Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic congestive heart failure is one of the risk groups of acquired hypercoagulant and hyperviscous state. In a group of patients with medium and severe cardiac failure the administration of sulodexide led to an increased activation of the fibrinolytic potential--a drop of PAI-1 and fibrinogen, to an increased activation of anticoagulatory potential--an increase of AT III and reduced plasma viscosity. Global coagulation and biochemical screening parameters were not affected by treatment. Administration of the preparation did not exert important undesirable effects and was well tolerated.
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PMID:[Hemocoagulation and hemorheology in heart failure and the possible effects of glycosaminoglycans]. 771 90

Coronary artery disease is the underlying cause in most of our patients with heart failure nowadays. The arguments put forward for treating these patients with ACE-inhibitors would be reinforced when convincing data are reported demonstrating 1) a reduction of malignant arrhythmias, 2) a reduction in reinfarction rate and 3) a reduction of progressive deterioration in left ventricular function. 1) ACE-inhibitors and malignant arrhythmias. The prolongation of life in heart failure patients treated with ACE-inhibitors might either derive from retarding the progression of heart failure (CONCENSUS I) or from reducing sudden cardiac death (VHeFT II-trial). However, it remains to be established whether the advantage for ACE-inhibitors in reducing sudden death only exists in comparison to a group of patients treated with the combination of hydralazine plus ISDN or whether this is true also in comparison to a placebo group. 2) ACE-inhibitors and reinfarction. Retrospective analysis of data from studies of left ventricular dysfunction (SOLVD) and from the survival and ventricular enlargement (SAVE) study suggested that ACE-inhibitors may reduce the reinfarction rate by about 20%. The underlying mechanisms are not well understood but could in part be mediated by improving endothelial function and/or attenuating the inhibition of PAI-1 through the administration of ACE-inhibitors. 3) ACE-inhibitors and progressive left ventricular dysfunction. ACE-inhibitors are effective means in retarding the remodeling process after myocardial infarction. This is not only true for the progressive increase in left ventricular dimension, but also for the progressive loss of contractile function in the primarily unaffected myocardium. Both, clinical and experimental studies suggest that the observed reduction in mortality is particularly related to the attenuation of the remodeling process by ACE-inhibitors.
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PMID:[New aspects of ACE inhibitor treatment of heart failure]. 906 71

In the early stages of left ventricular hypertrophy (LVH) acute adaptive changes occur in the coronary vasculature as it remodels. Plasminogen activators (PAs) and inhibitors (PAIs) have the potential effects of proteolytic degradation that is relevant to tissue remodeling and angiogenesis. Our study focused on the possible roles of PAI-1, PAI-2, and uPA in tPA in myocyte hypertrophy and angiogenesis in the early and late stages of pressure overload induced left ventricular hypertrophy (LVH). We divided seventeen adult swine, weighing 24.2 +/- 6.5 kg, into four groups: control, sham-operated, early LVH and late heart failure LVH group. At surgery we placed a fixed constrictor on the ascending aorta immediately above the aortic valve. This increased LV systolic pressure from 133 +/- 15 to 193 +/- 24 mm Hg after the surgery. We subdivided the early group into groups of 3 animals each that we euthanized at 8, 24 and 72 h after operation and obtained heart samples for analysis. In the late heart failure group individual animals were euthanized at 55, 59, 62 and 72 days after the detection of congestive heart failure. We also obtained tissue samples from the control and sham-operated swine. Sections for histologic analysis were fixed in 10% buffered formalin. We isolated RNA, size fractionated it using 1% formaldehyde-agarose gel electrophoresis and then did Northern blots. The mRNAs from both PAI-1 and PAI-2 showed a remarkable increase at 8 and 24 h after acute aortic constriction and returned to control by 72 h. Regional differences showed that most of the increases were in the endocardium. Three animals in the late heart failure LVH group were determined to be in congestive heart failure at about 2 months after the onset of aortic constriction. In these animals PAI-1 and PAI-2 were increased in both the left and right ventricles but remained low in an animal of the same elevation in aortic pressure seen by the LV who did not have congestive failure. These data suggest that PA and PAI gene expressions change before morphologic changes occur in the early stages of developing LVH. Also at the time of onset of congestive heart failure this increased expression reappears. PAs and PA inhibitors mRNA levels vary in the different regions of the heart reflecting changing wall stresses. Thus, the PAs and PA inhibitors may play an important role in angiogenesis that occurs during the early stages of LVH. The increased expression in the late stage of LVH may reflect further changes in wall stresses since these animals also showed overt clinical signs of heart failure.
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PMID:Increased gene expression of plasminogen activators and inhibitors in left ventricular hypertrophy. 940 71

