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)

A hundred and eighty three patients with a primary myocardial infarction less than 4 hours old were included in a double blind trial versus placebo comparing an isolated plasminogen streptokinase activator complex (APSAC: 30 mu in 5 mn) and tissue type plasminogen activator (rt PA: 10 mg bolus followed by 90 mg in 130 mn). Clinical evolution, side effects, patency of the artery responsible for infarction, left ventricular contractile function (contrast angiography on the 7th day and angioscintigraphy on the 21st day) and infarct size were studied. The two groups were comparable in age (54 +/- 11 years), delay in randomisation (170 +/- 50 mn), infarct site and severity of cardiac failure. There was no significant difference in hospital mortality (7 in the rt PA group and 5 in the APSAC group) or in adverse effects (haemorrhage: rt PA: 9 patients, APSAC: 11 patients). The patency was 72% in the APSAC and 76% in the rt PA group. Left ventricular function and infarct size were comparable in the two groups: angiographic EF (0.50 +/- 0.1 in the APSAC and 0.52 +/- 0.1 in the rt PA group: NS); asynergic score (11.3 +/- 1.7 in the APSAC and 10.5 +/- 1.8 in the rt PA group: NS); infarct size (10.9 +/- 8.0 in the APSAC and 9.4 +/- 7.2 in the rt PA group: NS). This trial shows that these two thrombolytic agents have the same efficacy. The authors recommend adaptation of the dosage of rt PA to body weight.
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PMID:[Study of new thrombolytic agents in myocardial infarction: a multicenter randomized trial (APSAC versus rt-PA)]. 130 Sep 57

In a study of biological risk factors for sudden death in patients with coronary artery disease, 320 patients were, prospectively, recruited and followed-up over two years. None of the patients had heart failure or recent myocardial infarction. The following variables were recorded: previous acute myocardial infarction, hypertension, smoking habits, ventricular arrhythmia; the angiographic variables included: left ventricular ejection fraction, Jenkins' and mean atherosclerotic scores; lipid profile: cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoproteins Al and B; hemostatic profile: fibrinogen, fibrinopeptide A, antithrombin III, factor VIII antigen, factor VIII coagulant, protein C, plasminogen, alpha 2-antiplasmin, euglobulin clot lysis time and tissue plasminogen activator before and after venous occlusion, tissue plasminogen activator inhibitor, platelet factor 4, beta-thromboglobulin. During the follow-up period, 12 of the patients died suddenly. In these patients, ejection fraction was lower: 49 +/- 16% versus 61 +/- 14% for the other patients (P less than 0.02), fibrinogen higher: 3.9 +/- 0.8 g/l versus 3.5 +/- 0.8 for the living patients (P less than 0.05) and protein C lower: 89 +/- 39% versus 111 +/- 39% (P = 0.06) for the other patients. In multivariate analysis: lower ejection fraction (P less than 0.008), older age (P less than 0.03) and lower protein C (P less than 0.01) were correlated with sudden death. Among the patients with coronary artery disease, the raised fibrinogen and the decreased protein C appeared to be risk factors for sudden cardiac death. These alterations reflected a prothrombotic state which might increase the ischemic risk, due to an acute thrombosis, leading to the fatal ventricular arrhythmia. Determination of these hemostatic variables might be a useful adjunct for assessment of the vital prognosis of patients with coronary artery disease, especially the risk of sudden death in addition to other known clinical, electrocardiographic, hemodynamic risk factors. This would also guide both the instigation of complementary investigations and appropriate therapy in such high risk group of patients.
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PMID:Biological risk factors for sudden death in patients with coronary artery disease and without heart failure. 156 56

