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

Thalassaemia is a group of genetic diseases where haemoglobin synthesis is impaired. This chronic anaemia leads to increased dietary iron absorption, which develops into iron overload pathology. Treatment through regular transfusions increases oxygen capacity but also provides iron through the red cells' haemoglobin. An essential treatment, in parallel with transfusions, is the use of chelating agents to remove the excess iron deposited in tissues. These deposits are found in the liver, spleen, heart, and pancreas and are associated with cardiac failure and diabetes. The deposits in these tissues of patients have been isolated as haemosiderin. Thalassaemia patients are particularly at risk of free radical induced damage. Thus, the present study has investigated, as a model system, human cells in vitro in the Comet assay in the presence of free radicals. This assay measures DNA damage, particularly DNA strand breakage. The effects of iron overload on cells oxidatively stressed with hydrogen peroxide (H(2)O(2)) have been determined as well as the effect of the chelating agent, deferoxamine. Iron overload was simulated with ferric (FeCl(3)) and ferrous chloride (FeCl(2)), ferrous sulphate (FeSO(4)) and haemosiderins. Both human lymphocytes from a male and a female donor and human adenocarcinoma colonic cells showed an increase in DNA damage in the Comet assay after treatment with H(2)O(2). Ferric chloride produced an increase in DNA damage in human colonic cells, but little or no damage in human lymphocytes. Ferrous chloride also produced weak DNA damage in human lymphocytes, but ferrous sulphate produced a dose-related response. Deferoxamine produced no DNA damage. When H(2)O(2) was combined with FeCl(3), FeCl(2), or FeSO(4), the DNA damage produced was as least as great as or slightly greater than with H(2)O(2) alone. When deferoxamine was combined with H(2)O(2) and FeSO(4) there was a consistent decrease in response. There was little or no decrease in response when deferoxamine was combined with H(2)O(2) and FeCl(3) or FeCl(2), but at high (100-300microm) doses there were changes in the appearance of cellular DNA from Comet tails to dense centres surrounded by a diffuse area. This was probably as a consequence of chelation processes. Haemosiderin produced no damage. The three fractions of haemosiderin examined were of three different densities and from a Thai patient where the oxyhydroxide phase is the ferrihydrite. The colour change was similar to that for FeCl(3), but the level of the ferric ion in the haemosiderin was possibly too low in the sample to produce a response. The next stage is to examine peripheral lymphocytes from thalassaemic patients, with and without chelation therapy, whose cells may be more sensitive to simulated iron overload and to lower levels of haemosiderin. Teratogenesis Carcinog. Mutagen. 20:11-26, 2000.
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PMID:Effects of iron salts and haemosiderin from a thalassaemia patient on oxygen radical damage as measured in the comet assay. 1060 74

The present study investigates intracellular enzymatic pathways involved in the elimination of reactive oxygen species in the left ventricular myocardium of 10 individuals without heart failure and 12 patients with end-stage heart failure due to idiopathic dilated cardiomyopathy. Left ventricular enzyme activities, mRNA and protein levels of the hydrogen peroxide scavenging enzymes catalase (CAT) and glutathione peroxidase (GPX), and the superoxide anion scavenging enzymes mitochondrial (Mn-SOD) and cytosolic (Cu/Zn-SOD) superoxide dismutases were measured. In failing myocardium, there was a significant decrease in CAT activity (4.83+/-0.32 U/mg v 6.59+/-0.52, P<0.01) despite unchanged mRNA expression and protein levels. GPX, Mn-SOD and Cu/Zn-SOD were similar concerning activity, mRNA and protein levels. As indirect free radical markers, similar levels of the products of lipid peroxidation, malondialdehyde and 4-hydroxy-alkenals, and similar tissue nitrotyrosin content were measured. The decrease in CAT activity appears to be a post-transcriptional mechanism. A decreased myocardial capacity to scavenge hydrogen peroxide might lead to a shift in the intracellular redox balance which potentially results in activation of redox sensitive signalling pathways. Direct reactive oxygen species mediated damage was not detected by the methods applied.
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PMID:Antioxidative enzymes in human hearts with idiopathic dilated cardiomyopathy. 1065 96

