Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the role of tissue-type plasminogen activator (t-PA) and immediate percutaneous transluminal coronary angioplasty (PTCA) in treating patients with evolving transmural myocardial infarction, 50 patients received t-PA (1.25 mg/kg iv over 3 hrs) or placebo according to 3:1 double-blind randomization 3.8 +/- 1.1 hr after onset of symptoms. At emergency coronary arteriography, patency of the infarct-related vessel was demonstrated in 32 of 38 (84%) patients receiving t-PA vs two of 12 (17%) receiving placebo (p less than .001). Of the 32 patients with recanalization after t-PA, 28 had a residual stenosis of at least 50% and underwent randomization a second time to immediate (n = 15) or no PTCA (n = 13). Immediate PTCA of the infarct-related vessel was successful in all 15 patients, with reduction of the residual diameter stenosis from 80.8 +/- 8.2% to 32.5 +/- 15.6% (p less than .001). The incidence of postinfarction angina (greater than or equal to 20 min of chest discomfort and reversible electrocardiographic changes) and reinfarction (documented by recurrent creatine kinase isoenzyme elevation) was reduced in the patients receiving t-PA and PTCA (2/15) compared with that in patients receiving t-PA alone (7/13; p = .006). At 1 week there was no difference in patency of the infarct-related vessel (12/15 t-PA and PTCA vs 9/13 t-PA only) or in global ventricular functional change between the two groups (0.5 +/- 10.4 SD/chord for t-PA and PTCA vs -2.1 +/- 8.2 SD/chord for t-PA only).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A randomized, placebo-controlled trial of intravenous recombinant tissue-type plasminogen activator and emergency coronary angioplasty in patients with acute myocardial infarction. 294 35

Patients presenting within four hours of the onset of acute myocardial infarction were randomly assigned to receive 80 to 100 mg of recombinant human-tissue plasminogen activator (t-PA) intravenously over a period of three hours (n = 72) or placebo (n = 66). Administration of the study drug was followed by coronary arteriography, and candidates for percutaneous transluminal coronary angioplasty were randomly assigned either to undergo angioplasty on the third hospital day (n = 42) or not to undergo angioplasty during the 10-day study period (n = 43). The patency rates of the infarct-related arteries were 66 percent in the t-PA group and 24 percent in the placebo group. No fatal or intracerebral hemorrhages occurred, and episodes of bleeding requiring transfusion were observed in 7.6 percent of the placebo group and 9.8 percent of the t-PA group. As compared with the use of placebo, administration of t-PA was associated with a higher mean (+/- SEM) ejection fraction on the 10th hospital day (53.2 +/- 2.0 vs. 46.4 +/- 2.0 percent, P less than 0.02), an improved ejection fraction during the study period (+3.6 +/- 1.3 vs. -4.7 +/- 1.3 percentage points, P less than 0.0001), and a reduction in the prevalence of congestive heart failure from 33 to 14 percent (P less than 0.01). Angioplasty improved the response of the ejection fraction to exercise (+8.1 +/- 1.4 vs. +1.2 +/- 2.2 percentage points, P less than 0.02) and reduced the incidence of postinfarction angina from 19 to 5 percent (P less than 0.05), but did not influence the ejection fraction at rest. These data support an approach to the treatment of acute myocardial infarction that includes early intravenous administration of t-PA and deferred cardiac catheterization and coronary angioplasty.
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PMID:A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty. 296 Aug 97

Unstable angina represents an indication for percutaneous transluminal coronary angioplasty (PTCA) provided it is based on a significant fixed lesion. A primary success rate of about 90% can be expected, but in 5% to 10% the intervention will cause a myocardial infarction. Mortality is higher than in patients with stable angina and does not differ from that of bypass surgery; however, it is still below 1%. At 1 year, 50% to 90% of the patients treated with initial success are asymptomatic if redilatations for recurrences (occurring in about one third) are included. - Acute myocardial infarction was introduced as an indication for PTCA in about 1980. PTCA was first used for failures, then for incomplete successes of intracoronary streptokinase therapy, and finally in patients without pretreatment. Currently, PTCA is being evaluated in multicenter studies as an adjunct to early intravenous fibrinolysis with clot specific agents (e.g., tissue-type plasminogen activator). PTCA achieves adequate initial reperfusion in about 80% irrespective of concomitant fibrinolytic therapy. It is complicated by occlusion of an already partially recanalized vessel in 4%. Late reocclusions occur in 15%, half of them accompanied by reinfarction. Intrahospital mortality is about 5% and increases by 1% up to 1 year. PTCA has its place in the treatment of unstable angina and acute infarction. In the latter it may be advantageous to precede it with early intravenous fibrinolysis.
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PMID:[Percutaneous coronary angioplasty in unstable angina and acute infarction]. 296 78

