UNIPROT:P00750 - FACTA Search

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)

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

The validity of markers in plasma of in vitro thrombolysis was investigated in 12 patients with extensive fibrinogen breakdown (greater than 80%, group 1) and in 12 patients with minimal breakdown (less than 20%, group 2). The patients were treated with 100 mg of recombinant tissue-type plasminogen activator (rt-PA) in the "Thrombolysis in Myocardial Infarction II" (TIMI II) trial. Cross-linked fibrin degradation product levels were measured with two variant enzyme-linked immunosorbent assays (ELISAs), both using a fibrin fragment D-dimer specific capture antibody. In one instance, a tag antibody was used that cross-reacts with fibrinogen (pan-specific tag ELISA); in the other, the tag antibody was specific for fibrin fragment D (fibrin-specific tag ELISA). Apparent concentrations of cross-linked fibrin degradation products at baseline were within normal limits with both assays in most patients. At 8 hours after rt-PA infusion, the measured cross-linked fibrin degradation products were increased about twofold to fourfold in group 2 with both assays. However, in group 1, levels were significantly higher with the pan-specific tag ELISA (5.8 +/- 4.2 micrograms/mL) compared with the fibrin-specific tag ELISA (1.5 +/- 1.3 micrograms/mL). This observation was most likely a result of detection of fibrinogen degradation products in the pan-specific ELISA. Apparent levels of fibrinopeptide B beta 1-42, a marker of fragment X formation, increased during thrombolysis from 4.2 +/- 2.8 pmol/mL to 2,000 +/- 230 pmol/mL in group 1 and from 4.1 +/- 2.1 pmol/mL to 300 +/- 43 pmol/mL in group 2, and were correlated significantly with the extent of fibrinogen breakdown (r = -0.8). Fibrinopeptide beta 15-42 levels increased from 4.3 +/- 3 pmol/mL to 70 +/- 19 pmol/mL in group 1, but did not increase in group 2. The apparent increase in group 1 could be explained by cross-reactivity of fibrinopeptide B beta 1-42 in the fibrinopeptide beta 15-42 assay. We conclude that cross-linked fibrin degradation product levels as measured with a pan-specific tag ELISA and fibrinopeptide beta 15-42 levels as measured with certain monoclonal antibody-based ELISA are influenced by the extent of fibrinogen degradation. Fibrinopeptide B beta 1-42 is a marker specific for fibrinogen breakdown. Cross-linked fibrin degradation product levels, measured with a fibrin-specific tag ELISA, appear to be markers specific for thrombolysis. Consequently, assays similar to the fibrin-specific tag ELISA may provide more accurate information when correlated with clinical endpoints.
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PMID:Fibrin fragment D-dimer and fibrinogen B beta peptides in plasma as markers of clot lysis during thrombolytic therapy in acute myocardial infarction. 211 27

Patients with unstable angina pectoris who remain symptomatic despite medical treatment are at high risk of death and myocardial infarction. The incidence of refractory unstable angina was examined in a consecutive series of 103 patients who received conventional medical treatment with nitrates, beta blockers, calcium antagonists and aspirin. During 48 hours of continuous electrocardiographic monitoring, 24 patients had greater than or equal to 1 anginal attack, 5 of whom had both painful and painless ischemic episodes. In these 24 patients with unstable angina refractory to conventional medical treatment, the short-term efficacy of recombinant tissue-type plasminogen activator (rt-PA) followed by heparin was assessed and compared with heparin alone in a randomized double-blind trial. Recurrences of ischemic attacks during a 72-hour follow-up period were documented in 9 of the 12 patients given heparin alone. All patients experienced at least 1 symptomatic ischemic episode and 1 patient had both painful and painless ischemia. No patient given rt-PA plus heparin had either symptomatic or asymptomatic ischemic attacks during follow-up. Kaplan-Meier curves analysis demonstrated a significantly higher probability of being ischemia free in the group of patients treated with rt-PA followed by heparin than in the group treated with heparin alone (p less than 0.01). Quantitative coronary arteriography failed to reveal any significant changes of ischemia-related lesions before and after each treatment. This study demonstrates that the combination of rt-PA and heparin has a greater protective effect than heparin alone in treating recurrent ischemic episodes in patients with refractory unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recombinant tissue-type plasminogen activator followed by heparin compared with heparin alone for refractory unstable angina pectoris. 212 Oct 16

