Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1 Cytokines may parallel or regulate the beneficial effects of beta-adrenoceptor antagonist treatment observed in chronic heart failure (CHF) patients. Therefore, this study was performed in order to investigate alterations of cytokine levels in beta-blocker-treated patients suffering from CHF. 2 We investigated plasma cytokine levels in eight healthy controls and 12 CHF patients. The patients were treated with standard medication (CHFstd) or with standard medication and additional beta1-blocker metoprolol (CHFmet). Interleukin-(IL)-1alpha, IL-1beta, IL-1 receptor antagonist (IL-1ra), IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF), soluble TNF receptor type 1 (sTNF-R1), sTNF-R2, and sCD14 were measured by ELISA. 3 IL-1alpha and IL-1beta were not detectable in any of the tested groups. IL-2, TNF, or sCD14 were not altered as compared with healthy control subjects. CHFstd patients expressed enhanced IL-1ra, IL-6, IL-8, IL-10, sTNF-R1 and sTNF-R2. In CHFmet patients IL-1ra, IL-6 and IL-8 remained at the same level. In contrast, sTNF-R1 levels were significantly reduced, although not to control, whereas the sTNF-R2 and IL-10 were reduced to control levels. 4 The cAMP levels of mononuclear cells--recalculated for the patients included in this study from previous work [Werner et al. (2001). Basic Res. Cardiol., 96, 290]--correlated inversely with the sTNF-R2 data (Pearson, r = -0.46; P = 0.041; Spearman, r = -0.64, P = 0.002). 5 The present data indicate an interaction of the neurohumoral and the cytokine system in CHF patients at the cAMP level. Thus, measurement and correlation of sTNF-R2 and cAMP may provide a tool useful during investigation of beta-blocker therapy.
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PMID:The enhanced plasma levels of soluble tumor necrosis factor receptors (sTNF-R1; sTNF-R2) and interleukin-10 (IL-10) in patients suffering from chronic heart failure are reversed in patients treated with beta-adrenoceptor antagonist. 1256 25

Transgenic (TG) TNF1.6 mice, which cardiac specifically overexpress tumor necrosis factor-alpha (TNF-alpha), exhibit heart failure (HF) and increased mortality, which is markedly higher in young (<20 wk) males (TG-M) than females (TG-F). HF in this model may be partly caused by remodeling of the extracellular matrix and/or structure/function alterations at the single myocyte level. We studied left ventricular (LV) structure and function using echocardiography and LV myocyte morphometry, contractile function, and intracellular Ca(2+) (Ca(i)(2+)) handling using cell edge detection and fura 2 fluorescence, respectively, in 12-wk-old TG-M and TG-F mice and their wild-type (WT) littermates. TG-F mice showed LV hypertrophy without dilatation and only a small reduction of basal fractional shortening (FS) and response to isoproterenol (Iso). TG-M mice showed a large LV dilatation, higher mRNA levels of beta-myosin heavy chain and atrial natriuretic factor versus TG-F mice, reduced FS relative to both WT and TG-F mice, and minimal response to Iso. TG-F and TG-M myocytes were similarly elongated (by approximately 20%). The amplitude of Ca(i)(2+) transients and contractions and the response to Iso were comparable in WT and TG-F myocytes, whereas the time to 50% decline (TD(50%)) of the Ca(i)(2+) transient, an index of the rate of sarcoplasmic reticulum Ca(2+) uptake, was prolonged in TG-F myocytes. In TG-M myocytes, the amplitudes of Ca(i)(2+) transients and contractions were reduced, TD(50%) of the Ca(i)(2+) transient was prolonged, and the inotropic effect of Iso on Ca(i)(2+) transients was reduced approximately twofold versus WT myocytes. Protein expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 and phospholamban was unaltered in TG versus WT hearts, suggesting functional origins of impaired Ca(2+) handling in the former. These results indicate that cardiac-specific overexpression of TNF-alpha induces myocyte hypertrophy and gender-dependent alterations in Ca(i)(2+) handling and contractile function, which may at least partly account for changes in LV geometry and in vivo cardiac function in this model.
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PMID:Morphological and functional changes in cardiac myocytes isolated from mice overexpressing TNF-alpha. 1257 19