The high risk of subsequent mortality and morbidity following the occurrence of a myocardial infarction (MI) underlies the importance of instituting effective preventive regimens as part of the overall management of these patients. The aim of such treatment is to prolong survival by preventing sudden and non-sudden death and further major cardiovascular events. Currently available data from randomised, controlled clinical trials in MI patients indicate that early treatment with thrombolytic agents [streptokinase, anisolyated plasminogen streptokinase activator complex (APSAC) or recombinant tissue-type plasminogen activator (rt-PA)] in the first few hours after onset of symptoms significantly reduces the short term mortality following MI, with follow-up studies at 1 year indicating that the early benefits persist long term. The optimum time for initiation of thrombolytic therapy is within 6 hours of onset, but treatment started between 7 and 24 hours after onset can also be beneficial. Similarly, there is good evidence that beta-blockers (e.g. propranolol, timolol, metoprolol, atenolol) and aspirin are effective in reducing both the mortality and reinfarction rate following MI. With beta-blockers, a policy of starting treatment early intravenously and continuing orally for 2 to 3 years seems likely to save more lives than either strategy alone; however, contraindications to beta-blockade reduce the number of patients eligible to receive this treatment. In the case of aspirin, the optimum dosage has yet to be determined, but on the basis of present evidence, it seems reasonable to start treatment early with doses of 160 to 325 mg daily and continue for a year or 2 after recovery. Other studies have shown that long term oral anticoagulant therapy is also effective in reducing the mortality and reinfarction rate after MI. Subcutaneous heparin therapy given for 10 days in patients with acute anterior MI reduces the frequency of left ventricular mural thrombosis, while intravenous heparin given for greater than or equal to 4 days improves coronary artery patency rates following administration of a thrombolytic agent. In a comparison with low dose aspirin, intravenous heparin proved more effective in maintaining coronary artery patency rates after rt-PA thrombolysis. There is also evidence that oral nitrates may reduce mortality in MI patients, especially in those with heart failure. However, current data on the use of antiarrhythmic drugs do not support the routine of these drugs following MI. Similarly, with lipid-lowering agents, the evidence that lowering cholesterol is beneficial in reducing mortality after MI is at present inconclusive. Further studies with these groups of drugs are awaited with interest.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:An overview of therapeutic interventions in myocardial infarction. Emphasis on secondary prevention. 171 3

To evaluate the effects of the fibrinolytic system on the development of coronary heart disease (CHD), the level of released plasminogen activator was measured by venous occlusion in 60 CHD cases, and 20 healthy subjects. The level of plasma basic plasminogen activator activity, plasminogen, fibrinogen and serum fibrin degradation products (FDP) were determined also. In comparison with control subjects, a lower level of released plasminogen activator was found in all CHD patients, being especially marked in those with unstable angina pectoris and acute myocardial infarction. The levels of plasma plasminogen, fibrinogen and FDP were also significantly changed in these patients. In acute myocardial infarction patients, the level of released plasminogen activator was lower in cases complicated with heart failure than in those without.
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PMID:Fibrinolytic activity in coronary heart disease. 251 77

To assess hemostatic risk factors for sudden death in patients with stable angina, 323 consecutive patients were recruited prospectively. Patients with clinical heart failure or recent myocardial infarction were excluded. The following clinical variables were recorded: age, gender, smoking habits, hypertension, previous myocardial infarction, left ventricular hypertrophy, and severe ventricular arrhythmia. Angiographic variables included coronary extent, assessed from Jenkins' and mean atherosclerotic scores, and left ventricular ejection fraction. Lipid variables included total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and apolipoproteins A-I and B. Hemostatic factors included fibrinogen, fibrinopeptide A, antithrombin III, factor VIII antigen, factor VIII coagulant, protein C, plasminogen, alpha 2 antiplasmin, euglobulin clot lysis time, tissue plasminogen activator before and after venous occlusion, and plasminogen activator inhibitor. There were 34 deaths, 19 of which were sudden during the follow-up period (60 +/- 17 months). The association between each variable and the risk of sudden death was assessed by calculating the relative risk with the Cox univariate model. All significant predictors from the univariate analysis were then incorporated in a Cox multivariate model to select the independent predictors of sudden death. The independent predictors of sudden death were left ventricular hypertrophy (p < 0.04), lower left ventricular ejection fraction (p < 0.04), and shorter euglobulin clot lysis time after venous occlusion (p < 0.02), whereas fibrinogen (p < 0.07) and Jenkins' score (p < 0.08) were borderline. Determination of hemostatic variables, especially those pertaining to dynamic fibrinolysis, may thus be of value in assessing risk of sudden death.
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PMID:Predictive value of hemostatic factors for sudden death in patients with stable angina pectoris. 761 16