The results of the major mortality studies of thrombolytic drugs in myocardial infarction demonstrate that streptokinase, APSAC and t-PA reduce mortality significantly. Large studies (GISSI-2 comparing Genentech t-PA with streptokinase and ISIS-3 comparing streptokinase, APSAC and Wellcome t-PA) are currently under way to identify which, if any, of the above agents is the most effective. Review of the results of the reported studies has emphasized the importance of treatment being given as soon as practical after the onset of symptoms. It has also revealed that substantial benefit is achievable in patients often not considered to be candidates for thrombolytic therapy, such as those presenting for treatment between 6 and 24 h after symptom onset, and elderly patients. It is emphasized that important benefit may be missed in clinical practice in deciding who should, or should not, receive thrombolytic drug therapy by complying too rigidly to what were investigative clinical study entry criteria.
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PMID:Survival following thrombolytic therapy. 212 86

This study assesses whether administration of recombinant tissue-type plasminogen activator (rt-PA) up to 8 hours after onset of symptoms of acute myocardial infarction (AMI) may result in a significant improvement in left ventricular function. Sixty patients were classified into 3 groups: group A (n = 21) received rt-PA within 4 hours from symptom onset; the remaining 39 patients, admitted between 4 and 8 hours, were randomized into 2 groups--group B (n = 19) received rt-PA, and group C (n = 21) was treated with conventional therapy. Coronary and left ventricular angiograms were recorded 8 to 10 days after rt-PA administration. The patency rate of the infarct-related artery was 76% in group A, and 63 and 35% in group B and C, respectively. The Thrombolysis in Myocardial Infarction trial perfusion grade was higher in group A and B than in group C (A vs C: p less than 0.005; B vs C: p less than 0.01). Left ventricular ejection fraction was significantly higher in group A (60.2 +/- 10%) and B (54.7 +/- 12%) compared with group C (44.2 +/- 12%) (A vs C: p less than 0.01; B vs C: p less than 0.05). Regional wall motion of the entire ischemic zone was better in group A and B than in group C (A vs C: p less than 0.001; B vs C: p less than 0.01). In contrast, the kinesis of the central ischemic zone was significantly better in group A than in both group B and C (A vs B: p less than 0.05; A vs C: p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Usefulness of late coronary thrombolysis (recombinant tissue-type plasminogen activator) in preserving left ventricular function in acute myocardial infarction. 212 72

In the conservative strategy arm of phase II of the Thrombolysis in Myocardial Infarction (TIMI) trial, 1,461 patients were treated with intravenous recombinant tissue-type plasminogen activator (rt-PA). Coronary angiography, with angioplasty if feasible, was to be performed only for recurrent spontaneous or exercise-induced ischemia. In this study results in patients treated by this strategy in community and tertiary hospitals are compared. Despite similar baseline findings in the two groups, coronary angiography was performed within 42 days in more patients (542 [48%] of 1,155) initially admitted to a tertiary hospital (on-site coronary angiography/angioplasty available) than in those (94 [32%] of 306) admitted to a community hospital (transfer to tertiary hospital for coronary angiography/angioplasty) (p less than 0.001). This different approach resulted in a greater use of coronary angioplasty (203 [18%] of 1,155 versus 32 [11%] of 306, p less than 0.01), coronary artery bypass surgery (133 [12%] of 1,155 versus 23 [8%] of 306, p less than 0.05) and blood transfusions (139 [12%] of 1,155 versus 17 [5.5%] of 306, p less than 0.001) in patients admitted to a tertiary than to a community hospital. However, there were no significant differences between the two groups in mortality, recurrent myocardial infarction or left ventricular function. These results demonstrate that a conservative strategy after treatment of acute myocardial infarction with rt-PA is applicable in the community hospital setting.
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PMID:Thrombolysis in Myocardial Infarction (TIMI) phase II trial: outcome comparison of a "conservative strategy" in community versus tertiary hospitals. The TIMI Research Group. 212 2