A 30-year-old man was admitted to our hospital for left lobar pneumonia with septic shock. Acute left-sided heart failure became evident as sepsis developed. Echocardiography revealed diffuse severe hypokinesis of the left ventricle (LV) and a pulmonary artery catheter showed Forrester subset II hemodynamics. Along with amelioration of sepsis and decrease of the serum concentrations of tumor necrosis factor-alpha and interleukin-6, LV hypokinesis improved. It is suggested that the patient's heart failure may have been due to functional depression of myocardial contractility resulting from a direct effect of the cytokines towards the cardiomyocytes, the so-called "septic myocardial depression".
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PMID:Acute reversible myocardial depression associated with sepsis. 1258 21

Immune system dysfunction is hypothesized to influence several disease states, including cardiovascular disease and psychological depression. The comorbidity of depression and coronary artery disease may be influenced by immune system-brain interactions involving proinflammatory cytokines. The present studies evaluated an index of depression in a rodent model of heart failure by measuring responses to rewarding electrical brain stimulation, which provides an experimental procedure to operationally define anhedonia in rats. Heart failure led to a rightward shift in the current-response relationship in the brain stimulation paradigm, indicative of reduced rewarding properties of the brain stimulation (i.e., anhedonia). Acute treatment with a tumor necrosis factor antagonist, etanercept, reduced circulating tumor necrosis factor- levels in rats with heart failure and restored responding for electrical brain stimulation. The current findings have implications for the study of pathophysiological mechanisms underlying the association of cardiovascular disease and depression.
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PMID:Cytokine mediation of experimental heart failure-induced anhedonia. 1261 91

Recent studies have identified the importance of proinflammatory mediators in regulating cardiac structure in health and disease. Recent studies suggest that cytokines that are expressed within the myocardium in response to a environmental injury, namely tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1) and the interleukin-6 (IL-6) family of cytokines play an important role in initiating and integrating homeostatic responses within the heart. However, these "stress-activated" cytokines all have the potential to produce cardiac decompensation when expressed at sufficiently high concentrations. Indeed, there is now a growing appreciation that these molecules may play an important role in mediating disease progression in the failing heart. The growing appreciation of the pathophysiological consequences of sustained expression of proinflammatory mediators in pre-clinical and clinical heart failure models culminated in a series of multicenter clinical trials that utilized "targeted" approaches to neutralize tumor necrosis factor (TNF) in patients with moderate to advanced heart failure. However, these targeted approaches have resulted in worsening heart failure, thereby raising a number of important questions about what role, if any, proinflammatory cytokines play in the pathogenesis of heart failure. This review will summarize the tremendous growth of knowledge that has taken place in this field, with a focus on what we have learned from the negative clinical trials, as well as the potential direction of future research in this area.
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PMID:Inflammatory mediators and the failing heart: a translational approach. 1263 May 62

Elevated levels of proinflammatory cytokines, such as tumor necrosis factor (TNF) and interleukin-6 (IL-6), have been demonstrated in patients with chronic heart failure (CHF). Evidence suggests that cytokines such as these may play a central role in the pathogenesis of this syndrome. TNF has several properties that are particularly detrimental in CHF, such as negatively inotropic effects, the promotion of left ventricular remodelling, and the induction of dilated cardiomyopathy in humans. Furthermore, TNF can cause skeletal muscle wasting and apoptosis, and, therefore, may be important in the development of cardiac cachexia. Although the precise stimulus for immune activation in CHF is unknown, one hypothesis is that endotoxin may be a significant trigger for cytokine release. This is supported by the finding that decompensated CHF patients have elevated endotoxin levels that normalize on diuretic therapy. The factors that influence endotoxin responsiveness in patients with CHF, in particular the potential importance of serum lipoproteins, will be discussed in this review.
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PMID:The importance of tumor necrosis factor and lipoproteins in the pathogenesis of chronic heart failure. 1263 90

Accumulating evidence indicates that inflammatory mediators are important in the pathogenesis of chronic heart failure. Several studies have shown raised levels of inflammatory cytokines in patients with congestive heart failure (CHF), in both plasma and circulating leukocytes, as well as in the failing myocardium itself. Importantly, many of the inflammatory cytokines (e.g. tumor necrosis factor-a and interleukin-6) have the potential to negatively influence heart contractility, induce hypertrophy, and promote apoptosis or fibrosis, thereby contributing to the continuous remodeling process in CHF. Traditional cardiovascular drugs seem to have little influence on the cytokine network in CHF patients, and immunomodulatory therapy, in addition to 'optimal' cardiovascular treatment regimens, has emerged as an option. Thus, several small studies with therapy targeted against inflammatory mediators have shown promising effects on functional capacity and myocardial performance. These studies suggest a potential for immunomodulating therapy, in addition to optimal conventional cardiovascular-treatment regimens in CHF patients. However, the results in these small studies will have to be confirmed in larger placebo-controlled mortality studies. More importantly, further research in this area will have to precisely identify the most important components in the immunopathogenesis of chronic heart failure, in order to develop more specific immunomodulating agents in this disorder.
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PMID:The cytokine network in heart failure: pathogenetic importance and potential therapeutic targets. 1263 93

