scholarly journals Shenlijia Attenuates Doxorubicin-Induced Chronic Heart Failure by Inhibiting Cardiac Fibrosis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xutao Sun ◽  
Yunjia Song ◽  
Ying Xie ◽  
Jieru Han ◽  
Fei Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cardiac Function ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Heart Function ◽  
Left Ventricular ◽  
Protein Chip ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Application of the anticancer drug doxorubicin (DOX) is restricted due to its adverse, cardiotoxic side effects, which ultimately result in heart failure. Moreover, there are a limited number of chemical agents for the clinical prevention of DOX-induced cardiotoxicity. Based on the theories of traditional Chinese medicine (TCM) on chronic heart failure (CHF), Shenlijia (SLJ), a new TCM compound, has been developed to fulfill multiple functions, including improving cardiac function and inhibiting cardiac fibrosis. In the present study, the protective effects and molecular mechanisms of SLJ on DOX-induced CHF rats were investigated. The CHF rat model was induced by intraperitoneal injection of DOX for six weeks with the cumulative dose of 15 mg/kg. All rats were then randomly divided into the control, CHF, CHF + SLJ (3.0 g/kg per day), and CHF + captopril (3.8 mg/kg per day) groups and treated for further four weeks. Echocardiography and the assessment of hemodynamic parameters were performed to evaluate heart function. A protein chip was applied to identify proteins with diagnostic values that were differentially expressed following SLJ treatment. The data from these investigations showed that SLJ treatment significantly improved cardiac function by increasing the left ventricular ejection fraction, improving the hemodynamic index, and inhibiting interstitial fibrosis. Protein chip analysis revealed that SLJ upregulated MCP-1, MDC, neuropilin-2, TGF-β3, thrombospondin, TIE-2, EG-VEGF/PK1, and TIMP-1/2/3 expressions and downregulated that of MMP-13. In addition, immunohistochemistry and western blot results further confirmed that SLJ promoted TIMP-1/2/3 and inhibited MMP-13 expression. The results of the present study suggest that SLJ was effective against DOX-induced CHF rats and is related to the improvement of heart function and ultrastructure and the inhibition of myocardial fibrosis.

Efficacy of Vitamin D on Chronic Heart Failure Among Adults

2020 ◽  
Vol 90 (1-2) ◽  
pp. 49-58 ◽  
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.

A translational model of chronic heart failure in rats

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.

scholarly journals A Randomized Controlled Trial to Study the Effect of Yoga Therapy on Cardiac Function and N Terminal Pro BNP in Heart Failure

2014 ◽  
Vol 9 ◽  
pp. IMI.S13939 ◽  
Author(s):  
Bandi Hari Krishna ◽  
Pravati Pal ◽  
G. K. Pal ◽  
J. Balachander ◽  
E. Jayasettiaseelon ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Medical Therapy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Tei Index ◽  
Ventricular Ejection Fraction ◽  
Yoga Therapy ◽  
Standard Medical Therapy

Aims The purpose of this study was to evaluate whether yoga training in addition to standard medical therapy can improve cardiac function and reduce N terminal pro B-type natriuretic peptide (NT pro BNP) in heart failure (HF). Methods 130 patients were recruited and randomized into two groups: Control Group (CG) ( n = 65), Yoga Group (YG). In YG, 44 patients and in CG, 48 patients completed the study. Cardiac function using left ventricular ejection fraction (LVEF), myocardial performance index (Tei index), and NT pro BNP, a biomarker of HF, was assessed at baseline and after 12 weeks. Result Improvement in LVEF, Tei index, and NT pro BNP were statistically significant in both the groups. Furthermore, when the changes in before and after 12 weeks were in percentage, LVEF increased 36.88% in the YG and 16.9% in the CG, Tei index was reduced 27.87% in the YG and 2.79% in the CG, NT pro BNP was reduced 63.75% in the YG and 10.77% in the CG. The between group comparisons from pre to post 12 weeks were significant for YG improvements (LVEF, P < 0.01, Tei index, P < 0.01, NT pro BNP, P < 0.01). Conclusion These results indicate that the addition of yoga therapy to standard medical therapy for HF patients has a markedly better effect on cardiac function and reduced myocardial stress measured using NT pro BNP in patients with stable HF.

