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)

In the conservative strategy arm of phase II of the Thrombolysis in Myocardial Infarction (TIMI) trial, 1,461 patients were treated with intravenous recombinant tissue-type plasminogen activator (rt-PA). Coronary angiography, with angioplasty if feasible, was to be performed only for recurrent spontaneous or exercise-induced ischemia. In this study results in patients treated by this strategy in community and tertiary hospitals are compared. Despite similar baseline findings in the two groups, coronary angiography was performed within 42 days in more patients (542 [48%] of 1,155) initially admitted to a tertiary hospital (on-site coronary angiography/angioplasty available) than in those (94 [32%] of 306) admitted to a community hospital (transfer to tertiary hospital for coronary angiography/angioplasty) (p less than 0.001). This different approach resulted in a greater use of coronary angioplasty (203 [18%] of 1,155 versus 32 [11%] of 306, p less than 0.01), coronary artery bypass surgery (133 [12%] of 1,155 versus 23 [8%] of 306, p less than 0.05) and blood transfusions (139 [12%] of 1,155 versus 17 [5.5%] of 306, p less than 0.001) in patients admitted to a tertiary than to a community hospital. However, there were no significant differences between the two groups in mortality, recurrent myocardial infarction or left ventricular function. These results demonstrate that a conservative strategy after treatment of acute myocardial infarction with rt-PA is applicable in the community hospital setting.
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PMID:Thrombolysis in Myocardial Infarction (TIMI) phase II trial: outcome comparison of a "conservative strategy" in community versus tertiary hospitals. The TIMI Research Group. 212 2

The effects of early coronary recanalization on the plasma levels of two procoagulant acute phase proteins, the fastacting plasminogen activator inhibitor and von Willebrand factor, were investigated in 24 patients with myocardial infarction receiving intravenous recombinant tissue-type plasminogen activator (rt-PA) within 6 h of the onset of symptoms. Coronary angiography was performed before and 90 min after the start of rt-PA infusion. Continuous electrocardiographic recordings and 4 h plasma creatine kinase MB isoenzyme (CK MB) were performed over the first 24 h. Plasma plasminogen activator inhibitor activity, von Willebrand factor and C-reactive protein were measured before rt-PA infusion, daily for the first 3 days and after 90 days. In the entire group, plasminogen activator inhibitor activity peaked at 24 h (day 1), representing a significant increase over values at all other times (p = 0.03). von Willebrand factor was higher in the first 2 days of infarction compared with after 90 days (p = 0.001). C-reactive protein peaked on day 2, with an eightfold increase over values on admission (p = 0.001). In the 16 patients with a patent infarct-related artery at 90 min, infarct size estimated by integrated 24 h CK MB, time for ST segment elevation to decrease to half-maximum and peak C-reactive protein were reduced significantly by more than twofold compared with values in the 8 patients with an occluded artery at 90 min. The patients with early recanalization also had lower plasminogen activator inhibitor activity on day 2 (p = 0.05) and day 3 (p = 0.02) and lower 0 to 72 h averaged von Willebrand factor (p = 0.01). Thus, early coronary recanalization curtails the response of plasminogen activator inhibitor activity and von Willebrand factor to myocardial infarction, most likely by reducing the extent of ischemia and necrosis and the consequent acute phase reaction. By blunting the early postinfarction procoagulant state, prompt recanalization may reduce the risk of thromboembolic complications in the first days after myocardial infarction.
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PMID:Early coronary reperfusion blunts the procoagulant response of plasminogen activator inhibitor-1 and von Willebrand factor in acute myocardial infarction. 212 6

