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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

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

The year 2000 provided many new articles in clinical pharmacology and therapeutics in the different fields of cardiology. The authors present some of them in this review. In the field of prevention, the statins were the object of complementary studies showing their value in high cardiovascular risk patients with benefits not only in the reduction of coronary but also cerebrovascular events. These benefits are maintained at long-term. The debate about the value of Vitamin E is still on-going with divergent results (HOPE, SPACE studies...). The absence of secondary coronary prevention by post-menopausal hormone replacement therapy seems to be confirmed. The arrhythmogenic risk of neuroleptic drugs is of increasing concern. New data also suggests the possibility of a venous thromboembolic risk. The NSAIDs are an important factor in the first episode of cardiac failure. The risk of thromboembolism with the 3rd generation of contraceptives has been confirmed. Some data has been published about the safety of drugs used in cardiology: the haemorrhagic risk of LMW heparin in renal failure and of aspirin, even at low doses, drug interactions, aspirin-ACE inhibitors interaction. Future perspectives include the potential value of vasopeptidase inhibitors, of cerebral natriuretic peptide and of therapeutic approaches to induce angiogenesis in ischaemic heart disease (gene therapy, recombining factors).
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PMID:[The best in 2000 on clinical pharmacology]. 1126 Aug 38

Oxidative stress has been implicated in the pathogenesis of both heart hypertrophy and heart failure. Hypertrophied heart, in response to pressure overload, is associated with an increase in antioxidant capacity and a decrease in oxidative stress. However, in the hypertrophied heart due to energy metabolic disorder, antioxidant capacity has not been investigated. Antioxidant changes in juvenile visceral steatosis (JVS) mice, a model of heart hypertrophy due to disorder of fatty-acid oxidation, were examined at 4 weeks (developing hypertrophy stage) and 8 weeks of age (established hypertrophy stage). Superoxide dismutase activity in the JVS mice was higher than that in control mice at 4 weeks of age and was not different from that in the control mice at 8 weeks of age. Glutathione peroxidase activity in the JVS mice at 8 weeks of age was lower than that in the control mice. Catalase activity showed no significant differences between the control and the JVS mice. Lipid peroxidation in the JVS mice was significantly reduced at 4 weeks of age and increased toward control levels at 8 weeks of age. The levels of vitamin E in the heart were increased in the JVS mice at 8 weeks of age. To determine whether antioxidants affect the pathogenesis of hypertrophy in this model, long-term treatments of vitamin E and 2-mercaptopropionyl glycine were performed. Vitamin E treatment partially reduced the heart hypertrophy in these mice. The present study shows that heart hypertrophy in the JVS mice is accompanied with increased antioxidant capacity as indicated in other animal models of heart hypertrophy. The precise mechanism of heart hypertrophy in JVS mice is still unknown, but oxidative stress may play a role in the pathogenesis of heart hypertrophy.
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PMID:Antioxidant changes in the hypertrophied heart due to energy metabolic disorder. 1160 89

Experimental and epidemiological evidence suggests that activation of the reninangiotensin-aldosterone system and oxidative modification of low density lipoprotein cholesterol both play important roles in atherosclerosis. A substudy of the HOPE (Heart Outcomes Prevention Evaluation) trial, the SECURE trial (Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E), evaluated the effects of long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor, ramipril, and with vitamin E on atherosclerosis progression in high risk patients. A total of 732 patients were enrolled into the study. These patients were 55 years or older, had vascular disease or diabetes with at least one other cardiovascular risk factor, but did not have heart failure or low ejection fraction. Patients were randomly assigned according to a three-by-two factorial design to receive placebo, ramipril 2.5 mg/day or ramipril 10 mg/day and placebo or vitamin E 400 IU/day. Progression of atherosclerosis was evaluated by B-mode carotid ultrasonography. The primary outcome evaluated was the annualised progression slope of the mean maximum carotid intimal-medial thickness (IMT) across 12 pre-selected carotid arterial segments. The average follow-up was 4.5 years. The progression slope of the mean maximum IMT was 0.0217 +/- 0.04 mm/year in the placebo group, 0.018 +/- 0.44 mm/year in the ramipril 2.5 mg/day group and 0.0137 +/- 0.04 in the ramipril 10 mg/day group (P = 0.33 for the overall effect of ramipril and P = 0.028 for the comparison between patients receiving ramipril placebo and ramipril 10 mg/day). The reduction in atherosclerotic progression observed with ramipril remained significant after adjusting for systolic and diastolic blood pressure changes (P = 0.043) and after multivariate adjustment (P = 0.046). Administration of vitamin E 400 IU/day had no impact on atherosclerosis progression. The SECURE study is the first demonstration, in human subjects, of an effect of ACE inhibition on atherosclerotic progression. This benefit cannot be explained by the lowering of blood pressure alone. Vitamin E 400 IU/day had a neutral effect on the ultrasound measurements of atherosclerosis progression in the SECURE trial.
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PMID:Modifying the natural history of atherosclerosis: the SECURE trial. 1171 53