The effects of early coronary recanalization on the plasma levels of two procoagulant acute phase proteins, the fastacting plasminogen activator inhibitor and von Willebrand factor, were investigated in 24 patients with myocardial infarction receiving intravenous recombinant tissue-type plasminogen activator (rt-PA) within 6 h of the onset of symptoms. Coronary angiography was performed before and 90 min after the start of rt-PA infusion. Continuous electrocardiographic recordings and 4 h plasma creatine kinase MB isoenzyme (CK MB) were performed over the first 24 h. Plasma plasminogen activator inhibitor activity, von Willebrand factor and C-reactive protein were measured before rt-PA infusion, daily for the first 3 days and after 90 days. In the entire group, plasminogen activator inhibitor activity peaked at 24 h (day 1), representing a significant increase over values at all other times (p = 0.03). von Willebrand factor was higher in the first 2 days of infarction compared with after 90 days (p = 0.001). C-reactive protein peaked on day 2, with an eightfold increase over values on admission (p = 0.001). In the 16 patients with a patent infarct-related artery at 90 min, infarct size estimated by integrated 24 h CK MB, time for ST segment elevation to decrease to half-maximum and peak C-reactive protein were reduced significantly by more than twofold compared with values in the 8 patients with an occluded artery at 90 min. The patients with early recanalization also had lower plasminogen activator inhibitor activity on day 2 (p = 0.05) and day 3 (p = 0.02) and lower 0 to 72 h averaged von Willebrand factor (p = 0.01). Thus, early coronary recanalization curtails the response of plasminogen activator inhibitor activity and von Willebrand factor to myocardial infarction, most likely by reducing the extent of ischemia and necrosis and the consequent acute phase reaction. By blunting the early postinfarction procoagulant state, prompt recanalization may reduce the risk of thromboembolic complications in the first days after myocardial infarction.
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PMID:Early coronary reperfusion blunts the procoagulant response of plasminogen activator inhibitor-1 and von Willebrand factor in acute myocardial infarction. 212 6

To evaluate the effects of late thrombolysis on left ventricular volume and function in acute myocardial infarction, two-dimensional echocardiography and radionuclide angiography were performed before discharge and after 1 year of follow-up study in 34 patients with acute anterior myocardial infarction. Of these, 10 admitted to the coronary care unit within 4 h from the onset of symptoms were treated with recombinant tissue-type plasminogen activator (rt-PA) (Group A) and 24 admitted between 4 and 8 h after onset were randomly assigned to receive either rt-PA (Group B, n = 12) or conventional therapy (Group C, n = 12). Seven to 10 days after admission, all patients underwent cardiac catheterization and coronary angiography. Patency of the infarct-related vessel was 70% in Group A, 66% in Group B and 33% in Group C and the average Thrombolysis in Myocardial Infarction (TIMI) coronary perfusion grade was 1.9 +/- 0.8 for Group A, 1.6 +/- 1.0 for Group B and 0.84 +/- 0.95 for Group C (Group A versus Group C p less than 0.01; Group B versus Group C p less than 0.05). At predischarge evaluation, mean left ventricular end-systolic and end-diastolic volumes were higher in Group C than in Group B (p less than 0.001 and 0.05, respectively) and Group A (p less than 0.005 for both); mean left ventricular ejection fraction at rest was lower in Group C than in Group B and Group A (p less than 0.05 for both). At 1 year follow-up study, end-systolic and end-diastolic volumes remained higher in Group C than in Group B (p less than 0.05 for both) and Group A (p less than 0.005 for end-systolic volume and p less than 0.001 for end-diastolic volume); ejection fraction at rest was lower in Group C than in Groups A and B (p less than 0.05 for both); during exercise, it increased more in Group A than in Group C (p less than 0.01). Comparison of data obtained before discharge and at the 1 year follow-up study revealed a significant differences in end-systolic volume (p less than 0.05) in Group C patients and in end-diastolic volume in patients in Groups B (p less than 0.05) and C (p less than 0.001). The beneficial effect of late thrombolysis with rt-PA may be related to a reduction in myocardial expansion and thus to a favorable influence on postinfarction left ventricular remodeling.
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PMID:Effects of late administration of tissue-type plasminogen activator on left ventricular remodeling and function after myocardial infarction. 212 7