Angiographic, angioscopic and pathologic reports have recently demonstrated a high incidence of intracoronary thrombus in patients with unstable angina. To determine if thrombolysis could be beneficial when combined with maximal medical therapy, 40 patients with rest angina, angiographically documented coronary artery disease and pacing-induced ischemia were randomly assigned to intravenous recombinant tissue-type plasminogen activator (rt-PA, 150 mg/8 h) or placebo in a prospective double-blind trial. All patients received nitrates, a beta-adrenergic blocking agent, a calcium channel blocker, aspirin and heparin. Pacing thresholds for ischemia and quantitative coronary stenosis were measured before and after infusion of the study medication. Intracoronary thrombus was identified angiographically before infusion of the study medication in 16 patients; 7 received rt-PA and 9 received placebo. The ischemic pacing threshold in patients treated with rt-PA increased from 112 +/- 4 beats/min at baseline to 127 +/- 5 beats/min (p = 0.007) by the end of the infusion versus an insignificant change in patients who received placebo (from 116 +/- 4 to 119 +/- 4 beats/min, p = NS). In patients with intracoronary thrombus, the ischemic pacing threshold increased 26 +/- 7 beats/min with rt-PA treatment versus 0 +/- 3 beats/min with placebo (p = 0.004). In contrast, in patients without thrombus, there was no difference in ischemic pacing threshold increments between treatment groups (7 +/- 11 beats/min for rt-PA versus 6 +/- 5 beats/min for placebo, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Randomized, double-blind, placebo-controlled trial of tissue plasminogen activator in unstable angina. 249 25

To determine the association of qualitative and quantitative measurements of the myocardial infarct-related coronary narrowing with subsequent recurrent ischemia/reocclusion after successful thrombolysis, 47 patients treated with high-dose (150 mg) tissue plasminogen activator over 6 to 8 hours were studied in the setting of acute myocardial infarction. No patient underwent emergent coronary angioplasty. All patients had Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow or higher at the baseline (90-minute) angiogram; 31 patients had a protocol 24-hour catheterization as well. Eighteen patients had recurrent ischemia/reocclusion whereas 29 had an uneventful hospital course. There was no significant difference in baseline clinical characteristics between the 2 groups. Twenty-five (86%) of those with an uneventful course had TIMI grade 3 flow at baseline angiogram compared with 56% of patients with recurrent events. No significant difference in angiographic morphologic characteristics was found between the 2 groups at baseline catheterization. At 24 hours, however, none of the patients who subsequently had recurrent events had a concentric narrowing, while 13 (58%) of them had a complex morphology. In contrast, quantitative parameters of minimal lumen diameter, percent area stenosis and percent diameter stenosis at baseline and 24 hours were not significantly different between those who did and did not have recurrent ischemia/reocclusion. These findings suggest that the degree and quality of coronary flow at baseline catheterization are more important determinants of sustained patency and event-free hospitalization than are quantitative dimensions or coronary morphology. In addition, narrowings that fail to become concentric within the first 24 hours are more likely to be associated with subsequent ischemia or reocclusion during the early periinfarct period.
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PMID:Prediction of early recurrent myocardial ischemia and coronary reocclusion after successful thrombolysis: a qualitative and quantitative angiographic study. 249 42

To improve further the patency rate of infarct-related coronary arteries, the following accelerated dosage regimen of recombinant tissue-type plasminogen activator (rt-PA) was administered to 80 patients with acute myocardial infarction of less than or equal to 6 h duration: 15 mg intravenous bolus, 50 mg infusion over 30 min and 35 mg infusion over the following 60 min. After coronary angiography at 90 min coronary angioplasty was performed in 16 patients and additional thrombolysis in 3 patients. Six patients were not included in the final angiographic analysis, mostly because of borderline ST segment elevations, in order to avoid overestimation of the efficacy of this dose regimen. Four of these had a patent infarct artery; no early angiogram was performed on two. Sixty minutes after the start of infusion, 54 (74%) of 73 patients had a patent infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3) as did 67 (91%) of 74 patients at 90 min. At 24 h, 61 (92.4%) of 66 patients showed a patent infarct artery. Recurrent myocardial ischemia was noted in 12 patients, 7 (9.4%) of whom experienced reinfarction during the hospital stay. Minor local bleeding complications were observed in 14 patients (17.5%). There were four in-hospital cardiac deaths; one patient who underwent additional thrombolysis for recurrent ischemia died from bleeding complications. These results show that a rapid infusion of 100 mg of rt-PA over 90 min yields a high early patency rate of the infarct-related artery without an increase in reocclusion rate and adverse reactions.
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PMID:Improved thrombolysis with a modified dose regimen of recombinant tissue-type plasminogen activator. 250 32

