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

BACKGROUND: Inflammatory mechanisms in heart disease are of great interest. The proinflammatory cytokine interleukin (IL) 6 has been linked to increased morbidity in unstable angina pectoris and depressed myocardial function in heart failure (HF). METHODS: We studied the relation of IL-6 levels to C-reactive protein (CRP), infarction size, left ventricular function, and HF in acute myocardial infarction (MI) and after hospital discharge in 31 consecutive patients (19 males, mean age 69+/-13 years). Blood sampling for IL-6 was performed on admittance, four times on day 1, twice on day 2, and once daily on days 3-5, and 6 and 12 weeks later. Clinical signs of HF were evaluated daily during hospitalization and after 6 and 12 weeks. Echocardiography was performed on day 3 and at 6 weeks. RESULTS: IL-6 showed a curved time course with elevated levels already on admittance (mean+/-S.D. 19.3+/-26.9 ng/l), thereafter increasing to a peak on days 1 and 2 (maximum 68.5+/-152.9 ng/l), and then declining rapidly to lower, although not normalized, levels during hospitalization and at 6 and 12 weeks. CRP showed a similar time pattern, but with a later peak and a seemingly less rapid decline in levels. Mean levels of IL-6 and CRP on days 1-5 correlated highly (r=0.794, p<0.0001). IL-6 and infarction size did not correlate. HF during hospitalization and at 6 weeks was not related to IL-6; however, patients with HF at 12 weeks had higher IL-6 levels, both at 6 and 12 weeks. Patients on ACE inhibitors or diuretics at discharge had higher IL-6 levels at 6 weeks. IL-6 during hospitalization was not related to LVF; yet, patients with depressed LVF in the hospital and at 6 weeks had higher IL-6 levels at 6 and 12 weeks. CONCLUSIONS: IL-6 in acute MI shows a curved time course and is highly correlated to CRP. It peaks on days 1 and 2 and remains elevated even after 12 weeks. Increased IL-6 levels after hospital discharge are associated with HF and depressed LVF. Whether anti-inflammatory agents will influence left ventricular dysfunction and outcome postacute MI has yet to be determined.
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PMID:IL-6 levels in acute and post myocardial infarction: their relation to CRP levels, infarction size, left ventricular systolic function, and heart failure. 1566 89

Ischemic heart disease is the most common cause of mortality worldwide. Cardiac fibroblasts and myofibroblasts, i.e., the hypersecretory, muscular, and contractile fibroblastic phenotype variant, play an important role in myocardial healing and are responsible for accumulation of collagen in the infarct scar as well as in viable myocardium. Thus, cardiac fibroblasts and myofibroblasts directly contribute to cardiac stiffness, altered performance, and ultimately to the onset of systolic and diastolic heart failure. Cardiotrophin-1 (CT-1) is a member of the IL-6 superfamily and is elevated in the serum of patients with ischemic heart disease and valvular heart disease; it is also known to induce cardiomyocyte hypertrophy in vitro. The recent, burgeoning awareness of the functions of IL-6 superfamily of cytokines within cardiovascular diseases predicates this summary of CT-1's effect in cardiac wound healing, and particularly after the induction of myocardial infarction. Further, we summarize recent results of cardiac CT-1 expression post-myocardial infarction (post-MI) as well as the effect of CT-1 on cultured primary adult rat cardiac fibroblasts with respect to proliferation and collagen secretion. It would appear that CT-1 plays an important and heretofore largely unrecognized role in infarct scar formation and angiogenesis in the rat model of chronic MI. Further work is required to determine factors that induce CT-1 expression, its interplay with other mediators of cardiac infarct wound healing in the setting of acute cardiac ischemia and chronic post-MI heart failure, and ultimately whether it confers a beneficial effect or contributes to maladaptive cardiac fibrosis.
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PMID:Emerging evidence for the role of cardiotrophin-1 in cardiac repair in the infarcted heart. 1572 58