To determine the role of intravenous tissue plasminogen activator (t-PA) in unstable angina, it was compared with placebo in a randomized, double-blind trial. Forty patients with angina at rest and provocable ischemia (pacing induced) had baseline coronary angiography, study drug infusion and then repeat angiography at 20 +/- 9 hours. All patients received diltiazem, nitrates, beta blockers, aspirin and intravenous heparin. During study drug infusion (150 mg over 8 hours), refractory ischemia necessitating emergency bypass surgery (CABG) or coronary angioplasty (PTCA) occurred in 4 of 20 t-PA patients compared with 1 of 20 placebo patients (p = 0.21). Before discharge, revascularization for persistent, provocable ischemia and a residual stenosis greater than or equal to 60% was as follows: t-PA patients, 8 PTCA and 7 CABG; placebo patients, 11 PTCA and 8 CABG (p = 0.39). Quantitative angiographic percent diameter stenosis of the culprit artery at baseline and follow-up was: t-PA 71 +/- 17 and 63 +/- 22; placebo 70 +/- 19 and 67 +/- 22 (difference not significant). However, 3 t-PA patients compared with no placebo patients demonstrated an insignificant (less than 60% diameter) residual stenosis and averted PTCA (p = 0.14). There were no complications of PTCA in the 8 t-PA patients; in contrast, 3 of 11 placebo patients had abrupt closure, necessitating emergency CABG in 2 (p = 0.23). Thus, intravenous t-PA in unstable angina can eliminate the need for PTCA in a few patients, does not appear to decrease the overall or emergency rate of revascularization procedures and may facilitate the safety of PTCA.
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PMID:Coronary revascularization after intravenous tissue plasminogen activator for unstable angina pectoris: results of a randomized, double-blind, placebo-controlled trial. 297 Jul 76

Several fibrinolytic variables, including plasminogen activator inhibitor activity, were studied before and after exercise in 67 normolipidaemic patients with coronary artery disease and in 25 hyperlipidaemic patients with coronary artery disease. Before exercise plasminogen activator inhibitor activity was higher in the patient groups than in a group of 10 healthy volunteers. For those who were normolipidaemic plasminogen activator inhibitor activity was greater in patients with angina pectoris who had had a myocardial infarction. The concentration of antigenic tissue-type plasminogen activator was similar in all the patients with coronary artery disease and higher than in the control group. After the exercise test fibrinolytic capacity was lower in the patients with angina pectoris and a previous history of myocardial infarction. After exercise both the released immunological tissue-type plasminogen activator and fibrinolytic capacity were lower in the hyperlipidaemic patients than in the normolipidaemic patients. The concentration of plasminogen activator inhibitor was also higher in the hyperlipidaemic patients. Patients with hyperlipidaemia IV had the highest plasminogen activator inhibitor activity. The increase in plasminogen activator inhibitor activity found in the patients was partially inhibited by antiserum against plasminogen activator inhibitor-1 in vitro. The formation of a complex of about 115,000 daltons between plasminogen activator inhibitor and purified tissue-type plasminogen activator was detected by a zymographic fibrin technique. These findings show that in patients with coronary artery disease fibrinolytic activity is impaired by an increase in plasminogen activator inhibitor. Impaired fibrinolysis may be related to the clinical evolution of coronary artery disease in these patients.
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PMID:Plasminogen activator inhibitor activity and other fibrinolytic variables in patients with coronary artery disease. 313 63

The ECAT Angina Pectoris Study is a European multicentre study with the aim of investigating the pathogenetic and predictive role of haemostatic factors in the progression of coronary heart disease. It is the largest study performed up to now with regard to both the number of patients with angina pectoris (n = 3043) and the number of haemostasis assays (n = 23) included. The present paper presents baseline cross-sectional data with particular reference to the relationship of haemostatic factors with each other and with the coronary risk factors age, gender and acute-phase reaction (1). Two clusters of haemostatic factors could be distinguished in which each variable was correlated (P < 0.001) to every other variable: (a) Eight fibrinolysis assays including t-PA, PAI-1 and euglobulin clot lysis time (ECLT), for which PAI-1 appeared to be the dominating factor; (b) antithrombin III, protein C, alpha 2-antiplasmin and plasminogen, the interdependence of which has no obvious explanation. (2). Twelve out of the 23 haemostasis assays were associated (P < or = 0.01) with age. Except for alpha 2-antiplasmin, these relationships indicated an increased tendency to thrombosis with increasing age. (3). Gender differences found in 14 haemostasis parameters do not indicate a consistent difference in the tendency to thrombosis between men and women. Eight haemostasis parameters were on average higher in female than in male patients in the age group over 50 years. (4). C-reactive protein, an acute-phase reactant, was positively correlated (P < 0.001) with fibrinogen, factor VIIIc, von Willebrand factor, the fibrinolysis assays t-PA, PAI-1, ECLT and plasminogen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Haemostasis factors in angina pectoris; relation to gender, age and acute-phase reaction. Results of the ECAT Angina Pectoris Study Group. 749 59

