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

Extramedullary hematopoiesis occurring in the myocardium has previously only been reported in a single case of a neonate with cyanotic congenital heart disease. Herein we report the incidental discovery of extramedullary hematopoiesis or pure erythropoiesis in four failing adult hearts with myocardial infarction. In two cases, extramedullary hematopoiesis or erythropoiesis was identified in cardiectomy specimens removed at orthotopic heart transplantation; in two other cases, erythropoiesis was found in left ventricular tissue removed at the time of implantation of left ventricular assist devices. Myocardial hematopoiesis/erythropoiesis was identified based on characteristic light-microscopic findings in routinely processed tissue and was confirmed by immunhistochemistry using monoclonal antibodies to the erythroid cell marker glycophorin A (positive in all cases), the megakaryocyte marker CD61, and the granulocyte marker neutrophil elastase (the latter two markers positive in one case only). None of the four patients had a myeloproliferative disorder or evidence of a myelophthisic process. No hematopoietic elements were identified in 109 cardiectomy specimens without acute or recent infarcts. Myocardial hematopoiesis or erythropoiesis could represent heretofore-unrecognized manifestations of altered cytokine expression in patients with heart failure due to myocardial infarction.
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PMID:Hematopoiesis/erythropoiesis in myocardial infarcts. 1140 61

Although an increased expression of proinflammatory cytokines has been reported in cardiac tissue samples from patients with congestive heart failure (CHF) and in various animal models of CHF, the role of these cytokines in the disease remains to be determined. Dahl salt-sensitive (DS) rats fed a high salt diet develop hypertension, cardiac hypertrophy and eventually CHF. In the present study, DS rats were treated with FR167653 (1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8-(4-pyridyl)pyrazolo[5,1-c][1,2,4]triazin-2-yl]-2-phenylethanedione sulfate monohydrate), a new low molecular weight inflammatory cytokine inhibitor. Treatment with 10 mg/kg per day of FR167653 significantly prolonged the survival of the animals and also prevented the bodyweight loss associated with heart failure. In conclusion, a non-peptide proinflammatory cytokine inhibitor improved the survival of animals with heart failure.
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PMID:Proinflammatory cytokine inhibitor prolongs the survival of rats with heart failure induced by pressure overload. 1140 47

A growing body of literature indicates that cytokines regulate skeletal muscle function, including gene expression and adaptive responses. Tumour necrosis factor-alpha (TNF-alpha) is the cytokine most prominently linked to muscle pathophysiology and, therefore, has been studied most extensively in muscle-based systems. TNF-alpha is associated with muscle catabolism and loss of muscle function in human diseases that range from cancer to heart failure, from arthritis to AIDS. Recent advances have established that TNF-alpha causes muscle weakness via at least two mechanisms, accelerated protein loss and contractile dysfunction. Protein loss is a chronic response that occurs over days to weeks. Changes in gene expression required for TNF-alpha induced catabolism are regulated by the transcription factor nuclear factor-kappaB which is essential for the net loss of muscle protein caused by chronic TNF-alpha exposure. Contractile dysfunction is an acute response to TNF-alpha stimulation, developing over hours and resulting in decreased force production. Both actions of TNF-alpha involve a rapid rise in endogenous oxidants as an essential step in post-receptor signal transduction. These oxidants appear to include reactive oxygen species derived from mitochondrial electron transport. Such information provides insight into the cellular and molecular mechanisms of TNF-alpha action in skeletal muscle and establishes a scientific basis for continued research into cytokine signalling.
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PMID:Cytokines and oxidative signalling in skeletal muscle. 1141 34

