Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Baseline plasminogen activator inhibitor (PAI) levels were examined for their influence on the responses to thrombolysis with recombinant tissue plasminogen activator (rt-PA) administered for acute myocardial infarction during the Thrombolysis and Myocardial Infarction (TAMI)-I study. Baseline PAI activity was 19 +/- 21 IU/ml (normal less than 5 IU/ml) and baseline PAI-1 antigen 54 +/- 53 ng/ml (normal 27 +/- 16 ng/ml), confirming previous findings of elevated PAI levels during acute myocardial infarction. Among clinical outcomes, lower PAI-1 antigen levels correlated weakly with greater patency at the 90 min angiogram. Thus, high baseline plasma PAI-1 levels may be detrimental to reperfusion with t-PA. There was no correlation with other major in-hospital clinical outcomes including reocclusion at the 7-10 day angiogram, survival to discharge, or bleeding. During the follow up period of 2.0 +/- 0.4 years, no relationship between baseline PAI levels and post-discharge reinfarction was observed.
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PMID:Correlation between baseline plasminogen activator inhibitor levels and clinical outcome during therapy with tissue plasminogen activator for acute myocardial infarction. 190 53

One hundred patients admitted to a centre of interventional cardiology with acute myocardial infarction of less than 6 hours, underwent coronary angioplasty of first intention because of contra-indications to thrombolytic therapy (n = 20) or after thrombolytic therapy with streptokinase (n = 54), acylenzymes (n = 12) or tissue type plasminogen activator (n = 14). The indication of angioplasty were those of the TIMI (Thrombolysis in Myocardial Infarction) classification (occluded artery, TIMI grade 0) (n = 60) (suboccluded artery, TIMI grade 1) (n = 40). The criterion of success of angioplasty was an increase greater than 1 of TIMI grade. Reperfusion of the coronary artery was obtained by angioplasty in 95% of failures of thrombolysis and in 90% of patients with contra-indications to thrombolytic therapy. The early reocclusion rate at D1 was 2%. Repeat angioplasty at D1 was successful in both these cases and the arteries were still patent at D21. The reocclusion rate at the third week in 75 patients who underwent control coronary angiography was 5.3%. In patients with arterial occlusion, immediate angioplasty attained two objectives in the same procedure: a high rate of emergency myocardial reperfusion and a low rate of reocclusion. The average left ventricular ejection fraction (all arteries) significantly improved (+9.2% in absolute values) when the artery remained patent (p less than 0.001), especially when the initial ejection fraction was low. In the patients who had occluded arteries at control angiography at 3 weeks, the ejection fraction decreased (-4% in absolute values) (NS). The following complications were observed: 4 coronary artery dissections and haematomas at the site of femoral puncture in patients who had received thrombolytic therapy (10 drained surgically). The hospital mortality was 3% and global mortality after an average follow-up period of 19.6 months was 5%. Coronary angioplasty in acute myocardial infarction carries a low risk and seems to be beneficial in patients with contra-indications to or failure of thrombolysis.
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PMID:[Acute myocardial infarction: immediate coronary angioplasty for failure or contra-indications of thrombolytic therapy. Apropos of a series of 100 cases]. 190 14

Twenty patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) had endogenous factor XII-dependent fibrinolytic activity levels measured throughout the hospital period and those levels were prospectively correlated with the incidence of recurrent myocardial infarction until 8 weeks after hospital discharge. Within the follow-up period, recurrent myocardial infarction was observed in 8 patients, whereas the remaining 12 patients showed no clinical evidence of recurrence. The patients in the reinfarction group were characterized by a more pronounced depletion of and sustained lower levels of factor XII-dependent fibrinolytic activity than were the patients with no reinfarction (p less than 0.05). The decrease in fibrinolytic activity during rt-PA therapy was significantly associated with a depletion of functional alpha 2-antiplasmin, the primary plasmin inhibitor. These results indicate that, paradoxically, coronary thrombolysis with rt-PA involves depletion of endogenous factor XII-dependent fibrinolytic activity levels, which constitutes a risk for early myocardial reinfarction.
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PMID:Depression of factor XII-dependent fibrinolytic activity characterizes patients with early myocardial reinfarction after recombinant tissue-type plasminogen activator therapy. 190 4