The immune system of higher vertebrates consists of two components: the innate and adaptive immunity. While the adaptive immune system relies on somatically generated and clonally selected antigen receptors, the innate immune system detects the presence of pathogens by their evolutionarily highly conserved, relatively invariant structural motifs. Interestingly, recent data suggest that activation of the innate immune system could play an important role in various diseases without the direct involvement of infectious pathogens. For example, a number of inflammatory cytokines, including TNF (tumor necrosis factor), IL (interleukin)-1beta, IL-6 and IL-8, as well as iNOS (inducible nitric oxide synthase), all components of innate immunity, are also implicated in ischemia/reperfusion injury, and in the abnormal myocardial remodeling characteristic of chronic heart failure. Understanding of the regulation and activation of the innate immune system in diseases not obviously related to an immune response to specific pathogen could provide new therapeutic targets for cardiovascular diseases. Thus, in this review, we provide a general overview of the components of innate immunity with a focus on humoral factors, their role in the response to foreign pathogens, and their potential role in the response to tissue injury (i.e., the "Expanded Self-Non-Self" and the "Danger" theories of immune activation).
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PMID:Innate immunity and the heart. 1585 84

Mechanical circulatory assist devices (MCADs) are increasingly utilized independently of cardiac transplantation in the management of heart failure. Though MCAD use incorporates inherent mechanical risks, the inevitable onset of chronic anemia, with its associated morbidity and mortality, is also a significant concern. MCAD support has been correlated with elevated plasma levels of inflammatory cytokines TNF-alpha, IL-1beta, and IL-6, which have separately been found to inhibit erythropoietin (Epo)-induced erythrocyte (RBC) maturation. Previous analysis of hematological parameters for MCAD-supported patients concluded that an amplified inflammatory response impedes RBC proliferation and recovery from hemolytic anemia. Additional analysis may bolster this assertion. Hemoglobin concentration (HC), RBC distribution width (RDW), mean cell volume (MCV), and cardiac index were retrospectively analysed for 78 MCAD-supported patients implanted for greater than 30 days at the University of Arizona Health Sciences Center from 1996 to 2002. Analysis confirms that the HC, a conventional marker for anemia, declines with MCAD placement and remains below the clinically defined, minimum normal value. Inversely, the RDW rises above maximum normal measure, signifying an increased fraction of juvenile RBCs. The MCV remains unchanged and within normal limits, demonstrating adequate substrate for RBC formation. MCAD performance also stabilizes as adequate perfusion returns. These results further support our previously published conclusion that a sufficient response of erythropoiesis occurs in reaction to the onset of anemia by an increased production of immature RBCs. However, the cells never fully mature and join circulation. The patient's inflammatory cytokine response to the implanted device most likely mediates the chronic MCAD-induced anemia by inhibition of Epo effects.
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PMID:Inflammatory cytokine inhibition of erythropoiesis in patients implanted with a mechanical circulatory assist device. 1591 45

Recent studies point to important interactions between proinflammatory cytokines and neurohumoral mediators in heart failure. Here we investigate the influence of the beta-adrenergic system on cytokines and neurohumoral factors and the sequelae of viral myocarditis. In an experimental model with virus-infected BALB/c mice, we studied the acute and chronic effects of epinephrine and propranolol on myocardial morphology, cytokine gene expression, and survival. BALB/c mice were inoculated with the encephalomyocarditis virus (EMCV) or sham inoculated with saline and followed for 30 days. Epinephrine increased the severity of inflammatory cell infiltration and myocardial necrosis induced by EMCV. Gene expression of TNF-alpha, IL-6, and IL-10 was markedly enhanced by epinephrine in EMCV-inoculated mice. Survival rate after 30 days was reduced to 40% in epinephrine-treated EMCV-inoculated mice compared with 70% in untreated EMCV-inoculated mice (P < 0.05). Treatment with the beta-blocker propranolol significantly decreased mortality, myocardial necrosis, and infiltration of inflammatory cells in EMCV-inoculated mice. Propranolol also suppressed gene expression of TNF-alpha, IL-6, and IL-10. A single dose of epinephrine 120 days after EMCV inoculation caused sudden death in 70% of infected mice; propranolol significantly reduced incidence of death to 33%. These results indicate that acute and chronic stages of viral myocarditis are modulated by the beta-adrenergic system and its interactions with proinflammatory cytokines.
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PMID:Propranolol ameliorates and epinephrine exacerbates progression of acute and chronic viral myocarditis. 1592 19