An activated renin-angiotensin system is a major risk factor for cardiovascular events. Angiotensin II acts on AT1 and AT2 receptors. Stimulation of AT1 receptors is associated with endothelial dysfunction, mainly as the consequence of an increased vascular production of superoxide radicals, vasoconstriction, platelet activation, enhanced release of plasminogen activator inhibitor-1, activation of immediate early genes c-fos and c-jun, myocyte hypertrophy, connective tissue formation, endothelin-1 synthesis, and activation of growth factors like PDGF and TGF-beta 1. Stimulation of AT2 receptors can mitigate or abolish the growth promoting effects of AT1 receptor stimulation. The contribution of these effects--single or in combination--on the progression of atherosclerotic lesions, the phenomenon of restenosis and the process of remodeling in heart failure is being progressively elucidated. With increasing knowledge about these relationships the inhibition of AT1 receptors appears as a main target in preventive and reparative strategies in cardiovascular diseases.
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PMID:Angiotensin II and coronary artery disease, congestive heart failure, and sudden cardiac death. 983 71

Angiotensin converting enzyme inhibitors (ACE-I) are a mainstay for the treatment of heart failure, and of diabetic microalbuminuria. Recently ACE-I have been found to decrease plasma levels of circulating vascular cell adhesion molecule-1 (cVCAM-1) in patients with congestive heart failure. As increased cVCAM-1 levels are pathognomonic for diabetics with microangiopathy, we investigated the effects of ACE-I on plasma levels of cVCAM-1, intercellular adhesion molecule (cICAM-1), and cE-selectin in microalbuminuric diabetics. In addition, the effects of ACE-I on plasma levels of plasminogen activator inhibitor (PAI-1) and of tissue plasminogen activator (TPA) were studied. Fosinopril (10 mg/day) was administered over 12 weeks to 11 microalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM). As expected, baseline plasma concentrations of cE-selectin, cICAM-1, and cVCAM-1 were markedly higher in patients than in healthy control subjects (n = 82; P < .001). PAI-1 levels in NIDDM were similar to those in control subjects, whereas TPA levels were about 25% lower in patients than in control subjects (P = .013). Serum levels of cVCAM-1 decreased by -19% (CI: -25% to -13%) after treatment with fosinopril (P = .003) and were no longer different from those of the control group. In contrast, plasma levels of cE-selectin, cICAM-1, PAI-1, and TPA were unaffected. As expected microalbuminuria decreased by -44% (CI: -65 to -22; P = .004). In conclusion, fosinopril lowered cVCAM-1 levels along with microalbuminuria in NIDDM. This may represent a novel mechanism of action of ACE-I in diabetes-associated endothelial dysfunction. Whether decreased VCAM-1 expression is responsible for the observed reduction in microalbuminuria, deserves further investigation.
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PMID:Fosinopril decreases levels of soluble vascular cell adhesion molecule-1 in borderline hypertensive type II diabetic patients with microalbuminuria. 1009 Mar 51

The use of angiotensin-converting-enzyme (ACE) inhibitors in patients with heart failure and after myocardial infarction (MI) is discussed, and results of relevant studies are reviewed. In several large trials, the administration of captopril or lisinopril within the first 36 hours after the onset of chest pain due to MI was associated with significant reductions in mortality risk, compared with placebo. Trials evaluating the use of captopril, ramipril, or trandolapril at least three days after the onset of chest pain due to MI also demonstrated significant reductions in mortality risk. Pivotal clinical trials of captopril, enalapril, lisinopril, and ramipril in the treatment of heart failure are presented. Overall, ACE inhibitor therapy was shown to reduce mortality by decreasing the progression of heart failure. Possible benefits of ACE inhibition in addition to reductions in afterload and preload and preservation of serum potassium are discussed. Certain ACE inhibitors may exert positive effects by modulating plasminogen activator inhibitor-1, endothelial function, and left ventricular remodeling. If not contraindicated, long-term therapy with captopril, lisinopril, or ramipril should be used in post-MI patients. Patients with heart failure should be treated with one of the ACE inhibitors that have been shown beneficial for this indication.
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PMID:Angiotensin-converting-enzyme inhibition in heart failure or after myocardial infarction. 1103 19

Activation of the RAAS has been linked with an increased risk of myocardial infarction and stroke,(1,2,37,38) and recently these beneficial effects have, in part, been attributed to the effects of the RAAS on the fibrinolytic system. Indeed, ACE seems to occupy a central position in modulating the fibrinolytic balance, where an angiotensin II-mediated increase of PAI-1 plays a major role. By contrast, the effect on bradykinin stimulated t-PA release may be of lesser importance, although the data are conflicting. Importantly, the impact of the RAAS on the fibrinolytic balance may also contribute to the favourable effects of ACE inhibition and AT1-receptor antagonists on cardiovascular events, particularly when considering the activation of the RAAS in hypertension and heart failure. More work is clearly required in this area to elucidate potential therapeutic targets.
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PMID:The renin-angiotensin-aldosterone system and fibrinolysis. 1188 Oct 31

