Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stroke is one of the leading causes of death in the industrial nations of the world. Up to now, there has been no therapeutic strategy available which has been proven by controlled clinical trials. In the majority of acute stroke patients acute thrombosis contributes to carotid and vertebrobasilar arterial occlusions. Therefore, significant interest has focused on the possible value of fibrinolytic therapy in acute stroke. The principal goal is the rapid lysis of occluding thrombus with a minimum risk of intracranial or systemic hemorrhage. Clinical investigations on thrombolysis in cerebrovascular ischemia included different plasminogen-activators such as urokinase, streptokinase, and tissue plasminogen activator, either given systemically or locally via an intraarterial catheter. The pivotal trials conducted so far have revealed a wide range of recanalization rates, an acceptable safety and, also, encouraging effects on neurologic outcome. Thrombolysis itself carries the risk of intracranial bleeding, a practical limitation of this approach in acute stroke. On the other hand, hemorrhagic infarction and parenchymatous hematoma are natural consequences of thromboembolic stroke, possibly as a result of persistent occlusion of an artery. Hemorrhage following thrombolysis seems to show the same features seen in untreated patients and with an incidence similar to that in untreated patients. Future developments in thrombolysis in acute stroke should include improved early recruitment of patients, evaluation of noninvasive techniques in the pretreatment assessment of patients, the evaluation of advanced invasive techniques for delivery of the thrombolytic agent and assessment of combined treatment strategies. Clinical studies evaluating these strategies are currently under way.
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PMID:Thrombolytic intervention in acute thrombotic and embolic stroke. 832 15

A thirty-one-year-old woman with long-standing mixed connective tissue disease and severe obliterative vasculopathy of the digits developed digital thrombosis of the first three digits of the left hand after using an electric blow dryer. The digits remained cool, cyanotic, and painful for thirty-six hours before medical evaluation. She was given 100 mg recombinant tissue plasminogen activator (TPA) intravenously. Within one hour the blood flow to the digits returned, accompanied by severe intermittent vasospasm of the digits. The thumb did not necrose; however, the second and third digits required amputation. No improvement was noted in the patient's baseline Raynaud's phenomenon or digital pressures of the uninvolved digits after TPA treatment. This case documents the usefulness of TPA for digital thrombosis in the setting of vasculopathy of connective tissue disease. However, it does not support the utility of a single dose of TPA for severe Raynaud's phenomenon and recurrent digital ischemia in patients with connective tissue disease.
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PMID:Tissue plasminogen activator treatment of digital thrombosis in severe Raynaud's phenomenon--a case report. 832 85

The purpose of this study was to investigate the effects of beraprost sodium, a stable prostacyclin analog, on the parameters of hemostasis, fibrinolysis, and myocardial ischemia in patients with exertional angina. Thirty-one patients with exertional angina who had significant organic coronary artery stenosis in at least one of the three major coronary arteries were selected. All patients underwent quantitative exercise thallium-201 emission computed tomography before and 1 month after 120 micrograms per day of beraprost sodium administration. Before exercise, blood samples were collected from 8:30 a.m. to 9:30 a.m. after the patients had been lying in bed undisturbed for at least 10 minutes. Plasma platelet factor 4 (PF4), fibrinopeptide A (FPA), tissue plasminogen activator antigen (t-PA), and plasminogen activator inhibitor-1 activity (PAI-1) were measured. There were no significant differences in exercise parameters on both exercise tests. However, both the extent and severity scores of ischemia were significantly aggravated (p < 0.05 for both) during beraprost sodium administration. Plasma FPA levels decreased significantly during beraprost sodium administration (p < 0.01). Likewise, plasma PF4 levels decreased significantly during beraprost sodium administration (p < 0.05). As for plasma t-PA antigen levels, there was no significant difference before versus during beraprost sodium administration. Plasma PAI-1 activity levels decreased significantly during beraprost sodium administration (p < 0.05). The results indicate that beraprost sodium has strong antithrombogenic properties. However, its aggravation of myocardial ischemia may limit clinical usage.
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PMID:Effects of beraprost sodium, a new prostaglandin I2 analog, on parameters of hemostasis, fibrinolysis, and myocardial ischemia in patients with exertional angina. 854 11