The finding of cardiac failure in a neonate led to the diagnosis of congenital mitral regurgitation complicating dystrophic valves. After failed surgical valvuloplasty, the child underwent mitral valve replacement with a Saint-Jude medical prosthesis at the age of 4 months. The child developed four episodes of prosthetic valve thrombosis in the two years that followed. The first was treated surgically but the three others were treated by thrombolysis associating plasminogen tissue activator and urokinase. All but one of the thromboses occurred in a context of recent destabilisation of oral anticoagulant therapy despite the initiation of heparin. Repeat thrombolysis was successfully undertaken, thereby widening the indications of this type of treatment in the infant. This case also underlines the difficulties of oral anticoagulants in infants.
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PMID:[Repeated thrombolysis and difficulties in treatment with antivitamin K in an infant with mitral valve prosthesis]. 764 92

Platelet function, antithrombin and plasminogen activities, and fibrinolytic capabilities in 11 cats with acquired heart disease were compared with results in 4 healthy cats. Of 11 cats with heart disease, 9 had hyperthyroidism with secondary cardiac dysfunction. One cat with hyperthyroidism had renal disease and heart failure, and of 2 cats with idiopathic hypertrophic cardiomyopathy, 1 also had renal disease. At the time of testing, 3 cats had thromboembolic events associated with the disease. Compared with healthy cats, cats with acquired heart disease had increased activity of antithrombin III, a protein that behaves as an acute-phase reactant. Plasminogen activity was decreased, although not significantly, in cats with acquired heart disease, compared with results in healthy cats. In cats with left ventricular dysfunction, clot retraction was decreased (marginal significance, P = 0.058) and might be attributed, in some cases, to the medications received by the cats. Dilute whole blood clots from all cats failed to lyse in vitro. This observation, at present, lacks adequate explanation. Platelets from cats with acquired heart disease, compared with platelets from healthy cats, had decreased responsiveness (aggregation and [14C]serotonin release) to adenosine diphosphate and increased responsiveness to collagen. Hyperthyroid cats were receiving various drugs (propranolol, atenolol, or diltiazem) to empirically treat clinical signs of disease attributable to cardiac dysfunction. Although numbers of cats in each group were small, definite trends were observed in the results of tests. Platelets from cats receiving atenolol had decreased responsiveness to adenosine diphosphate and unaltered responsiveness to collagen, compared with platelets from healthy cats, and may have decreased risk of thrombus formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Platelet function and antithrombin, plasminogen, and fibrinolytic activities in cats with heart disease. 806 8

In a subgroup of 45 patients with acute myocardial infarction (AMI) from the German multicenter trial of anisoylated plasminogen streptokinase activator complex (APSAC) (n = 20) versus heparin (n = 25), simultaneous thallium (TI)-201 technetium (Tc)-99m pyrophosphate (PYP) tomography was initiated to elucidate a possible benefit of APSAC over heparin. Findings in the 2 treatment groups were similar with respect to TI-201 defect score, relative scintigraphic infarct size, and in keeping with the main group coronary artery patency, global ejection fraction and maximal creatine kinase level. However, 2 different TI-201/Tc-99m PYP accumulation patterns within the area of infarction (homogeneous, group A; inhomogeneous, group B) were identified. Both treatment groups were similar with regard to the frequency of the homogeneous and inhomogeneous pattern. In comparing the 2 accumulation patterns, creatine kinase peaked earlier in group A than in group B, and global left ventricular ejection fraction was significantly higher in group A than in group B. In Group A, 30 of 31 patients and in group B 7 of 11 patients had a patent infarct-related vessel (p < 0.025). TI-201 defect score was lower in group A than in group B. Likewise, relative size of the infarction as determined from Tc-99m PYP images was significantly lower in group A than in group B. Fifteen patients experienced cardiogenic shock or severe heart failure. Patients in group B had a higher incidence of these in-hospital complications than patients in group A (92 vs 12%, p < 0.0005). Scintigraphic infarct size and TI-201 defect score were greater in patients with the aforementioned clinical events.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison in acute myocardial infarction of anisoylated plasminogen streptokinase activator complex versus heparin evaluated by simultaneous thallium-201/technetium-99m pyrophosphate tomography. 842 Feb 41

