Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure

2011 ◽  
Vol 301 (2) ◽  
pp. H459-H468 ◽  
Author(s):  
Meimei Yin ◽  
Iwan C. C. van der Horst ◽  
Joost P. van Melle ◽  
Cheng Qian ◽  
Wiek H. van Gilst ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Oral Glucose ◽  
Mrna Levels ◽  
Ventricular Ejection Fraction ◽  
Glucose Levels ◽  
First Choice

Metformin is the first choice drug for the treatment of patients with diabetes, but its use is debated in patients with advanced cardiorenal disease. Epidemiological data suggest that metformin may reduce cardiac events, in patients both with and without heart failure. Experimental evidence suggests that metformin reduces cardiac ischemia-reperfusion injury. It is unknown whether metformin improves cardiac function (remodeling) in a long-term post-MI remodeling model. We therefore studied male, nondiabetic, Sprague-Dawley rats that were subjected to either myocardial infarction (MI) or sham operation. Animals were randomly allocated to treatment with normal water or metformin-containing water (250 mg·kg−1·day−1). At baseline, 6 wk, and 12 wk, metabolic parameters were analyzed and oral glucose tolerance tests (OGTT) were performed. Echocardiography and hemodynamic parameters were assessed 12 wk after MI. In the MI model, infarct size was significantly smaller after 12-wk metformin treatment (29.6 ± 3.2 vs. 38.0 ± 2.2%, P < 0.05). Moreover, metformin resulted in less left ventricular dilatation (6.0 ± 0.4 vs. 7.6 ± 0.6 mm, P < 0.05) and preservation of left ventricular ejection fraction (65.8 ± 3.7% vs. 48.6 ± 5.6%, P < 0.05) compared with MI control. The improved cardiac function was associated with decreased atrial natriuretic peptide mRNA levels in the metformin-treated group (50% reduction compared with MI, P < 0.05). Insulin resistance did not occur during cardiac remodeling (as indicated by normal OGTT) and fasting glucose levels and the pattern of the OGTT were not affected by metformin. Molecular analyses suggested that altered AMP kinase phosphorylation status and low insulin levels mediate the salutary effects of metformin. Altogether our results indicate that metformin may have potential to attenuate heart failure development after myocardial infarction, in the absence of diabetes and independent of systemic glucose levels.

scholarly journals Velvet Antler Ameliorates Cardiac Function by Restoring Sarcoplasmic Reticulum Ca2+-ATPase Activity in Rats With Heart Failure After Myocardial Infarction

2021 ◽  
Vol 12 ◽  
Author(s):  
Haoyue Shi ◽  
Tianzi Zhao ◽  
Yanjun Li ◽  
Xiang Xiao ◽  
Jiayun Wu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Protein Expression ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Histopathological Analysis ◽  
Mrna Levels ◽  
Ventricular Ejection Fraction ◽  
Velvet Antler

Objective: Velvet antler (VA; cornu cervi pantotrichum), a well-known traditional Chinese medicine, has been shown to exert cardioprotective effects. The purpose of this study was to investigate the effect of VA on heart failure (HF) caused by ischemia-reperfusion, and explore its possible mechanism from the regulation of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2 alpha (SERCA2a).Methods: A rat model of HF was established by ligating the left anterior descending coronary artery of male Sprague–Dawley rats (n = 88). One week after surgery, VA (200, 400, or 800 mg/[kg day−1]) or enalapril (1 mg/[kg day−1]) was administered daily for the next 4 weeks. Heart function was detected by echocardiography and histopathological analysis. The serum BNP level was measured by ELISA, and the expression of SERCA2a, PLB, PLB-Ser16, and PKA was determined by western blotting. SERCA2a and PLB mRNA levels were determined by real-time quantitative PCR.Results: Compared with the sham group, cardiac function in the HF group, including the serum BNP level, heart mass index, myocardial collagen deposition, and left ventricular ejection fraction, was markedly reduced; however, these changes could be reversed by VA treatment. In addition, VA (200 mg/[kg·d−1]) inhibited the decrease of SERCA2a and PLB mRNA levels and SERCA2a, PLB, PLB-Ser16, and PKA protein expression and restored the activity of SERCA2a and PKA. Enalapril affected only PLB protein expression.Conclusion: VA can improve myocardial fibrosis and ventricular remodeling in rats, thereby helping to restore cardiac function. The underlying mechanism may be related to the upregulation of the expression and activation of PKA and PLB and the restoration of the expression and activity of SERCA2a.

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.

scholarly journals Long-term clinical prognosis predictors in patients with chronic heart failure and reduced left ventricular ejection fraction

2019 ◽  
Vol 26 (5) ◽  
pp. 33-43 ◽  
Author(s):  
L. G. Voronkov ◽  
К. V. Voitsekhovska ◽  
S. V. Fedkiv ◽  
T. I. Gavrilenko ◽  
V. I. Koval
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Left Atrium ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
C Reactive Protein ◽  
Ventricular Ejection Fraction ◽  
Reactive Protein ◽  
Vasodilator Response