Clinical trials designed to evaluate the effect of drugs and devices on the symptoms and clinical status in chronic heart failure have frequently produced conflicting, inconclusive, or misleading results. These difficulties can be explained by the fact that previous studies have relied on efficacy measures that have inherent limitations and have been analyzed using statistical approaches that ignored episodes of clinical deterioration. Recognition of these pitfalls has led to the development of a new clinical composite score, which combines changes in the New York Heart Association class and the global assessment together with the information provided from the occurrence of major clinical events. Use of this score would have correctly distinguished active therapy from placebo in earlier trials and thus would have avoided some of their misleading conclusions. The new clinical composite score has been prospectively incorporated into the design of studies evaluating the efficacy of endothelin antagonists, cytokine antagonists, vasopressin antagonists, and cardiac resynchronization in the treatment of chronic heart failure. In the trials that have been completed to date, the clinical composite score has been more sensitive than conventional approaches in discerning the presence or absence of a true treatment effect.
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PMID:Proposal for a new clinical end point to evaluate the efficacy of drugs and devices in the treatment of chronic heart failure. 1142 Jul 70

Myocarditis is a principal cause of heart disease among young adults and is often a precursor of heart failure due to dilated cardiomyopathy. We show here that complement is critical for the induction of experimental autoimmune myocarditis and that it acts through complement receptor type 1 (CR1) and type 2 (CR2). We also found a subset of CD44(hi)CD62L(lo) T cells that expresses CR1 and CR2 and propose that both receptors are involved in the expression of B and T cell activation markers, T cell proliferation and cytokine production. These findings provide a mechanism by which activated complement, a key product of the innate immune response, modulates the induction of an autoimmune disease.
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PMID:Contribution of the innate immune system to autoimmune myocarditis: a role for complement. 1147 11

Chronic inflammation is a common feature of end-stage renal disease (ESRD) that is gaining increasing attention as a major cause of morbidity and mortality. It is well established that ESRD per se carries a heightened risk of inflammatory disorders and other co-morbid conditions, but it should also be pointed out that dialysis treatment per se can bring additional risk factors for inflammation, such as impure dialysate or bio-incompatible membranes. Inflammation has recently been associated with atherosclerosis and malnutrition in ESRD, and this link has led to the development of the malnutrition, inflammation, atherosclerosis (MIA) hypothesis. This describes a syndrome whereby raised levels of pro-inflammatory cytokines (such as IL-1, IL-6 and TNF-alpha) are a common link between malnutrition, inflammation and atherosclerosis. Also, anaemia appears to be an important element linking elevated cytokine levels with poor patient outcomes. Several mechanisms for cytokine-induced anaemia have been proposed, including intestinal bleeding, impaired iron metabolism and suppression of bone marrow erythropoiesis and erythropoietin production. These effects suggest that pro-inflammatory cytokines may also be an important cause of lack of response to recombinant human erythropoietin (rh-Epo) therapy. In the light of this putative role of pro-inflammatory cytokines, anti-cytokine agents may prove useful to optimize efficacy of rh-Epo in anaemic chronic renal failure patients. Other potential therapeutic strategies include minimizing exposure to causes of inflammation from various co-morbid conditions, such as persistent infections and chronic heart failure.
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PMID:The role of inflammation in the anaemia of end-stage renal disease. 1159 Feb 55

Recent studies have emphasized the importance of biologically active molecules, termed cytokines, in the development and progression of the syndrome of chronic heart failure. This article summarizes a glossary of major cytokines and other cytokine-related inflammatory factors implicated in the pathophysiology of chronic heart failure, describing the source of their synthesis and factors regulating their secretion and analyzing their biologic effects on the cardiovascular system.
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PMID:A glossary of circulating cytokines in chronic heart failure. 1159 99

