Butein Inhibits Oxidative Stress Injury in Rats with Chronic Heart Failure via ERK/Nrf2 Signaling

Background. Chronic heart failure (CHF) is a serious heart disease resulting from cardiac dysfunction. Oxidative stress is an important factor in aging and disease. Butein, however, has antioxidant properties. To determine the effect of butein on oxidative stress injury in rats, a CHF rat model was established. Methods. The CHF rat model was induced by abdominal aortic coarctation (AAC). Rats in CHF+butein and sham+butein group were given 100 mg/kg butein via gavage every day to detect the effect of butein on oxidative stress injury and myocardial dysfunction. The cardiac structural and functional parameters, including the left ventricular end-systolic dimension (LVESD), the left ventricular end-diastolic dimension (LVEDD), the left ventricular ejection fraction (LVEF), and the left ventricular fractional shortening (LVFS), were measured. Oxidative stress was measured through the production of reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA). Cardiac injury markers like creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) were evaluated. Hematoxylin and eosin (H&E) staining was used to observe the myocardial cell morphology. The effect of butein on the extracellular signal-regulated kinase (ERK)/nuclear factor-E2 p45-related factor (Nrf2) signaling was confirmed by Western blot analysis. Results. Butein had a significant effect on CHF in animal models. In detail, butein inhibited oxidative stress, relieved cardiac injury, and alleviated myocardial dysfunction. Importantly, butein activated the ERK1/2 pathway, which contributed to Nrf2 activation and subsequent heme oxygenase-1 (HO-1) and glutathione cysteine ligase regulatory subunit (GCLC) induction. Conclusions. In this study, butein inhibits oxidative stress injury in CHF rat model via ERK/Nrf2 signaling pathway.

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Chronic Heart Failure in Rheumatoid Arthritis Patients (Part II): Difficulties of Diagnosis

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2018-14-6-879-886 ◽

2019 ◽

Vol 14 (6) ◽

pp. 870-878 ◽

Cited By ~ 2

Author(s):

D. S. Novikova ◽

H. V. Udachkina ◽

I. G. Kirillova ◽

T. V. Popkova

Keyword(s):

Rheumatoid Arthritis ◽

Heart Failure ◽

Chronic Heart Failure ◽

Ejection Fraction ◽

Natriuretic Peptides ◽

Myocardial Dysfunction ◽

Left Ventricular ◽

Myocardial Deformation ◽

Left Ventricular Ejection

Rheumatoid arthritis (RA) is characterized by a twofold increase in morbidity and mortality due to chronic heart failure (CHF). At the same time, the prevalence of CHF among RA patients is significantly underestimated. The aim of the review was to analyze the results of the main studies on the features of the clinical presentation of heart failure (HF) in RA patients, the role of visualization techniques and biomarkers in the diagnosis of HF and preclinical dysfunction of the myocardium. HF in patients with RA is characterized by a predominance of HF with a preserved left ventricular ejection fraction (LVEF). The use of clinical diagnostic criteria in RA patients can lead to both over- or underdiagnosis of CHF. Systolic dysfunction estimated by LVEF is rare in RA and does not reflect the real frequency of myocardial dysfunction. Echocardiography (ECHO-CG) with tissue Doppler echocardiography (TDE) and visualization of myocardial deformation, magnetic resonance imaging (MRI) of the heart in RA patients revealed a high frequency of HF with preserved ejection fraction, left ventricular remodeling and hypertrophy, pre-clinical systolic and diastolic dysfunction. Determination of natriuretic peptides is useful for verifying the diagnosis of HF and estimating the prognosis in this cohort, despite the possible decrease in the sensitivity and specificity of these indicators in RA patients. The review discusses the advantages of MRI of the heart, including quantitative T1 and T2 regimens, in the diagnosis of myocarditis, myocardial fibrosis, and myocardial perfusion disorders in RA patients. In order to verify the diagnosis of heart failure and detect pre-clinical myocardial dysfunction in RA patients, the determination of natriuretic peptides concentration should become part of the routine examination, beginning with the debut of the disease, along with the collection of a cardiological history, physical examination, ECHO-CT with TDE, and visualization of myocardial deformation. Evaluation of the quantitative characteristics of tissue according to MRI of the heart could improve the diagnosis of myocardial damage.

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Modern vision on the problem of chronic heart failure in the older persons

Russian Journal of Geriatric Medicine ◽

10.37586/2686-8636-1-2021-65-75 ◽

2021 ◽

pp. 65-75

Author(s):

V. N. Larina

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Primary Care Physicians ◽

Older Persons ◽

Clinical Symptoms ◽

Morphological Changes ◽

Myocardial Dysfunction ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction

