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

In situations of depressed myocardial function, the role of immunological mechanisms has been studied recently. In different pathophysiological situations, such as chronic heart failure, open heart surgery with extracorporal circulation, cardiac transplantation, myocardial infarction and angina pectoris, patterns have been described with elevation of proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1, interleukin-6, and reversible myocardial dysfunction, which may represent a final common pathway. The available data suggest a modulation of important determinants of pump function, i.e., contractility, preload, afterload, and heart rate, by cytokines. Potential mechanisms include the beta-adrenoceptor- and nitric oxide pathway, as well as a direct impact on intracellular calcium homeostasis. Interventional strategies based on this understanding are beginning to emerge.
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PMID:[Proinflammatory cytokines and cardiac pump function]. 945 46

Cytokines are being increasingly recognized as important factors in the pathogenesis and pathophysiology of heart failure. Elevated levels of circulating cytokines have been reported in patients with heart failure, and various cytokines have been shown to depress myocardial contractility in vitro and in vivo. We have recently compared the effects on cytokine production of drugs for therapy of heart failure that have different effects on survival. Amrinone, pimobendan and vesnarinone, phosphodiesterase III inhibitors that have been shown to have short term haemodynamic benefits, inhibited TNF-alpha production. Differential modulation of the production of IL-1beta and IL-6 was observed; amrinone and pimobendan enhanced the production of IL-1beta, whereas vesnarinone did not. As inotropic agents differentially modulate cytokine production, these agents may interfere with induction of inducible nitric oxide (NO) synthase through an inhibition of cytokine formation. Although differential modulation of the production of NO by inotropic agents may explain their different effect in patients with heart failure, further study is necessary to reach this conclusion. We have shown that amlodipine increases the survival of mice with viral myocarditis and inhibits expression of inducible NO synthase and production of NO in vivo and in vitro. The therapeutic effect of amlodipine may in part result from inhibition of overproduction of NO. As we learn more about the pathophysiological and pathogenetic role of cytokines in heart failure, it should be possible to design better and more targeted pharmacological agents. Furthermore, the investigation of inotropic agents that are effective against the production of cytokines may help in the classification of these agents.
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PMID:The use of cytokine inhibitors. A new therapeutic insight into heart failure. 946 76

The therapeutic effects of calcium channel blockers on heart failure are controversial. However, a recent clinical trial demonstrated a favorable effect of amlodipine on survival rates in patients with heart failure resulting from nonischemic dilated cardiomyopathy. There are a number of studies showing that cytokines generated by activated immune cells cause an increase in nitric oxide (NO) via induction of NO synthase (NOS), which results in a direct negative inotropic effect and a modulation of inotropic responsiveness. Increases in inflammatory circulating cytokines have been detected in patients with heart failure and cardiomyopathy, elevated plasma levels of nitrite/nitrate in patients with heart failure have been reported, and inducible NOS (iNOS) has been found in ventricular tissue from patients with dilated cardiomyopathy. In our recent study, amlodipine improved histopathological lesions in the heart and survival rates in a murine model of nonischemic heart failure induced by encephalomyocarditis virus. Amlodipine inhibited NO production in vitro and decreased the number of iNOS positive cells in vivo. In this model, the therapeutic effect of amlodipine on myocardial injury is considered in part to result from inhibition of overproduction of NO. In this review, the possible roles of cytokines and NO in the pathophysiology of heart failure are discussed, along with the opportunities for therapeutic intervention.
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PMID:Calcium channel blocker-induced protection against cardiovascular damage. 948 94

