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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Consecutive survivors of a first Q wave anterior myocardial infarction were studied to observe the impact of recombinant tissue-type plasminogen activator (rt-PA) therapy on the incidence and associations of left ventricular thrombus. Fifty-four patients received rt-PA within 4 hours after the onset of cardiac pain, followed by heparin infusion. Forty-four patients who did not qualify for rt-PA therapy but who were anticoagulated with heparin served as a control group. Two-dimensional echocardiography was performed in all patients on days 3 and 7 to detect thrombi and analyze wall motion. Ejection fraction was determined by radionuclide angiography in all patients on day 7. Apical thrombi were detected on day 3 in three patients (5.5%) who received rt-PA and in eight control patients (18%) (p less than 0.05). All patients with a thrombus had apical dyskinesis and 8 of 11 (73%) had an aneurysm. Of the 87 patients without thrombosis, apical dyskinesis and aneurysm were present in 42 (48%) and 11 (13%) patients, respectively (p less than 0.01). Ejection fractions and wall motion scores of patients without a thrombus were significantly better when compared with data from those with a thrombus. There were fewer patients with apical dyskinesis (17 of 54) in the group receiving rt-PA therapy compared with the control group (36 of 44) (p less than 0.01). Ejection fractions and wall motion scores were better in patients who received rt-PA compared with control subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of intravenous recombinant tissue-type plasminogen activator therapy on the incidence and associations of left ventricular thrombus in patients with a first acute Q wave anterior myocardial infarction. 165 66

Ventricular arrhythmias during thrombolysis for acute myocardial infarction and their relation to coronary artery patency were examined. Twenty-four-hour Holter monitoring was begun 3.1 +/- 0.2 hours after onset of pain in 40 patients (age 54 +/- 1.6 years; anterior infarction 42.5%) treated with streptokinase (42.5%) or recombinant tissue-type plasminogen activator (57.5%) (delay from pain 3.3 +/- 0.2 hours). A Marquette 8000 computer was used for Holter analysis. The infarct-related artery was considered as patent (72.5%) or non-patent (27.5%) according to coronary angiography (delay from pain 26.7 +/- 2.5 hours; 60% less than 24 hours). Ventricular arrhythmias were present in all patients. Tolerance was good (1 cardioversion for ventricular fibrillation). The incidence of accelerated idioventricular rhythm was not different between patients with a patent and nonpatent artery (90 vs 82%), nor for ventricular tachycardia (VT) (83 vs 73%). Coronary artery patency was associated with a 14-, 13- and 32-fold increase of ventricular premature complexes, VT and accelerated idioventricular rhythms, respectively. The increased incidence of sustained VT (patent 38%; nonpatent 0%; p less than 0.05) and early (before the first 6 hours) accelerated idioventricular rhythm (patent 76%; nonpatent 18%; p less than 0.01) associated with artery patency suggests that these arrhythmias may be noninvasive diagnostic criteria for reperfusion (sensitivity 38 vs 76%, and specificity 100 vs 82%). A positive correlation was found between the frequency of ventricular premature complexes and VT, and peak creatine kinase.
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PMID:Holter recording of ventricular arrhythmias during intravenous thrombolysis for acute myocardial infarction. 173 50

