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)

Intravenous (i.v.) metoprolol preceding thrombolysis in an anesthetized dog model of thrombotic occlusion of the anterior descending coronary artery helps limit infarct size (IS). We wished to determine whether these effects are caused at least in part by enhancement of collateral blood flow to the area at risk (AAR). Thrombotic occlusion was provoked by a copper-coil technique. We measured intracardiac pressures and their derivatives by catheter-tip micromanometers, cardiac output (CO) by thermodilution method, regional myocardial blood flow (RMBF) by radioactive microspheres technique, global and regional left ventricular (LV) function by ventriculography, and IS with triphenyltetrazolium at the end of the experiment. Measurements were performed before and after 60-min occlusion and after 30- and 90-min reperfusion. Received fifteen minutes after occlusion, 12 dogs metoprolol 0.3 mg/kg i.v. followed by 0.3 mg/kg/h; 12 received saline. Thrombolysis was performed in all dogs after 60-min occlusion with recombinant tissue-type plasminogen activator (rt-PA) 10 micrograms/kg/min for 30 min. Hemodynamic findings were similar in both groups. During occlusion, collateral flow to total AAR (18.6 +/- 7.5 vs. 11.0 +/- 6.1 ml/min/100 g), to its subepicardial (22.1 +/- 8.1 vs. 12.2 +/- 7.2 ml/min/100 g), midmyocardial (16.0 +/- 8.9 vs. 8.0 +/- 5.5 ml/min/100 g), and endocardial (14.1 +/- 8.1 vs. 7.3 +/- 6.0 ml/min/100 g) layers was higher (p < or = 0.03) in metoprolol than in placebo-treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intravenous metoprolol preceding thrombolysis in acute thrombotic myocardial infarction in the dog; effects on infarct size, myocardial blood flow, and left ventricular function. 752 94

We compared the thrombolytic activity of a novel modified tissue-type plasminogen activator (t-PA; del 92-173, 275Arg-->Glu), YM866, with that of t-PA in a platelet-rich thrombosis model. Thrombus was induced in guinea pig mesenteric artery by irradiation with filtered light in combination with intravenous (i.v.) administration of fluorescent dye. When occlusion by the thrombus extended to 99% of the luminal area of the vessel, test drug (YM866, t-PA, or saline) was administered by i.v. bolus injection under heparinization. Both YM866 and t-PA exhibited dose-dependent thrombolytic activity; however, the improvement in occlusion rate and the incidence of successful thrombolysis induced by YM866 were three times higher than those induced by t-PA. With YM866 1 mg/kg, alpha 2-plasmin inhibitor levels decreased significantly to 58% of saline group values, but no change was noted in fibrinogen levels. YM866 antigen levels at this dose were seven times higher than those of t-PA. These results suggest that YM866 in single bolus injection is a thrombolytic agent superior to t-PA in platelet-rich thrombi without systemic fibrinolytic activation and that this efficacy is due to the prolonged half-life (t1/2) of the drug.
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PMID:Thrombolytic activity of YM866, a novel modified tissue-type plasminogen activator, in a photochemically induced platelet-rich thrombosis model. 752 79

