Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twelve centers participated in a double-blind study in which 63 patients with angiographically documented acute massive pulmonary embolism were randomly assigned to treatment with either urokinase (4,400 U/kg as an intravenous bolus infusion, then 4,400 U/kg per h over 12 h; n = 29) or alteplase (10 mg as an intravenous bolus infusion, then 90 mg over 2 h) followed by heparin (n = 34). The primary objective was to compare the resolution of pulmonary embolism as judged by the change in total pulmonary resistance over the initial 2 h. Further objectives were to evaluate the changes in total pulmonary resistance over the next 10 h and the degree of angiographic resolution at 12 to 18 h. At 2 h, total pulmonary resistance decreased by 18 +/- 22% in the urokinase group and by 36 +/- 17% in the alteplase group (p = 0.0009). Continuous monitoring of pulmonary artery mean pressure, cardiac index and total pulmonary resistance revealed that these variables improved faster in the alteplase group, with consistently significant intergroup differences from 30 min up to 3 to 4 h. After 12 h, the decrease in total pulmonary resistance was 53 +/- 19% in the urokinase group compared with 48 +/- 17% in the alteplase group and the reduction in the angiographic severity score was 30 +/- 25% compared with 24 +/- 18%, respectively, with no significant intergroup differences. Bleeding was equally frequent in the two treatment groups, except that more urokinase-treated patients experienced hematomas at puncture sites.
J Am Coll Cardiol 1992 Feb
PMID:Effects of intravenous urokinase versus alteplase on total pulmonary resistance in acute massive pulmonary embolism: a European multicenter double-blind trial. The European Cooperative Study Group for Pulmonary Embolism. 173 48

The thrombolytic and systemic effects of BM 06.022 were evaluated and compared with those of alteplase, anistreplase, streptokinase and urokinase in a canine model of coronary artery thrombosis. BM 06.022 consists of the kringle-2 and protease domains of human tissue plasminogen activator (t-PA) and is unglycosylated because of its expression in Escherichia coli cells. Thrombus formation in anesthetized open chest dogs was induced by electrical injury to the intimal surface of the left circumflex coronary artery at a high level site of obstruction. In heparinized dogs, none of six vehicle-treated animals exhibited reperfusion. Reperfusion was achieved in four of six dogs at 18.3 +/- 6 min after intravenous bolus injection of 140 kU/kg (0.24 mg/kg) of BM 06.022, whereas four of six dogs exhibited reperfusion later (p less than 0.05) at 76.5 +/- 16.1 min during infusion of 1.33 mg/kg of alteplase (0.13 mg/kg as initial bolus injection, followed by 0.66 mg/kg over 1 h and 0.53 mg/kg over 2 h). Significantly later (p less than 0.05) reperfusion than that achieved with BM 06.022 was achieved in five of six dogs at 57.8 +/- 12.1 min after intravenous injection of 0.4 U/kg of anistreplase. Streptokinase (21,000 IU/kg over 60 min) and urokinase (20,000 IU/kg as an intravenous bolus injection, followed by 20,000 IU/kg over 89 min) each induced reperfusion in three of six dogs but at 67 +/- 12 and 84.3 +/- 17.1 min (p less than 0.05 vs. BM 06.022), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
J Am Coll Cardiol 1992 Feb
PMID:Evaluation of thrombolytic and systemic effects of the novel recombinant plasminogen activator BM 06.022 compared with alteplase, anistreplase, streptokinase and urokinase in a canine model of coronary artery thrombosis. 173 72

Whereas in vitro studies showed that plasmin may induce both inhibition and activation of platelets, in vivo and ex vivo investigations suggested that thrombolytic agents are responsible for platelet stimulation. To gain further information on this topic, ex vivo platelet function was studied in 24 subjects with acute myocardial infarction treated with streptokinase or recombinant tissue-type plasminogen activator (rt-PA). Ten patients with acute myocardial infarction who did not receive thrombolytic treatment were also investigated. The data shows that at the end of thrombolytic infusion, the maximal extent of platelet aggregation and adenosine triphosphate release was reduced in treated patients compared with that in untreated ones. In subjects treated with streptokinase, the defect in platelet aggregation derived from both cellular and plasmatic defects. Plasmatic beta-thromboglobulin concentration was significantly reduced after streptokinase, but unchanged after rt-PA. Three days after thrombolytic treatment, platelet aggregation of patients receiving streptokinase or rt-PA was not significantly different from that of untreated subjects. A similar defect in platelet function was obtained in vitro, incubating normal platelet-rich plasma with pharmacologic concentrations of streptokinase. Again, platelet function defect derived from both cellular and plasmatic damages. It cannot be excluded that platelet activation occurs in patients with acute myocardial infarction during the very early phases of thrombolytic treatment. However, it is suggested that a transient defect in platelet function follows both streptokinase and rt-PA infusion.
Am J Cardiol 1992 Feb 15
PMID:Platelet function after in vivo and in vitro treatment with thrombolytic agents. 138 58

