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

Changes in cardiac metabolism in myocardial failure and after alcohol ingestion are discussed. The main effect of alcohol ingestion is loss of cardiac contractility. Since heart muscle does not contain alcohol dehydrogenase, its toxicity is probably the result of a direct toxic effect of ethanol and acetaldehyde on the myocardial cell, possibly involving various membrane systems. Alcohol inhibits mitochondrial respiration and the activity of enzymes in the tricarboxylic acid cycle, and its interferes with both mitochondrial calcium uptake and binding. Ethanol profoundly affects myocardial lipid metabolism. Acetaldehyde diminishes myocardial protein synthesis and inhibits Ca++-activated myofibrillar ATPase. In myocardial failure, a series of possibilities may be responsible for the loss of contractility. Excitation-contraction coupling could be disturbed at the level of the sarcolemma, at the sarcoplasmic reticulum, at the mitochondria, and between calcium and the regulatory proteins. Deficiencies in Ca++ delivery systems of excitation-contraction coupling on the myosin ATPase activity could be responsible for the dimunition in cardiac contractility. Mitochondrial function may also be involved, since mitochondria from failing human hearts are defective with respect to respiratory control and calcium accumulation. Under certain conditions, the relationship of mitochondria to calcium sequestration is very important in influencing contractility. The involvement of contractile and regulatory proteins in myocardial failure cannot be excluded.
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PMID:Cardiac metabolsim: its contributions to alcoholic heart disease and myocardial failure. 15 68

Acute iron poisoning and chronic iron overload are well-known causes of myocardial failure. Although the exact mechanism is not known, excess iron-catalyzed free radical generation is conjectured to play a role in damaging the myocardium and altering cardiac function. We report here on the effects of acute and chronic iron-loading on the total iron concentration, glutathione peroxidase activity, and cytotoxic aldehyde production in the heart of a murine model (n = 35). Light microscopic examination for the presence of ferrous and ferric iron was undertaken following histochemical staining for these species. In addition, examination of representative samples by transmission electron microscopy was performed. Our findings show that iron-loading can result in significant increases in total iron concentrations, alterations to glutathione peroxidase activity, and increases in cytotoxic aldehyde concentrations in the hearts of mice. Furthermore, we observe that iron-loading can significantly alter and damage various cellular constituents (e.g., mitochondria, lysosomes, sarcoplasmic reticulum) and this may have bearing on the mechanism of iron-induced heart failure.
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PMID:A biochemical, histochemical, and electron microscopic study on the effects of iron-loading on the hearts of mice. 1061 16

Although the mechanism of myocardial failure following acute iron poisoning is not known, excess iron-catalyzed free radical generation is conjectured to play a role. The effects of time (0 to 360 minutes) on total iron concentrations, glutathione peroxidase activity, and cytotoxic aldehyde production in heart of mice (B6D2F1, n = 65) were first investigated following acute iron-loading (20 mg iron dextran i.p./mouse). In a subsequent experiment, the effects of dose (0 to 80 mg iron dextran i.p./mouse, n = 75) on the aforementioned parameters were investigated. Our results show that the concentrations of cytotoxic aldehydes: (1) significantly differ over-time, with corresponding increases in total concentrations of iron (r = 0.93, p < 0.001); and (2) increase parallel to the total dose of iron administered (r = 0.95, p < 0.001). Furthermore, dose-and time-dependent alterations to glutathione peroxidase activity are observed, which is most likely due to an acute up-regulation of the enzyme as an endogenous protective response to increased free radical activity in the heart subsequent to iron-loading. While no single mechanism is likely to account for the complex pathophysiology of acute iron-induced heart failure, our results shown that iron-loading can result in significant free radical generation, as quantified by cytotoxic aldehydes, in heart tissue of mice. This is the first report on the effects of time and dose on cytotoxic aldehyde generation and glutathione peroxidase activity in heart of mice following acute iron-loading.
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PMID:Cytotoxic aldehyde generation in heart following acute iron-loading. 1083 29

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

Whether alcohol-induced heart failure is caused by a direct toxic effect of ethanol, metabolites, or whether it is a secondary result of neurohumoral, hormonal, or nutritional factors is not clear. To address this question a Langendorff retrograde coronary perfusion model of rat heart was used to study the effect of 0.5% (v/v) ethanol (n = 7) and 0.5 mM acetaldehyde (n = 9) on left ventricular expression of ANP, BNP, p53, p21, TNF-alpha,bax, bcl-2 as well as on DNA-fragmentation. Ethanol infusion of 150 min duration significantly induced both ANP and p21 mRNA expression of ventricular myocardium compared with hearts infused with vehicle (n = 8). Acetaldehyde did not exert any significant effects on any of the parameters studied, although the mean expression of TNF-alpha tended to be lower in the acetaldehyde-treated hearts than in control hearts. No evidence of increased DNA-fragmentation was found in ethanol or acetaldehyde treated groups. We conclude that ethanol per se is capable of inducing genes associated with hypertrophy and impaired function of the heart whereas a significant apoptosis is not involved in the initial phase of alcohol-induced cardiac injury.
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PMID:Ethanol infusion increases ANP and p21 gene expression in isolated perfused rat heart. 1118 Oct 50