Increased neurohormone and cytokine concentrations are associated with adverse outcome in patients with congestive heart failure, so minimizing these increases may improve outcome, even in the acute phase of decompensated heart failure. The present study was designed to test the hypothesis that phosphodiesterase inhibitors, but not catecholamines, could favorably affect neurohormone and cytokine profiles in patients with acutely decompensated heart failure. Twenty-nine patients underwent monitoring using a Swan-Ganz catheter and were randomly allocated to receive phosphodiesterase inhibitors (PDEI group, n=19) or catecholamines (CA group, n=10). Pulmonary capillary wedge pressure decreased significantly in both groups and cardiac output showed a slight, but not statistically significant increase, in both groups. There was a significant decrease in plasma brain natriuretic peptide concentration in the PDEI group, but not in the CA group, whereas plasma interleukin-6 concentration increased in the CA group, but not in the PDEI group. Phosphodiesterase inhibitors favorably affect neurohormone and cytokine concentrations in patients with acutely decompensated heart failure.
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PMID:Randomized trial of phosphodiesterase inhibitors versus catecholamines in patients with acutely decompensated heart failure. 1166 88

Patients with heart failure are predisposed to infections and anemia, possibly due to reduced hematopoiesis. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) is increased in heart failure, and it inhibits normal hematopoiesis, partly due to apoptosis through the effector molecule Fas. We examined bone marrow progenitor cells of mice with heart failure induced by acute myocardial infarction. The fraction of progenitor cells in mice with heart failure was only approximately 40% of control. Measured with in vitro clonal assays, the proliferative capacity of the progenitor cells in mice with heart failure was reduced to approximately 50% of control. Flow cytometry with specific markers revealed a threefold increase in apoptosis among progenitor cells from mice with heart failure. In these mice, TNF-alpha/Fas expression was increased in bone marrow natural killer (NK) and T cells, and these lymphocytes showed increased cytolytic activity in vitro against progenitor cells. We conclude that the TNF-alpha/Fas pathway in lymphocytes is activated in the bone marrow during heart failure, which may play a pathogenic role in the observed decrease in hematopoiesis.
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PMID:Decreased hematopoiesis in bone marrow of mice with congestive heart failure. 1174 35

One of the major therapeutic goals of modern cardiology is to design strategies aimed at minimizing myocardial necrosis and optimizing cardiac repair following myocardial infarction. However, a sound understanding of the biology is necessary before a specific intervention is pursued on a therapeutic basis. This review summarizes our current understanding of the cellular and molecular mechanisms regulating the inflammatory response following myocardial ischemia and reperfusion. Myocardial necrosis induces complement activation and free radical generation, triggering a cytokine cascade initiated by Tumor Necrosis Factor (TNF)-alpha release. If reperfusion of the infarcted area is initiated, it is attended by an intense inflammatory reaction. Interleukin (IL)-8 synthesis and C5a activation have a crucial role in recruiting neutrophils in the ischemic and reperfused myocardium. Neutrophil infiltration is regulated through a complex sequence of molecular steps involving the selectins and the integrins, which mediate leukocyte rolling and adhesion to the endothelium. Marginated neutrophils exert potent cytotoxic effects through the release of proteolytic enzymes and the adhesion with Intercellular Adhesion Molecule (ICAM)-1 expressing cardiomyocytes. Despite this potential injury, substantial evidence suggests that reperfusion enhances cardiac repair improving patient survival; this effect may be in part related to the inflammatory response. Monocyte Chemoattractant Protein (MCP)-1 is also markedly upregulated in the infarcted myocardium inducing recruitment of mononuclear cells in the injured areas. Monocyte-derived macrophages and mast cells may produce cytokines and growth factors necessary for fibroblast proliferation and neovascularization, leading to effective repair and scar formation. At this stage expression of inhibitory cytokines such as IL-10 may have a role in suppressing the acute inflammatory response and in regulating extracellular matrix metabolism. Fibroblasts in the healing scar undergo phenotypic changes expressing smooth muscle cell markers. Our previous review in this journal focused almost exclusively on reduction of the inflammatory injury. The current update is prompted by the potential therapeutic opportunity that the open vessel offers. By promoting more effective tissue repair, it may be possible to reduce the deleterious remodeling, that is the leading cause of heart failure and death. Elucidating the complex interactions and regulatory mechanisms responsible for cardiac repair may allow us to design effective inflammation-related interventions for the treatment of myocardial infarction.
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PMID:The inflammatory response in myocardial infarction. 1174 11


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