The aim – to identify prognostic factors for the development of adverse cardiovascular events (death and hospitalization) in patients with chronic heart failure (CHF) and left ventricular ejection fraction (LVEF) ≤ 35 % after long-term observation. Materials and methods. 120 stable patients with CHF, aged 18–75, II–IV functional classes according to NYHA, with LVEF ≤ 35 % were examined. Using multiple logistic regression according to the Cox method, we analyzed independent factors that affect the long-term prognosis of patients with heart failure. Results and discussion. During the observation period, out of 120 patients, 61 patients reached combined critical point (CCР). In the univariate regression model, predictors of CCР reaching were NYHA functional class, weigh loss of ≥ 6 % over the past 6 months, systolic and diastolic blood pressure, patient’s history of myocardial infarction, angina pectoris, anemia, number of hospitalizations over the past year and parameters reflecting the functional state of the patient (6-minute walk distance, number of extensions of the lower limb). The risk of CCP developing is significantly higher in patients with lower body mass index, shoulder circumference of a tense and unstressed arm, hip, thickness of the skin-fat fold over biceps and triceps, estimated percentage of body fat. Рredictors CCP reaching are higher levels of uric acid and C-reactive protein. Echocardiographic predictors of CCP onset were LVEF, size of the left atrium, TAPSE score, as well as its ratio to systolic pressure in the pulmonary artery, index of final diastolic pressure in the left ventricle. Also, the risk of CCP reaching is greater at lower values of the flow-dependent vasodilator response. Independent predictors of CCP onset were the circumference of the shoulder of an unstressed arm, the level of C-reactive protein in the blood, and the rate of flow-dependent vasodilator response. When analyzing the indices in 77 patients, who underwent densitometry, it was revealed that the E/E´ index, the index of muscle tissue of the extremities, the index of fat mass, and the ratio of fat mass to growth affect CCP reaching. In a multivariate analysis, taking into account densitometry indices, independent predictors of CCP onset were the size of the left atrium, the index of muscle mass of the extremities, the rate of flow-dependent vasodilator response and the presence of myocardial infarction in anamnesis. Conclusions. Independent predictors of CCP reaching in patients with CHF and LVEF ≤ 35 % are myocardial infarction in anamnesis, lower arm circumference of the arm, limb muscle mass index, flow-dependent vasodilator response, higher levels of C-reactive protein, sizes of the left atrium.

scholarly journals Systematic Review of Compound Danshen Dropping Pill: A Chinese Patent Medicine for Acute Myocardial Infarction

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Jing Luo ◽  
Hao Xu ◽  
Keji Chen
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Cardiac Death ◽  
Data Extraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Quality Of Evidence

Objective. This paper systematically evaluated the efficacy and safety of compound Danshen dropping pill (CDDP) in patients with acute myocardial infarction (AMI).Methods. Randomized controlled trials (RCTs), comparing CDDP with no intervention, placebo, or conventional western medicine, were retrieved. Data extraction and analyses were conducted in accordance with the Cochrane standards. We assessed risk of bias for each included study and evaluated the strength of evidence on prespecified outcomes.Results. Seven RCTs enrolling 1215 patients were included. CDDP was associated with statistically significant reductions in the risk of cardiac death and heart failure compared with no intervention based on conventional therapy for AMI. In addition, CDDP was associated with improvement of quality of life and impaired left ventricular ejection fraction. Nevertheless, the safety of CDDP was unproven for the limited data. The quality of evidence for each outcome in the main comparison (CDDP versus no intervention) was “low” or “moderate.”Conclusion. CDDP showed some potential benefits for AMI patients, such as the reductions of cardiac death and heart failure. However, the overall quality of evidence was poor, and the safety of CDDP for AMI patients was not confirmed. More evidence from high quality RCTs is warranted to support the use of CDDP for AMI patients.

Heart failure is a common complication after acute myocardial infarction in patients with diabetes: A nationwide study in the SWEDEHEART registry

2020 ◽  
Vol 27 (17) ◽  
pp. 1890-1901 ◽  
Author(s):  
Viveca Ritsinger ◽  
Thomas Nyström ◽  
Nawsad Saleh ◽  
Bo Lagerqvist ◽  
Anna Norhammar
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Common Complication ◽  
Ventricular Ejection Fraction ◽  
Patients With Diabetes

Background Several glucose lowering drugs with preventive effects on heart failure and death have entered the market, however, still used in low proportions after acute myocardial infarction. We explored the complication rates of heart failure and death after acute myocardial infarction in patients with and without diabetes. Methods All patients ( N = 73,959) with acute myocardial infarction admitted for coronary angiography included in the SWEDEHEART registry during the years 2012–2017 were followed for heart failure (until 31 December 2017) and mortality (until 30 June 2018); mean follow-up time 1223 (SD ± 623) days. Results Mean age was 69 years (SD ± 12), 69% were male and 24% had diabetes. Heart failure occurred more often in diabetes (22% vs. 12% if no diabetes), especially if previous MI (33% vs. 23%). Patients with diabetes had increased risk of HF regardless of previous myocardial infarction (MI); with previous MI adjusted hazard ratio 2.09 (95% confidence interval 1.96–2.20) and without MI 1.52 (1.44–1.61) respectively when non-diabetes patients with first MI served as reference. In patients with no previous heart failure or MI and discharged with left ventricular ejection fraction ≥50% the risk of heart failure was particularly high in those with diabetes (1.56; 1.39–1.76) when compared with those without. Similar findings were seen for death and combined event (heart failure and death). Conclusions Heart failure is a common complication after acute myocardial infarction in diabetes, increasing the risk by 50–60% regardless of previous heart failure or MI. This risk is present even with normal reported left ventricular ejection fraction, indicating the existence of a large diabetes population at heart failure risk after acute myocardial infarction.

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