Recent studies have identified the importance of biologically active molecules, such as neurohormones, as mediators of disease progression in heart failure. More recently, it has become apparent that, in addition to neurohormones, another portfolio of biologically active molecules, termed cytokines, are also expressed in the setting of heart failure. This article will review recent clinical material that suggests that tumor necrosis factor, a pro-inflammatory cytokine, may contribute to disease progression in heart failure by virtue of the direct toxic effects that this molecule exerts on the heart and circulation. In addition, this article reviews the existing clinical literature, which suggests that cytokine antagonism is safe and potentially effective in patients with heart failure.
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PMID:Experimental options in the treatment of heart failure: the role of cytokine antagonism. 1263 95

In epidemiological surveys and in large-scale therapeutic trials, the prognosis of patients with ischemic heart failure is worse than in patients with a non-ischemic etiology. Even heart transplant candidates may respond better to intensified therapy if they have non-ischemic heart failure. The term 'non-ischemic heart failure' includes various subgroups such as hypertensive heart disease, myocarditis, alcoholic cardiomyopathy and cardiac dysfunction due to rapid atrial fibrillation. Some of these causes are reversible. The therapeutic effect of essential drugs such as angiotensin-converting enzyme inhibitors, beta-blockers and diuretics does not, in general, significantly differ between ischemic and non-ischemic heart failure. However, in some trials, response to certain drugs (digoxin, tumor necrosis factor-alpha, inhibition with pentoxifylline, growth hormone and amiodarone) was found to be better in non-ischemic patients. Patients with ischemic heart failure and non-contracting ischemic viable myocardium may, on the other hand, considerably improve following revascularization. In view of prognostic and possible therapeutic differences, the etiology of heart failure should be determined routinely in all patients.
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PMID:Ischemic versus non-ischemic heart failure: should the etiology be determined? 1263 96

Experimental studies have shown that cytokine production by the heart may be regulated by sympathetic nervous system stimulation of cardiac beta-adrenergic receptors. Proinflammatory cytokine levels are increased in heart failure, whereas cardiac fixation of 123-I-metaiodobenzylguanidine (MIBG) has been used to study myocardial adrenergic innervation. This study was designed to assess the relation between cardiac MIBG uptake and circulating levels of proinflammatory cytokines in patients with idiopathic dilated cardiomyopathy (IDC). Forty-seven patients (12 women; mean age 56.5 +/- 9 years) with angiographically proved IDC, in New York Heart Association functional classes II to III, and who had left ventricular ejection fraction 30.6 +/- 9.5%, and 20 healthy controls were studied with planar MIBG. The early (10 minutes) and late (4 hours) heart to mediastinum uptake ratio and washout were calculated. Circulating plasma levels of interleukins (IL)-1 and IL-6, tumor necrosis factor-alpha, and solube receptors of TNF (sTNFR) I and II were measured. The patient group had significantly lower values of MIBG uptake at 10 minutes (p <0.001) and 4 hours (p <0.001) and higher washout (p <0.001) than the controls. Late MIBG uptake was significantly correlated with New York Heart Association class (r = -0.42, p = 0.02), left ventricular ejection fraction (r = 0.34, p = 0.01), left ventricular systolic wall stress (r = -0.40, p = 0.05), oxygen consumption at peak exercise (r = 0.32, p = 0.03), IL-1 (r = -0.55, p <0.001), TNF (r = -0.33, p = 0.02), and sTNFRII (r = -0.44, p = 0.001). Multivariate linear regression analysis revealed that MIBG at 4 hours was independently associated with IL-1 levels (p <0.001). Thus, reduced cardiac sympathetic innervation in heart failure is associated with elevated levels of inflammatory cytokines, suggesting that it has a potential inflammatory effect via modulation of the cardiac production of these cytokines.
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PMID:Relation of cardiac sympathetic innervation to proinflammatory cytokine levels in patients with heart failure secondary to idiopathic dilated cardiomyopathy. 1274 1


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