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

Antioxidant enzyme activities and oxidative stress were evaluated in the myocardium in relation to hemodynamic function subsequent to myocardial infarction in rats. One week after the coronary ligation, the left ventricular peak systolic pressure, left ventricular end-diastolic pressure, and aortic pressures remained near control values and there were no differences in lung and liver wet/dry weight ratios between experimental and control animals. In the 4-, 8-, and 16-week experimental animals, there was a progressive drop in left ventricular peak systolic pressure and an increase in left ventricular end-diastolic pressure. Aortic systolic pressure was depressed at 8 and 16 weeks. In myocardial infarct rats, there was a significant increase in wet/dry weight ratio of lungs at 8 weeks and at 16 weeks; this ratio was increased for lungs as well as liver. Based on the hemodynamic data as well as other observations, animals in the 1-, 4-, 8-, and 16-week groups were arbitrarily categorized into nonfailure and mild, moderate, and severe failure stages, respectively. In the nonfailure stage, there was a marginal increase in superoxide dismutase, glutathione peroxidase, and catalase activities as well as vitamin E levels. The redox state in these hearts, assessed by the reduced/oxidized glutathione ratio, was significantly increased. Superoxide dismutase activity was unchanged in mild and moderate failure stages but significantly depressed at 16 weeks. Glutathione peroxidase and catalase activities showed progressive decreases through mild, moderate, and severe failure stages. Vitamin E levels were significantly depressed at moderate and severe failure stages. There was a progressive increase in lipid peroxidation at mild, moderate, and severe stages of heart failure and the redox ratio was significantly depressed in the severe failure stage. These data suggest that heart failure subsequent to myocardial infarction may be associated with an antioxidant deficit as well as increased myocardial oxidative stress.
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PMID:Antioxidant and oxidative stress changes during heart failure subsequent to myocardial infarction in rats. 854 18

In this study, total cytoplasmic (Cu,Zn-SOD) and mitochondrial (Mn-SOD) superoxide dismutase activities were measured in sera and pleural fluids from patients with squamous cell carcinoma of the lung. The results were compared with those of control subjects and those of patients with tuberculosis and chronic heart failure. Serum activities were found higher in all patient groups compared to control group. Highest values were however in tuberculosis group. In the correlation analysis, meaningful intra- and inter-correlations were established between enzyme activities in the samples. Results suggest that high serum and pleural fluid SOD activities are not specific biochemical parameters for carcinogenesis and, activities may also increase in some other degenerative diseases such as tuberculosis, chronic heart failure, etc. Therefore, we believe that it is not useful to use serum and pleural fluid SOD activities for diagnostic purposes in cancer. However, the activities of these enzymes in the biological samples might be used as nonspecific prognostic markers in assessing cellular and mitochondrial tissue destruction.
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PMID:Activities of total, cytoplasmic, and mitochondrial superoxide dismutase enzymes in sera and pleural fluids from patients with lung cancer. 892 62

Twenty patients of heart failure and ten matched healthy controls were included in the trial. Out of these 20 patients of heart failure, 12 patients were also studied prospectively. Plasma levels of superoxide anion and malonyldialdehyde were increased while the levels of superoxide dismutase, catalase and glutathione reductase were decreased in patients of heart failure as compared to control subjects. The alteration in oxidative stress and antioxidant system did not correlate with the age and sex of patients or the etiology of heart failure. With the increasing severity of heart failure the malonyldialdehyde and superoxide anion increased significantly and catalase, glutathione reductase and superoxide dismutase levels decreased. The group of heart failure patients with ejection fraction < 40% (n = 7) exhibited significantly higher levels of malonyldialdehyde than those with an ejection fraction > 40% (n = 13). The superoxide anion and malonyldialdehyde levels were significantly higher in patients of heart failure in the pre-treatment state as compared to those in post-treatment state. Conversely catalase, glutathione reductase and superoxide dismutase were higher in the post-treatment period as compared to their values before treatment. The addition of vitamin E in doses of 400 mg once a day orally for 4 weeks significantly reduced the malonyldialdehyde and superoxide anion levels and produced an elevation of the antioxidant enzymes. Thus, there is an apparent normalisation of the indices of oxidative stress following treatment of heart failure and a markedly improved response on vitamin E supplementation which may be more beneficial.
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PMID:Oxy free radical system in heart failure and therapeutic role of oral vitamin E. 901 63

