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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pro-inflammatory cytokine, tumor necrosis factor alpha (TNF alpha), in concert with neurohormones, contributes to chronic heart failure (CHF) progression. This implies that TNF a antagonism may constitute an important target for CHF therapy. However, clinical trials in CHF patients using compounds that trap TNF alpha, comprising infliximab, an antibody directed to TNF alpha, and etanercept, a soluble recombinant receptor of TNF alpha, gave disappointing results bringing back to light the dual, short-term beneficial and long-term harmful effect of TNF alpha. This review focuses on the dual, concentration- and time-related effects of TNF alpha, the yin and yang action of TNF alpha in cardiac ischemia/reperfusion and contraction. Importantly, the harmful effects of TNF a are related to glutathione deficiency, a common hallmark to several other chronic inflammatory diseases. Recently, in rat models of CHF, oral administration of the glutathione precursor, N-acetylcysteine (NAC), was shown to hinder pathways of TNF alpha harmful signalling and to rescue cardiac structure and function. These results suggest that glutathione deficiency in association with TNF alpha activation may play a role in the pathophysiology of CHF and that NAC may represent a potential therapy in CHF.
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PMID:Tumor necrosis factor alpha and glutathione interplay in chronic heart failure. 1623 78

Renal dysfunction is a constant feature of congestive heart failure and is a stronger predictor of mortality than left ventricular ejection fraction or New York Heart Association classification. In heart failure, a reduction of glomerular filtration rate and renal plasma flow occurs, although the filtration fraction increases. There are many reason for this pattern. A reduction in effective circulating volume stimulates sympathetic activity and the renin-angiotensin-aldosterone system, and it is associated with increased concentrations of atrial natriuretic peptide, brain natriuretic peptide, and tumor necrosis factor alpha. Because in chronic kidney disease heart dysfunction commonly is present, an efficient cardiologist-nephrologist interaction should be promoted.
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PMID:The kidney in heart failure. 1629 63

Studies of cardiac pathology and heart failure have implicated cardiomyocyte apoptosis as a critical determinant of disease. Recent evidence indicates that the intracellular protozoan parasite Trypanosoma cruzi, which causes heart disease in chronically infected individuals, impinges on host apoptotic pathways in a cell type-dependent manner. T. cruzi infection of isolated neuronal cells and cardiomyocytes protects against apoptotic cell death, whereas apoptosis is triggered in T cells in T. cruzi-infected animals. In this study, we demonstrate that the ability of T. cruzi to protect cardiac cells in vitro from apoptosis triggered by a combination of tumor necrosis factor alpha and serum reduction correlates with the presence of intracellular parasites and involves activation of host cell NF-kappaB. We further demonstrate that the apoptotic block diminishes activation of caspase 3. The ability of T. cruzi to prevent apoptosis of infected cardiomyocytes is likely to play an important role in establishment of persistent infection in the heart while minimizing potential damage and remodeling that is associated with cardiomyocyte apoptosis in cardiovascular disease.
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PMID:Trypanosoma cruzi infection and nuclear factor kappa B activation prevent apoptosis in cardiac cells. 1649 29

A component of multiorgan dysfunction in burned patients is heart failure. Burn trauma induces cytokine synthesis of interleukin (IL) 1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) which can negatively impact cardiac function. Infectious complications are common following severe burn injury. We hypothesized that burn injury and lipopolysaccharide (LPS) exposure independently influence peak cardiomyocyte contraction and cytokine secretion. Rats underwent a full-thickness 30% total body surface area scald or sham burn. At 1, 6, 12, and 24 h after burn, cardiomyocytes were isolated and incubated with increasing LPS doses. Peak sarcomere shortening and contractile velocity parameters were recorded using a variable-rate video camera with sarcomere length detection software. Supernatants were assayed for IL-1beta, IL-6, and TNF-alpha by ELISA. Peak sarcomere shortening was decreased in the burn group at 1, 6, 12, and 24 h after burn. IL-1beta, IL-6, and TNF-alpha levels were increased in cardiomyocytes isolated 1 h after burn compared with sham controls, but returned to sham levels at 6, 12, and 24 h after burn. LPS exposure caused dose-dependent decreases in sarcomere shortening in sham and burn animals. LPS exposure did not produce increased cardiomyocyte cytokine expression. Burn injury diminished peak sarcomere shortening. Whereas exposure to LPS did not have an effect on cardiomyocyte cytokine expression, LPS significantly inhibited sarcomere shortening in a dose-dependent fashion. Combined burn and LPS exposure inhibited sarcomere shortening more than each alone. These results demonstrate that LPS exposure and burn injury independently decrease peak cardiac shortening. These decreases did not directly correlate with the levels of cytokines released in response to each stressor.
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PMID:Cardiomyocyte function after burn injury and lipopolysaccharide exposure: single-cell contraction analysis and cytokine secretion profile. 1652 57