It is shown that, in a multicompartmental homeostatic system, the extent of interaction between any two compartments can be assessed by determination of the difference in free energy change of one particular reaction, or a series of coupled reactions, operative in both of the compartments under consideration. Hydrogen ion concentration and carbon dioxide tension have been used to determine free energy change difference relationships between the venous and arterial compartments (-deltadeltaG(a-v)) of the circulatory system. Data from the literature (from two studies of congestive heart failure and one study of experimentally induced cardiac arrest) are used to calculate -deltadeltaG(a-v). It was found that in control subjects -deltadeltaG(a-v) is close to zero, whereas in congestive heart failure or cardiac arrest, the value rises to 150 cal mol(-1) or more, whereas in blood, the approach towards equilibrium between hydrogen and bicarbonate ions and dissolved carbon dioxide (aqueous CO2) is known to be only moderately rapid. It is concluded that, in the system under study, and with respect to the reaction H+ + HCO3- = CO2 + H2O, a high value for the free energy change difference between the two compartments (high -deltadeltaG(a-v)) must be due to an insufficient blood circulation rate. Accordingly, -deltadeltaG(a-v) is probably a quantitative measure of cardiac insufficiency.
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PMID:Thermodynamic considerations of arteriovenous gradients of hydrogen ion concentration and carbon dioxide tension. 1073 55

A sensitive sandwich enzyme immunoassay for human pulmonary surfactant protein D (SP-D) was developed and used to examine the blood SP-D levels of drowning victims. Human SP-D was purified from amniotic fluid by chromatographic methods, and an antibody against human SP-D was prepared. A polystyrene ball coated with anti-SP-D IgG was incubated with purified human SP-D, and then with anti-SP-D Fab'-peroxidase conjugate. Peroxidase activity bound to the polystyrene ball was assayed by fluorometry using 3-(4-hydroxyphenyl)propionic acid as the hydrogen donor. The detection limit of human SP-D was 5.2 pg per assay tube. Examination of cross-reactions of this sandwich enzyme immunoassay with proteins from other human organs showed it to be highly specific for lung, and Northern blot analysis detected specific SP-D mRNA expression only in lung. The SP-D concentration of normal human serum was 6.4+/-2.7 (mean+/-S.D.) ng ml(-1) (n=20). The recovery rates of 0.52 ng and 5.2 ng SP-D added to 5 microl normal human serum were 93.6+/-2.7% and 93.6+/-6.1%, respectively. Blood SP-D levels of victims from the saltwater drowning group (n=14) revealed higher concentrations (105.8+/-53.7 ng ml(-1)), while freshwater drowning victims (n=12) were estimated to be 74.1+/-43.9 ng ml(-1). The SP-D levels of 15 subjects who died of hemorrhage (n=5), heart failure (n=8), traumatic shock (n=1), and electrocution (n=1) were lower (22.0+/-8.5 ng ml(-1)), and those of asphyxia victims (n=10) were slightly higher (36.2+/-17.1 ng ml(-1)) than those of other causes of death, except for drowning. These results suggest that in drowning victims, SP-D flowed into the systemic circulation by physiological and physical mechanisms, and the differences of blood SP-D levels between saltwater drowning and freshwater drowning victims are presumed to be influenced by the type of agony and/or the length of survival time in water.
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PMID:A sandwich enzyme immunoassay for pulmonary surfactant protein D and measurement of its blood levels in drowning victims. 1075 71

Reactive oxygen species (ROS) such as the superoxide anion radical (O2.-) hydrogen peroxide (H2O2) and hydroxyl radical (.OH) have been implicated in the pathophysiology of various states, including ischemia reperfusion injury, haemorrhagic shock, atherosclerosis, heart failure, acute hypertension and cancer. The free radicals, nitric oxide (NO) and O2.- react to form peroxynitrite (ONOO-), a potent cytotoxic oxidant. A potential mechanism of oxidative damage is the nitration of tyrosine residues of protein, peroxidation of lipids, degradation of DNA and oligonucleosomal fragments. Several mechanisms are responsible for the protection of the cells from potential cytotoxic damage caused by free radicals. Cells have developed various enzymatic and nonenzymatic defense systems to control excited oxygen species, however, a certain fraction escapes the cellular defense and may cause permanent or transient damage to nucleic acids within the cells, leading to such events as DNA strand breakage and disruption of Ca2+ metabolism. There is currently great interest in the possible role of ROS in causing DNA damage that leads to cancer and spontaneous mutations. A high rate of oxidative damage to mammalian DNA has been demonstrated by measuring oxidized DNA bases excreted in urine after DNA repair. The rate of oxidative DNA damage is directly related to the metabolic rate and inversely related to life span of the organism.
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PMID:Reactive oxygen species and oxidative DNA damage. 1087 42