Although coronary thrombosis is thought to play a pivotal role in the pathogenesis of unstable angina and non-Q wave myocardial infarction and antithrombotic therapy is a mainstay in the early management of these patients, the relation between measures of systemic anticoagulation and clinical events has not been defined clearly. In the Thrombolysis in Myocardial Ischemia III trial, 1473 patients with ischemic chest pain at rest evaluated within 24 hours of symptom onset were randomized to (1) tissue plasminogen activator (TPA) or placebo and (2) an early invasive or an early conservative strategy. All patients received a full complement of anti-ischemic medication, aspirin, and continuous intravenous heparin titrated to an activated partial thromboplastin time (aPTT) of 1.5 to 2.0 times control for 72 to 96 hours. The median aPTT in all study groups exceeded the minimum threshold (45 seconds) by 24 hours and remained within the designated range during the protocol-directed heparin infusion. No differences in median aPTT values for the 72- to 96-hour study period were observed between groups (p=not significant). Median 12-hour heparin concentrations were >0.2 U/ml in all groups; however, values <0.2 U/ml were common thereafter, particularly in TPA-treated patients. Time-dependent covariate analyses failed to identify statistically significant differences in either aPTT or heparin levels between patients with in-hospital clinical events (spontaneous ischemia, myocardial infarction, or death) and those without events (p=0.27). Furthermore, early clinical events occurred in a similar percentage of patients with optimal anticoagulation (all aPTTs >60 seconds, all heparin levels>0.2 U/ml), and those with aPTTs or heparin levels below these thresholds. Aggressive (high-intensity) anticoagulation with heparin to achieve aPTTs >2.0 times control does not appear to offer additional clinical benefit to lower levels (1.5 to 2.0 times control) among patients with unstable angina and non-Q wave myocardial infarction receiving intravenous heparin and oral aspirin. Therefore, the optimal level of anticoagulation in this common clinical setting is between 45 and 60 seconds when heparin is included in the treatment strategy. Direct plasma heparin measurement does not offer an advantage to routine aPTT monitoring. The occurrence of spontaneous ischemia, myocardial infarction, and death in spite of antischemic therapy and optimal anticoagulation (as it is currently defined) with heparin supports ongoing efforts to develop more effective antithrombotic agents.
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PMID:Relation between systemic anticoagulation as determined by activated partial thromboplastin time and heparin measurements and in-hospital clinical events in unstable angina and non-Q wave myocardiaL infarction. Thrombolysis in Myocardial Ischemia III B Investigators. 860 20

Intravenous heparin is routinely given after thrombolytic therapy for patients with acute myocardial infarction in the United States and in some, but by no means all, other countries. Several trials have documented improved infarct-artery patency in patients treated with heparin; however, none was large enough individually to assess the effect of heparin on clinical outcomes. We performed a systematic overview of the 6 randomized controlled trials (1,735 patients) to summarize the available data concerning the risks and benefits of intravenous heparin versus no heparin after thrombolytic therapy. Mortality before hospital discharge was 5.1% for patients allocated to intravenous heparin compared with 5.6% for controls (relative risk reduction of 9%, odds ratio 0.91, 95% confidence interval 0.59 to 1.39). Similar rates of recurrent ischemia and reinfarction were observed among those allocated to heparin therapy or control. The rates of total stroke, intracranial hemorrhage, and severe bleeding were similar in patients allocated to heparin; however, the risk of any severity of bleeding was significantly higher (22.7% vs 16.2%; odds ratio 1.55, 95% confidence interval 1.21 to 1.98). There was no significant difference in the observed effects of heparin between patients receiving tissue-type plasminogen activator and those receiving streptokinase or anisoylated plasminogen streptokinase activator complex, or between patients who did and did not receive aspirin. The findings of this overview demonstrate that insufficient clinical outcome data are available to support or to refute the routine use of intravenous heparin therapy after thrombolysis. It is not known if these findings are due to lack of statistical power, inappropriate levels of anticoagulation, or lack of benefit of intravenous heparin. Large randomized studies of heparin (and of new antithrombotic regimens) are needed to establish the role of such therapy.
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PMID:Overview of randomized trials of intravenous heparin in patients with acute myocardial infarction treated with thrombolytic therapy. 861 Jun 1