1. We studied DMP728, a non-peptide glycoprotein (GP) IIb/IIIa receptor antagonist, for prevention of coronary artery thrombosis or rethrombosis in a chronic canine model subjected to arterial injury. 2. In protocol I, DMP728 (1.0 mg kg-1, i.v., n = 8) or saline (n = 8) was administered and a 150 microA anodal current was applied to the intimal surface of the left circumflex coronary artery (LCX). Dogs were monitored for 6 h and again on each of 5 subsequent days. 3. Ex vivo platelet aggregation was inhibited but returned to baseline 1 day after drug administration. Thrombus weight was reduced (saline, 20.7 +/- 5.0 mg; DMP728 1.7 +/- 0.4 mg; P < 0.05), as was infarct size [saline, 27.5 +/- 4.3; DMP728, 1.6 +/- 0.7 (per cent left ventricle); P < 0.05]. All control animals died by day 3, while all but one of the treated dogs survived the entire protocol (P < 0.05). 4. In protocol II, an LCX thrombus was induced and thrombolytic therapy was initiated 30 min later. DMP728 (1.0 mg kg-1, i.v., n = 8) or saline (n = 8) was administered 5 min after recombinant tissue-type plasminogen activator infusion had begun. The incidence of reocclusion was reduced by DMP728 (saline, 4/8; DMP728, 1/8). One day after thrombolysis, 7/8 DMP728-treated animals were alive compared with 1/8 in the control group (P = 0.01). 5. DMP728 inhibited ex vivo platelet aggregation, prevented primary and secondary occlusive thrombus formation, reduced thrombus weight and infarct size and increased survival in a chronic canine model of coronary artery thrombus formation. DMP728 is an effective anti-platelet intervention when used as the singular adjunctive agent in association with thrombolytic therapy.
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PMID:Prevention of thrombosis and rethrombosis and enhancement of the thrombolytic actions of recombinant tissue-type plasminogen activator in the canine heart by DMP728, a glycoprotein IIb/IIIa antagonist. 788 89

Thrombotic obstruction of glomerular capillaries causes acute renal failure in patients with hemolytic-uremic syndrome (HUS). Recanalization of occluded vessels normally occurs by activation of the endogenous fibrinolytic system, mediated by plasminogen activators, which are stored and synthesized in the endothelial cells. However, endothelial injury is considered the primary event in the pathogenesis of HUS, and this may result in impaired fibrinolysis. In five children with HUS we performed a prospective study of plasminogen activator activity and two plasminogen activator antigens: tissue-type plasminogen activator and urokinase-type plasminogen activator before and after intravenous desmopressin. Plasminogen activator inhibitor type-1 antigen was also studied. In the acute stage of HUS plasminogen activating activity was low, in spite of elevated levels of total plasminogen activator antigens. This decrease of plasminogen activating activity was due to high levels of the plasminogen activator inhibitor. Improvement of fibrinolysis paralleled recovery from HUS. We conclude that decreased fibrinolysis is an important pathophysiologic feature of HUS.
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PMID:Impaired fibrinolysis in the hemolytic-uremic syndrome of childhood. 811 Aug 78

The effects of intrathrombic and intravenous injection of prostaglandin E1 (PGE1) during pulse-spray thrombolysis were studied in a rabbit model. Thrombi were produced in the inferior vena cava of 46 rabbits by means of vessel wall injury and placement of steel coils. At 2 days, pulse-spray thrombolysis was performed by using a catheter with multiple side holes spanning the clot. A control group received injections of saline. In all other rabbits, 3 mg of tissue-type plasminogen activator (tPA) was injected into the thrombus over 1 hour, and 500 U of heparin was intravenously administered. PGE1 was administered either intravenously (50 micrograms) or directly into the thrombus (10, 25, or 50 micrograms) in four groups. After treatment, the rabbits were killed and the residual clot was weighed. The relationship between clot length and volume measured on angiograms and clot weight was assessed in 13 additional untreated rabbits. Linear regression analysis was used to estimate the initial clot weight on the basis of measured clot length in treated animals. The extent of clot lysis was significantly greater with injection of tPA and 10-, 25-, or 50-micrograms PGE1 directly into the thrombous than with administration of tPA alone.
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PMID:Effects of intrathrombic administration of prostaglandin E1 during pulse-spray thrombolysis with tissue-type plasminogen activator in experimental thrombosis. 843 Feb 1