Coronary angioplasty following unsuccessful tissue plasminogen activator (t-PA) therapy for acute myocardial infarction has been associated with a high incidence of subsequent reocclusion of the infarct-related artery, and a relatively high in-hospital mortality. In contrast, the combination of t-PA and urokinase, when given intravenously prior to coronary angiography, appears to be associated with a low incidence of post-rescue angioplasty reocclusion. In order to determine whether intraprocedural urokinase, given at the time of rescue coronary angioplasty for failed t-PA therapy, improves long-term patency of the infarct vessel to the same extent as preangiographic, combination t-PA/urokinase therapy, three thrombolytic treatment strategies were retrospectively compared. The first group included 86 patients undergoing rescue angioplasty after t-PA monotherapy (t-PA alone). The clinical and angiographic outcomes of these patients were compared with those of 24 patients who received intravenous or intracoronary urokinase during rescue angioplasty following unsuccessful t-PA therapy (sequential t-PA/urokinase therapy), and with those of 34 patients undergoing rescue coronary angioplasty following unsuccessful therapy with the combination of intravenous t-PA and urokinase (simultaneous therapy). There was no difference in postangioplasty patency rate of the infarct-related artery between the three groups. However, the sequential t-PA/urokinase regimen was associated with a subsequent reocclusion rate that was lower than the rate that occurred in the t-PA monotherapy group but higher than the rate in the simultaneous t-PA/urokinase group (13 versus 29 versus 2%, respectively; p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Combination thrombolytic therapy: a comparison of simultaneous and sequential regimens of tissue plasminogen activator and urokinase. 190 86

The levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI) and other substances of coagulation-fibrinolysis, such as fibronectin (Fn) and von willebrand factor (vWF) as well as the activity content of antithrombin-III(AT-III) in plasma were determined in 20 patients with acute myocardial infarction (AMI). In 11 of them these measurements were carried out before and after the treatment with urokinase (UK1000 000 IU). The results suggested that the function of coagulation-fibrinolytic system was disturbed in AMI. Thrombolytic treatment with UK could interfere and improve the stabilization of fibrinolytic activity in the body, but these actions last only short time. Some substances of coagulation showed change with UK treatment.
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PMID:[The kinetics of plasma coagulation fibrinolysis levels in acute myocardial infarction before and after treatment with intravenous urokinase]. 190 71

The current mode of administration of recombinant tissue-type plasminogen activator (rt-PA) in acute myocardial infarction is rather complex, although the rationale for the different components of this scheme is not clearly established. We compared pharmacokinetics of a continuous infusion of 38.5 MU of Burroughs Wellcome t-PA (duteplase) over 90 minutes in nine patients (phase I) with a scheme including a 0.04 MU/kg bolus, a 60-minute 0.36 MU/kg lytic infusion and a 180-minute 0.21 MU/kg maintenance infusion in 15 patients with acute myocardial infarction (Phase II). t-PA activity and antigen were fitted in a one-compartment model from which model-dependent and model-independent parameters were derived. Clearance of t-PA activity was 1020 +/- 465 (mean +/- SD) ml/min in phase I and 1359 +/- 590 ml/min in phase II. Clearance of t-PA antigen was 666 +/- 230 ml/min in phase I and 704 +/- 199 ml/min in phase II. Clearance of activity was significantly (p less than 0.01) higher than of antigen. Clearance and steady-state plasma levels showed a large interindividual variability (coefficient of variation, 56.4%), but this was significantly reduced by dosing by weight (coefficient of variation, 28.9%; p = 0.031). A 10% bolus in phase II shortened the time to reach 75% and 90% of the steady-state plasma level by 4 and 5 minutes, respectively, not significantly different from phase I. A simulation study showed that a bolus should be approximately 15% of the lytic dose to achieve a maximal level in the shortest period.
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PMID:The pharmacokinetics of recombinant double-chain t-PA (duteplase): effects of bolus injection, infusions, and administration by weight in patients with myocardial infarction. 191 61

Potentially life-threatening immediate hypersensitivity reactions are extremely rare among patients treated with thrombolytic agents for suspected acute myocardial infarction. A patient who developed a severe reaction during an infusion of recombinant tissue-type plasminogen activator is described. Potential causal mechanisms for the reaction could be related either to nonmedicinal additives or complement activation. Implications for treatment in the setting of acute myocardial infarction are discussed.
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PMID:Anaphylactoid reaction during an infusion of recombinant tissue-type plasminogen activator for acute myocardial infarction. 193 36