This study was designed to evaluate the effects of tissue-type plasminogen activator (tPA) and 21- amino steroid (U74006F) in experimental embolic stroke in rabbits. The size of infarction from embolism was compared to controls with tPA alone, 21-amino steroid alone, and in combination. The middle cerebral artery of the rabbit was embolized by injecting an arterial ('white') thrombus in the right internal carotid artery. The rabbit treatment was 2 mg kg-1 of tissue-type plasminogen activator and/or 3 mg kg-1 of 21 amino steroid started at 2 h post-embolization. The animals were terminated 4 h post-treatment and brains were examined for evidence of ischemia and/or hemorrhage. Administration of tissue-type plasminogen activator and/or 21-amino steroid in the raw data show that there is a tendency for all treatments to reduce the ischemic volume when compared to the control group, also it is evident the standard deviation of these estimates is rather large when compared to the differences between treatments. The results of the analysis of variance shows that the differences expressed are not statistically significant. (No statistical differences were found between the treatment groups and the control group.) The results show that administration of tissue-type plasminogen activator and/or 21 amino steroid at 2 h post-embolization alone or in simultaneous administration does not significantly reduce the volume of infarction. Further studies need to be addressed in regards to the region of viable brain in the peri-infarct area, in reducing the time to treatment.
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PMID:Influence of a 'brain protector' drug 21-amino steroid on the effects of experimental embolic stroke treated by thrombolysis. 862 95

We investigated the reversibility of compound action potential (CAP) changes induced after transitory local ischemia induced by rose bengal photochemically induced thrombosis of the rat anterior inferior cerebellar artery (AICA). Cochlear blood flow (CBF) was measured with a laser-Doppler flowmeter positioned on the lateral bony wall of the basal turn of the cochlea, and the CAP to an 8-kHz half-wave of sinusoid sound at 100 dB sound pressure level was monitored. The irradiation was started 5 minutes before the rose bengal administration and continued through the thrombosis formation. Tissue-type plasminogen activator (t-PA, 1 mg/kg) dissolved in saline was injected intravenously 2 minutes after complete photothrombotic blockade of the AICA in the rats presenting complete abolition of CAPs just after the vascular occlusions. Nineteen of the 51 rats presented complete abolition of the CAP just after the AICA occlusion, and the thrombosed AICA was successfully reperfused by t-PA administration in 11 of the 19 rats. The result showed that duration of ischemia was the more important determinant for the reversibility of CAPs during the acute phase (p = .00001), and the residual level of cochlear blood flow during ischemia was also an important factor (p = .066). It appeared that the critical time of ischemia for the complete recovery of CAPs was around 5 minutes, and that the critical limit for the irreversibility of CAPs within the acute phase was between 20 and 25 minutes.
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PMID:Reversibility of compound action potential during the acute phase after transitory local ischemia. 863