Abstract 1213: Cardiac Overexpression of Epac1 in Transgenic Mice Protects Heart from Lipopolysaccharide-induced Cardiac Dysfunction and Inhibits JAK-STAT Pathway

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Satoshi Okumura ◽  
Yunzhe Bai ◽  
Meihua Jin ◽  
Sayaka Suzuki ◽  
Akiko Kuwae ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cyclic Amp ◽  
Transgenic Mice ◽  
Cardiac Function ◽  
Proinflammatory Cytokines ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Stat Pathway

The sympathetic nervous system and proinflammatory cytokines are believed to play independent roles in the pathophysiology of heart failure. However, the recent identification of Epac (exchange protein activated by cyclic AMP), a new cyclic AMP-binding protein that directly activates Rap1, have implicated that there may be a potential cross talk between the sympathetic and cytokine signals. In order to examine the role of Epac in cytokine signal to regulate cardiac function, we have generated transgenic mice expressing the human Epac1 gene under the control of alpha-cardiac myosin heavy chain promoter (Epac1-TG), and examined their response in lipopolysaccharide (LPS)-induced cardiac dysfunction, a well established model for sepsis-induced cardiac dysfunction. Sepsis-induced cardiac dysfunction results from the production of proinflammatory cytokines. At baseline, left ventricular ejection fraction (LVEF) was similar (TG vs. NTG, 67±1.7 vs. 69±2.1%, n =7–9). The degree of cardiac hypertrophy (LV(mg)/tibia(mm)) was also similar at 3 months old (TG vs. NTG 4.0±0.1 vs. 4.2±0.1, n =5–6), but it became slightly but significantly greater in Epac1-TG at 5 month old (TG vs. NTG 4.9±0.1 vs. 4.4±0.1, p< 0.05, n =5–7). LPS (5mg/kg) elicited a significant and robust reduction of LVEF in both Epac1-TG and NTG, but the magnitude of this decrease was much less in Epac1-TG at 6 hr after injection (TG vs. NTG 48±2.4 vs. 57±1.8%, p< 0.01, n =6–9). At 24 hr after injection, cardiac function was restored to the baseline in both Epac1-TG and NTG. We also examined the activation of JAK-STAT pathway at 24 hr after injection. The tyrosine phosphorylation of STAT1 (Tyr701) and STAT3 (Tyr705) in LV, which is an indicator of STAT activation, was reduced to a greater degree in Epac1-TG by 31±8.8% ( p< 0.05, n =4) and 29±5.9% ( p< 0.05, n =7), respectively, relative to that in NTG. Taken together, Epac1 protects the heart from the cytokine-induced cardiac dysfunction, at least in part, through the inhibition of the JAK-STAT pathway, suggesting the beneficial role played by sympathetic signal to antagonize proinflammatory cytokine signal in heart failure.

Abstract 3791: Improved Ventricular-Arterial Coupling After 4 Weeks of Exercise Training in Patients with Chronic Heart Failure

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Marcus Sandri ◽  
Stephan Gielen ◽  
Norman Mangner ◽  
Volker Adams ◽  
Sandra Erbs ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Exercise Training ◽  
Endothelial Function ◽  
Training Group ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Lv Function ◽  
Ventricular Ejection Fraction

Background: The concept of ventricular-arterial coupling implies that LV-function is determined by the three factors left ventricular diastolic, left ventricular systolic and arterial elastance. We have previously documented an improvement in endothelial function and systolic LV-function in patients with chronic heart failure (CHF) after 6 months of exercise training (ET). It remains, however, unclear, how shorter ET periods may affect endothelial, systolic and diastolic ventricular function as echocardiographic parameters related to ventricular arterial coupling in patients with CHF. METHODS: In this ongoing study we randomised 43 patients with stable CHF (age 60.3 ± 2.9 years, EF 27.4 ± 1.7%, VO 2 max 14.7 ± 4.3ml/kg*min) to a training or a control group (C). Patients in the training group exercised 4 times daily at 70% of the individual heart rate reserve for 4 weeks under supervision. At baseline and after 4 weeks the E/A ratio and septal/lateral E’/A’ velocities were determined by echocardiography with tissue Doppler. Exercise capacity was measured by ergospirometry and flow-mediated dilatation (FMD) was assessed by high-resolution radial ultrasound. RESULTS: After only 4 weeks of ET oxygen uptake at peak exercise increased from 14.9 ± 3.3 to 18.1 ± 4.7 ml/min/kg, (p<0.01 vs. C) in training subjects. Left ventricular ejection fraction improved from 26.8 ± 4.6 to 33.1 ± 5.5% (p<0.05 vs. C) in patients of the training group while it remained unchanged in the control group. E/A-ratio mended from 0.63 ± 0.12 to 0.81 ± 0.22 (p<0.01 vs. C) in training patients. Septal E’ velocities increased from 5.5 ± 0.5 to 7.8 ± 1.4 cm/s in training patients (p<0.05 vs. C). FMD of the radial artery improved from 8.2 ± 2.1 to 15.2 ± 3.8% (p<0.01 vs. C) as a result of ET. CONCLUSIONS: Only 4 weeks of endurance training are highly effective with significantly improved FMD accompanied by an emended systolic and diastolic LV-function. We hypothesise that the improvement in LV-EF in training patients may be caused by a corrected ventricular-arterial coupling: ventricular diastolic relaxation and effective endothelial function are ameliorated resulting in an augmentation of stroke volume.

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