The Heart Outcomes Prevention Evaluation (HOPE) study conclusively demonstrated that ramipril, an angiotensin-converting enzyme (ACE) inhibitor, reduces the risk of cardiovascular death, myocardial infarction (MI), and death in patients at risk for cardiovascular events but without heart failure. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) substudy demonstrated that ramipril also reduced atherosclerosis. These results suggest that the renin-angiotensin system (RAS) has a more important role in the development and progression of atherosclerosis than previously believed, and they indicate the need for further clinical studies to define the range of benefits available from modifying the RAS. Achieving maximum benefit may require treatment with both an ACE inhibitor and an angiotensin II type-1 receptor blocker (ARB). The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) study indicated that combining an ACE inhibitor with an ARB decreased blood pressure and improved the ejection fraction more than treatment with either drug alone in patients with congestive heart failure. The Valsartan in Heart Failure Trial (Val-HeFT) showed that the combination of an ACE inhibitor and an ARB reduced hospitalization for heart failure in patients with congestive heart failure by 27.5%, although no decrease in all-cause mortality was observed. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) is a large, long-term study (23,400 patients, 5.5 years). It will compare the benefits of ACE inhibitor treatment, ARB treatment, and treatment with an ACE inhibitor and ARB together, in a study population with established coronary artery disease, stroke, peripheral vascular disease, or diabetes with end-organ damage. Patients with congestive heart failure will be excluded. In a parallel study, patients unable to tolerate an ACE inhibitor will be randomized to receive telmisartan or placebo (the Telmisartan Randomized Assessment Study in ACE-I Intolerant Patients with Cardiovascular Disease [TRANSCEND]). The primary endpoint for both trials is a composite of cardiovascular death, MI, stroke, and hospitalization for heart failure. Secondary endpoints will investigate reductions in the development of diabetes mellitus, nephropathy, dementia, and atrial fibrillation. These 2 trials are expected to provide new insights into the optimal treatment of patients at high risk of complications from atherosclerosis.
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PMID:From the HOPE to the ONTARGET and the TRANSCEND studies: challenges in improving prognosis. 1183 7

Experimental and clinical evidence suggest that angiotensin converting enzyme (ACE) inhibition may reduce cardiovascular (CV) risk by directly affecting endothelial dysfunction, atherosclerosis and thrombus formation. These direct effects are in addition to effects on vascular tone or pressure. The Health Outcomes and Prevention Evaluation (HOPE) study assessed the role of an ACE inhibitor ramipril in reducing CV events in 9297 patients > or = 55 years who were at high risk of CV events but did not have left ventricular dysfunction, heart failure, or high blood pressure at the time of study entry. In the overall HOPE population, the risk of the primary composite outcome (cardiovascular death, myocardial infarction, or stroke) was reduced by 22% (p < 0.001), and in patients with diabetes plus one other CV risk, it was reduced by 25% (p = 0.0004). Ramipril treatment achieved risk reduction in patients with mild renal insufficiency (serum creatinine > or = 1.4 mg/dl). Ramipril treatment did not increase adverse events in patients with renal insufficiency. The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and Vitamin E (SECURE) demonstrated that ramipril 10 mg significantly reduced the rate of carotid intimal medial thickening, suggesting a direct effect on atherosclerotic progression.
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PMID:What should the role of ACE inhibitors be in the treatment of diabetes? Lessons from HOPE and MICRO-HOPE. 1184 51