To assess the role of oxidative stress in exercise intolerance in patients with heart failure, a symptom-limited exercise test was performed with a bicycle ergometer in 12 patients with heart failure and in 7 members of a healthy control group. Level of plasma malondialdehyde, a marker of lipid peroxidation, at rest was significantly higher in patients than in the control group. The level further increased at peak exercise in patients but not in the control group. A significant inverse correlation was observed in patients between exercise-induced changes in malondialdehyde level and erythrocyte superoxide dismutase activity (r = -0.73, p < 0.01), and those exercise-induced changes in malondialdehyde level and superoxide dismutase activity had a close correlation with peak VO2 (r = -0.63, p < 0.05 and r = 0.67, p < 0.05, respectively), whereas no such correlation was observed in the control group. These findings suggest that the oxidative stress could be related to exercise intolerance in patients with heart failure.
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PMID:Oxidative stress is related to exercise intolerance in patients with heart failure. 945 30

We performed experiments to test the hypothesis that experimental heart failure (HF) is associated with altered nitric oxide (NO)-dependent influences on the renal microvasculature, including diminished modulation of constrictor responses to ANG II. Eight to ten weeks after inducing HF in rats by coronary artery ligation, we administered enalaprilat to suppress ANG II synthesis and studied renal arteriolar function using the in vitro blood-perfused juxtamedullary nephron technique. In kidneys from sham-operated rats, NO synthase inhibition [100 microM Nomega-nitro-L-arginine (L-NNA)] reduced afferent arteriolar diameter by 4.1 +/- 0.6 microm and enhanced ANG II responsiveness (10 nM ANG II decreased afferent diameter by 10.1 +/- 1.4 micrometer before and 12.8 +/- 1.6 micrometer during L-NNA treatment; P < 0.05). In kidneys from HF rats, L-NNA did not alter afferent arteriolar baseline diameter or ANG II responsiveness (10 nM ANG II decreased diameter by 12.5 +/- 1.5 micrometer before and 12.5 +/- 2.3 micrometer during L-NNA). The effects of L-NNA on efferent arteriolar function were also abated in HF rats. In renal cortex of HF rats, NO synthase activity was decreased by 63% and superoxide dismutase activity was diminished by 39% relative to tissue from sham-operated rats. Urinary nitrate/nitrite excretion was also reduced in HF rats. Thus both diminished synthesis and augmented degradation are likely to contribute to a decreased renal microvascular impact of endogenous NO during chronic HF, the consequences of which include loss of NO-dependent modulation of ANG II-induced vasoconstriction.
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PMID:Suppressed impact of nitric oxide on renal arteriolar function in rats with chronic heart failure. 988 83

Although researchers in radiation and cancer biology have known about the existence of free radicals and their potential role in pathobiology for several decades, cardiac biologists only began to take notice of these noxious species in the 1970s. Exponential growth of free radical research occurred after the discovery of superoxide dismutase in 1969. This antioxidant enzyme is responsible for the dismutation of superoxide radical--a free radical chain initiator. A fine balance between free radicals and a variety of endogenous antioxidants is believed to exist. Any disturbance in this equilibrium in favour of free radicals causes an increase in oxidative stress and initiates subcellular changes leading to cardiomyopathy and heart failure. Our knowledge about the role of free radicals in the pathogenesis of cardiac dysfunction is fast approaching the point where newer therapies employing antioxidants are in sight.
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PMID:The role of oxidative stress in the genesis of heart disease. 1053 10

Oxidative stress has been implicated in the pathophysiology of myocardial failure. We tested the hypothesis that inhibition of endogenous antioxidant enzymes can regulate the phenotype of cardiac myocytes. Neonatal rat ventricular myocytes in vitro were exposed to diethyldithiocarbamic acid (DDC), an inhibitor of cytosolic (Cu, Zn) and extracellular superoxide dismutase (SOD). DDC inhibited SOD activity and increased intracellular superoxide in a concentration-dependent manner. A low concentration (1 micromol/L) of DDC stimulated myocyte growth, as demonstrated by increases in protein synthesis, cellular protein, prepro-atrial natriuretic peptide, and c-fos mRNAs and decreased sarcoplasmic reticulum Ca(2+)ATPase mRNA. These actions were all inhibited by the superoxide scavenger Tiron (4,5-dihydroxy-1,3-benzene disulfonic acid). Higher concentrations of DDC (100 micromol/L) stimulated myocyte apoptosis, as evidenced by DNA laddering, characteristic nuclear morphology, in situ terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL), and increased bax mRNA expression. DDC-stimulated apoptosis was inhibited by the SOD/catalase mimetic EUK-8. The growth and apoptotic effects of DDC were mimicked by superoxide generation with xanthine plus xanthine oxidase. Thus, increased intracellular superoxide resulting from inhibition of SOD causes activation of a growth program and apoptosis in cardiac myocytes. These findings support a role for oxidative stress in the pathogenesis of myocardial remodeling and failure.
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PMID:Inhibition of copper-zinc superoxide dismutase induces cell growth, hypertrophic phenotype, and apoptosis in neonatal rat cardiac myocytes in vitro. 1041 96