Sustained infarct artery patency is an important determinant of survival in patients with acute myocardial infarction. We studied 61 patients with acute myocardial infarction who received intravenous recombinant tissue-type plasminogen activator, aspirin or heparin within 6 hours of symptom onset, to determine if infarct artery patency after intravenous thrombolytic therapy influences myocardial electrical stability as measured by the prevalence of spontaneous ventricular ectopy or late potential activity. Infarct artery patency was determined by angiographic evaluation 2.5 +/- 3 days after infarction. Forty-eight patients (79%) had a patent infarct-related artery and 13 (21%) patients had an occluded vessel. The mean number of ventricular premature complexes (VPCs)/hour (p less than 0.01) and the prevalence of late potentials (54 vs 19%; p less than 0.03) were significantly higher in patients with an occluded versus patent-infarct related vessel. Although VPC frequency and late potentials were not influenced by the time to thrombolytic treatment, patients with a patent infarct-related artery had a lower prevalence of late potentials regardless of whether treatment was initiated less than or equal to 2 hours (25% patent vs 50% occluded; p = not significant) or 2 to 6 hours (16% patent vs 55% occluded; p greater than 0.03) after symptom onset. Thus, successful thrombolysis decreases the frequency of ventricular ectopic activity and late potentials in the early postinfarction phase. The reduction in both markers of electrical instability may help explain why the prognosis after successful thrombolysis is improved after acute myocardial infarction.
Am J Cardiol 1991 Dec 01
PMID:Importance of myocardial infarct artery patency on the prevalence of ventricular arrhythmia and late potentials after thrombolysis in acute myocardial infarction. 174 20

Underlying the use of thrombolytic therapy is the hypothesis that reestablishment and maintenance of coronary blood flow (coronary patency) are the primary mechanisms of therapeutic benefit in patients with acute myocardial infarction. Early achievement and maintenance of adequate coronary blood flow (patency) in the infarct-related artery are the primary goals of thrombolytic therapy. One third of patients may achieve spontaneous patency within a few days following acute myocardial infarction. When antithrombotic therapy (i.e., heparin) is administered, this rate increases to greater than 50%, but patency is achieved only gradually and mortality reductions comparable to thrombolytic therapy are not achieved. After administration of a thrombolytic agent, early (90-minute) patency rates are greater with alteplase or anistreplase than with streptokinase. However, patency rates for alteplase decline by 10-30% if intravenous heparin is not given concurrently. When patency is assessed greater than 24 hours following thrombolytic therapy, no significant difference exists among the agents. A single angiographic observation of the artery at 90 minutes, although useful, may be inadequate to distinguish among the beneficial clinical effects of different thrombolytic regimens. The overall reperfusion or patency profile is probably a better basis for assessing relative benefits. Intravenous thrombolytic regimens that are increasingly effective in rapidly achieving and maintaining coronary patency are now available and in further development.
Am J Cardiol 1991 Dec 05
PMID:Overview of patency as an end point of thrombolytic therapy. 174 46

Based on apparent higher recanalization rates of the infarct-related artery, preferential use of thrombolytic agents with high clot specificity has been proposed for treating patients with acute myocardial infarction. In the Thrombolysis in Myocardial infarction (TIMI-I) and European Cooperative Group studies, higher reperfusion rates were observed with alteplase compared with streptokinase, causing many to assume that the former would achieve a greater reduction in early hospital mortality. However, the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI-2) and its associated International Study Group failed to show any differences in 15-day mortality between these agents in more than 20,000 patients. This apparent lack of correlation between reperfusion rates and early mortality may be explained in part when one considers that recanalization or patency rates measured at a given point in time, such as 90 minutes after onset of therapy, fail to define the subsequent vessel status. Early reocclusion is the major reason for this and is a major limitation to the clinical efficacy of thrombolytic drugs. Following recanalization, residual fibrin-bound thrombin adherent to the site of arterial injury from plaque rupture strongly promotes rethrombosis. Although antiplatelet and antithrombin agents such as aspirin and heparin help to decrease rethrombosis, these agents are far from ideal. Thrombolytic agents that produce a significantly prolonged systemic thrombolytic state, such as streptokinase and anistreplase, are likely to result in less rethrombosis. Therefore, a systemic fibrinolytic state would appear to be an advantage rather than a disadvantage, particularly because the incidence of intracerebral hemorrhage does not appear to be greater with their use compared with agents producing less systemic fibrinolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Cardiol 1991 Dec 05
PMID:Thrombolysis, anticoagulation, and reocclusion. 174 47