The gain in survival by thrombolytic therapy in patients with myocardial infarction is determined by the delay between coronary occlusion and reperfusion. The REPAIR study was designed to examine the feasibility and safety of prehospital thrombolysis with alteplase (rt-PA, Actilyse). Indications and contraindications are verified by general practitioner or ambulance nurse with a short questionnaire. A small portable ECG computer system is used to confirm the presence of a large evolving myocardial infarction 'on the spot'. Between June 1988 and May 1990, 150 patients were treated by the ambulance service. Therapy could be initiated within an average of 91 (+/- 40) minutes (sd) after the onset of symptoms, and within 23 (+/- 9) minutes after ambulance arrival. Three patients were defibrillated during transportation, in one of these therapy had to be discontinued because of cardiac massage. No other complications were observed. Five patients (3%) died after arrival in the hospital. The time gained by prehospital treatment averaged 47 (+/- 2) minutes in comparison with 220 patients who received thrombolytic therapy after hospital admission. The procedure allows rapid and safe initiation of thrombolytic therapy in selected patients, even in the absence of a physician.
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PMID:[Earlier treatment of acute myocardial infarction with administration of alteplase (rt-PA) before hospitalization]. 212 55

Although the efficacy of tissue-type plasminogen activator (t-PA) for coronary thrombolysis is well established, its direct cardioprotective effect - independent of its thrombolytic effect - is still controversial. In addition, the potentiation of t-PA's direct cardioprotective effect by thromboxane A2 synthetase inhibitor has recently been reported. In this study, the authors examined whether t-PA alone or in combination with DP1904, a thromboxane A2 synthetase inhibitor, is able to salvage ischemic myocardium via a direct action on myocardium. In addition, the effect of these interventions on intramyocardial hemorrhage in reperfused infarcts was assessed. A branch of the coronary artery of the rabbit was occluded for 30 mins and then reperfused for 72 h. Myocardial infarct size and 'area at risk' were determined by histology and fluorescent particles, respectively. The extent of intramyocardial hemorrhage was graded using scores. Rabbits were divided into three groups: control, t-PA and DP1904 plus t-PA. The t-PA was administered intravenously at 500 iu/kg/min for 30 mins starting 5 mins prior to reperfusion. DP1904 was injected intravenously at a dosage of 10 mg/kg every 24 h starting 2 hr prior to coronary occlusion. Mortality was similar and hemodynamic parameters and area at risk were comparable between all three groups. The myocardial infarct size as a percentage of area at risk was 44.5 +/- 3.8% (mean +/- standard error) (n = 9) in the control group, 41.6 +/- 4.6% in the t-PA group (n = 8) and 51.3 +/- 5.2% in DP1904 plus t-PA group (n = 8), not significantly different (ANOVA). Neither were the hemorrhage scores significantly different between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tissue-type plasminogen activator alone or in combination with thromboxane A2 synthetase inhibitor for ischemic myocardium. 212 35

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