Atrial arrhythmias (AA), especially atrial fibrillation (AF), during acute myocardial infarction (AMI) are often associated with increased mortality and heart failure. Impaired fibrinolysis with elevated plasminogen activator inhibitor-1 (PAI-1) activity is associated with resistance to fibrinolytic therapy in AMI patients, but it is also found in patients with AF. Our aim was a prospective study of the role of pre-treatment PAI-1 levels for the presence of AA in AMI patients and the influence of AA on in-hospital mortality. In 116 AMI patients, treated with streptokinase, pre-treatment PAI-1 levels were estimated by the chromogenic method (normal levels, 0.3-3.5 U/ml) and in-hospital AA were assessed as atrial fibrillation, flutter and/or tachycardias. Between patients with and without AA, a significant difference was observed in mean pre-treatment PAI-1 levels, in several in-hospital complications and mortality (24 versus 4.4%; P < 0.01; odds ratio, 6.45; 95% confidence interval, 1.66-25.0). The PAI-1 level > 7 U/ml was the most significant independent pre-treatment risk factor for AA (P < 0.05; odds ratio, 3.5; 95% confidence interval, 1.15-10.6). We conclude that AA were a significant risk for in-hospital mortality of AMI patients, treated with streptokinase. A pre-treatment PAI-1 level > 7 U/ml was the most significant pre-treatment risk for AA in these patients.
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PMID:Plasminogen activator inhibitor-1 in patients with atrial arrhythmias during acute myocardial infarction, treated with streptokinase. 1244 14

The aim of our study was to evaluate endothelium-dependent dilatation induced by an ACE-inhibitor, calcium antagonist and beta blocker in patients suffering from heart failure (NYHA class II and III). We studied 34 patients (19M, 15F, mean age 76.96+/-8.82) in pharmacological wash-out for at least one week, divided into 3 groups: Group A (15 patients, 9M and 6F) taking ramipril (5 mg/die); Group B (10 patients, 6M and 4F) taking amlodipine (10 mg/die), Group C: (9 patients, 4M and 5F) taking carvedilole (25 mg/die). The groups were homologous for NYHA class and instrumental echographic parameters (mean EF=22.5+/-6.7 and mean sAPP 38.4+/-8.7). At the beginning and after 3 weeks of therapy, we performed a clinical and instrumental assessment; we studied endothelial function by determination of L-arginine and L-citrulline (amino acids of the nitric oxide metabolic pathway), the L-citrulline/L-arginine ratio (an index of NOS activity) and VCAM-1 (endothelial dysfunction index); haemorheological parameters (blood viscosity, plasma fibrinogen and erythrocyte morphology); coagulative/fibrinolytic parameters (PT, aPTT, fibrinogen and PAI-1). The results show that L-citrulline and L-arginine increase, while VCAM-1 decreases. The L-citrulline/L-arginine ratio increases in a statistically significant way. This trend is maintained in each group. These results demonstrate that the drugs used induce an improvement of endothelium-dependent dilatation. In addition, there is progressive haemorheological and fibrinolytic improvement, with a reduction of PAI-1 and blood viscosity.
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PMID:Haemorheological and endothelial-dependent alterations in heart failure after ACE inhibitor, calcium antagonist and beta blocker. 1245 78

The effect of acute myocardial infarction on plasma levels of testosterone in men is unclear. No previous studies have evaluated the bio-available fraction of testosterone. Low plasma testosterone levels have been associated with several risk factors for myocardial infarction, including an unfavorable fibrinolytic profile. In a prospective, case control study, we examined changes in plasma levels of sex hormones, including bio-available testosterone, in patients with acute myocardial infarction and in control subjects. In addition, changes in hormone levels in patients were compared with alterations in the fibrinolytic profile. Thirty male patients admitted with chest pain were studied. Twenty two had acute myocardial infarction and eight had non-specific chest pain. Plasma levels of total and bio-available testosterone, 17beta-estradiol, sex hormone binding globulin and insulin were measured at baseline and throughout admission. In addition, fibrinolytic factors (plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and fibrinogen) were measured in patients who received fibrinolysis. Height and weight, and the subsequent development of heart failure or myocardial dysfunction were also recorded. Patients had lower levels of bio-available testosterone (2.07 +/- 0.75 nmol/L vs. 5.3 +/- 1.7 nmol/L, p < 0.05) and higher levels of 17beta-estradiol (87.9 +/- 39.5 pmol/L vs. 48.1 +/- 18.4 pmol/L, p < 0.001) than controls. Total and bio-available testosterone levels fell acutely following myocardial infarction (11.9 +/- 3.8 nmol/L to 9.7 +/- 3.3 nmol/L, p < 0.05; 1.95 +/- 0.76 nmol/L to 1.55 +/- 0.67 nmol/L, p < 0.05). This reduction was associated with elevation of PAI-I activity and reduction of tPA activity, independent of changes in plasma insulin levels. Patients with lower baseline levels of testosterone and higher levels of 17beta-estradiol had a relatively pro-thrombotic fibrinolytic profile and increased risk of complications. In conclusion, total and bio-available levels of testosterone fall following acute myocardial infarction in men, in association with adverse changes in fibrinolytic profile. It is not clear whether this association represents a direct effect of testosterone on thrombotic tendency but warrants further investigation.
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PMID:Bio-available testosterone levels fall acutely following myocardial infarction in men: association with fibrinolytic factors. 1248 66


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