinical heart failure, left ventricular dilation, and decline of left ventricular fractional shortening. This was associated with an increase in left ventricular end-diastolic pressure, decrease in left ventricular first derivative of left ventricular pressure, and myocyte hypertrophy. Tissue oxidative stress measured by GSH/GSSG was increased in the heart with increased oxidation product of mitochondrial DNA, 8-oxo-7,8-dihydro-2′-deoxyguanosine, increase of Bax, decrease of Bcl-2, and increase of apoptotic myocytes as measured by anti-single-stranded DNA monoclonal antibody. Administration of carvedilol and metoprolol, which had no effect in sham animals, attenuated cardiac ventricular remodeling, cardiac hypertrophy, oxidative stress, and myocyte apoptosis in CHF. In contrast, propranolol plus doxazosin, which has less antioxidant effects, produced smaller effects on left ventricular function and myocyte apoptosis. In all animals, GSH/GSSG correlated significantly with changes of left ventricular end-diastolic dimension ( r = −0.678, P < 0.0001), fractional shortening ( r = 0.706, P < 0.0001), and apoptotic myocytes ( r = −0.473, P = 0.0001). Thus our findings suggest antioxidant and antiapoptotic actions of carvedilol and metoprolol are important determinants of clinical beneficial effects of β-receptors in the treatment of CHF.

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