1. We compared the direct thrombin inhibitor, desulfatohirudin (REVASC) and the indirect thrombin inhibitor, heparin, as adjuncts to thrombolytic therapy with reteplase in a canine model of coronary artery thrombosis. 2. Reteplase (BM 06.022) is a recombinant unglycosylated variant of human tissue-type plasminogen activator. Thrombus formation in anaesthetized open chest dogs was induced by electrical injury. Left circumflex coronary artery blood flow was monitored for 210 min with an electromagnetic flow probe. Twenty eight dogs were randomized to receive i.v. heparin (120 iu kg-1 bolus plus 80 iu kg-1 per h) or i.v. hirudin (2.0 mg kg-1 bolus plus 2.0 mg kg-1 per h) 10 min before thrombolysis preceded by i.v. acetylsalicyclic acid (20 mg kg-1) 5 min prior to anticoagulation. Every dog received an i.v. double bolus injection of 0.14 + 0.14 u kg-1 ( = 0.24 + 0.24 mg kg-1) reteplase, 30 min apart, 1 h after thrombus formation. 3. At comparable reperfusion rates (12 out of 12 vs. 15 out of 16 dogs), hirudin enhanced time to reperfusion (14.3 +/- 1.4 vs. 23.2 +/- 3.4 min; P < 0.05) and completely prevented reocclusion after reperfusion in contrast to heparin (0 out of 11 vs. 7 out of 11 dogs; P < 0.05). Coronary blood flow quality was improved by hirudin as shown by a higher maximum blood flow after reperfusion (130 +/- 14.3 vs. 83 +/- 9.3% of baseline; P < 0.05), a higher blood flow level at 20, 30, 40, and 50 min after onset of thrombolysis (P < 0.05) and a longer cumulative patency time (195 +/- 1.7 vs. 166 +/- 12 min; P < 0.05). Activated partial thromboplastin time and buccal mucosa bleeding time were prolonged (P < 0.05) by either anticoagulant, but did not differ significantly between groups. 4. The direct thrombin inhibitor, desulfatohirudin, enhanced thrombolysis, prevented reocclusion and increased blood flow as compared with the indirect thrombin inhibitor, heparin, when investigated at one dose level each and used in conjunction with reteplase.
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PMID:Comparison of desulfatohirudin (REVASC) and heparin as adjuncts to thrombolytic therapy with reteplase in a canine model of coronary thrombosis. 873 26

The efficacy of the local delivery of an antithrombotic drug in preventing thrombosis and enabling thrombolysis was investigated in 29 dogs. An antithrombotic drug (heparin, 25 U/kg), or an antithrombin (argatroban, 0.05 mg/kg) was infused into injured canine iliac arteries, using a double-occlusion balloon catheter, and the preventive effect of the drug was evaluated. Local delivery of low-dose tissue-type plasminogen activator (t-PA; Tisokinase, 50,000 U; Kowa, Nagoya and Asahi Chemical Industries, Fuji, Japan) into thrombosed canine iliac arteries, using the same catheter, or intravenous infusion of low-dose or high-dose t-PA (30,000 U/kg) was also performed. Angiographically, stenotic thrombosis was 2% by local delivery of argatroban and 7% by local delivery of heparin (P < 0.01 vs each control; 47% and 51% respectively). Thrombotic stenosis, as observed by angiography, decreased from 91% to 9% after local delivery of t-PA, and from 94% to 52% in controls. Local delivery of t-PA effectively reduced the thrombus size (P < 0.01 vs control). After systemic intravenous delivery of low-dose t-PA, no reduction of residual thrombotic stenosis, was observed. Reduction of residual thrombotic stenosis after intravenous delivery of high-dose t-PA, was similar to that achieved by local delivery of the drug. Angioscopy demonstrated a similar trend. High-dose drug delivery reduced systemic coagulability. Local delivery of an antithrombotic drug, using a double-occlusion balloon catheter, effectively prevented thrombus formation, and local delivery of t-PA induced thrombolysis without exerting a significant influence on coagulability.
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PMID:Induction of thrombolysis and prevention of thrombus formation by local drug delivery with a double-occlusion balloon catheter. 889 61

