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

Ischemic events after successful thrombolysis have been reported to occur in 18-32% of patients treated for acute myocardial infarction with thrombolytic therapy, and previous studies in which patients received streptokinase suggest that risk of early recurrent ischemia is closely related to the presence of a high-grade residual stenosis. If these events are predictable after intravenous recombinant tissue-plasminogen activator (rt-PA) thrombolytic therapy, then further intervention after its use could be targeted at selected patients. One-hundred ninety-two patients from the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I and TAMI III trials had successful rt-PA-mediated thrombolysis without immediate coronary angioplasty (PTCA). One-hundred seventy-four of these patients (92%) had prehospital discharge angiography. The mean age was 56 +/- 11 years; 81% were men; the infarct-related artery was the left anterior descending in 76 (39.8%), the left circumflex in 24 (12.6%), and the right coronary artery in 91 (47.6%). Thrombolysis with rt-PA resulted in a residual 73 +/- 13% diameter and 0.95 +/- 0.51 mm stenosis by quantitative coronary arteriography, and Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 in 59.2% and 3 in 40.8% of stenoses as assessed on angiograms obtained 90 minutes after the initiation of rt-PA therapy. Recurrent ischemic events (ischemia requiring emergency percutaneous transluminal coronary angioplasty or urgent bypass surgery, reocclusion of the infarct-related artery, or cardiac death) occurred in 41 patients (21.3%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recurrent ischemia without warning. Analysis of risk factors for in-hospital ischemic events following successful thrombolysis with intravenous tissue plasminogen activator. 280 79

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

In this three year prospective study of 177 patients with acute peripheral arterial ischemia those subjects with acute iliofemoral emboli or ischemia with a neurosensory deficit had urgent operations. The remainder included patients less likely to have limb salvage after surgery and who therefore were treated with thrombolytic therapy. This was done in three open studies of intravenous, acylated, plasminogen-streptokinase activator complex, low dose intraarterial streptokinase and intraarterial tissue-plasminogen activator (t-PA). The overall outcome after 30 days of thrombolytic therapy was limb salvage (55%), amputation (15%), and death (30%). The severity of the presenting ischemia was the most important prognostic indicator. In patients with a neurosensory deficit, limb salvage after either embolectomy or surgical reconstruction (59%) was more likely than after thrombolysis (31%). In patients without a neurosensory deficit, limb salvage after thrombolysis (68%) was better, though not significantly, than after surgery (53%). Local intraarterial thrombolysis with either streptokinase or t-PA produced an encouraging 66% limb salvage in 59 cases. In management of acute peripheral arterial occlusions an approach based on the severity of ischemia is optimal, with urgent surgery for patients with a neurosensory deficit and intraarterial thrombolytic therapy reserved as an alternative in selected cases with stable ischemia.
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PMID:Acute peripheral arterial ischemia: a prospective evaluation of differential management with surgery or thrombolysis. 251 79

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

Plasminogen activator is one of the principal enzymes involved in the fibrinolytic system. The plasminogen activator activity in placental tissue was examined using a chromogenic substrate in 9 patients with pre-eclampsia and in 9 women with uncomplicated pregnancy, who were delivered between 37 and 42 weeks of gestation. In the patients with pre-eclampsia, the plasminogen activator activity was significantly (P less than 0.05) decreased compared with that in the control group of normal pregnant women. The present findings suggest a decreased fibrinolytic activity in the placental tissue of pre-eclamptic patients, which is responsible for fibrin deposition in the placental tissue and may contribute to placental ischemia and insufficiency in pre-eclampsia.
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PMID:Placental plasminogen activator activity in pre-eclampsia. 286 18

