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

We studied body composition and cytokine levels in 58 patients with heart failure and 16 control patients using dual-energy x-ray absorptiometry. Bone mineral content and density, and lean and fat tissue content, were reduced in cachectic compared with noncachectic patients and control subjects, with negative relations between indexes of bone composition and tumor necrosis factor and tumor necrosis factor receptor 1.
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PMID:Loss of bone mineral in patients with cachexia due to chronic heart failure. 1007 75

Mechanical assist devices have been used increasingly to support patients who await heart transplantation. The initial goal was to provide sufficient circulatory function to keep these patients alive and to allow them to recover from secondary organ dysfunction. A recent observation showed an improvement in native heart performance in some transplant candidates who receive support with mechanical assist devices. Under these conditions, myocardial recovery has been mostly restricted to patients with primary dilated cardiomyopathy and with extended periods of ventricular support. Also, the exact mechanisms that lead to substantial myocardial recovery remain unknown. Several investigations have demonstrated improved myocyte performance, reduced fibrosis, reduced cytokine levels, and reduced autoantibodies during long-term mechanical support; therefore, the observation of cardiac recovery during mechanical support is in accordance with currently discussed models of end-stage heart failure.
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PMID:Ventricular assistance for recovery of cardiac failure. 1035 96

The current interest in understanding the role of stress-induced cytokines in heart failure relates to the observation that many of the untoward pathophysiologic responses of the failing circulation might be explained by these compounds. These small molecules appear to cause left ventricular dysfunction, precipitate pulmonary edema, cause cardiomyopathy, reduce peripheral organ perfusion, induce ventricular remodeling, activate the fetal gene program in animal models, and cause anorexia and cachexia. Thus, the elaboration of cytokines, similar to the upregulation of neurohormones, may represent a biochemical mechanism that is responsible for producing symptoms and remodeling in heart failure patients. To better understand how cytokines play a role in heart failure, it is important to delineate the concept of cytokine bioactivity in this setting.
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PMID:Cytokines and heart failure. 1042 71

Expression of innate immune response proteins, including IL-1beta, TNF, and the cytokine-inducible isoform of nitric oxide synthase (iNOS), have been documented in the hearts of humans and experimental animals with heart failure regardless of etiology, although the proximal events leading to their expression are unknown. Noting that expression of a human homologue of Drosophila Toll, a proximal innate immunity transmembrane signaling protein in the fly, now termed human Toll-like receptor 4 (hTLR4), appeared to be relatively high in the heart, we examined TLR4 mRNA and protein abundance in isolated cellular constituents of cardiac muscle and in normal and abnormal murine, rat, and human myocardium. TLR4 expression levels in cardiac myocytes and in coronary microvascular endothelial cells could be enhanced by either LPS or IL-1beta, an effect inhibited by the oxygen radical scavenger PDTC. Transfection of a constitutively active TLR4 construct, CD4/hTLR4, resulted in activation of a nuclear factor-kappaB reporter construct, but not of an AP-1 or an iNOS reporter construct, in cardiac myocytes. In normal murine, rat, and human myocardium, TLR4 expression was diffuse, and presumably cytoplasmic, in cardiac myocytes. However, in remodeling murine myocardium remote from sites of ischemic injury and in heart tissue from patients with idiopathic dilated cardiomyopathy, focal areas of intense TLR4 staining were observed in juxtaposed regions of 2 or more adjacent myocytes; this staining was not observed in control myocardium. Increased expression and signaling by TLR4, and perhaps other Toll homologues, may contribute to the activation of innate immunity in injured myocardium.
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PMID:Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. 1043 Jun 8

Cardiotrophin-1, a member of the interleukin-6 related cytokine family which acts via the glycoprotein 130 signalling pathway, may be involved in the process of ventricular remodelling. Its presence in human plasma has never been reported. We have devised a non-radioactive immunoluminometric sensitive and specific assay for CT-1 based on a competitive ligand binding principle. The chemiluminescent label 4-(2-succinimidyl-oxycarbonylethyl)phenyl-10-methylacridinium 9-carboxylate fluorosulfonate was used to label a peptide representing a domain in the middle section of CT-1. Assay of this domain of CT-1 (amino acids 105-120) in patients with heart failure revealed elevated CT-1 values median 87 [range 74.3-182.8] fmol/ml) compared to normal controls (CT-1 median 29.55 [range 6.9-48.3] fmol/ml, P<0.0005). The molecular weight of human CT-1 was estimated to be 26.7 kD from sodium dodecyl sulphate polyacrylamide gel electrophoresis. This is the first quantitative assessment of CT-1 in humans. Furthermore, this is the first demonstration of significant elevation of plasma CT-1 in patients with heart failure.
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PMID:An immunoluminometric assay for cardiotrophin-1: a newly identified cytokine is present in normal human plasma and is increased in heart failure. 1044 67