The use of the potent antitumor antibiotic doxorubicin (DOX) is hampered because of its severe cardiac toxicity that leads to the development of cardiomyopathy and heart failure. In this study, we have developed a cell culture model for DOX-induced myocardial injury using primary adult rat cardiomyocytes that were cultured in serum-free medium and exposed to 1 to 40 microM DOX. DOX caused a dose-dependent release of sarcosolic enzyme lactate dehydrogenase (LDH) from cultured myocytes. The release of LDH was prevented by the cell-permeable superoxide dismutase (SOD) mimetic (MnTBAP), but was unaffected by either cell-impermeable SOD enzyme, or manganese (II) sulfate. Ebselen, a glutathione peroxidase (GPx) mimetic, enhanced the protection of cardiomyocytes afforded by MnTBAP. DOX caused the increased formation of oxidants in cardiomyocytes, and MnTBAP lowered the amount of intracellular oxidants induced by DOX. In addition, DOX selectively inactivated aconitase in cardiomyocytes, and MnTBAP partially reversed this inactivation. Ebselen further amplified the protective effect of MnTBAP on aconitase activity. These results suggest that the SOD mimetic MnTBAP prevents DOX-induced damage to cardiomyocytes and that the GPx mimetic ebselen synergistically enhanced the cardioprotection afforded by MnTBAP. Relevance of these findings to minimizing cardiotoxicity in cancer treatment is discussed.
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PMID:Cell-permeable superoxide dismutase and glutathione peroxidase mimetics afford superior protection against doxorubicin-induced cardiotoxicity: the role of reactive oxygen and nitrogen intermediates. 1044 96

The suggested role of oxidative stress in the pathogenesis of heart failure is largely based on utilizing left heart failure models. The present study on rats evaluated changes in antioxidants as well as oxidative stress in relation to hemodynamic function subsequent to the right heart failure induced by monocrotaline (50 mg/kg, i.p.). During the post-injection period, monocrotaline (MCT)-treated rats demonstrated a persistent growth depression. Two to three weeks after the injection, MCT-treated rats showed signs of fatigue, peripheral cyanosis and dyspnea. In these rats, right heart hypertrophy was confirmed by a significant increase in right ventricular weight as well as right ventricle to body weight ratio. In MCT-treated rats, there was also a significant increase in right ventricular systolic as well as end diastolic pressures. No change in lung and liver wet/dry weight ratios between MCT-treated and control animals was observed. Based on the hemodynamic data as well as other clinical observations, the functional stage achieved was compensated heart failure. Myocardial antioxidant enzymes, catalase, glutathione peroxidase and superoxide dismutase, in the MCT-treated rats were not different compared to control rats. Vitamin E levels were significantly depressed in the RV and there was no change in retinol levels. There was a significant increase in lipid hydroperoxide concentrations in MCT-treated rats as compared to the control group. These data provide evidence that right heart failure is associated with an increase in oxidative stress.
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PMID:Myocardial oxidative stress changes during compensated right heart failure in rats. 1044 2

Resveratrol (trans-3,4',5-trihydroxystibene) is a phytopolyphenol isolated from the seeds and skins of grapes. Recent studies indicate that resveratrol can block the process of multistep carcinogenesis, namely, tumor initiation, promotion and progression. Resveratrol can also reduce the risk of cardiovascular disease in man. The molecular mechanisms of resveratrol in chemoprevention of cancer and cardiovascular disease are interesting and under intensive investigation. Resveratrol was found to strongly inhibit nitric oxide (NO) generation in activated macrophages, as measured by the amount of nitrite released into the culture medium, and resveratrol strongly reduced the amount of cytosolic inducible nitric oxide synthase (iNOS) protein. The activation of nuclear factor kappa B (NF kappa B) induced by lipopolysaccharide (LPS) was inhibited by resveratrol. The phosphorylation and degradation of nuclear factor inhibitor kappa B alpha (I kappa B alpha) were inhibited by resveratrol simultaneously. Reactive oxygen species (ROS) are regarded as having carcinogenic potential and have been associated with tumor promotion. Resveratrol may act as a reactive oxygen species scavenger to suppress tumor development. In addition, resveratrol may block multistep carcinogenesis through mitotic signal transduction blockade. Reactive oxygen species are pivotal factors in the genesis of heart disease. Meanwhile, efficient endogenous antioxidants, including superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and catalase, are present in tissues. A fine balance between reactive oxygen species and endogenous antioxidants is believed to exist. Any disturbance of this balance in favor of reactive oxygen species causes an increase in oxidative stress and initiates subcellular changes, leading to cardiomyopathy and heart failure. The experimental results indicate that exogenous antioxidant resveratrol is of value in chemopreventing the development of heart disease. It is urgent that more efforts be made to investigate newer therapies employing antioxidants for the chemoprevention of cardiovascular disease and cancer.
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PMID:Chemoprevention of cancer and cardiovascular disease by resveratrol. 1049 90


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