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

The nature, mechanism of action, and roles of endothelium-derived relaxant factor (EDRF) are reviewed, particularly in relation to the coordination of vascular behavior in response to changes in flow, coronary spasm, and platelet aggregation. Vascular endothelium performs a multiplicity of roles. It is an active sieve for macromolecules and leukocytes, a negatively charged "lubricant" for passage of negatively charged red cells and platelets, and a factory for Von Willebrand factor, glycoaminoglycans, and plasminogen activator and its inhibitor. It is also a processing plant that metabolizes adenosine nucleotides to adenosine and activates angiotensin. Endothelium also produces prostacyclin and endothelium-derived relaxant factor, which act synergistically and through different pathways to the common ends of relaxing vascular smooth muscle and inhibiting platelet aggregation. Most recently it has been shown to also produce a constrictor agent called endothelin, a peptide whose structure has now been elucidated. This review will concentrate on EDRF, the recently discovered vasodilator agent that is continuously released by all vascular endothelium. It would be premature to define the role of EDRF in ischemic heart disease. It may, however, be timely to consider the ways in which EDRF might be relevant, based on a review of what is at present known.
Cardiovasc Drugs Ther 1989 Jun
PMID:Vascular endothelium in ischemic heart disease: possible role for endothelium-derived relaxing factor. 248 97

To test the utility and safety of percutaneous transluminal coronary angioplasty (PTCA) after recombinant tissue plasminogen activator (t-PA), we performed the procedure in all suitable candidates with acute myocardial infarction (MI) who had successful t-PA mediated coronary thrombolysis. Twenty consecutive patients with MI received t-PA after coronary angiographic conformation of total occlusion. Successful recanalization with t-PA was achieved in 13 patients, leaving a residual obstruction of 84 +/- 6% in the nine patients for whom PTCA was attempted at a mean of 21.6 h. Success was achieved in seven patients, leading to a residual lesion of 29 +/- 7%. In the two patients for whom PTCA was unsuccessful, total reocclusion occurred prior to the attempt despite therapy with heparin, aspirin, dipyridamole, and nifedipine. All PTCA procedures were uncomplicated. Serial two-dimensional echocardiography at 10 days, compared to admission, demonstrated infarct zone wall motion index improvement in the patients with successful PTCA (group A, 0.83 +/- 0.36 to 1.46 +/- 0.49) as compared to the 13 patients without thrombolysis or successful PTCA (group B, 0.61 +/- 0.26 to 0.66 +/- 0.39), (P less than 0.05). One patient of group A sustained a massive stroke at 2 weeks after hospital discharge. In the remaining six patients, follow-up exercise testing and/or coronary arteriography demonstrated a negative treadmill test and/or patent infarct vessel, respectively. After successful PTCA, no patient had clinical signs of reocclusion, reinfarction, postinfarction angina, or congestive heart failure. At 9.4 +/- 2 months, all six patients are asymptomatic and have returned to work. Thus, sequential PTCA after t-PA can be performed safely and successfully in patients with MI and this approach may be associated with improved regional function and a favorable post-MI course.
Cathet Cardiovasc Diagn 1985
PMID:Applicability of percutaneous transluminal coronary angioplasty to patients with recombinant tissue plasminogen activator mediated thrombolysis. 293 Nov 76

Early reperfusion of occluded coronary arteries offers great promise as a method for minimizing myocardial damage after acute myocardial infarction. Such reperfusion is usually attempted via administration of fibrinolytic agents. Urokinase may hold marginal advantages over streptokinase, especially in patients with high preexisting titers of antistreptokinase antibodies. These minor differences, however, pale in comparison to important advantages demonstrated by the newly developed agent, tissue plasminogen activator (t-PA). The advantages of t-PA derive primarily from its property of binding to, and being activated by, fibrin. Consequently the generated plasmin is also fibrin-bound, the bound plasmin is protected from circulating antiplasmin and therefore more efficiently utilized, and circulating fibrinogen is spared. Preliminary clinical experience indicates that the frequency of favorable response after intravenous administration of t-PA is considerably greater than after SK. A major determinant of clinical benefit after reperfusion is the brevity of ischemia. Selective intracoronary infusion of fibrinolytic agent produces faster lysis than does intravenous infusion, and rate of lysis may be further accelerated by transcatheter disruption of clot and intrathrombic injections of highly concentrated urokinase or t-PA. Even maximally accelerated lysis, however, cannot fully compensate for the inherent delay imposed by catheterization. For that reason, prompt intravenous infusion of fibrinolytic agents, presumably t-PA, seems preferable to the intracoronary route. In the effort to initiate fibrinolytic therapy at the earliest feasible time after infarction, administration by paramedics, or even home administration after training, is a program worthy of exploration.
Cardiovasc Intervent Radiol 1986
PMID:Streptokinase, urokinase, and tissue plasminogen activator: pharmacokinetics, relative advantages, and methods for maximizing rates and consistency of lysis. 310 38