The prevalence of nonischemic heart failure including idiopathic dilative cardiomyopathy is not well known. It may vary considerably in different population sub-groups and geographic areas. In ambulatory and hospitalized patients with clinically manifest heart failure primary cardiomyopathy is diagnosed in 2-15%, while in recent large scale therapeutic trials the proportion of patients with nonischemic heart failure ranged from 18% to 53%. There is a relation between sex, age and etiology of chronic heart failure, nonischemic cardiomyopathy being more frequent in women and in younger individuals. In contrast to ischemic heart failure, where the severity usually correlates with the extent of coronary artery lesions, the pathophysiology of cardiomyopathy is less clear. Genetic factors, myocarditis from infectious agents, auto-immune mechanisms, cytokine activation, hormonal and metabolic influences can play a role. The functional consequences of myocardial damage in nonischemic heart failure is a global instead of localized abnormality of ventricular contractility. There is epidemiological evidence that in general the prognosis of nonischemic heart failure is better than in ischemic heart failure. The mortality of patients with ischemic heart failure was usually higher in the placebo groups of recent heart failure trials than in patients with nonischemic etiology. Furthermore, therapeutic responses to angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, amlodipine and amiodarone were also different in some studies. The outcome of nonischemic heart failure is better even in transplant candidates with the most advanced stages of heart failure, they survive longer and respond better to intensified drug regimens than patients with similar clinical severity of ischemic heart failure. Thus, an early and precise diagnosis of the etiology of heart failure should be encouraged not only in clinical trials but also in every day patient management. As more therapeutic options are developed, individualized drug selection for patients with various etiologies of heart failure may become possible.
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PMID:Nonischemic heart failure: epidemiology, pathophysiology, and progression of disease. 1044 82

Viral myocarditis is an important cause of heart failure and dilated cardiomyopathy. T lymphocytes are implicated in myocardial damage in murine models of coxsackievirus B3 (CVB3) myocarditis. We used knockout mice lacking CD4 (CD4(-/-)), CD8 (CD8(-/-)), both coreceptors (CD4(-/-)CD8(-/-)), or the T-cell receptor beta chain (TCRbeta(-/-)) to address the contribution of T-cell subpopulations to host susceptibility to CVB3 myocarditis. Severity of disease was magnified in CD8(-/-) mice but attenuated in CD4(-/-) mice, consistent with a pathogenic role for CD4(+) lymphocytes. Elimination of both CD4 and CD8 molecules from T lymphocytes by genetic knockout better protected mice from myocarditis, demonstrating that both CD4(+) and CD8(+) T cells contribute to host susceptibility. The same benefit occurred in TCRbeta(-/-) mice, with prolonged survival and minimal myocardial disease observed after CVB3 infection. Elevated interferon-gamma and decreased tumor necrosis factor-alpha expression are associated with attenuated myocardial damage in CD4(-/-)CD8(-/-) mice. These results show that the presence of TCRalphabeta(+) T cells enhances host susceptibility to myocarditis. The severity of myocardial damage and associated mortality are dependent on the predominant T-cell type available to respond to CVB3 infection. One mechanism by which CD4(+) and CD8(+) T-cell subsets influence the pathogenesis of myocarditis may involve specific cytokine expression patterns.
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PMID:Susceptibility to myocarditis is dependent on the response of alphabeta T lymphocytes to coxsackieviral infection. 1048 59

An increasing body of experimental and clinical work suggesting that tumor necrosis factor alpha plays a pathogenic role in heart failure continues to accumulate. This cytokine is produced in failing but not in normal hearts and experimentally, it's expression is induced by hemodynamic conditions of pressure or volume overload. Specific receptors for this cytokine are present in the heart and dynamic regulation in tumor necrosis factor receptor expression occurs in failing myocardium. In addition, tumor necrosis factor alpha may exert major cardiac effects that contribute to the development of the failing phenotype: induces negative contractil dysfunction, promotes fibrosis, induces cardiomyopathy in experimental animals and it is a major mediator of apoptosis in vivo and in vitro. The knowledge gained from studying the role of tumor necrosis factor alpha in cardiac function draws attention to a series of molecules previously unrecognized as potential mediators in the pathogenesis of heart failure.
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PMID:[Tumor necrosis factor-alpha: a mediator in the pathogenesis of cardiac insufficiency]. 1064 Feb 10

There is now considerable evidence to suggest that neurohormonal and immune mechanisms may play a central role in the pathogenesis of chronic heart failure (CHF), which is likely to have important implications for the management of this condition. It has been proposed that CHF is a state of immune activation with inflammatory cytokines contributing to both the central and the peripheral manifestations of this syndrome. The immune system is the body's natural defence mechanism against infection and other stresses, which has several different components that interact with each other in a complex manner. The main components which are thought to be relevant to the pathogenesis of CHF are: cytokines, adhesion molecules, autoantibodies, nitric oxide, and endothelin-1, and this review will concentrate on these factors. This article will also discuss the potential role of anti-cytokine therapies in the treatment of CHF.
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PMID:The role of inflammatory mediators in chronic heart failure: cytokines, nitric oxide, and endothelin-1. 1064 59

Experimental observations made over the past two decades have led to a profound shift in the conceptual paradigms about the syndrome of heart failure and dilated cardiomyopathy. As a consequence, heart failure is currently considered a complex disease and is not merely characterized by hemodynamic disturbances. It is now believed that the syndrome is governed and impelled by neurohormonal imbalances and intracardiac paracrine processes. The latter processes are mediated by activated cardiac endothelial cells and cytokines, creating a state of cardiac maladaption and leading to disease progression. Therapeutic interventions such as operative left ventricular volume reduction or mitral valve reconstruction should therefore no longer be solely interpreted in terms of hemodynamics (i.e., symptomatic improvements). Effects on neurohormonal, endothelial, and cytokine activities should be taken equally into account.
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PMID:Dilated cardiomyopathy: changing pathophysiological concepts and mechanisms of dysfunction. 1067 49


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