Aim. To analyze the factors associated with the development of chronic heart failure (CHF) in older age and to evaluate possible approaches to managing outpatients.Material and methods. The search for domestic and foreign publications in Russian and international systems (PubMed, eLibrary, Medscape, etc.) for the last 0.5–15 years has been carried out. The analysis includes articles from the peer-reviewed literature.Results. During aging, a number of structural changes and changes at the cellular level occur in the cardiovascular system, predisposing to the development of myocardial dysfunction, which explains the variety of manifestations of heart failure and the prevalence of preserved left ventricular ejection fraction (LVEF). Involutional functional and morphological changes in organs and systems form multimorbidity and nonspecificity of clinical symptoms and signs. «Cross symptoms» of frailty and CHF often complicate the timely diagnosis of the heart failure. Medications used for the treatment of CHF in older and younger patients are similar, but when choosing a specific drug, caution should be exercised in the group of the most vulnerable patients: over the age of 85, in the first two weeks after discharge from the hospital and in the presence of frailty.Conclusion. Based on the available results of studies, it is necessary to be alert of primary care physicians regarding the presence of CHF with preserved LVEF in older persons with multimorbidity and geriatric syndromes. The therapeutic strategy for CHF older patients is complex and involves an individualized approach, depending on the clinical situation.

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Analysis of levels of oxidative stress markers depending on the left ventricular ejection fraction in patients with chronic heart failure

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2018-5-34-39 ◽

2018 ◽

Vol 17 (5) ◽

pp. 34-39

Author(s):

E. A. Polunina ◽

L. P. Voronina ◽

E. A. Popov ◽

O. S. Polunina

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Chronic Heart Failure ◽

Left Ventricular Ejection Fraction ◽

Ejection Fraction ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Control Group ◽

Sod Activity ◽

Ventricular Ejection Fraction

Aim.To study and analyze the levels of oxidative stress (OS) markers (malondialdehyde (MDA), superoxide dismutase (SOD), advanced oxidation protein products (AOPPs)) depending on the left ventricular ejection fraction (LVEF) and functional class (FC) in patients with chronic heart failure (CHF).Material and methods.We examined 60 somatically healthy individuals and 345 patients with CHF, which were divided into three main groups depending on the LVEF and subgroups depending on FC. The levels of OS markers were determined in blood serum — MDA, SOD and AOPPs.Results.In the group of patients with preserved LVEF and FC II-IV CHF, levels of MDA and AOPPs were statistically significantly higher, and the SOD level was lower compared to the control group. In the group of patients with moderately reduced and reduced LVEF, the levels of MDA and AOPPs were statistically significantly higher, and SOD activity was lower compared with the control group and the group of patients with CHF and preserved LVEF. In patients with CHF with higher FC, there was a statistically significant increase of MDA and AOPPs levels and decrease of SOD activity. The most pronounced changes in the levels of above-mentioned markers were recorded in patients with reduced LVEF. According to the correlation analysis a direct relationship between the levels of markers of the OS and clinical manifestations of the disease was found.Conclusion.Changes in levels of MDA, SOD and AOPPs in patients with CHF were detected already in the early stages of the disease compared with the control group. In patients with higher FC CHF and preserved, moderately reduced and reduced LVEF, a statistically significant increase in the levels of MDA and AOPPs and a decrease of SOD activity were observed. The most pronounced changes in the levels of the markers were indicated in patients with reduced LVEF.

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Efficacy of Vitamin D on Chronic Heart Failure Among Adults

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000487 ◽

2020 ◽

Vol 90 (1-2) ◽

pp. 49-58 ◽

Cited By ~ 1

Author(s):

Wang Chunbin ◽

Wang Han ◽

Cai Lin

Keyword(s):

Heart Failure ◽

Vitamin D ◽

Chronic Heart Failure ◽

Left Ventricular Ejection Fraction ◽

Confidence Interval ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Controlled Trials ◽

Ventricular Ejection Fraction ◽

Randomized Controlled

Abstract. Vitamin D deficiency commonly occurs in chronic heart failure. Whether additional vitamin D supplementation can be beneficial to adults with chronic heart failure remains unclear. We conducted a meta-analysis to derive a more precise estimation. PubMed, Embase, and Cochrane databases were searched on September 8, 2016. Seven randomized controlled trials that investigated the effects of vitamin D on cardiovascular outcomes in adults with chronic heart failure, and comprised 592 patients, were included in the analysis. Compared to placebo, vitamin D, at doses ranging from 2,000 IU/day to 50,000 IU/week, could not improve left ventricular ejection fraction (Weighted mean difference, WMD = 3.31, 95% confidence interval, CL = −0.93 to 7.55, P < 0.001, I2 = 92.1%); it also exerts no beneficial effects on the 6 minute walk distance (WMD = 18.84, 95% CL = −24.85 to 62.52, P = 0.276, I2 = 22.4%) and natriuretic peptide (Standardized mean difference, SMD = −0.39, 95% confidence interval CL = −0.48 to 0.69, P < 0.001, I2 = 92.4%). However, a dose-response analysis from two studies demonstrated an improved left ventricular ejection fraction with vitamin D at a dose of 4,000 IU/day (WMD = 6.58, 95% confidence interval CL = −4.04 to 9.13, P = 0.134, I2 = 55.4%). The results showed that high dose vitamin D treatment could potentially benefit adults with chronic heart failure, but more randomized controlled trials are required to confirm this result.