In chronic heart failure (CHF), activation of the immune system occurs, which results in the production and release of proinflammatory cytokines, activation of the complement system, and production of autoantibodies. Thus, it is important to consider CHF as a systemic illness, not just a disease of the "pump." Immune activation in CHF can be divided into 2 broad categories: (1) immune activation by direct antigenic stimulation, or (2) immune activation secondary to cardiac injury that exposes "new antigens" capable of triggering an immune response against the heart. Cytokines are essential for the propagation and magnification of the immune response. They are involved in recruiting cells to the area of inflammation, stimulating cell division, proliferation, and differentiation. Circulating levels of the cytokine tumor necrosis factor-alpha (TNF-alpha) are increased in patients with CHF. Thus, cytokines are key elements of immune activation. Studies to investigate the role of increased TNF-alpha levels have failed to show a correlation with worsening CHF, most likely because the immune system is redundant, and other proinflammatory cytokines (interleukin [IL]-1 and IL-6) are known to be elevated in CHF. Approaches showing promise are those that enhance the natural anti-inflammatory response (eg, intravenous immunoglobulin (IVIG), immunoadsorption, immune-modulation therapy [IMT]), rather than those that specifically target a single type of cytokine. The mechanism by which IVIG modulates the immune system is unknown. Immunoadsorption involves the removal of specific antibodies from circulation. IMT works by inducing apoptosis in a sample of blood, which is then administered back to the patient. The immune system reacts by removing the apoptotic cells, thus inducing a systemic anti-inflammatory response.
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PMID:Immune activation in chronic heart failure. 1592 58

Accumulating evidence indicates that inflammatory mediators are important in the pathogenesis of chronic heart failure (CHF), contributing to cardiac remodeling and peripheral vascular disturbances. Several studies have shown increased levels of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 in patients with CHF in both plasma and circulating leukocytes as well as in the failing myocardium itself. Importantly, this increase in inflammatory mediators does not seem to be accompanied by a corresponding increase in anti-inflammatory cytokines, such as IL-10 and transforming growth factor-beta, resulting in an inflammatory imbalance in the cytokine network. Traditional cardiovascular drugs seem to have little influence on the cytokine network in patients with CHF, and immunomodulatory therapy in addition to "optimal" cardiovascular treatment regimens has emerged as an option. Thus, several animal studies as well as some clinical pilot trials have suggested that downregulation of inflammatory cytokines may improve cardiac performance. On the other hand, preliminary results from placebo-controlled anti-TNF studies suggest no effect, or even an adverse effect of anti-TNF therapy on mortality and hospitalization. Although somewhat disappointing, these negative results do not necessarily argue against the cytokine hypothesis. These studies only underscore the difficulties and challenges in developing treatment modalities that can modulate the cytokine network in patients with CHF, resulting in anti-inflammatory and beneficial net effects. Further research in this area will have to more precisely identify the most important "actors" in the immunopathogenesis of CHF to improve the immunomodulatory treatment regimens in this disorder.
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PMID:Review of trials in chronic heart failure showing broad-spectrum anti-inflammatory approaches. 1592 60