Growing evidence from patients with heart failure and from experimental animal models implicates effectors of innate immunity in the pathogenesis of this syndrome. The expression of the innate immunity signaling protein, Toll-like receptor 4 (TLR4), is increased in cardiac myocytes in situ and in failing myocardium, but the mechanism by which TLRs may be activated in the failing heart remains unclear. We report that TLR2, which is expressed in cardiac myocytes, participates in the response of these cells to oxidative stress, a major contributor to the pathogenesis of cardiac dysfunction. Hydrogen peroxide increased nuclear factor kappaB (NF-kappaB) activation in Chinese hamster ovary fibroblasts that overexpress TLR2 but not in normal or TLR4-overexpressing Chinese hamster ovary cells, an effect that was abrogated by an alpha-TLR2 antibody. In neonatal rat ventricular myocytes, the alpha-TLR2 antibody inhibited hydrogen peroxide-induced nuclear translocation of NF-kappaB and activator protein-1 (AP-1). Inhibition of TLR2 had no effect on tumor necrosis factor alpha-induced NF-kappaB or AP-1 activation, on the DNA binding of the basal transcription factor Oct-1, or on hydrogen peroxide-induced phosphorylation of p38 MAP kinase. Importantly, oxidative stress-induced cytotoxicity was enhanced by blocking TLR2. Given the importance of cytotoxicity and apoptosis to the pathology of the ischemic heart, an anti-apoptotic effect of TLR2 in cardiac myocytes exposed to elevated levels of ROS may limit further cardiac dysfunction.
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PMID:Role of TLR-2 in the activation of nuclear factor kappaB by oxidative stress in cardiac myocytes. 1108 76

We investigated the effect of sodium/hydrogen exchange inhibition (NHE-1) on hypertrophy and heart failure after coronary artery ligation (CAL) in the rat. Animals were subjected to occlusion (or sham) of the left main coronary artery and immediately administered a control diet or one consisting of the NHE-1 inhibitor cariporide for 13-15 wk. Hearts were separated by small [</=30% of left ventricle (LV)] and large (>30% of LV) infarcts. CAL depressed change in left ventricular increase in pressure over time (LV +dP/dt) in small and large infarct groups by 18.8% (P < 0.05) and 34% (P < 0.01), respectively, whereas comparative values for the cariporide groups were 8.7% (not significant) and 23.1% (P < 0.01), respectively. LV end-diastolic pressure was increased by 1,225% in the control large infarct group but was significantly reduced to 447% with cariporide. Cariporide also significantly reduced the degree of LV dilation in animals with large infarcts. Hypertrophy, defined by tissue weights and cell size, was reduced by cariporide, and shortening of surviving myocytes was preserved. Infarct sizes were unaffected by cariporide, and the drug had no influence on either blood pressure or the depressed inotropic response of infarcted hearts to dobutamine. These results suggest an important role for NHE-1 in the progression of heart failure after myocardial infarction.
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PMID:Na(+)/H(+) exchange inhibition reduces hypertrophy and heart failure after myocardial infarction in rats. 1115 73