The efficacy, safety, and effects on hemostasis and coagulation of two doses of human tissue-type plasminogen activator in patients with acute and subacute peripheral arterial occlusion were compared. Seven patients with lower extremity ischemia and one patient with upper extremity ischemia had peripheral arterial thromboses (five arteries, three grafts) confirmed by clinical history, physical examination, and angiography. The duration of occlusion ranged from 31 hours to 30 days (mean 11.9 days). Tissue-type plasminogen activator was infused via a catheter directly into the thrombus at a randomly assigned dose of 0.05 mg/kg/hr (n = 4) or 0.025 mg/kg/hr (n = 4). Thrombolysis was complete in seven patients and partial in one. Duration of infusion ranged from 1 hour to 21 hours (mean 7.4 hours). The low dose required a longer infusion than did the high dose, but they were both successful in achieving thrombolysis. The one patient with partial thrombolysis had abrupt discontinuation of infusion when extravasation through a recently endarterectomized femoral artery developed. Otherwise there were no significant complications from tissue-type plasminogen activator therapy. Secondary procedures to correct underlying arterial disease were performed in five of the seven patients (71%) who had complete thrombolysis. Even at low dosages, infusion of tissue-type plasminogen activator into arteries or bypass graft thrombus produced complete thrombolysis, and no major complications occurred. This allowed more systematic effects to diagnose and treat underlying arterial disease.
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PMID:Recombinant human tissue-type plasminogen activator is an effective agent for thrombolysis of peripheral arteries and bypass grafts: preliminary report. 211 66

Thrombolytic therapy in AMI restores infarct artery patency, preserves LV function, and decreases hospital mortality. Although hemorrhagic complications including stroke can occur, the incidence of stroke is not increased compared with control groups. Aspirin must be administered as soon as possible to inhibit platelet function, and an adjunctive role for early beta-blocker therapy may be important. Acute cardiac catheterization and coronary angioplasty need not be routinely performed in stable patients after tPA therapy, but should be considered in unstable patients. Two trials suggest that aggressive use of coronary angioplasty or bypass graft surgery before hospital discharge to preserve infarct artery patency and to prevent postinfarction ischemia is associated with an important improvement in long-term prognosis. Thrombolytic therapy should be considered standard care for patients whose ischemic chest pain lasts 20 min to at least 6 h in duration and who have an injury current on their ECG unless they are at increased risk for bleeding. The need for and timing of cardiac catheterization, coronary angioplasty, and surgical revascularization after AMI requires further evaluation.
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PMID:Thrombolytic therapy for acute myocardial infarction. 252 96

We treated 3262 patients with intravenous recombinant tissue plasminogen activator (rt-PA) within four hours of the onset of chest pain thought to be caused by myocardial infarction. Of these patients, 1636 were then randomly assigned to treatment according to an invasive strategy consisting of coronary arteriography 18 to 48 hours after the administration of rt-PA, followed by prophylactic percutaneous transluminal coronary angioplasty (PTCA) if arteriography demonstrated suitable anatomy; 1626 patients were randomly assigned to treatment according to a conservative strategy, as part of which arteriography and PTCA were to be performed only in patients with spontaneous or exercise-induced ischemia. In the group assigned to the invasive strategy, PTCA was attempted in 928 of the 1636 patients (56.7 percent); the procedure was anatomically successful in 93.3 percent. In the group assigned to the conservative strategy, 216 patients (13.3 percent) underwent clinically indicated PTCA within 14 days of the onset of symptoms. Reinfarction or death within 42 days, the primary end point, occurred in 10.9 percent of the group assigned to the invasive strategy and in 9.7 percent of those assigned to the conservative strategy (P not significant). There were no significant differences between the two groups in the ejection fraction at rest or during exercise, either at hospital discharge or six weeks after randomization. Eleven of 582 patients (1.9 percent) who received 150 mg of rt-PA and 15 of 2952 patients (0.5 percent) who received 100 mg of rt-PA had intracranial hemorrhage. A subgroup of 1390 patients who were eligible for short-term intravenous beta-blockade were randomly assigned to receive 15 mg of intravenous metoprolol immediately, followed by oral metoprolol, or oral metoprolol begun on day 6. The ejection fraction and the incidence of death in the two groups were similar during the hospital period. Total mortality within the first 6 days and at 42 days was also similar. However, in the group that received intravenous metoprolol, 16 patients had nonfatal reinfarctions and 107 patients had recurrent ischemic episodes by six days after entry into the study, as compared with 31 and 147 patients, respectively, among those randomly assigned to deferred oral beta-blockade (P = 0.02 and P = 0.005, respectively); the latter comparison was considered statistically significant according to the study criteria.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) phase II trial. 250 26