Chronic iron overload is a major cause of cardiac failure throughout the world, but its pathogenesis remains to be clarified. It is conjectured that the toxicity of iron is due to its ability to catalyze the formation of oxygen free radicals (OFR), which can damage cellular membranes, proteins, and DNA. The authors report on the cardioprotective effects of the glutathione peroxidase (GPx) mimic ebselen on iron concentrations in the heart and GPx activity, and on the production of the cytotoxic aldehydes hexanal, 4-hydroxyl-2-nonenal (HNE), and malondialdehyde (MDA). Fifteen B6D2F1 mice were randomized to 1 of 3 treatment groups for a total of 20 treatments: 1) control (0.1 mL normal saline i.p. per mouse, per day); 2) iron-only (10 mg iron dextran i.p. per mouse, per day); 3) iron plus ebselen (25 mg/kg p.o. per mouse, per day). In comparison to iron-only treated mice, the authors' findings show that supplementation with ebselen can decrease both cytotoxic aldehyde and iron concentrations in heart tissue. Additionally, mice supplemented with ebselen had an increase in GPx activity level in comparison to iron-only treated mice. To the authors' knowledge, this is the first study to examine the cardioprotective effects of ebselen against OFR damage in a model of chronic iron overload. These findings suggest that ebselen may have significance in the management of disorders of iron overload.
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PMID:Ebselen decreases oxygen free radical production and iron concentrations in the hearts of chronically iron-overloaded mice. 1518 6

Heart failure is associated with increased myocardial expression of TNF-alpha. However, the role of TNF-alpha in the development of heart failure is not fully understood. In the present study, we investigated the contribution of TNF-alpha to myocardial mitochondrial dysfunction, oxidative stress, and apoptosis in a unique dog model of heart failure characterized by an activation of all of these pathological processes. Male mongrel dogs were randomly assigned (n = 10 each) to 1) normal controls; 2) chronic pacing (250 beats/min for 4 wk) with concomitant administration of etanercept, a soluble p75 TNF receptor fusion protein, 0.5 mg/kg subcutaneously twice weekly; 3) chronic pacing with administration of saline vehicle. Mitochondrial function was assessed by left ventricular (LV) tissue mitochondrial respiratory enzyme activities. Oxidative stress was assessed with aldehyde levels, and apoptosis was quantified by photometric enzyme immunoassay for cytoplasmic histone-associated DNA fragments and terminal deoxynucleotide transferase-mediated nick-end labeling (TUNEL) assays. LV activity levels of mitochondrial respiratory chain enzyme complex III and V were reduced in the saline-treated dogs and restored either partially (complex III) or completely (complex V) in the etanercept-treated dogs. Aldehyde levels, DNA fragments, and TUNEL-positive cells were increased in the saline-treated dogs and normalized in etanercept-treated dogs. These changes were accompanied by an attenuation of LV dilatation and partial restoration of ejection fraction. Our data demonstrate that TNF-alpha contributes to progressive LV dysfunction in pacing-induced heart failure, mediated in part by a local impairment in mitochondrial function and increase in oxidative stress and myocyte apoptosis.
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PMID:In vivo TNF-alpha inhibition ameliorates cardiac mitochondrial dysfunction, oxidative stress, and apoptosis in experimental heart failure. 1520 65

Iron's chemical structure and its ability to initiate one-electron reactions are properties that cause it to play a major role in the production and metabolism of oxygen free radicals in biological systems. Oxygen free radicals are conjectured to cause cardiac failure in individuals afflicted with disorders of iron overload. We report on the use of both acyloins and aldehydes as markers of oxidative stress in a murine model of chronic iron-overload cardiomyopathy. Twenty mice were randomized to four treatment groups: (1) control (0.2 mL normal saline ip/mouse/d); (2) 100 mg iron (0.05 mL iron dextran/mouse/d); (3) 200 mg iron (0.1 mL iron dexxtran/mouse/d); (4) 400 mg iron (0.2 mL iron dextran/mouse/d). Significant dose-dependent increases in both total heart aldehyde and total heart acyloin concentrations were found. Furthermore, a significant positive correlation existed between the dose of iron administered and each quantified aldehyde and acyloin found in the heart.
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PMID:Dose-dependent effects of chronic iron burden on heart aldehyde and acyloin production in mice. 1523 57

By the method of autopsy in patients with ischemic heart disease (IHD) who died of acute heart failure we took samples of myocardium from 6 parts of the heart: left and right atrium, left and right ventricle, region of myocardial infarction, and scar of the left ventricle. Simultaneously we conducted histological study of these parts of myocardium. For the control we investigated content of chemical elements in myocardium of healthy victims of traffic accidents. By the method of roentgen fluorescent analysis with the use of synchrotron emission we detected content of 17 chemical elements: 4 macroelements (S, Cl, K, Ca) and 13 microelements (Cr, Mn, Fe, Ni, Cu, Zn, Se, Br, Rb, Sr, As, Mo, Hg). It was established that in patients with IHD who had died of acute heart failure content of Ca was elevated 4-8 fold in all parts of the heart. In infarction zone compared with other regions of the heart maximal quantity of Sr, Cr, Hg was contained. These elements can be looked upon as markers of infarction. In myocardium of patients with IHD especially in the zone of infarction elevation of activity of processes of lipid peroxidaton has been noted (calculated activity of malone aldehyde as example).
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PMID:[Distribution of chemical elements in various parts of the heart of patients with acute heart failure]. 1826 Oct 8

A total of 99 patients with systolic chronic cardiac insufficiency (CCI) of NYHA functional class II-III (ejection fraction below 45%) were examined to evaluate cytokine activities, levels of oxidative stress markers and BNP fragment of brain natriuretic peptide. Patients aged 65-75 yr (group 2) had much higher levels of IL-1-beta, FNO-a, and malonic aldehyde than 26-56 year-old ones (group 1). The latter had a higher catalase activity. It is concluded that elderly patients with CCI develop more pronounced inflammatory reaction manifest as elevated C-reactive protein level, activated cytokine system, and endothelial dysfunction due to a longer history of the disease, higher frequency of ischemic etiology of CCI, and impaired NO-production in endothelium.
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PMID:[Disturbances in the cytokine system and oxidative stress in patients with chronic cardiac insufficiency]. 2036 76


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