Many clinical and experimental studies have established the beneficial effect of kinins in hypertension, heart failure and ischaemia-reperfusion syndrome, but little attention has been given to the role of kinins in hyperglycaemic conditions. The purpose of the present study was to determine the influence of bradykinin on the levels of glucose, insulin, malondialdehyde and hydrogen peroxide, as well as antioxidative enzyme activity in rats with streptozotocin (STZ)-induced acute hyperglycaemia. In STZ-induced hyperglycaemic rats the levels of glucose, hydrogen peroxide and malondialdehyde were increased by 256% (from 6.0+/-0.3 to 21.4+/-1.3 mmol/l, P<0.001), 33% (from 1.9+/-0.1 to 5.6+/-0.3 mmol H(2)O(2)/ml, P<0.001) and 19% (from 3.7+/-0.3 to 4.9+/-0.2 nmol/l, P<0.001) respectively. The activity of superoxide dismutase, catalase and glutathione peroxidase and the level of insulin were decreased by 46% (from 1367+/-73 to 737+/-59 U/g Hb, P<0.001), 36% (from 2.3+/-0.3 to 1.4+/-0.1 U Bergmayera/g Hb, P<0.001), 31% (from 236+/-19 to 163+/-24 U/g Hb, P<0.001) and 91% (from 47.5+/-1.7 to 2.4+/-0.5 mU/l, P<0.001) respectively in rats treated with streptozotocin. The administration of bradykinin caused the decrease in glucose, hydrogen peroxide and malondi-aldehyde levels by 38% (from 21.4+/-1.3 to 13.3+/-1.0 mmol/l, P<0.001), 37% (from 5.6+/-0.3 to 4.3+/-0.2 mmol H2O2/ml, P<0.001), 39% (from 4.9+/-0.2 to 3.0+/-0.2 nmol/l, P<0.001) respectively and the increase in insulin level and superoxide dismutase, catalase and glutathione peroxidase activity by 62% (from 2.4+/-0.5 to 4.0+/-0.4 mU/l, P<0.001), 23% (from 736.8+/-58.5 to 906.7+/-47.8 U/g Hb, P<0.001), 23% (from 1.4+/-0.1 to 1.9+/-0.1 U Bergmayera/g Hb, P<0.01) and 19% (from 163.1+/-23.6 to 202.3+/-11.7 U/g Hb, P<0.001) respectively in rats with hyperglycaemia. Thus, bradykinin is able to reduce oxidative stress in hyperglycaemic conditions.
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PMID:The effect of bradykinin on the oxidative state of rats with acute hyperglycaemia. 1116 87

The myocardial sodium-hydrogen exchanger (NHE), and more specifically the NHE-1 isoform is now well-recognized to be a major contributor to ischemic and reperfusion injury. Recent evidence suggests that NHE-1 is also potential candidate for targeted intervention in terms of attenuation of the remodelling and hypertrophic processes which contributes to heart failure. Experimental studies have shown that NHE-1 inhibitors attenuate cardiomyocyte hypertrophy induced by various factors and reduce heart failure in vivo, independently of infarct size reduction. Although the precise cellular mechanisms for NHE-1 involvement remain to be elucidated, current data suggest a potentially effective new therapeutic approach for the treatment of heart failure via NHE-1 inhibition.
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PMID:Role of sodium-hydrogen exchange in cardiac hypertrophy and heart failure: a novel and promising therapeutic target. 1151 88

Growth hormone (GH) has been reported to be useful to treat heart failure. To elucidate whether GH has direct beneficial effects on the heart, we examined effects of GH on oxidative stress-induced apoptosis in cardiac myocytes. TUNEL staining and DNA ladder analysis revealed that hydrogen peroxide (H2O2)-induced apoptosis of cardiomyocytes was significantly suppressed by the pretreatment with GH. GH strongly activated extracellular signal-regulated kinases (ERKs) in cardiac myocytes and the cardioprotective effect of GH was abolished by inhibition of ERKs. Overexpression of dominant negative mutant Ras suppressed GH-stimulated ERK activation. Overexpression of Csk that inactivates Src family tyrosine kinases also inhibited ERK activation evoked by GH. A broad-spectrum inhibitor of protein tyrosine kinases (PTKs), genistein, strongly suppressed GH-induced ERK activation and the cardioprotective effect of GH against apoptotic cell death. GH induced tyrosine phosphorylation of EGF receptor and JAK2 in cardiac myocytes, and an EGF receptor inhibitor tyrphostin AG1478 and a JAK2 inhibitor tyrphostin B42 completely inhibited GH-induced ERK activation. Tyrphostin B42 also suppressed the phosphorylation of EGF receptor stimulated by GH. These findings suggest that GH has a direct protective effect on cardiac myocytes against apoptosis and that the effect of GH is attributed at least in part to the activation of ERKs through Ras and PTKs including JAK2, Src, and EGF receptor tyrosine kinase.
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PMID:Growth hormone signalling and apoptosis in neonatal rat cardiomyocytes. 1168 20


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