Thrombotic occlusion of coronary arteries is the reason of most acute coronary syndromes. A significant role in their prevention and therapy is taken by antiplatelet therapy. Acute coronary syndrome justifies also the use of anticoagulation therapy, name by heparin. The adjuvant therapy by means of heparin in thrombolysis seems to be necessary especially when alteplase (t-PA) is used. Peroral anticoagulants represent a further therapeutical procedure in patients with coronary ischaemia. Regarding the increased risk of bleeding, the cost and difficulties coinciding with therapy by cumarine derivates, the antiplatelet therapy is currently preferred. Cumarine derivates, however, should be used in patients with simultaneous atrial fibrillation, venous thromboembolism and it should be considered in patients with heart failure and pre-thrombotic states. Studies aimed at the assessment of the role of low-molecular heparin in acute coronary ischaemia currently take place. Encouraging results are gained from experience with high effective direct inhibitors of thrombin (e.g. hirudin) and antagonists of glycoprotein IIb/IIIa. It seems that they soon will find justification in the therapy of arterial thrombosis. Interesting field of the research is represented by the studies which compare low doses of acetylosalicylic acid with low doses of cumarine derivates. (Ref. 43.)
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PMID:[Antithrombotic therapy in acute myocardial infarct]. 896

Thrombotic complications constitute an important risk in transplant recipients, in whom a hypercoagulable state and hypofibrinolysis have been associated with immunosuppressive treatment, especially with cyclosporine. In no case have clotting and fibrinolytic abnormalities been correlated with steroid immunosuppression, even though steroids were always administered. Previous studies found a relationship between hypercorticism and hypofibrinolysis both in Cushing's disease and after renal transplantation. The aim of this investigation was to compare fibrinolytic potential using the venous occlusion test in two similar groups of heart transplant patients treated with or without steroids. Euglobulin lysis time, tissue-type plasminogen activator and plasminogen activator inhibitor-1 (PAI-1) activities, and antigens were determined before and after the venous occlusion test. A reduced fibrinolytic potential (significant prolongation of lysis time) due to a significant increase in PAI-1 activity and antigen levels was found in heart transplant patients treated with steroids, as compared with patients without steroid treatment and control subjects. The prevalence of reduced fibrinolytic potential was 69.2% (18 cases) in the steroid-treated group and 34.8% (8 cases) in the non-steroid-treated group. In every case, the impaired fibrinolytic potential was due to high basal PAI-1 levels. Our results are compatible with the presence of a hypofibrinolytic state secondary to long-term steroid treatment. In heart transplant recipients, steroid-induced hypofibrinolysis may constitute a further risk factor for thrombotic disease.
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PMID:Impairment of fibrinolytic potential in long-term steroid treatment after heart transplantation. 941 68

Thrombotic risk factors may be important in determining cardiovascular outcome in patients with symptomatic peripheral arterial disease. A cohort study with a 6-year follow-up period was established to determine the relationships between haemostatic and rheological factors and incident ischaemic heart disease (IHD) and stroke events in patients with peripheral arterial disease. A consecutive series of 607 patients with intermittent claudication was examined between 1989 and 1990 at the Peripheral Vascular Clinic, Royal Infirmary of Edinburgh. Main outcome measures were combined fatal and non-fatal stroke, non-fatal myocardial infarction (MI), coronary death and total coronary events. A total of 210 patients died during follow-up. 203 patients did not experience a vascular event or deterioration of limb ischaemia. Median levels of fibrinogen, von Willebrand factor (VWF), tissue plasminogen activator (t-PA) antigen, fibrin D-dimer and whole blood viscosity were significantly higher in those who experienced an event compared with those who did not. After adjusting for age and sex, fibrin D-dimer was significantly associated with risk of non-fatal myocardial infarction (RR 1.50, 95% CI 1.09-2.06, P < or = 0.01). Both fibrinogen and fibrin D-dimer were associated with risk of total coronary events (P < or = 0.05). The risk of stroke was related to baseline levels of t-PA antigen (RR 1.87, 95% CI 1.04-3.34, P < or = 0.05) and whole blood viscosity (RR 1.33, 95% CI 1.07-1.65, P < or = 0.01). All the relationships became weaker and statistically non-significant after further adjustment for cigarette smoking, systolic blood pressure, glucose and baseline IHD. The associations of these factors to IHD and stroke may therefore be partly related to cardiovascular risk factors, but are likely to be important in the pathogenesis of future atherothrombotic events in subjects with peripheral arterial disease.
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PMID:Haemostatic factors and prediction of ischaemic heart disease and stroke in claudicants. 953 45


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