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A translational model of chronic heart failure in rats

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/0031-2991.2018.02.136-148 ◽

2018 ◽

pp. 136-148

Author(s):

С.А. Крыжановский ◽

И.Б. Цорин ◽

Е.О. Ионова ◽

В.Н. Столярук ◽

М.Б. Вититнова ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Chronic Heart Failure ◽

Left Ventricular ◽

Compensatory Hypertrophy ◽

Experimental Myocardial Infarction ◽

Left Ventricular Ejection ◽

Translational Model ◽

Innovative Drug ◽

Ventricular Ejection Fraction

Цель исследования - разработка трансляционной модели хронической сердечной недостаточности (ХСН) у крыс, позволяющей, с одной стороны, изучить тонкие механизмы, лежащие в основе данной патологии, а с другой стороны, выявить новые биомишени для поиска и изучения механизма действия инновационных лекарственных средств. Методика. Использован комплекс эхокардиографических, морфологических, биохимических и молекулярно-биологических исследований, позволяющий оценивать и дифференцировать этапы формирования ХСН. Результаты. Динамические эхокардиографические исследования показали, что ХСН формируется через 90 дней после воспроизведения переднего трансмурального инфаркта миокарда. К этому времени у животных основной группы отмечается статистически значимое по сравнению со 2-ми сут. после воспроизведения экспериментального инфаркта миокарда снижение ФВ левого желудочка сердца (соответственно 55,9 ± 1,4 и 63,9 ± 1,6%, р = 0,0008). Снижение насосной функции сердца (на 13% по сравнению со 2-ми сут. после операции и на ~40% по сравнению с интактными животными) сопровождается увеличением КСР и КДР (соответственно с 2,49 ± 0,08 до 3,91 ± 0,17 мм, р = 0,0002, и с 3,56 ± 0,11 до 5,20 ± 0,19 мм, р = 0,0001), то есть к этому сроку развивается сердечная недостаточность. Результаты эхокардиографических исследований подтверждены данными морфометрии миокарда, продемонстрировавшими дилатацию правого и левого желудочков сердца. Параллельно проведенные гистологические исследования свидетельствуют о наличии патогномоничных для данной патологии изменений миокарда (постинфарктный кардиосклероз, компенсаторная гипертрофия кардиомиоцитов, очаги исчезновения поперечной исчерченности мышечных волокон и т.д.) и признаков венозного застоя в легких и печени. Биохимические исследования выявили значимое увеличение концентрации в плазме крови биохимического маркера ХСН - мозгового натрийуретического пептида. Данные молекулярно-биологических исследований позволяют говорить о наличии гиперактивности ренин-ангиотензин-альдостероновой и симпатоадреналовой систем, играющих ключевую роль в патогенезе ХСН. Заключение. Разработана трансляционная модель ХСН у крыс, воспроизводящая основные клинико-диагностические критерии этого заболевания. Показано наличие корреляции между морфометрическими, гистологическими, биохимическими и молекулярными маркерами прогрессирующей ХСН и эхокардиографическими диагностическими признаками, что позволяет использовать неинвазивный метод эхокардиографии, характеризующий состояние внутрисердечной гемодинамики, в качестве основного критерия оценки наличия/отсутствия данной патологии. Aim. Development of a translational model for chronic heart failure (CHF) in rats to identify new biotargets for finding and studying mechanisms of innovative drug effect in this disease. Methods. A set of echocardiographic, morphological, biochemical, and molecular methods was used to evaluate and differentiate stages of CHF development. Results. Dynamic echocardiographic studies showed that CHF developed in 90 days after anterior transmural myocardial infarction. By that time, left ventricular ejection fraction was significantly decreased in animals of the main group compared with rats studied on day 2 after experimental myocardial infarction (55.9 ± 1.4% vs . 63.9 ± 1.6%, respectively, p<0.0008). The decrease in heart’s pumping function (by 13% compared with day 2 after infarction and by approximately 40% compared to intact animals) was associated with increased ESD and EDD (from 2.49 ± 0.08 to 3.91 ± 0.17 mm, p = 0.0002, and from 3.56 ± 0.11 to 5.20 ± 0.19 mm, respectively, p = 0.0001); therefore, heart failure developed by that time. The results of echocardiographic studies were confirmed by myocardial morphometry, which demonstrated dilatation of both right and left ventricles. Paralleled histological studies indicated presence of the changes pathognomonic for this myocardial pathology (postinfarction cardiosclerosis, compensatory hypertrophy of cardiomyocytes, foci of disappeared transverse striation of muscle fibers, etc.) and signs of venous congestion in lungs and liver. Biochemical studies demonstrated a significant increase in plasma concentration of brain natriuretic peptide, a biochemical marker of CHF. Results of molecular studies suggested hyperactivity of the renin-angiotensin-aldosterone and sympathoadrenal systems, which play a key role in the pathogenesis of CHF. Conclusions. A translational model of CHF in rats was developed, which reproduced major clinical and diagnostic criteria for this disease. Morphometric, histological, biochemical, and molecular markers for progressive CHF were correlated with echocardiographic diagnostic signs, which allows using this echocardiographic, noninvasive method characterizing the intracardiac hemodynamics as a major criterion for the presence / absence of this pathology.

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