The troublesome sequelae of pulmonary embolism (PE) and deep vein thrombosis (DVT) justify an aggressive therapeutic approach. Results of anticoagulation in patients with DVT have shown that a significant percentage of patients have no clot resolution and may progress to develop the postphlebitic syndrome. Lytic therapy has been more effective, with patients showing improvement within 24 h of treatment. This approach has also been found to compare favorably with anticoagulation in the treatment of PE. Preliminary research also suggests a potential role for recombinant human tissue-type plasminogen activator to resolve PE.
Cardiovasc Intervent Radiol 1988
PMID:Fibrinolytic therapy for deep vein thrombosis and pulmonary embolism. 313 Oct 6

Clinical experience with the use of intracoronary tissue plasminogen activator (t-PA) is limited. We therefore undertook this study to document current clinical usage of intracoronary t-PA during a 2-yr period in a multicenter registry. Intracoronary t-PA was utilized on 206 occasions in 198 patients (154 men and 44 women; mean age, 59 +/- 12 yr). The mean dose of intracoronary t-PA was 31 +/- 15 mg. Indications for use included acute myocardial infarction (MI) (n = 83), preexisting thrombus with (n = 49) or without (n = 41) percutaneous transluminal coronary angioplasty (PTCA), unstable angina (n = 14), abrupt vessel closure (n = 11), and post-PTCA "clean-up" (n = 8). The Thrombolysis in Myocardial Infarction (TIMI Phase I) criteria were used to assess perfusion and degree of thrombus formation. Overall, the mean TIMI flow grade increased from 1.2 +/- 1.1 before treatment to 2.3 +/- 1.0 after treatment (P < 0.0001); the mean TIMI thrombus grade decreased from 3.2 +/- 1.0 before treatment to 1.6 +/- 1.4 after treatment (P < 0.0001). Complications included bleeding (9.2%), MI (17.6%), need for coronary artery bypass grafting (CABG) (9.2%), need for repeat PTCA/atherectomy/stents (4.9%), and ventricular fibrillation (1.7%, all associated with opening totally occluded vessels). There were 14 subsequent in-hospital deaths: 13 of the patients who died had originally presented with MI; the other had experienced abrupt vessel closure during a PTCA procedure. Intracoronary t-PA appears to be effective in improving distal flow and decreasing thrombus burden; however, intracoronary delivery of t-PA has associated risks.(ABSTRACT TRUNCATED AT 250 WORDS)
Cathet Cardiovasc Diagn 1995 Mar
PMID:Clinical experience with intracoronary tissue plasminogen activator: results of a multicenter registry. Intracoronary t-PA Registry Investigators. 749 84

We examined the thrombolytic properties of a novel modified human tissue plasminogen activator (PA) (E6010), in which cysteine 84 is replaced by serine, and which has a prolonged biologic half-life (t1/2). We compared the thrombolytic efficacy of continuous intracoronary (i.c.) infusion of E6010 with that of recombinant human tissue PA (rt-PA) in a canine model with copper coil-induced 1-h-old coronary artery thrombi and also compared the relation between thrombolytic efficacy and plasma clearance represented by pharmacokinetic parameters of i.c.-infused E6010 and rt-PA. Sixty-minute E6010 and rt-PA i.c. infusions were compared. The thrombolytic effects of i.c.-infused E6010 and rt-PA, represented by time to reperfusion (TR), reperfusion rate at 60 min (RR), and reocclusion rates at 60 min after reperfusion (OR) were as follows. E6010: Dose 0.06, 0.15, 0.3 (mg/kg/h); TR 25 +/- 10, 15 +/- 10, 13 +/- 5 (min); RR 100, 100, 100 (%); and OR 0, 0, 17 (%), respectively. Recombinant t-PA: Dose 0.06, 0.15, 0.3 (mg/kg/h); TR 47 +/- 12, 18 +/- 17, 14 +/- 4 (min); RR 50, 75, 100 (%); and OR 100, 33, 33 (%), respectively. These findings indicate that E6010 has more potent thrombolytic activity than rt-PA.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1993 Dec
PMID:Intracoronary infusion of E6010 has more potent thrombolytic activity than tissue plasminogen activator (t-PA) in dogs: a higher plasma level of E6010 than t-PA causes potent thrombolytic activity. 750 1