Recombinant tissue-type plasminogen activator (rt-PA), streptokinase (SK), and anisoylated plasminogen-streptokinase activator complex (APSAC) have salutary effects on mortality when administered to patients with evolving acute myocardial infarction (MI). Studies suggest that intravenous rt-PA is more effective in reperfusing occluded infarct-related arteries than SK, and the results of ongoing studies directly comparing the influence of SK and rt-PA on mortality are awaited. The clinical role of agents such as APSAC, urokinase, and pro-urokinase, used alone or in combination, remains to be determined. It is evident that a variety of thrombolytic agents will be effective, and variables such as ease of administration, pharmacokinetics, fibrin specificity, effects on blood viscosity, and incidence of adverse effects need to be assessed to determine which agents are the most suitable for clinical use. There is an increased risk of bleeding at vascular puncture sites with all thrombolytic agents. Current indications for thrombolytic therapy include ischemic chest pain of at least 30 min duration that is unrelieved by nitroglycerin and is associated with ST-segment elevations of at least 0.1 mV in two contiguous electrocardiographic leads. Such therapy is usually reserved for patients less than 75 years old who are not at increased risk for bleeding and whose chest pain began less than 4-6 prior to treatment. Trials are under way to determine whether patients with shorter pain duration, transient ST-segment changes (ie, unstable angina patients), chest pain associated with ST-segment depressions or T-wave inversions (ie, non-Q-wave infarction patients), or patients whose pain began more than 4 to 6 h earlier will benefit from early thrombolytic therapy. Other factors such as patient age, the likelihood of the diagnosis of MI, and the estimated risk of bleeding should also be considered. The findings of available major randomized trials indicate that early invasive procedures are generally unnecessary and that meticulous care must be exercised in the selection and management of patients subjected to thrombolytic therapy.
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PMID:Thrombolytic therapy in acute myocardial infarction. 210 51

Increased plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been shown to exist in 40 to 60% of patients with stable coronary artery disease and have been suggested to be responsible for the development of coronary thrombotic complications. However, it is also discussed whether PAI-1 elevation might mainly be due to variables like increased age or to reactive mechanisms caused e.g. by the chest pain itself. To exclude age dependent or pain related influences, age-matched patients with stable angina pectoris (NHYA II) and angiographically proven coronary artery disease (CAD, n = 16) or without evidence for coronary sclerosis (variant angina, n = 10; angina-like syndrome with normal coronary angiogram, n = 5; non-CAD, n = 15) have been investigated for their plasma PAI-1 activity and t-PA antigen levels. The mean PAI activity in CAD patients (17.5 U/ml) was significantly higher than in non-CAD patients (9.6 U/ml) (p less than 0.0001). In the CAD patients no significant variation in plasma PAI-1 values could be demonstrated when related to the extent of the disease or to a history of previous myocardial infarction. t-PA antigen was also elevated in CAD patients as compared to the non-CAD group (p less than 0.02). The results suggest therefore a strong correlation between coronary artery disease itself and elevated levels of components of the plasma fibrinolytic system.
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PMID:Plasminogen activator inhibitor-1 levels in patients with chronic angina pectoris with or without angiographic evidence of coronary sclerosis. 211 22

When conventional treatment of patients with early clinical reinfarction after thrombolytic therapy fails, mechanical revascularization may be attempted. An alternative strategy, repeat thrombolytic infusions, is reported. Fifty-two patients with acute myocardial infarction were treated with one or two additional thrombolytic infusions of recombinant tissue-type plasminogen activator (rt-PA) because of nonsustained ischemia after initial treatment with rt-PA or streptokinase. Thirty-five patients received the second infusion within 1 h of the first; 13 patients received the second infusion 1 to 72 h after the first and 4 patients received it later during their hospitalization. Bleeding complications occurred in 10 patients (19%); however, most of these were minor (no intracranial bleeding) and only 2 patients required blood transfusion. In 14 patients in whom the decrease in fibrinogen and plasminogen levels was measured after the first and second infusions, this decrease was only 25% and 63%, respectively--only slightly higher than the 22% and 53% decreases measured in 63 patients who had only one rt-PA infusion. In 44 patients (85%), the acute ischemia resolved completely within 1 h after initiation of the second infusion. In 23 patients (44%), pain and ST segment elevation did not recur and invasive coronary intervention was avoided. Thus, repeat rt-PA infusions can stabilize a substantial number of patients with acute reinfarction and, even when relief is temporary, repeat rt-PA infusions can minimize myocardial damage while patients await mechanical revascularization.
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PMID:Repeat infusion of recombinant tissue-type plasminogen activator in patients with acute myocardial infarction and early recurrent myocardial ischemia. 212 Mar 9

