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

Myocardial adenine nucleotides (nicotinamide adenine nucleotides included), glutathione, catecholamines (DOPA, dopamine, noradrenaline, adrenaline) and some enzymes in correlation were investigated in dogs with cardiac failure induced by bilateral iliac arteriovenous fistulas, and unilateral (left) heart vagotomy was also studied for its influence on the changes in the myocardial amounts of these compounds occuring in this pathological circumstance. The cardiac failure in arteriovenous fistula was characterized by the following myocardial metabolic aspects: (I) no change in the amount of proteins (although an important cardiac hypertrophy was present); (II) decreases in the amounts of adenine nucleotides (especially ADP and ATP), without significant variations in the adenosine concentration, accompanied by increases in the concentrations of nicotinamide adenine nucleotides (in both their oxidized and reduced forms) in the heart mitochondria; (III) no change in the amounts of oxidized and reduced glutathione and in the activity of NADH2-dependent glutathione reductase; (IV) a very significant increase in the activity of MAO without significant influences on the levels of the studied catecholamines. The partial vagal denervation of the heart was found to attenuate substantially the changes in the amounts of adenine nucleotides and nicotinamide adenine nucleotides in the myocardial mitochondria and to facilitate the action of MAO on noradrenaline leading to a significant decrease in its myocardial level.
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PMID:Role of the vagus nerves and catecholamines in the production mechanism of the myocardial failure induced by arteriovenous fistulas. 21 43

Lipid peroxidation (LPO) was studied in 90 patients with chronic heart failure (CHF) in relation to the disease stage. The patients with various CHF showed increased LPO and decreased antioxidative function. Impaired LPO was more pronounced in patients with Stage II CHF. To correct LPO processes, emoxipine, a new synthetic antioxidant, was used in 48 patients. The agent in a dose of 40 mg/day was ascertained to have a regulatory effect on the oxidative-antioxidative system in patients with heart failure. A more profound effect was observed in patients with Stage I patients. The main mechanism of the antioxidative action of emoxipine in CHF was to enhance glutathione reductase and glutathione peroxidase and to lower the level on dienic conjugates in patients with Stage IIB CHF.
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PMID:[Effects of emoxipine on lipid peroxidation in patients with chronic heart failure]. 180 67

Cardiac hypertrophy in rats was induced by the narrowing of the abdominal aorta 3.14 and 30 days before the experiment. It has been shown that activation of NADP.H production under these conditions leads to elevation of NADP.H-dependent lipid peroxidation (LPO) level and to decrease of glutathione reductase (GR) activity, that means that changes take place in the antioxidant state of the cardiac tissue. Use of alpha-tocopherol and thiamine normalizes LPO level and induces elevation of GR activity. These data when compared with those obtained in investigation of the cardiac pumping function during its intensive activity could be estimated as favourable prerequisites for prevention of cardiac insufficiency.
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PMID:[The role of alpha-tocopherol and thiamine in the correction of lipid peroxidation in compensatory myocardial hypertrophy]. 183 83

It is found that glutathione reductase and superoxidismutase activity decreases in postmitochondrial fraction of the myocardium tissue under cardiovascular insufficiency of the hemodynamic type. In erythrocytes the activity of lipoperoxide-detoxicating glutathione peroxidase--GSH-peroxidase II lowers and that of hydrogen peroxide-utilizing GSH-peroxidase I grows. Disturbances in the antioxidant enzymic systems are discussed for their role in development of cardiac insufficiency.
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PMID:[Activity of enzymes with an antioxidant action in the myocardium and blood of the rat during cardiovascular insufficiency]. 671 Jun 16

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

Myocardial activity and gene expression of antioxidant defenses and oxidative damage were examined in an experimental model of pressure overload hypertrophy. Male Wistar rats were divided into abdominal aortic-banded or sham-operated groups. After 30 days, arterial pressure and heart rate were measured. Heart, lung, and liver were extracted and weighted to evaluate cardiac hypertrophy and pulmonary and hepatic congestion. Heart homogenates were prepared to quantify lipid peroxidation (LPO); the activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR); and Cu-Zn SOD and GST concentrations. Total glutathione (GSH) myocardial content was also measured. Arterial pressure (142 +/- 17 mmHg) and cardiac hypertrophy index (3.4 +/- 0.45 mg/g) were significantly increased (by 38% and 22%, respectively, p<0.0001) in the aortic-banded group. LPO was enhanced by 55% in the aortic-banded group (11891 +/- 766 cps/mg protein, p<0.001) compared with that in the controls. SOD activity and concentration were higher (40% and 38%, 15.15 +/- 1.03 U/mg protein, 49.187 pixels, respectively, p<0.05) in the aortic-banded group than in the controls. Aortic-banding induced a decrease by 28% in GST (48 +/- 10 pmol/min/mg protein, p<0.005), by 36% in GPx (38.2 +/- 9.5 nmol/min/mg protein, p<0.005), by 31% in GR activities (1.55 +/- 0.23 nmol/mg protein, p<0.0005), and by 43% in GSH content (0.13 +/- 0.02 nmol/mg protein, p<0.005). In conclusion, in this model it was observed that myocardial oxidative stress induces alterations in antioxidant enzyme activities and protein expression. The follow up of these parameters could afford an early therapeutical window to avoid heart failure progression.
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PMID:Aortic-banding induces myocardial oxidative stress and changes in concentration and activity of antioxidants in male Wistar rats. 1695 25

