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

The thrombolytic activity of tissue plasminogen activator was evaluated in a rabbit model of thromboembolic stroke using both various concentrations (3, 5, and 10 mg/kg; 20% bolus with the remaining 80% given over 30 min.) and routes of administration (intravenous versus regional intra-arterial). An autologous tin-tagged clot was embolized to the brain via the carotid artery. Tissue plasminogen activator was then given at the doses and routes noted (n = 3 in all groups). Thrombolytic activity was followed by serial x-rays of the tin-laden clot over a four-hour period. The brains were then removed and subjected to gross inspection. Only the intravenous dose of 5 mg/kg tissue plasminogen activator produced greater than 50% clot lysis in all animals. Doses of t-PA higher (10 mg/kg) or lower (3 mg/kg) than this were less effective in producing thrombolysis, demonstrating greater than 50% clot lysis in only one animal of each group. We conclude that in this model of thromboembolic stroke the intravenous administration of tissue plasminogen activator is more effective than intra-arterial, and that the optimal dose is in the range of 5 mg/kg.
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PMID:Tissue plasminogen activator: comparison of dose and route of administration in a rabbit model of thromboembolic stroke. 790 9

Endothelial release of tissue plasminogen activator (t-PA) may initiate fibrinolysis. Fibrinolysis and coagulation were investigated in 12 patients undergoing elective coronary artery bypass surgery. Cardiopulmonary bypass (CPB) was 108 +/- 7 min (mean +/- SEM), the time of cold, crystalloid, retrograde cardioplegia 53 +/- 5 min. Arterial and coronary sinus blood were sampled concomitantly before cardioplegia and after release of the aortic cross-clamp, for measurement of t-PA antigen (Ag) and activity, plasminogen activator inhibitor (PAI-1) Ag and activity, t-PA/PAI-1 complex, single chain urokinase (sc-uPA) and urokinase (uPA) plasminogen activators, the fibrin split product D-dimer, thrombin-antithrombin complex (TAT), and the prothrombin split product F 1 + 2. Cardiopulmonary bypass significantly increased t-PA Ag and activity, t-PA/PAI complex, D-dimer, TAT, and F 1 + 2, and decreased PAI-1 Ag and activity in arterial blood; uPA and sc-uPA were unchanged. The tissue plasminogen activator antigen was higher in coronary sinus than arterial blood after 1 (39 +/- 5 vs 24 +/- 4 ng/ml, P < 0.003), 4 (P < 0.003), and 10 min (P < 0.004) reperfusion. Tissue plasminogen activator activity and t-PA/PAI complex increased, PAI-1 activity decreased, while all other parameters were unchanged across the coronary circulation. In conclusion, CPB induces fibrinolysis and coagulation. Cold cardioplegia induces t-PA release in the coronary circulation, denoting a postischemic antithrombotic function of the coronary endothelium. Tissue plasminogen activator may be used to evaluate endothelial stimulation or injury induced by CPB, or by different regimens of myocardial protection.
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PMID:Fibrinolysis during cardiac surgery. Release of tissue plasminogen activator in arterial and coronary sinus blood. 808 78

We studied extrinsic and intrinsic fibrinolysis in 20 patients with cirrhosis (nine mild/moderate, group 1; 11 severe, group 2) and 19 normal controls to define the role of intrinsic (contact factor medaited) fibrinolysis in cirrhosis. Global plasma fibrinolytic activity (fibrin plate lysis) was similar in all groups. Dextran sulphate activated contact factor mediated fibrinolysis was decreased in group 2 (median 95.2%) compared with group 1 (121.0%) and controls (131.7%). Tissue plasminogen activator antigen (t-PA Ag) levels were increased in group 2 (28.2 ng/ml) compared both with group 1 (8.5 ng/ml) and controls (5.9 ng/ml). Plasma t-PA activity was raised in group 2 (5.50 IU/ml) and group 1 (5.25 IU/ml) versus controls (0.82 IU/ml). Plasminogen activator inhibitor-1 (PAI-1 Ag) levels were raised in group 2 (28.0 IU/ml) versus controls (8.5 IU/ml) but PAI activity was similar in all groups. Factor XII activity was decreased in group 2 (48.76 u/dl), but not group 1, versus controls (89.1 u/dl). Prekallikrein activity was decreased both in group 2 (27.27 u/dl) and group 1 (33.01 u/dl) versus controls (108.59 u/dl) and was lower in group 2 than group 1. C1-esterase inhibitor chromogenic activity was decreased in group 1 (102.30 u/dl) and group 2 (58.76 u/dl) versus controls (116.24 u/dl). The normal global fibrinolytic activity despite increased t-PA activity may be due to a concomitant increase in PAI. The decreased intrinsic fibrinolysis in severe cirrhosis, unaccompanied by a rise in C1-esterase inhibitor, may be explained by the decreased factor XII and prekallikrein activity. These changes are probably due to reduced liver cell mass.
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PMID:Decreased contact factor mediated fibrinolysis in cirrhosis. 813 76