The degree of structural and functional heart changes was evaluated by means of Doppler echocardiography in 120 patients with chronic obstructive pulmonary disease (COPD) of different degrees of severity. Conventional immunological laboratory techniques were used in all the patients to evaluate the condition of cell-mediated, humoral, and cytokine-mediated immunity; inflammatory process activity and the degree of endotoxicosis were evaluated by measuring blood levels of acute phase proteins and medium mass molecules. The study showed that the character of heart remodeling depended on COPD severity. Only severe COPD was associated with a significant right atrial enlargement, as well as structural and functional changes in the left heart. The results demonstrated a distinct correlation between the variables of structural and functional condition of the heart and immunity parameters in COPD patients. The variables of right and left ventricular function moderately correlated with inflammatory and endotoxicosis indices. Decompensation of patients with severe COPD and cor pulmonale is accompanied by a pronounced immunodeficiency. An increase in blood levels of cytokines, tumor necrosis factor alpha in particular, may serve as a marker of early stages of chronic heart failure, while an increase in blood levels of interleukin-6 may be a marker of its severity.
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PMID:[Cardiac remodeling in the light of immune status changes in patients with chronic obstructive pulmonary disease]. 1675 53

There has been increasing evidence that tumor necrosis factor alpha (TNF-alpha) is synthesized by cardiomyoctes and contributes to their impaired function and to cardiac failure. Because the Na(+)-K(+) ATPase is a key player in the contraction of cardiomyocytes, this work was undertaken to study the effect of TNF-alpha on the Na(+)-K(+) ATPase in rat heart. Sprague Dawley rats (Rattus norvegicus) were injected with TNF-alpha (270 ng/100 g body weight) and 4 h later the ventricles were isolated, homogenized and assayed for their Na(+)-K(+) ATPase activity. The effect of TNF-alpha on the pump was studied also in isolated myocytes treated in suspension. The involvement of PGE2 was investigated by pre-treating animals or cells with indomethacin, an inhibitor of COX enzymes. The involvement of NF-kappaB and AP-1 was studied using their respective inhibitors PDTC and curcumin. A time response study showed an increase in the activity of the Na(+)-K(+) ATPase in the left and right ventricles of animals treated with the cytokine, with no change in its protein expression. This effect disappeared in the presence of indomethacin suggesting an involvement of PGE(2) in the action of TNF-alpha. Rats and cells treated directly with PGE(2) showed a dose-dependent response. A decrease in the activity of the Na(+)-K(+) ATPase was observed at a low dose and an increase at a high dose in both ventricles. Since PGE(2) is suspected to be the active mediator in TNF-alpha signaling, inhibiting its synthesis by inhibiting some suspected transcription factors was attempted. PDTC abrogated fully, and curcumin partially the effect of the cytokine. It was concluded that TNF-alpha activates NF-kappaB and AP-1 and induces PGE(2) release which alters dose-dependently the activity of the pump by activating different EP receptors with different affinities for PGE(2).
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PMID:Tumor necrosis factor alpha alters Na+-K+ ATPase activity in rat cardiac myocytes: involvement of NF-kappaB, AP-1 and PGE2. 1702 35

Multiple lines of evidence support the "cytokine hypothesis," which suggests that inflammation plays an important role in the development and progression of heart failure. Circulating markers of inflammation, such as tumor necrosis factor alpha, interleukin 6, and C-reactive protein, may be useful in establishing the diagnosis, gauging prognosis, and evaluating the response to therapy in patients with heart failure. In addition to their potential as heart failure biomarkers, inflammatory cytokines have been investigated as targets of heart failure therapy. Although results for therapies directed against specific cytokines (such as tumor necrosis factor alpha) have thus far been disappointing, multiple studies continue to address the therapeutic potential of modulating the immune response in heart failure. In this review, the authors analyze available data supporting the use of inflammatory markers both as biomarkers and as potential therapeutic targets.
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PMID:Inflammatory biomarkers in heart failure. 1717 May 86