A previously healthy woman presented with ischemic cardiac pain and ST elevation suggestive of acute myocardial infarction following a 45 min argument. Despite receiving tissue plasminogen activator, she developed cardiogenic shock and objective evidence of recurrent ischemia, with only a small creatine kinase rise. Angiography revealed the unexpected findings of normal coronary anatomy and akinesis of the distal two-thirds of the left ventricle. Apart from an iliac vein thrombosis, the remainder of her course was characterized by dramatic recovery of cardiac function. The differential diagnosis of myocardial infarction with angiographically normal coronary arteries is discussed, with emphasis on aspects relevant to this case. The presence of high titre anticentromere antibodies, anticardiolipin antibodies, protein S deficiency and supportive physical findings, suggested the diagnosis of concurrent antiphospholipid antibody syndrome (with secondary acquired protein S deficiency) and CREST syndrome. The pathogenesis likely involved an interaction between stress, vasospasm, and thrombosis.
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PMID:Reversible cardiogenic shock in an angry woman--case report and review of the literature. 868 41

Surgical revascularization as the initial therapy in acute lower limb ischemia (ALLI) is associated with a high cumulative mortality and amputation rate. Catheter-directed delivery of low-dose thrombolytic agents (intra-arterial thrombolysis, IAT) offers the possibility for a gentle revascularization with a minimum of stress for the patients. In two randomized studies, the primary rates of revascularization, amputation, and mortality did not differ significantly between IAT and surgical revascularization. However, in one study the 6-month event-free survival rate was 85% in the IAT group, and 63% in the surgical group. Also in the second study the 12-month results were significantly better in the IAT group (event-free survival 75%) than in the surgical group (event free survival 52%). The high-dose urokinase regimen recommended by some authors in IAT is associated with an unacceptable cerebral bleeding rate of up to 2%. Low-dose recombinant tissue-type plasminogen activator (rt-PA) (0.02 to 0.05 mg/h) is the most suitable agent in IAT because of rapid lysis and low bleeding complications. Patients with ALLI, classified as viable or threatened without neurologic deficit, benefit most from the IAT as the initial therapy in ALLI. When IAT is performed as the initial therapy in ALLI, surgical intervention becomes unnecessary in approximately one-third of the patients. In another third the subsequent correction of the cause of the ALLI can be performed electively, which reduces mortality and morbidity rates.
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PMID:Thrombolytic therapy in acute lower limb ischemia. 871 91

In the Primary Angioplasty in Myocardial Infarction trial, 395 patients with acute myocardial infarction (AMI) were prospectively randomized to tissue plasminogen activator (tPA) or primary percutaneous transluminal coronary angioplasty (PTCA). In 138 patients with anterior wall AMI, in-hospital mortality was significantly reduced by treatment with PTCA compared with tPA (1.4% vs 11.9%, p = 0.01). PTCA also resulted in lower rates of death or reinfarction (1.4% vs 18.0%, p = 0.0009), recurrent myocardial ischemia (11.3% vs 28.4%, p = 0.01), and stroke (0.0% vs 6.0%, p = 0.037) in anterior wall AMI. The independent beneficial effect of treatment with primary PTCA rather than tPA in anterior wall AMI was confirmed by multivariate analysis and interaction testing. The in-hospital mortality of 257 patients with nonanterior wall AMI was similar after PTCA and tPA (3.2% vs 3.8%, p = 0.82). Compared with tPA, however, primary PTCA resulted in a markedly lower rate of recurrent myocardial ischemia (9.7% vs 27.8%, p = 0.0002), fewer unscheduled catheterization and revascularization procedures, and a shorter hospital stay (7.0 vs 8.6 days, p = 0.01) in nonanterior wall AMI. Thus, compared with tPA, primary PTCA in patients with anterior wall AMI results in significantly improved survival, with lower rates of stroke, reinfarction, and recurrent myocardial ischemia. In nonanterior wall AMI, treatment with PTCA and tPA results in similar early mortality, although PTCA-treated patients have a more stable hospital course characterized by reduced recurrent ischemia, fewer subsequent invasive procedures, and earlier discharge.
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PMID:Influence of acute myocardial infarction location on in-hospital and late outcome after primary percutaneous transluminal coronary angioplasty versus tissue plasminogen activator therapy. 871 12


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