The immune system is a system of dynamic equilibrium, with inflammatory responses (mediated by T helper type 1 cells, interleukin [IL]-1beta, interferon-gamma, and tumor necrosis factor-alpha [TNF-alpha]) being balanced by anti-inflammatory responses (mediated by T regulatory type 1 cell, T helper type 3 cells, IL-4, IL-10, and transforming growth factor-beta). Therefore, neutralization of inappropriate inflammatory cytokines is a therapeutic strategy that has been attempted in many chronic inflammatory conditions, mostly targeting TNF-alpha, using either monoclonal antibodies or modified receptor proteins (etanercept). There is functional redundancy among the inflammatory cytokines. For example, in addition to TNF-alpha, both IL-1beta and IL-6 are elevated in patients with chronic heart failure (CHF); thus neutralizing the activity of TNF-alpha alone may be an inadequate approach in this patient group. Immune-modulation therapy (IMT) results in downregulation of proinflammatory cytokine levels and upregulation of anti-inflammatory cytokines. This alteration in the balance between proinflammatory and anti-inflammatory cytokines may be more appropriate than neutralizing the activity of a single cytokine in the treatment of conditions such as CHF. Several animal studies investigating the effect of IMT in inflammatory conditions including allergic contact hypersensitivity, ischemia reperfusion injury, and atherogenesis are reviewed.
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PMID:Biologic effects and basic science of a novel immune-modulation therapy. 1592 61

Hyperlipidemia is a cardiovascular risk factor. In patients with idiopathic dilated cardiomyopathy (IDC), prognostic roles of endogenous lipoproteins are not fully clarified. It has been known that there is a direct relationship between the levels of cytokines (tumor necrosis factor-alpha [TNF-alpha] and interleukin-6 [IL-6]) and deteriorating functional classes of heart failure and mortality. The present study compared the levels of circulating TNF-alpha, IL-6, lipoproteins, and apolipoproteins in patients with stable IDC (n = 28) with those of patients with unstable IDC (n = 26) and controls (n = 24). Mean serum total cholesterol (TC) was significantly lower in stable IDC patients than controls (p < 0.05). In unstable IDC patients, mean serum TC was also lower than controls but not statistically significant. The IDC patients had significantly higher concentrations of IL-6 and TNF-alpha than the controls (p < 0.01). Serum IL-6 and Apo AI levels were significantly different between stable and unstable IDC patients (p = 0.021 and p = 0.012, respectively). Increased levels of IL-6 were associated with decreased levels of TC (r = -0.266, p = 0.019), LDL-C (r = -0.376, p = 0.001) and apolipoprotein AI (apo AI) (r = -0.495, p < 0.001) in all IDC patients. TNF-alpha was also inversely related to apo AI (r = -0.455, p < 0.001) and LDL-C (r = -0.364, p = 0.001) in all patients. Thus, elevated serum levels of cytokines in patients with IDC are associated with decreased lipoprotein concentrations, which may indicate impaired prognosis.
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PMID:Decreased serum lipoprotein levels as a guide for clinical severity in patients with idiopathic dilated cardiomyopathy. 1594 48

Recent experimental and clinical observations indicate that over-expression of pro-inflammatory cytokines is actively implicated to chronic heart failure progression through their cytotoxic and negative inotropic effects. Calcium-sensitizing agents, such as levosimendan, promotes inotropy by stabilizing troponin C in a configuration that enhances the calcium sensitivity of cardiac myofilaments, preserving also diastolic relaxation. Levosimendan also opens ATP-dependent potassium channels in peripheral vessels, leading to vasodilatation. Large scale randomized clinical trials have shown that levosimendan administration in patients with severe heart failure due to left ventricular systolic dysfunction results in favorable hemodynamic changes, symptomatic benefit, and a reduction in short-term morbidity and mortality. This review describes current knowledge about novel cellular mechanisms associated with beneficial effects of levosimendan on cardiac contractile performance, focusing mainly on its immunomodulatory and anti-apoptotic properties. Levosimendan-induced improvement in contractile reserve and clinical status of severe heart failure patients, seems to be related with the reduction of major pro-inflammatory cytokines (TNF-alpha, IL-6) and soluble apoptosis signaling molecules Fas/Fas Ligand. Modulation of pro-inflammatory and pro-apoptotic pathways into the failing heart by levosimendan may be an additional pathophysiologic mechanism that prevents further clinical and hemodynamic consequences of abnormal immune responses in decompensated heart failure and beneficially affects the progression of the syndrome.
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PMID:Anti-inflammatory and anti-apoptotic effects of levosimendan in decompensated heart failure: a novel mechanism of drug-induced improvement in contractile performance of the failing heart. 1597 88


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