Recent epidemiological research indicates that a coexistent anemia among patients with heart failure might worsen their prognosis. However, whether the reduced synthesis of red blood cells is a contributing factor to the development and progression to overt heart failure, or whether it simply is a mere consequence of a dysfunctional heart, remains to be elucidated. Studies in mice with experimentally induced acute myocardial infarction leading to subsequent development of a postinfarction congestive heart failure have shed some light on this problem. Careful analyses of the number and of the functions of various hematopoietic cells residing in either blood or bone marrow point to a possible inhibitory role of cytokines, such tumor necrosis factor alpha, on hematopoiesis. The present protocols will hopefully encourage further studies of hematopoiesis and immunity in heart failure by using a combination of animal models with state-of-the-art techniques in molecular biology to define and validate possible targets for therapy.
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PMID:A murine model for studying hematopoiesis and immunity in heart failure. 1717 34

Apelin is a recently discovered peptide ligand reported to be involved in the regulation of cardiovascular homeostasis. The exact role of apelin in the pathophysiology of congestive heart failure has remained obscure, and the reported circulating levels of apelin in patients with heart failure have been contradictory. To establish the role of apelin in the assessment of cardiac dysfunction we measured plasma apelin levels in 65 patients with congestive heart failure caused by idiopathic dilated cardiomyopathy (IDC) and 14 healthy volunteers by specific radioimmunoassay. IDC patients were carefully examined including echocardiography, both-sided cardiac catheterization and cardiopulmonary exercise test. In addition, plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), N-terminal pro-atrial natriuretic peptide (NT-proANP), interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), epinephrine and norepinephrine were determined. Plasma apelin levels were similar in IDC patients (median 26.5 pg/ml, range<3.40-97.6 pg/ml) and in control subjects (median 24.1 pg/ml, range 19.0-28.7 pg/ml; p=NS). Unlike the levels of NT-proBNP, IL-6, TNF-alpha, and norepinephrine, plasma apelin levels did not reflect the severity of heart failure. Our study demonstrates that although disturbed apelin-APJ signalling in heart may play a role in the pathophysiology of heart failure, circulating apelin levels cannot be applied in the clinical assessment of patients with chronic left ventricular dysfunction.
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PMID:Utility of plasma apelin and other indices of cardiac dysfunction in the clinical assessment of patients with dilated cardiomyopathy. 1722 9

Epimedium, a traditional Chinese herb, has been used for the remedy of coronary heart disease, impotence and osteoporosis in traditional oriental medicine. However, despite extensive pharmacological studies, the molecular mechanism of the anti-heart failure effect of epimedium is little known. In the present study, we investigated the pharmacological action mechanism of ethanol extract of epimedium (EPI-ext) on isoproterenol-induced congestive heart failure (CHF) in rats. Isoproterenol administration resulted in severe heart failure, as shown by the increased levels of left ventricular (LV) weight index and heart rate, as well as LV end diastolic pressure, and by the decreased levels of LV systolic pressure, maximal rate of LV pressure rise, and maximal rate of LV pressure decline. EPI-ext dose-dependently reversed the changes of these cardiac morphometric and hemodynamic parameters. In addition, EPI-ext significantly inhibited the serum levels of tumor necrosis factor alpha, norepinephrine, angiotensin II and brain natriuretic peptide in rats with CHF and improved the histological changes including cadiocyte hypertrophy, cadiocyte degeneration, inflammatory infiltration, and cardiac desmoplasia. Furthermore, the expression and activities of matrix metalloproteinase-2 and -9, which regulate collagen production, were also blocked by EPI-ext. Moreover, myocardial apoptosis was remarkably attenuated by EPI-ext through the regulating Bcl-2/Bax axle. In conclusion, EPI-ext ameliorates LV dysfunction and cardiac remodeling through down-regulating matrix metalloproteinase-2 and -9 activity and myocardial apoptosis in rats with CHF.
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PMID:Ethanol extract from Epimedium brevicornum attenuates left ventricular dysfunction and cardiac remodeling through down-regulating matrix metalloproteinase-2 and -9 activity and myocardial apoptosis in rats with congestive heart failure. 1809 24


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