The platelet glycoprotein IIb/IIIa receptor (GPIIb/IIIa, fibrinogen receptor) represents the final common pathway for platelet aggregation. Inhibition of GPIIb/IIIa with antibodies or peptides containing the RGD sequence has been reported to prevent arterial thrombosis. We examined DMP 728 [(cyclic[D-2-amino-butyryl-N2-methyl-L-arginyl-glycyl-L-aspartyl-3-(a min o- methyl-benzoic acid], methanesulfonic acid salt], a cyclic peptidomimetic, GPIIb/IIIa receptor antagonist, for prevention of thrombosis and rethrombosis in a canine model of carotid artery thrombosis. Dogs were anesthetized, and both carotid arteries were instrumented with an electrode, a flow probe, and a stenosis. A 300-microA current was applied to the intimal surface in the right carotid artery (RCA, control) through the electrode; time to occlusive thrombus formation and thrombus mass was noted. The RCA served as the control vessel; the left carotid artery (LCA) served as the test vessel after DMP 728 administration (0.1 or 1. mg/kg, intravenously, i.v.). As compared with controls, occlusive thrombus formation was reduced by both doses of DMP 728 (control 100% n = 12; 0.1 mg/kg i.v. 17%, p < 0.05, n = 6; 1.0 mg/kg i.v. 0%, p < 0.05, n = 6), time to occlusion was increased (p < 0.05), and thrombus weight was reduced (p < 0.05). Ex vivo platelet aggregation was inhibited in all groups. In a second group of animals, a carotid artery thrombus was formed and lysed with anisoylated plasminogen activator complex (APSAC; 0.05 U/kg intraarterially, i.a.) with or without DMP 728.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1994 Apr
PMID:Antithrombotic effects of DMP 728, a platelet GPIIb/IIIa receptor antagonist, in a canine model of arterial thrombosis. 751 23

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)
J Cardiovasc Pharmacol 1994 Jul
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.
J Cardiovasc Pharmacol 1994 Jun
PMID:Thrombolytic activity of YM866, a novel modified tissue-type plasminogen activator, in a photochemically induced platelet-rich thrombosis model. 752 79

Anistreplase is a thrombolytic agent comprising a complex of streptokinase, lys-plasminogen, and a p-anisoyl group, which temporarily protects the catalytic center of the enzyme complex. Streptokinase was previously shown to reduce infarct size (IS) in dogs with a fibrin-rich clot in the left anterior descending coronary artery (LAD) without necessarily producing reperfusion. Therefore, we hypothesized that IS in this model would be reduced by anistreplase. In addition, we studied the effect of tissue-type plasminogen activator (t-PA) on IS, testing our hypothesis in anesthetized dogs in which thrombin (100 U) and calcium (50 microliters, 0.05 M) were sequentially injected into the LAD to form a thrombus, anistreplase [0.01, 0.05, or 0.10 U/kg intravenous (i.v.) bolus], t-PA (0.1, 0.5, 2, or 8 micrograms/kg/min infusion for 60 min) or vehicle (VEH) was administered 55 min later. Anistreplase (0.05 or 0.10 U/kg) significantly (p < 0.05) reduced clot weight (VEH 22 +/- 3 mg; anistreplase 0.05 U/kg, 13 +/- 4 mg; anistreplase 0.10 U/kg, 0.7 +/- 0.6 mg), increased incidence of reperfusion (VEH 0%; anistreplase 0.05 U/kg, 42%; anistreplase 0.10 U/kg, 100%) and reduced IS (VEH 23 +/- 3%; anistreplase, 0.05 U/kg, 14 +/- 2%; anistreplase 0.10 U/kg, 15 +/- 2%). t-PA reduced thrombin weight (VEH 26 +/- 3 mg; 2 micrograms/kg/min t-PA 12 +/- 4; 8 micrograms/kg/min t-PA 2 +/- 2 mg) and increased incidence of reperfusion (VEH 0%; 2 micrograms/kg/min 75%; 8 micrograms/kg/min 100%), but IS was not altered (VEH 19 +/- 3%; 0.1 microgram/kg/min 18 +/- 3%; 0.5 microgram/kg/min 23 +/- 2%; 2 micrograms/kg/min 16 +/- 5%; 8 micrograms/kg/min: 19 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1995 Apr
PMID:Cardioprotection and thrombolysis by anistreplase in anesthetized dogs. 759 32


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