Treatment of metastatic breast cancer with doxorubicin (Doxo) in combination with trastuzumab, an antibody targeting the ErbB2 receptor, results in an increased incidence of heart failure. Doxo therapy induces reactive oxygen species (ROS) and alterations of calcium homeostasis. Therefore, we hypothesized that neuregulin-1 beta (NRG), a ligand of the cardiac ErbB receptors, reduces Doxo-induced alterations of EC coupling by triggering antioxidant mechanisms. Adult rat ventricular cardiomyocytes (ARVM) were isolated and treated for 18-48 h. SERCA protein was analyzed by Western blot, EC coupling parameters by fura-2 and video edge detection, gene expression by RT-PCR, and ROS by DCF-fluorescence microscopy. At clinically relevant doses Doxo reduced cardiomyocytes contractility, SERCA protein and SR calcium content. NRG, similarly as the antioxidant N-acetylcystein (NAC), did not affect EC coupling alone, but protected against Doxo-induced damage. NRG and Doxo showed an opposite modulation of glutathione reductase gene expression. NRG, similarly as NAC, reduced peroxide- or Doxo-induced oxidative stress. Specific inhibitors showed, that the antioxidant action of NRG depended on signaling via the ErbB2 receptor and on the Akt- and not on the MAPK-pathway. Therefore, NRG attenuates Doxo-induced alterations of EC coupling and reduces oxidative stress in ARVM. Inhibition of the ErbB2/NRG signaling pathway by trastuzumab in patients concomitantly treated with Doxo might prevent beneficial effects of NRG in the myocardium.
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PMID:Neuregulin-1 beta attenuates doxorubicin-induced alterations of excitation-contraction coupling and reduces oxidative stress in adult rat cardiomyocytes. 1700 95

The autosomal dominant mutation in the human alphaB-crystallin gene inducing a R120G amino acid exchange causes a multisystem, protein aggregation disease including cardiomyopathy. The pathogenesis of cardiomyopathy in this mutant (hR120GCryAB) is poorly understood. Here, we show that transgenic mice overexpressing cardiac-specific hR120GCryAB recapitulate the cardiomyopathy in humans and find that the mice are under reductive stress. The myopathic hearts show an increased recycling of oxidized glutathione (GSSG) to reduced glutathione (GSH), which is due to the augmented expression and enzymatic activities of glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase, and glutathione peroxidase. The intercross of hR120GCryAB cardiomyopathic animals with mice with reduced G6PD levels rescues the progeny from cardiac hypertrophy and protein aggregation. These findings demonstrate that dysregulation of G6PD activity is necessary and sufficient for maladaptive reductive stress and suggest a novel therapeutic target for abrogating R120GCryAB cardiomyopathy and heart failure in humans.
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PMID:Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. 1769 48

The impact of heart failure and its treatment on specific nutrient requirements is unknown. Furthermore, depletion of water-soluble B vitamins that play key roles in the production of cellular energy in patients with heart failure can contribute to depletion of energy reserves observed in the failing heart. A cross-sectional study recently reported that approximately one third of hospitalized patients with heart failure had tissue levels suggestive of thiamin deficiency (vitamin B-1). Riboflavin (vitamin B-2) and pyridoxine (vitamin B-6) are similar to thiamin in that they are water-soluble, subject to renal excretion, have limited tissue storage, and are dependent on intake. Therefore, it was hypothesized that the status of these B vitamins may also be adversely affected by heart failure. As a result, the prevalence of patients at risk of vitamin B-2 (erythrocyte glutathione reductase activity coefficient > or = 1.2) and B-6 deficiency (plasma B-6 < or = 20 nmol/L) was determined in a cross-section of 100 patients hospitalized with heart failure between April 2001 and June 2002 as well as in a group of volunteers without heart failure. Twenty-seven percent of patients with heart failure had biochemical evidence of vitamin B-2 deficiency, while 38% had evidence of B-6 deficiency. These prevalence rates were significantly higher than those observed in the volunteers without heart failure (2% and 19%, respectively; P < or = 0.02). Use of common B-vitamin-containing supplements by patients with heart failure did not significantly reduce deficiency rates in comparison with those who did not use supplements (B-2 P=0.38 or B-6 P=0.18)). Finally, while 80% of patients with heart failure took diuretics, neither the dose nor the duration of furosemide use was related to the presence of either B-2 or B-6 deficiency. Given the physiologic importance of these vitamins, further investigations aimed at determining the effect of heart failure on specific nutrient requirements as well as the safety and efficacy of B-vitamin supplementation are warranted.
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PMID:B-vitamin deficiency in hospitalized patients with heart failure. 1963 Oct 47

Although the functional role of nicotinamide nucleotide transhydrogenase (Nnt) remains to be fully elucidated, there is strong evidence that Nnt plays a critical part in mitochondrial metabolism by maintaining a high NADPH-dependent GSH/GSSG ratio, and thus the control of cellular oxidative stress. Using real-time PCR, spectrophotometric and western blotting techniques, we sought to determine the presence, abundance and activity level of Nnt in human heart tissues and to discern whether these are altered in chronic severe heart failure. Left ventricular levels of the NNT gene and protein expression did not differ significantly between the non-failing donor (NF) and heart failure (HF) group. Notably, compared to NF, Nnt activity rates in the HF group were 18% lower, which coincided with significantly higher levels of oxidized glutathione, lower glutathione reductase activity, lower NADPH and a lower GSH/GSSG ratio. In the failing human heart a partial loss of Nnt activity adversely impacts NADPH-dependent enzymes and the capacity to maintain membrane potential, thus contributing to a decline in bioenergetic capacity, redox regulation and antioxidant defense, exacerbating oxidative damage to cellular proteins.
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PMID:Diminished NADPH transhydrogenase activity and mitochondrial redox regulation in human failing myocardium. 2038 92


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