Among endothelial secretogogues prostacyclin (PGI2), nitric oxide (NO) and tissue plasminogen activator (t-PA) play a crucial role in maintaining thromboresistance, tone and structure of the vascular wall. Most receptor agonists, such as B2 kinin receptor agonists, or shear force produce a coupled release of all three secretogogues, and therefore interactions between them are to be expected. Essentially, PGI2 is a platelet suppressant, NO a vasodilator and t-PA a fibrinolytic agent. These and other properties of endothelial secretogogues supplement each other in protecting the cardiovascular system from injuries. It is not surprising that disturbances of the secretory function of endothelial cells are associated with atherosclerosis, diabetes, thrombosis or hypertension. Traditionally, PGI2, NO, t-PA or their substitutes are used individually for the treatment of peripheral arterial disease, angina pectoris or acute myocardial infarction. In light of recent findings, their joint administration can be advocated. For instance, NO donors will potentiate platelet-suppressant action of PGI2 analogues, whereas exogenous PGI2 or TXA2 synthase inhibitors (i.e. following increase in endogenous PGI2) will abolish a paradox of prothrombotic action of t-PA or streptokinase. The replacement therapy with PGI2, NO or t-PA should match as closely as possible the physiologically coupled release of these secretogogues.
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PMID:Interactions between endothelial secretogogues. 754 32

Ischemic electrocardiographic changes were recorded within 2 hours of admission using a 12-lead electrocardiographic continuous monitor with a 20-second scanning interval and an alarm mode for asymptomatic events. Blood samples were obtained at admission and at the moment of asymptomatic events (group A). In the other patients who did not develop ischemia, a second blood sample was taken 12 hours later (group B). We determined prothrombin time, activated partial thromboplastin time, clotting factor VIII activity, tissue plasminogen activator activity, tissue plasminogen activator inhibitor-1, cross-linked fibrin degradation product, and thrombin-antithrombin III complexes. There was a statistically significant difference between group A and B patients when the basal samples were analyzed for thrombin-antithrombin III (p = 0.046) and d-Dimer (p = 0.005). Prothrombin fragment 1 + 2 were significantly reduced, and d-Dimer was elevated when basal blood samples were compared with the second sample in patients who developed silent events (p = 0.008 and 0.055, respectively). A plasma concentration of thrombin-antithrombin III complex was also significantly decreased when sample 2 was compared with the basal blood sample (p = 0.039). Five recurrent episodes of angina and 2 nonfatal infarctions occurred, and 4 urgent revascularization procedures were performed in group A. In group B, there was only 1 nonfatal infarction (p = 0.01). The results of the present study suggest that a time-dependent thrombotic process is detectable in the blood stream as a cyclic movement. Further studies are needed to determine if some other factors, such as intensive shear stress in the vessel wall, may activate plaque instability during asymptomatic episodes.
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PMID:Time significance of acute thrombotic reactant markers in patients with and without silent myocardial ischemia and overt unstable angina pectoris. 761 Nov 44

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

Among patients with recent-onset unstable angina and evidence of ischemia or coronary artery disease, the incidence of subsequent cardiovascular events is high. The aim of this study was to investigate, in this high-risk population, whether unstable angina was associated with abnormalities of tissue-type plasminogen activator (t-PA) or plasminogen activator inhibitor (PAI) activities and whether, in a prospective study, any of these parameters would identify patients with an adverse cardiovascular prognosis. A group of 22 high-risk patients with unstable angina (64% event rate at 3 months) was studied prospectively for 12 weeks, and the fibrinolytic parameters measured at presentation were related to subsequent cardiovascular progress. A group of 20 age- and sex-matched healthy subjects acted as control subjects. Patients who had subsequent cardiovascular events (acute myocardial infarction or severe recurrent angina +/- intervention) had significantly elevated PAI activity at presentation compared with both those who remained event-free (p < 0.05) or with control subjects (p < 0.02). In addition, basal activation of fibrinolysis was demonstrated in unstable angina at presentation; this persisted at 9 weeks in patients with a favorable outcome (p < 0.02 vs control subjects), whereas it was no longer evident in those who developed cardiac events. These findings suggest that measurements of t-PA/PAI activity may reflect the underlying pathophysiologic state and relate to subsequent cardiovascular events in unstable angina.
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PMID:Tissue-type plasminogen activator and plasminogen activator inhibitor activities as predictors of adverse events in unstable angina. 805 19


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