Increased activity of matrix metalloproteinases (MMPs) has been implicated in numerous disease processes, including tumor growth and metastasis, arthritis, and periodontal disease. It is now becoming increasingly clear that extracellular matrix degradation by MMPs is also involved in the pathogenesis of cardiovascular disease, including atherosclerosis, restenosis, dilated cardiomyopathy, and myocardial infarction. Administration of synthetic MMP inhibitors in experimental animal models of these cardiovascular diseases significantly inhibits the progression of, respectively, atherosclerotic lesion formation, neointima formation, left ventricular remodeling, pump dysfunction, and infarct healing. This review focuses on the role of MMPs in cardiovascular disease, in particular myocardial infarction and the subsequent progression to heart failure. MMPs, which are present in the myocardium and capable of degrading all the matrix components of the heart, are the driving force behind myocardial matrix remodeling. The recent finding that acute pharmacological inhibition of MMPs or deficiency in MMP-9 attenuates left ventricular dilatation in the infarcted mouse heart led to the proposal that MMP inhibitors could be used as a potential therapy for patients at risk for the development of heart failure after myocardial infarction. Although these promising results encourage the design of clinical trials with MMP inhibitors, there are still several unresolved issues. This review describes the biology of MMPs and discusses new insights into the role of MMPs in several cardiovascular diseases. Attention will be paid to the central role of the plasminogen system as an important activator of MMPs in the remodeling process after myocardial infarction. Finally, we speculate on the use of MMP inhibitors as potential therapy for heart failure.
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PMID:Matrix metalloproteinase inhibition after myocardial infarction: a new approach to prevent heart failure? 1148 70

Vascular remodeling, defined as lasting structural changes in the vessel wall in response to hemodynamic stimuli, plays a role in many (patho)physiological processes requiring cell migration and degradation of extracellular matrix (ECM). Two proteolytic systems, the fibrinolytic (plasminogen/plasmin) and matrix metalloproteinase (MMP) systems can degrade most ECM components. The availability of mice models with deficiency of main components of both systems has allowed to study their contribution to vascular remodeling in several biological processes. In mouse models of atherosclerosis, urokinase-mediated plasmin generation plays a role in activation of several macrophage-derived MMPs (MMP-3, -9, -12 and -13), triggering elastolysis and collagenolysis, resulting in media destruction and aneurysm formation. Neointima formation after vascular injury, a process that depends on smooth muscle cell migration, is reduced in mice with plasminogen or urokinase deficiency and enhanced in mice with deficiency of TIMP-1 (type 1 tissue inhibitor of MMPs). Also in allograft transplant arteriosclerosis and in abdominal aortic aneurysm both proteolytic systems contribute to matrix degradation. In a mouse model of myocardial infarction, urokinase deficiency protects totally and MMP-9 deficiency partially against cardiac rupture, but these animals suffer cardiac failure. Thus, the plasminogen/plasmin and MMP systems, in concert, contribute to vascular remodeling in the setting of cardiovascular disease.
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PMID:Plasmin and matrix metalloproteinases in vascular remodeling. 1148 21


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