1 Characteristics of cyclic GMP- and cyclic AMP-mediated relaxation in aortic segments of rats with chronic heart failure (CHF) and the effects of chronic treatment with an angiotensin I converting enzyme (ACE) inhibitor, trandolapril, were examined 8 weeks after coronary artery ligation. 2 Cardiac output indices of coronary artery-ligated and sham-operated rats were 125+/-8 and 189+/-10 ml min(-1) kg(-1), respectively (P<0.05), indicating the development of CHF at this period. 3 The maximal relaxant response of aortic segments to 10 microM acetylcholine in rats with CHF and sham-operated rats was 64.0+/-5.7 and 86.9+/-1.9%, respectively (P<0.05), whereas the relaxant response to sodium nitroprusside (SNP) remained unchanged. Tissue cyclic GMP content in rats with CHF was lower than that of sham-operated rats. 4 In endothelium-intact segments of rats with CHF, the maximal relaxant response to 10 microM isoprenaline (44.5+/-6.7%) was lower that sham-operated rats (81.3+/-2.5%, P<0.05) and the concentration-response curve for NKH477, a water-soluble forskolin, was shifted to the right without a reduction in the maximal response. Isoprenaline-induced relaxation of aortic segments was attenuated by NG-nitro-L-arginine methyl ester (L-NAME) in sham-operated rats, but not in rats with CHF. Relaxation to 30 microM dibutyryl cyclic AMP in rats with CHF (26.8+/-2.7%) was lower than that in sham-operated rats (63.4+/-11.8%, P<0.05). 5 Trandolapril (3 mg kg(-1) day(-1)) was orally administered from the 2nd to 8th week after the operation. Aortic blood flow of rats with CHF (38.5+/-3.6 ml min(-1)) was lower than that of sham-operated rats (55.0+/-3.0 ml min(-1)), and this reduction was reversed (54.1+/-3.4 ml min(-1)) by treatment with trandolapril. The diminished responsiveness described above was normalized in the trandolapril-treated rat with CHF (i.e., the maximal relaxation to acetylcholine, 94.7+/-1.0%; that to isoprenaline, 80.5+/-2.8%; that to dibutyryl cyclic AMP, 54.7+/-6.2%). However, aortic segments of trandolapril-treated rats with CHF, L-NAME did not attenuate isoprenaline-induced relaxation and the tissue cyclic GMP level was not fully restored, suggesting that the ability of the endothelium to produce NO was still partially damaged. 6 The results suggest that vasorelaxation in CHF, diminished mainly due to dysfunction in endothelial nitric oxide (NO) production and cyclic AMP-mediated signal transduction, was partially restored by long-term treatment with trandolapril. The mechanism underlying the restoration may be attributed in part to prevention of CHF-induced endothelial dysfunction.
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PMID:The effect of chronic treatment with trandolapril on cyclic AMP-and cyclic GMP-dependent relaxations in aortic segments of rats with chronic heart failure. 948 24

It has been suggested that the myocardial production of nitric oxide, as a consequence of expression of the inducible isoform of nitric oxide synthase (NOS), plays an important role in the pathophysiology of heart failure. We determined the net cardiac production of nitrogen oxides (NOx), as a measure of NOS activity, by performing arterial and coronary sinus sampling in healthy control subjects (n=6) and patients with end-stage heart failure (n=10). The arterial plasma NOx concentration was significantly elevated in heart failure patients (58.4 +/- 7.0 vs 36.9 +/- 4.9 microM, p<0.05). However, we found net extraction of NOx across the heart, with no difference between the two groups. Therefore, the heart does not appear to be a source of NOx in heart failure, and this study does not support a pathophysiological role for NOx in this condition.
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PMID:The failing human heart does not release nitrogen oxides. 949 10

1. Transport of L-arginine was investigated under zero-trans conditions in human erythrocytes from healthy donors and patients with heart failure. 2. Saturable influx of L-arginine was mediated by the classical cationic amino acid transport systems y+ and y+L. 3. The Vmax for L-arginine transport via system y+ increased from 292 to 490 mumol h-1 l-1 of cells in heart failure. 4. With system y+ inhibited by N-ethylmaleimide (0.2 mmol/l), the Vmax for the transport of L-arginine via system y+L was unaffected in erythrocytes from patients with heart failure. 5. The inhibition of L-arginine and L-leucine influx by NG-monomethyl-L-arginine was similar in erythrocytes from control and heart failure patients. 6. Plasma L-arginine levels were reduced in patients with heart failure (59 mumol/l) compared with controls (125 mumol/l). Plasma from patients with heart failure also contained the endogenous L-arginine analogue NG-monomethyl-L-arginine, which was undetectable in plasma from controls. 7. Intracellular concentrations of L-arginine and NG-monomethyl-L-arginine were significantly elevated in erythrocytes from patients with heart failure compared with controls, consistent with an increased transport capacity for L-arginine and NG-monomethyl-L-arginine. 8. The present study provides the first evidence that system y+ mediates the increased transport of L-arginine in human erythrocytes from patients with chronic heart failure. These findings are similar to our previous results obtained in patients with chronic renal failure. Since both pathologies seem to present with an increased synthesis of nitric oxide, studies of L-arginine transport in erythrocytes may provide a valuable paradigm to study abnormalities of the L-arginine-nitric oxide signalling pathway.
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PMID:Increased L-arginine transport in human erythrocytes in chronic heart failure. 950 65

The objective of this study was to examine the endothelial function of internal mammary artery in patients with coronary artery disease and in heart transplant recipients. Therefore the response of this artery to increasing concentrations of acetylcholine (1, 10, 20 microg/min for 2.5 minutes each) was assessed in 6 patients in a control group, 16 patients with coronary artery disease (CAD group) matched for risk factors with 16 heart graft recipients (who underwent transplantation for nonischemic heart failure), and 12 patients with coronary artery disease and peripheral vascular disease (PVD group). Diameters of proximal and middle segments of internal mammary artery were measured by quantitative angiography. The responses to the first concentration of acetylcholine were attenuated in these three groups compared with the control group. At the highest concentration of acetylcholine the diameter increase was similar in the control and CAD groups, whereas the responses remained significantly impaired in the transplant and PVD groups. However, after selective infusion of L-arginine (30 mg/min for 11 minutes), the precursor of endothelium-derived nitric oxide, was performed, the responses to acetylcholine were restored in these two latter groups. Endothelin plasma levels were significantly enhanced in the PVD group, which exhibited the most severe impairment in acetylcholine-induced vasodilation. Thus some patients with CAD, mainly those with advanced atherosclerosis, and cardiac transplant recipients exhibit internal mammary artery endothelial dysfunction, and this abnormality seems reversible.
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PMID:Endothelial function of internal mammary artery in patients with coronary artery disease and in cardiac transplant recipients. 950 35