Exogenous n-3 polyunsaturated fatty acids (PUFA) and specially docosahexaenoic acid (DHA) have been previously reported to potentiate the efficacy of anticancer agents that generate an oxidative stress, such as anthracyclines, by enhancing the susceptibility of cell membranes to lipid peroxidation. Since lipid peroxidation has also been suggested to mediate anthracycline-induced heart failure, we designed a study aimed at investigating whether a DHA-enriched diet coupled with controlled oxidative conditions prevents or aggravates this serious side effect in vivo. Female Sprague-Dawley rats were submitted for at least 3 weeks to diet enriched in DHA, which was provided either as natural oil (sardine oil, experiment 1) or in a purified form (DHASCO, experiment 2). At the same time, to constrain the nutritional oxidative status, the anti-oxidant Vitamin E or the pro-oxidant menadione/sodium ascorbate redox mixture was added. Then, epirubicin was administered weekly at two cumulative doses, 9 mg x kg(-1) (experiment 1) or 15 mg x kg(-1) (experiment 2). Cardiotoxicity was assessed by electrocardiographic (ECG) and hemodynamic measurements, completed with histological examination. Epirubicin-induced dose-dependent mortality, alterations of hemodynamic parameters and histological damages, all features characterizing the occurrence of congestive heart failure. Moreover, the addition of anti- or pro-oxidant did not change the hemodynamics either at the lowest (experiment 1) or the highest dose (experiment 2). Similarly, the ECG measurements and histological examinations did not reveal any difference. DHA was actually incorporated, as evaluated through the adipose tissue fatty acid composition. All these observations indicated that the DHA-enriched diet, placed under controlled oxidative conditions, did not appear to prevent but neither to aggravate epirubicin-induced cardiotoxicity. These findings support the idea that DHA improves the anthracycline therapeutic index.
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PMID:Anthracycline-induced cardiac toxicity is not increased by dietary omega-3 fatty acids. 1254 58

Vitamin E has many reported health effects and is recognized as the most important lipid-soluble, chain-breaking antioxidant in the body. Vitamin E has also been reported to play a regulatory role in cell signalling and gene expression. Epidemiological studies show that high blood concentrations of vitamin E are associated with a decreased risk of cardiovascular diseases and certain cancers. Yet, high doses of supplemental vitamin E have been associated with an elevated risk of heart failure and all-cause mortality. Therefore, establishing alternative strategies to improve vitamin E status without potentially increasing mortality risk may prove important for optimal nutrition. To identify dietary phenolic compounds capable of increasing blood and tissue concentrations of vitamin E, selected polyphenols were incorporated into standardized, semi-synthetic diets and fed to male Sprague-Dawley rats for 4 weeks. Blood plasma and liver tissue concentrations of alpha-T and gamma-Twere determined. The flavanols (+)-catechin and (-)-epicatechin, the flavonol quercetin, and the synthetic preservative butylated hydroxytoluene (BHT) markedly elevated the amount of alpha-T in plasma and liver. The sesame lignan sesamin and cereal alkylresorcinols substantially increased the concentrations of gamma-T, but not alpha-T, in the liver. Sesamin also increased gamma-T concentrations in plasma. In order to study the impact of selected polyphenols on the enzymatic degradation of vitamin E, HepG2 cells were incubated together with phenolic compounds in the presence of tocopherols and the formation of metabolites was determined. Sesamin, at concentrations as low as 2 microM, almost completely inhibited tocopherol side-chain degradation and cereal alkylresorcinols inhibited it, dose-dependently (5-20 microM), by 20-80%. BHT, quercetin, (-)-epicatechin, and (+)-catechin had no effect on tocopherol-omega-hydroxylase activity in HepG2 cells. In order to confirm the inhibition of gamma-T metabolism by sesame lignans in humans, sesame oil or corn oil muffins together with deuterium-labelled d6-alpha-Tand d2-gamma-Twere given to volunteers. Urine samples were collected for 72 h and analysed for deuterated and non-deuterated tocopherol metabolites. Consumption of sesame oil muffins significantly reduced the urinary excretion of d2-gamma-CEHC and total (sum of labelled and unlabelled) gamma-CEHC. Overall, the findings from these studies show that the tested dietary phenolic compounds increase vitamin E concentrations through different mechanisms and, thus, have the potential to improve vitamin E status without the use of vitamin E supplements.
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PMID:Beyond vitamin E supplementation: an alternative strategy to improve vitamin E status. 1600 12

The HOPE study was a 19 country, prospective randomized trial in which the ACE-inhibitor Ramipril but not Vitamin E significantly reduced the risk of future cardiovascular events in a high-risk population of men and women, including many with diabetes. The benefits were present in all sub-groups, independent of the presence or absence of diabetes, hypertension, evidence of cardiovascular disease, microalbuminuria, blood pressure lowering, the use of aspirin, lipid-lowering or antihypertensive medication. It provided clear evidence that Ramipril should safely and cost-effectively be used in individuals not known to have low ventricular ejection fraction or heart failure but at high-risk of cardiovascular events. It was also beneficial in patients with renal insufficiency, reducing progression of proteinuria and development of new microalbuminuria. It provided micro- and macrovascular benefits in people with diabetes, reduced the development of new cases of diabetes and showed a positive and graded association between the waist-to-hip ratio and the risk of developing diabetes. Sub-studies completed and on-going into the predictive role of natriuretic peptides, infectious and inflammatory markers, provide insight into possible mechanisms of action of Ramipril.
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PMID:The HOPE (Heart Outcomes Prevention Evaluation) Study and its consequences. 1611 72


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