Streptokinase, the first of the thrombolytic agents to be used in acute myocardial infarction, has now been administered to many thousands of patients with this condition. Since early intervention and accessibility of care is paramount in these patients, intravenous infusion of streptokinase has largely replaced intracoronary use. Results of major trials (GISSI, ISIS-2 and ISAM) comparing streptokinase with standard treatment in more than 30,000 patients prove convincingly that intravenous streptokinase increases patient survival after myocardial infarction. The largest trial, ISIS-2, demonstrated a 23% reduction in 5-week vascular mortality after streptokinase use. The greatest benefits occur where streptokinase infusion is initiated early after symptom onset, although late benefit has been observed in patients treated up to 24 hours after pain onset. Importantly, mortality is further decreased by combining streptokinase with aspirin, as shown by a 53% reduction in mortality using the combination in the ISIS-2 trial. Mortality has also been reduced in trials investigating the use of the thrombolytic agents rt-PA and anistreplase. Streptokinase and rt-PA produced similar reductions in mortality in the recent GISSI-2 and International t-PA/Streptokinase Mortality trials, findings which may be further clarified by ongoing comparative trials such as ISIS-3. Reperfusion of about 50 to 60% of occluded coronary arteries occurs with intravenous streptokinase, and left ventricular function is improved. Direct comparisons with rt-PA show a superior effect for the newer agent on early reperfusion, but a similar ability to salvage myocardial function. The complexities of the relationship between reperfusion, left ventricular function and mortality constitute an area of considerable clinical interest requiring further study to clearly differentiate between the drugs available to the physician. The most common adverse events observed during intravenous streptokinase infusion are bleeding complications. An incidence of 3.6% for minor bleeding and 0.4% for major haemorrhage (requiring transfusion) is derived from the combined results of the GISSI and ISIS-2 studies. Bleeding does not appear to be more frequent or severe with intravenous streptokinase than with the more fibrin-selective agent, rt-PA. While the risk to benefit ratio of sequential heparin following streptokinase therapy remains equivocal, the adjuvant use of aspirin confers a clinical advantage over streptokinase alone. In conclusion, streptokinase has now been proven to reduce mortality in patients with acute myocardial infarction, with an acceptable risk of bleeding complications. Given the substantial data that have now accumulated with extensive clinical experience, intravenous streptokinase should be considered a first-line agent in suitable patients.
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PMID:Intravenous streptokinase. A reappraisal of its therapeutic use in acute myocardial infarction. 219 49

All thrombolytic agents convert plasminogen to plasmin, either directly as urokinase, saruplase and alteplase or indirectly as streptokinase. In the majority of recent clinical trials with streptokinase, a high-dose (0.7 to 1.5 mega-units), brief-duration (30 to 90 minutes) drug regimen has been used. After a mean time interval of 4.2 hours from onset of pain to intravenous infusion of streptokinase, a repeat angiography performed 60 to 90 min after start of thrombolytic treatment gives a reperfusion rate of 43%, the corresponding figures for anistreplase, saruplase and alteplase are 56%, 67% and 69%. The patency rates of similar studies with the same endpoint are for streptokinase 56%, for anistreplase 77%, for urokinase 62%, for saruplase 71% and for alteplase 75%. The reduction in hospital mortality in randomized trials with intravenous streptokinase (high-dose) is in 6 large studies in a total of 23,267 randomized patients from 10.7% in the control group to 7.0% in the streptokinase group. In a mortality study involving 1,004 patients randomized to intravenous anistreplase or placebo the 30-day mortality was reduced by 47%, from 12.2% to 6.4%. A large trial in which 5,011 patients were randomized to alteplase or placebo, the 30-day mortality was 7.2% compared to 9.8% in controls, a reduction of 27% by alteplase. In another trial 721 patients were randomized to placebo or alteplase; all patients were on aspirin. The 14-day mortality was only 2.8%, 51% less than that in the control group. It is most important that the favourable impact on hospital survival is maintained at 1 year with any thrombolytic drug. Large scale trials directly comparing mortality after alteplase, streptokinase or anistreplase are being performed or in the planning phase. The risk of bleeding exists with any thrombolytic agent but intracranial bleeding is the most serious one. In a large trial on 5,011 patients with acute myocardial infarction, stroke occurred in 1.1% of alteplase treated patients compared with 1.0% in placebo treated controls. Crucial problems are residual stenosis of the coronary artery and reocclusion. Urgent angioplasty does not seem to be the right answer; more effective antithrombotic strategies still have to be developed.
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PMID:[Thrombolytic therapy in acute myocardial infarct]. 219 44