From the vascular point of view, cardiac failure is characterised by increased systemic resistances secondary to an increased concentration of a number of vasoconstrictor substances and also to decreased endothelium dependent vasodilatation. Endothelial dysfunction has been described both in man and in animal models, but its causes are not well understood. Such dysfunction could be due to a decrease in the production of nitric oxide, a decrease in its vasodilator effect due to an increased degradation or an increased vasoconstrictor tone. Recent data suggests an improvement or prevention of this endothelial dysfunction observed in cardiac failure by physical training and by chronic treatment with an angiotensin converting enzyme inhibitor. The improvement or preservation of endothelial function induced by exercise or ACE inhibitor could explain some of the benefits of these treatments in terms of tissue perfusion and haemodynamic conditions.
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PMID:[Endothelial dysfunction in cardial failure: potential mechanisms]. 951 11

Oxidative stress is a condition in which oxidant metabolites exert toxic effects because of their increased production or an altered cellular mechanism of protection. The heart needs oxygen but it is also susceptible to oxidative stress, which occurs during post-ischaemic reperfusion, for example. Ischaemia causes alterations in the defence mechanisms against oxygen free radicals. At the same time, production of oxygen free radicals increases. In man, there is evidence of oxidative stress during surgical reperfusion of the whole heart, or after thrombolysis, and it is related to transient left ventricular dysfunction or stunning. At present, there are few data on oxidative stress in the failing heart. It is not clear whether the defence mechanisms of the myocyte are altered or whether the production of oxygen free radicals is increased, or both. Recent data have shown a close link between oxidative stress and apoptosis. Importantly, tumour necrosis factor causes a rapid rise in intracellular reactive oxygen intermediates and apoptosis. This series of events is not confined to the myocytes, but also occurs at the level of endothelium, where tumour necrosis factor causes expression of inducible nitric oxide synthase, production of the reactive radical nitric oxide, oxidative stress and apoptosis. The immunological response to heart failure may result in endothelial and myocyte dysfunction through oxidative stress-mediated apoptosis. A better understanding of these mechanisms may lead to novel therapeutic strategies.
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PMID:Oxidative stress during myocardial ischaemia and heart failure. 951 46

Nitric oxide (NO) is a free radical gas and a short-lived messenger which has many paracrine functions. Direct assessment of NO production is very difficult in vivo. However, the paranasal cavities generate a high amount of NO which diffuses in the nasal cavity where it can be easily measured. Several studies have suggested alterations of the NO production in heart failure. Thus, we assessed nasal NO concentration in normal subjects and in heart failure patients. The nasal NO concentration averaged 227 +/- 10 ppb in the control group (n = 20), and 210 +/- 10, 198 +/- 20 and 159 +/- 54 ppb in New York Heart Association (NYHA) class II (n = 30), III (n = 28) and IV (n = 7) patients, respectively (mean +/- standard error [SE], not significant using analysis of variance [ANOVA]). Nasal NO level was not influenced by age, sex or etiology of the heart failure or by treatment with frusemide, angiotensin-converting enzyme inhibitor or digoxin. However, treatment with NO-releasing drugs (nitrates or molsidomine) significantly decreased the nasal NO level in heart failure patients. A two-way ANOVA revealed that treatment with a NO-releasing drug influenced nasal NO concentration (P = 0.0005), whereas NYHA class did not (P = 0.23), with a trend towards an interaction between the two parameters (P = 0.09): the inhibitory effect of NO-releasing drug on nasal NO concentration was more pronounced in severe heart failure. In an additional group of 12 patients (NYHA class II or III), the nasal NO concentration was 174 +/- 19 ppb during NO-releasing drug treatment and increased to 231 +/- 27 ppb 3 days after withdrawal of the nitrates (P = 0.0007 using paired t-test). Conversely, the nasal NO concentration in another group of seven patients (NYHA class II or III) was 219 +/- 32 ppb without nitrate treatment and decreased to 188 +/- 28 ppb 7 days after nitrate addition (P = 0.02 using paired t-test). In contrast, the nasal NO concentration in another group of ten ischemic patients without heart failure was 203 +/- 25 ppb without nitrate treatment and was similar (207 +/- 28 ppb) 7 days after nitrate addition (not significant using paired t-test). In conclusion, nasal NO production is normal in heart failure, except in patients receiving NO-releasing drugs. Nasal NO concentration could be useful for investigating the mechanism(s) by which exogenous NO donors decrease endogenous NO production.
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PMID:Nasal nitric oxide concentration is decreased in heart failure patients receiving nitrates. 952 91


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