In recent acute myocardial infarction, early reperfusion of the infarct-related artery by intracoronary or intravenous thrombolytic therapy induces a significant limitation of infarct size, provided reperfusion occurs within a time frame that myocardial salvage can still be expected. Limitation of infarct size reduces scar tissue formation, aneurysm formation, infarct zone expansion, left ventricular volume enlargement, and eventually results in higher left ventricular ejection fraction. Infarct size limitation and left ventricular function preservation occur with all thrombolytic agents currently in clinical use: streptokinase, alteplase and, more recently, anistreplase. When anistreplase is compared with conventional heparin therapy, a 31% reduction in infarct size is found (estimated from single photon emission computed tomography, or SPECT). This translates into a significant preservation of left ventricular ejection fraction as observed in anistreplase-treated patients compared with heparin-treated patients (0.53 +/- 0.13 vs 0.47 +/- 0.12, p less than 0.002). In comparative trials of 2 thrombolytic agents, anistreplase was demonstrated to be as efficient as alteplase on left ventricular ejection fraction preservation and infarct size limitation.
Am J Cardiol 1991 Dec 05
PMID:Use of left ventricular function as an end point of thrombolytic therapy. 174 48

Three thrombolytic agents are frequently used in the United States for treating patients with acute myocardial infarction: streptokinase, alteplase (tissue plasminogen activator [t-PA]), and anistreplase (anisoylated plasminogen-streptokinase activator complex [APSAC]). A fourth agent, urokinase, is occasionally used but clinical experience is considerably more limited with this agent. Streptokinase, alteplase, and anistreplase differ in a number of pharmacologic properties, which include half-life, enzymatic efficiency, and induction of platelet aggregation; these differences may be clinically important. For example, anistreplase and alteplase have high affinity for fibrin and bind to intravascular thrombi after intravenous administration, which may result in higher clot specificity. Anistreplase has the longest half-life of the 3 agents and, therefore, can be administered conveniently and quickly. Alteplase has a shorter half-life and heparin is generally a necessary adjunctive agent. These differences can be clinically significant in various settings and application of such theoretical advantages is just beginning.
Am J Cardiol 1991 Dec 05
PMID:Importance of the pharmacological profile of thrombolytic agents in clinical practice. 174 49

Three available thrombolytic agents, streptokinase, alteplase, and anistreplase, have been shown to have similar effects on preservation of left ventricular function and mortality reduction after acute myocardial infarction (AMI). The agents are, however, quite different with respect to their safety profiles. Clinical trials to date suggest that alteplase (tissue plasminogen activator) or anistreplase administration is associated with a high incidence of cerebral hemorrhage. In contrast, streptokinase is associated with a low rate of cerebral hemorrhage. Streptokinase and anistreplase are associated with a higher risk of allergic reaction when compared with alteplase. Hypotension is also more common with streptokinase and anistreplase, but occurs significantly with alteplase as well. Alteplase is associated with a lower reinfarction rate when compared with streptokinase and anistreplase. The Third International Study of Infarct Survival (ISIS-3), a direct comparison of 3 thrombolytic agents (streptokinase, anistreplase, and duteplase), may provide some insight regarding the safety of these agents. Because these agents have been shown to be equally effective, selection of an appropriate agent for an individual patient may depend more on assessment of the likelihood of an adverse event or other factors, such as cost or convenience of administration, rather than assessment of the probability of greater benefit with a particular agent.
Am J Cardiol 1991 Dec 05
PMID:Comparative safety of thrombolytic agents. 174 50

The effect of simultaneous infusions of low-dose recombinant tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA, pro-urokinase) on coronary arterial thrombolysis was investigated in 23 patients treated within 6 hours (mean 2.6 +/- 1.1, range 1.2 to 5.9) of symptoms of an acute myocardial infarction. Infarct artery patency at 90 minutes was achieved in 16 (70%, 95% confidence limits of 0.47 to 0.87) of 23 patients after a 1-hour intravenous infusion of 20 and 16.3 mg of t-PA and scu-PA, respectively. At 90 minutes, the fibrinogen concentration decreased from 369 +/- 207 to 316 +/- 192 mg/dl (p = not significant), while plasminogen decreased to 69 +/- 24% (p = 0.001) and alpha-2-antiplasmin to 77 +/- 24% (p = 0.001) of pretreatment values. Although no bleeding requiring termination of drug infusion or transfusion occurred, 1 patient with cerebrovascular amyloidosis had a fatal intracerebral hemorrhage. These findings suggest that combination therapy may allow substantial reductions in total thrombolytic doses while still achieving effective fibrin-specific coronary thrombolysis.
Am J Cardiol 1991 Dec 15
PMID:Clot-selective coronary thrombolysis with low-dose synergistic combinations of single-chain urokinase-type plasminogen activator and recombinant tissue-type plasminogen activator. The Pro-Urokinase for Myocardial Infarction Study Group. 174 55


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>