Both activation of platelets and elevation of plasminogen activator inhibitor type 1 (PAI-1) activity in plasma have been associated with acute myocardial infarction. Growth factors from platelet alpha-granules have been shown to increase PAI-1 synthesis in liver and endothelial cells in culture. The present study was designed to determine whether activation of platelets in vivo increases PAI-1 activity in plasma, thereby potentially attenuating thrombolysis. Carotid arteries in rabbits were stimulated with transluminal anodal current to initiate thrombosis manifested initially by cyclic flow variations known to reflect platelet activation. Flow was monitored with Doppler flow probes. Plasma PAI-1 activity (mean +/- SEM) assayed spectrophotometrically increased from 6.8 +/- 0.8 arbitrary units (AU)/ml to a peak of 19.1 +/- 2.9 AU/ml (n = 15) 4.8 +/- 0.6 h after the onset of cyclic flow variations. The magnitude of peak PAI-1 values correlated closely with the frequency and duration of antecedent cyclic flow variations. Complete thrombotic occlusion did not elevate PAI-1 beyond that seen with severe, repetitive partial occlusions (18.7 +/- 4.6 vs. 19.6 +/- 3.8 AU/ml). However, when recanalization of completely occluded vessels was induced with tissue-type plasminogen activator (t-PA), plasma PAI-1 increased more markedly (from 5.6 +/- 0.7 to 112.8 +/- 22.3 AU/ml, n = 11), exceeding the increase after corresponding intervals in animals in which t-PA failed to induce recanalization (from 5.2 +/- 1.1 to 28.3 +/- 6.1 AU/ml, n = 6). Thus, activation of platelets accompanying thrombosis or thrombolysis, or both, markedly increases PAI-1 activity in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Augmentation of plasminogen activator inhibitor type 1 activity in plasma by thrombosis and by thrombolysis. 193 60

The (Thrombolysis in Myocardial Infarction) TIMI-I trial led to the hypothesis that the greater reperfusion rate seen with recombinant tissue-type plasminogen activator (rt-PA) versus streptokinase would result in greater reductions in infarct size and mortality in patients with acute myocardial infarction. Despite extensive investigation, no trial comparing rt-PA with streptokinase (European Cooperative Study Group, Plasminogen Activator Italian Multicenter Study [PAIMS], Gruppo Italiano per lo Studio della Sopravvivenze nell'Infarto Miocardico [GISSI-2], International Study on Infarct Survival [ISIS-3], even TIMI-I itself) nor rt-PA and anisoylated plasminogen-streptokinase activator complex (APSAC or anistreplase) (Bassand, TEAM-3, ISIS-3), have confirmed this hypothesis. In a reversal of traditional scientific method, the studies, rather than the unconfirmed hypothesis, have been rejected. A lack of independent review of this subject may have contributed to this outcome. It is proposed that standards of review and editorial comment mandating true critical distance and independence be followed, permitting greater independence of scientific inquiry, review and debate.
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PMID:Thrombolysis: the need for a critical review. 193 63

This study sought to determine whether clinical variables can be used to identify patients at high risk of recurrent spontaneous myocardial ischemia or hemodynamic compromise during the 1st 4 days after intravenous thrombolysis for acute myocardial infarction. Of 288 patients randomly assigned to a conservative postthrombolysis strategy, 54 (19%) required urgent cardiac catheterization within 24 h; 75 (26%) underwent urgent cardiac catheterization within 4 days of admission. Of the clinical variables examined by multiple logistic regression analysis, only patient age and anterior wall myocardial infarction correlated with the need for urgent cardiac catheterization (p = 0.0016 and p = 0.017, respectively). Compared with recombinant tissue-type plasminogen activator or urokinase monotherapy, combination therapy with these agents was associated with a lower need for acute intervention during the 1st 24 h after admission, but the difference did not reach statistical significance (14% for combination therapy vs. 21% for each agent alone, p = 0.30). Of the 75 patients undergoing urgent coronary angiography, only 39% had an occluded infarct-related artery. Emergency coronary angioplasty was performed in 49% of the patients and coronary artery bypass graft surgery was performed urgently in 3%. Despite these interventions, the need for urgent cardiac catheterization was associated with an in-hospital mortality rate of 7% (vs. 3% in the group not requiring urgent angiography, p = 0.36); mean left ventricular ejection fraction was 50.5 +/- 11% (vs. 54.3 +/- 10.8%, p = 0.12) and regional infarct zone wall motion was -2.68 +/- 1.07 SD/chord (vs. -2.46 +/- 1.19 SD/chord; p = 0.44).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Determinants of the need for early acute intervention in patients treated conservatively after thrombolytic therapy for acute myocardial infarction. TAMI-5 Study Group. 196 Mar 2


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