According to recent reports, fibrinolytic activity may be enhanced during hemodialysis. The aim of this work was to study the fibrinolytic activity in uremic patients, and to evaluate the effect of membrane biocompatibility on the fibrinolytic system during hemodialysis. Tissue plasminogen activator (t-PA), t-PA antigen, plasminogen activator-inhibitor (PAI), plasminogen (PL) and alpha-2-antiplasmin (AP) were measured in 10 uremic patients on maintenance hemodialysis treated sequentially with Cuprophane and polyacrylonitrile (AN69) membranes. Blood samples were obtained before and at 15, 60 and 120 minutes after the initiation of dialysis. Blood was also collected from 20 healthy individuals who served as controls. During cuprophane dialysis, t-PA increased significantly at 60 minutes (14.8 vs. 8.4 IU/ml, P < 0.05) and at 120 minutes (13.8 P < 0.01). This was accompanied by an increase in t-PA antigen, which was significant at 15 (5.1 vs. 13.1 ng/ml), 60 (15.2) and 120 (9.6) minutes (P < 0.05) of dialysis. However, during AN69 dialysis t-PA and t-PA antigen plasma levels remained stable. No significant changes were observed in PL, AP or PAI during hemodialysis with either membrane. In conclusion, hemodialysis enhances fibrinolytic activity, which is likely the result of t-PA Ag release. Therefore, this phenomenon seems to be closely related to dialysis membrane biocompatibility.
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PMID:Fibrinolytic activity during hemodialysis: a biocompatibility-related phenomenon. 832 Sep 24

Fibrinolytic activity and tissue plasminogen activator (t-PA) level were measured in 33 healthy individuals prior to and after fibrinolytic system stimulation (i.e. a ten-minute venous stasis). Fibrinolytic activity was measured with the aid of euglobin lysis time, and lysis test on the fibrin plates (in own modification). Tissue plasminogen activator concentration was assayed spectrophotometrically with the COA-SET t-PA (Kabi Vitrum). No fibrinolytic activity of plasma specimens taken before the venous stasis was noted during fibrin lysis plate test whereas it was seen in 13 subjects after the venous stasis. Fibrinolytic activity of the plasma euglobins, measured as a surface on fibrin plates, increased significantly after the venous stasis in both sexes (by 35.5 mm2 on the average, i.e. by 51%). It was more marked in men than in women both prior to and after venous stasis (by 10.9% and 19.0%, respectively). A time of plasma euglobin lysis was shorter after venous stasis (by 110 minutes, on the average). There was no significant difference between the sexes. Tissue plasminogen activator concentration increased by 5.8 times (from 1.7 IU/ml to 9.9 IU/ml) after the stasis. Correlation between t-PA concentrations and fibrinolytic activity, measured on the fibrin plates, was highly positive. No such a correlation existed between t-PA concentrations and the time of euglobin lysis. The obtained results indicate variety of assessments of fibrinolytic system activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Fibrinolytic activity and tissue plasminogen activator level in healthy individuals prior to and after a ten-minute venous stasis]. 836 5

Fluctuations in tissue plasminogen activator (t-PA) activity, t-PA antigen, and plasminogen activator inhibitor-I (PAI-1) antigen levels were evaluated in blood samples obtained from 84 patients with initial uneventful acute myocardial infarction (AMI) and 35 patients with reinfarction and fatal infarction (patients with bad prognoses). Patients with initial AMI had significantly higher levels of t-PA activity than those of 14 patients with angina pectoris. Tissue plasminogen activator activity peaked between day 7 and 19 after the initial attack of AMI. Plasminogen activator inhibitor-I antigen level decreased significantly between day 2 and 19, then returned to the baseline levels of patients with angina pectoris nearly 4 weeks later. The t-PA activity levels of patients with reinfarction were significantly lower than those in patients without events between day 0 and 3 and between day 7 and 19. The percentage stenosis in the coronary arteries measured by coronary angiography was negatively correlated with t-PA activity. This information may help in selecting aggressive treatments such as thrombolysis by recombinant t-PA and predicting the prognosis for patients with AMI.
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PMID:Evaluation of tissue plasminogen activator and plasminogen activator inhibitor-I levels in acute myocardial infarction. 864 3