Criteria for selecting patients for thrombolytic therapy are presented, the major benefits of the currently approved thrombolytic agents are reviewed, and management considerations, including contraindications and the role of ancillary therapy, are discussed. Coronary thrombosis is now believed to play a central role in the pathogenesis of acute myocardial infarction (AMI). Re-establishment of coronary perfusion by thrombolysis has been extensively studied in the past decade and is now regarded as established therapy for patients with ischemic pain of brief (less than six hours') duration who have electrocardiographic ST-segment elevation, are less than 75 years of age, and have no contraindications. Studies supporting thrombolytic therapy have focused on the endpoints of (1) coronary artery patency or reperfusion, (2) improvement in left ventricular function, and (3) reduction in mortality. Benefits for each of these three endpoints have been established and are reviewed with respect to streptokinase, alteplase, and anistreplase, the three agents that have been approved for intravenous use in patients with AMI. The risk of bleeding, including intracranial hemorrhage, remains a concern for all patients. Ancillary therapies to be considered include aspirin, heparin, nitroglycerin, and beta blockers. Recent studies testing different strategies for coronary angiography and angioplasty plus surgery have generally supported a conservative approach, with interventions performed for clinical reasons rather than prophylaxis. Although the currently approved agents have differing pharmacologic profiles, none has yet proved to be clearly superior in the management of patients with AMI. Nonetheless, these agents remain the most promising means of treating selected patients.
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PMID:Therapeutic management of acute myocardial infarction. 220 53

There is abundant evidence from angiographic studies that reperfusion and/or patency rates are greater when thrombolysis is initiated earlier. Evidence of a reduction in infarct size has been provided by a number of studies, which have also suggested that earlier therapy preserves left ventricular function. The major intravenous thrombolytic mortality trials appear to confirm the importance of delivering therapy soon after the onset of symptoms e.g. GISSI and ISIS-2. However, the benefit reported in the first hour in GISSI may be questioned. Furthermore, it seems probable that those coming in late to trials are patients who did not have a sudden onset of symptoms, but whose symptoms persisted, perhaps with recurrent pain, or with heart failure symptoms. This may account for the fact that the benefit seen relatively late, particularly in ISIS-2, does not seem to accord with reperfusion, infarct size and LVEF findings. The true benefits of earlier therapy will be established only when patients are randomized to active therapy or placebo at one point in time and then switched to alternative therapy at a specified later time. This has been done in a small trial with alteplase in Belfast. The findings were suggestive but not conclusive of an improvement in LVEF in those treated earlier. The European Myocardial Infarction Project (EMIP) should go far towards answering the question. In most European cities the time between onset of symptoms and the initiation of skilled treatment for myocardial infarction is of the order of 5-6 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Time as a factor in thrombolytic therapy. 222 42

The dynamics of disorders in haemostasis and fibrinolysis upon continuous stress was studied in model experiments with rats exposed to emotional-pain-stress. It was shown that the plasminogen activator (PA) is released into the blood within the first few minutes of exposure to stress. Four hours after cessation of continuous stress (6 hours) the enzyme depletion and fibrinolysis depression occurred. Such stress-induced changes in the blood system function can be regarded as a risk factor in the development of thrombosis.
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PMID:Depletion of fibrinolysis activators as a result of continuous stress. 246 30


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