Studies have suggested that intracoronary and intravenous thrombolysis and emergency PTCA result in decreased infarct size, improved left ventricular function, and decreased in-hospital mortality. Significant problems remain with all three treatment modalities. Thrombolysis is associated with significant bleeding, especially if acute catheterization also is performed. The intracoronary method of thrombolysis requires cardiac catheterization facilities and entails a significant delay in reperfusion. Lower rates of reperfusion initially were found with intravenous than intracoronary streptokinase, but the intravenous administration of t-PA has been associated with a reperfusion rate (75 per cent) similar to that of intracoronary streptokinase. Significant bleeding complications occur with t-PA just as with streptokinase. Furthermore, there are patients in whom thrombolysis is contraindicated because of the high risk of life-threatening hemorrhagic complications. Once thrombolysis is achieved, an underlying significant coronary artery lesion usually is present so that a significant risk of recurrent ischemia and/or reinfarction still exists. In controlled studies, the addition of cardiac catheterization and angioplasty after thrombolytic therapy is associated with a further increase in significant bleeding episodes. Also, in low-risk subgroups of patients randomized to emergency angioplasty versus elective angioplasty or noninvasive treatment after thrombolytic therapy, the complications of angioplasty may outweigh the benefits of further reduction in lesion severity. Potential problems of emergency angioplasty following thrombolytic therapy include: (1) hemorrhage into ischemic myocardium, which may have a deleterious effect on ultimate muscle recovery; (2) hemorrhage at the angioplasty site caused by thrombolytic therapy, with a resultant increased chance of occlusion of the vessel post-angioplasty, and (3) production of reperfusion arrhythmias and hypotension, predisposing to vessel reclosure and infarct extension. With primary angioplasty therapy, the reperfusion success rate is 85 to 90 per cent. This is higher than the approximately 75 per cent success rate with thrombolytic therapy alone. If angioplasty can be performed expeditiously, within 6 hours of the onset of ischemia, potential advantages of this technique include: (1) rapid reperfusion, possibly comparable to thrombolytic therapy alone; (2) higher success rate for reperfusion than thrombolytic therapy; (3) alleviation of underlying stenosis usually present after thrombolytic therapy alone; (4) avoidance of systemic thrombolysis, with a concomitant decrease in hemorrhagic risk; (5) possible avoidance of hemorrhagic infarction, which may have a deleterious effect on ultimate muscle recovery; and (6) applicability to patients in cardiogenic shock, who presently respond poorly to thrombolytic therapy alone. No large controlled randomized study exists comparing primary angioplasty with thr
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PMID:Percutaneous transluminal coronary angioplasty for acute myocardial infarction. 268 85

After reviewing the principles, results and complications of thrombolytic therapy with "classical" agents (Streptokinase and Urokinase) used via intravenous, intraarterial route, or intraoperatively, and with more "modern" agents (APSAC, scuPA, tPA), we discuss the future of thrombolysis in the treatment of arterial ischemia of the limbs. Several items need to be clarified: --indication of thrombolysis among other treatments, mainly surgery, of arterial ischemia depends on the clinical staging of ischemia, its causes and the site of arterial obstruction; --method of delivery of the thrombolytic agent must provide the highest local concentration and the lowest systemic side effects; --efficacy of each thrombolytic agent must be analyzed when used in peripheral arterial ischemia, but also in other diseases such as myocardial infarction.
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PMID:Results of thrombolysis in the treatment of arterial ischemia of the limbs according to mode of administration. 269 81


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