The expression of components of the plasminogen activator system was investigated in patients with oesophageal carcinoma. Tumour and normal mucosa were obtained from resected oesophageal carcinomas and antigens were measured by enzyme-linked immunosorbent assay. Median levels of urokinase plasminogen activator (uPA) and the uPA receptor were higher in carcinoma than in matched normal mucosa (squamous cell carcinoma: uPA 4.05 versus 0.66 ng antigen per mg protein, uPA receptor 1.95 versus 0.50 ng/mg, n = 10, P < 0.05; adenocarcinoma: uPA 2.16 versus 0.61 ng/mg, uPA receptor 2.01 versus 0.49 ng/mg, n = 8, P < 0.05). Tissue plasminogen activator (tPA) level was lower than control values in squamous cell carcinoma but not in adenocarcinoma (1.97 versus 4.70 ng/mg, P < 0.05). There was no difference in plasminogen activator inhibitor (PAI) 1 level between carcinoma and normal mucosa. The PAI-2 level was lower than that in normals in adenocarcinoma only (6.0 versus 64.77 ng/mg, P < 0.05). These data support the hypothesis that membrane-bound uPA has a role in the breakdown of extracellular matrix in invasive oesophageal carcinoma.
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PMID:Plasminogen activators in oesophageal carcinoma. 886 32

To evaluate the toxicity of lead on the blood fibrinolytic system during hemostasis, human aortic smooth muscle cells and human fetal lung fibroblasts were cultured in the presence of lead chloride. Tissue plasminogen activator antigen (t-PA:Ag) and plasminogen activator inhibitor-1 antigen (PAI-1:Ag) released were determined by enzyme immunoassay. It was found that lead decreased the release of both t-PA:Ag and PAI-1:Ag from vascular smooth muscle cells. On the other hand, in fibroblasts, the release of t-PA:Ag was markedly decreased whereas that of PAI-1:Ag was markedly increased by the metal. Fibrin zymography showed that lead reduced the plasminogen activator activity in the conditioned medium of both cell types. However, lead did not cause a nonspecific cell damage and an alteration of protein synthesis when evaluated by lactate dehydrogenase leakage and [14C]leucine incorporation, respectively. Lead accumulated within either vascular smooth muscle cells or fibroblasts in a dose-dependent manner; intracellular accumulation of calcium could be increased by lead. However, the effects of lead on the release of t-PA:Ag and PAI-1:Ag were different from those of calcium ionophore A23187. It was therefore suggested that regulation of spontaneous release of fibrinolytic proteins from subendothelial cells is disturbed by lead through intracellular calcium-independent pathway.
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PMID:Lead perturbs the regulation of spontaneous release of tissue plasminogen activator and plasminogen activator inhibitor-1 from vascular smooth muscle cells and fibroblasts in culture. 905 94

Thromboelastography (TEG) has been used after cardiopulmonary bypass (CPB) to diagnose excessive postoperative hemorrhage. Conventional TEG during CPB is not possible due to the sensitivity of the TEG to even small amounts of heparin, which produces a nondiagnostic tracing. The purpose of this study was to compare heparin neutralization using heparinase or protamine in TEG blood samples obtained during CPB. TEG testing was performed on 48 patients before, during and after CPB. Tissue plasminogen activator activity and antigen were measured on a subset of 32 patients. We found: 1) heparinase neutralized at least 10 IU/ml heparin while 1.6 ug/ml protamine neutralized up to 7 IU/ml heparin, 2) in samples with complete heparin neutralization by both methods, there was no significant difference in the R values, 3) while there was good correlation for other TEG parameters between heparinase and protamine treated samples, heparinase treatment produced shorter K values and higher angle, MA and A60, 4) while fibrinolysis was detected using both methods, heparinase treatment suppressed fibrinolysis in the TEG in both samples from patients and after in vitro addition of tissue plasminogen activator, 5) TEG was not a sensitive indicator of t-PA activity, detecting only 21% of samples with increased t-PA activity during bypass, and 5) heparinase was at least 100 times more expensive than protamine. We conclude that while both heparinase and protamine can be used to neutralize heparin in TEG samples obtained during CPB, protamine neutralization is more sensitive to fibrinolysis and less expensive, but the protamine dose must be carefully selected to match the heparin level used at individual institutions.
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PMID:A comparison of thromboelastography with heparinase or protamine sulfate added in vitro during heparinized cardiopulmonary bypass. 926 78

The aim of this study was to evaluate the changes in fibrinolysis parameters during pregnancy. Normal pregnant women (n = 60) formed the study population. Blood samples were taken in the first, second and third trimester, during delivery and three days after delivery. Fibrinolysis parameters were estimated using commercial tests. Tissue plasminogen activator, D-dimer and plasminogen activator inhibitors (PAI-1 and PAI-2) were determined. Tissue plasminogen activator and D-dimer increased after the first trimester and reached maximum levels during delivery. Plasminogen activator inhibitors type 1 and type 2 were also higher, in particular PAI-2, and reached maximum levels in the third trimester. On the third day after delivery, fibrinolysis activity recovered, but D-dimer and PAI-2 levels remained above the normal non-pregnant range.
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PMID:Fibrinolysis changes in normal pregnancy. 935 Jun 8


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