We compared the efficacy of immediate coronary angioplasty after acute myocardial infarction with that of elective angioplasty at 7 to 10 days in patients treated initially with intravenous tissue plasminogen activator. The plasminogen activator (150 mg) was administered 2.95 +/- 1.1 hours after the onset of symptoms, to 386 patients with acute myocardial infarction. Ninety minutes later, patency of the coronary artery serving the area of the infarct was demonstrated by coronary angiography in 288 patients (75 percent). Bleeding problems were frequently encountered, as evidenced by an average drop in hematocrit of 11.7 +/- 6.5 points from base line to nadir and by a need for transfusion not related to bypass surgery in 70 patients (18 percent). After successful thrombolysis, 197 patients with a patent but severely stenotic vessel suitable for angioplasty were randomly assigned to immediate angioplasty (n = 99) or, if indicated 7 to 10 days after infarction, to deferred (elective) angioplasty (n = 98). The incidence of reocclusion was similar in the two groups: 11 percent in the group assigned to immediate angioplasty and 13 percent in the group assigned to elective angioplasty. Neither group had a significant improvement in global left ventricular function, and regional wall motion in the infarct zone improved to a similar extent in the two groups. In the elective-angioplasty group, the rate of crossover to emergency angioplasty for recurrent ischemia was 16 percent (whereas 5 percent of the immediate-angioplasty group required emergency repeated angioplasty; P = 0.01). In 14 percent of the patients in the elective group, the stenosis was substantially reduced by the time of the seven-day follow-up angiography, obviating the need for angioplasty. We conclude that in patients with initially successful thrombolysis and suitable coronary-artery anatomy, immediate angioplasty offers no clear advantage over delayed elective angioplasty.
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PMID:A randomized trial of immediate versus delayed elective angioplasty after intravenous tissue plasminogen activator in acute myocardial infarction. 295 16

To determine the role of intravenous tissue plasminogen activator (t-PA) in unstable angina, it was compared with placebo in a randomized, double-blind trial. Forty patients with angina at rest and provocable ischemia (pacing induced) had baseline coronary angiography, study drug infusion and then repeat angiography at 20 +/- 9 hours. All patients received diltiazem, nitrates, beta blockers, aspirin and intravenous heparin. During study drug infusion (150 mg over 8 hours), refractory ischemia necessitating emergency bypass surgery (CABG) or coronary angioplasty (PTCA) occurred in 4 of 20 t-PA patients compared with 1 of 20 placebo patients (p = 0.21). Before discharge, revascularization for persistent, provocable ischemia and a residual stenosis greater than or equal to 60% was as follows: t-PA patients, 8 PTCA and 7 CABG; placebo patients, 11 PTCA and 8 CABG (p = 0.39). Quantitative angiographic percent diameter stenosis of the culprit artery at baseline and follow-up was: t-PA 71 +/- 17 and 63 +/- 22; placebo 70 +/- 19 and 67 +/- 22 (difference not significant). However, 3 t-PA patients compared with no placebo patients demonstrated an insignificant (less than 60% diameter) residual stenosis and averted PTCA (p = 0.14). There were no complications of PTCA in the 8 t-PA patients; in contrast, 3 of 11 placebo patients had abrupt closure, necessitating emergency CABG in 2 (p = 0.23). Thus, intravenous t-PA in unstable angina can eliminate the need for PTCA in a few patients, does not appear to decrease the overall or emergency rate of revascularization procedures and may facilitate the safety of PTCA.
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PMID:Coronary revascularization after intravenous tissue plasminogen activator for unstable angina pectoris: results of a randomized, double-blind, placebo-controlled trial. 297 Jul 76

In the first three phases of Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) multicenter trials, 708 patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and underwent detailed assessment of clinical, angiographic and ventriculographic outcomes. The cumulative experience and data base afford the opportunity to address several important questions regarding aggressive therapy of myocardial infarction. These include predictive factors of in-hospital mortality, improvement of left ventricular function and the occurrence of recurrent ischemia. Consideration of practical issues, such as thrombolytic therapy for patients with cardiopulmonary resuscitation or previous stroke, use of coronary artery bypass surgery and the effect of operator experience on angioplasty success rate, has also been made possible. The major accomplishments as well as the deficiencies of the current approach to patient management after thrombolysis are reviewed, and the new TAMI trials currently underway are discussed.
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PMID:Insights derived from the thrombolysis and angioplasty in myocardial infarction (TAMI) trials. 297 86

Fundamental observations and the conceptual framework underlying coronary thrombolysis have a history dating back to 1789. Recent enthusiasm for it is predicated on the recently established safety of cardiac catheterization in critically ill patients, the high incidence of coronary thrombosis underlying acute transmural myocardial infarction and demonstrable benefit conferred to the heart and the patient when thrombolysis is initiated early after the onset of ischemia. Clot-selective activators of the fibrinolytic system offer promise for safe induction of coronary thrombolysis without marked predisposition to bleeding. One such activator, tissue-type plasminogen activator (t-PA), has been synthesized by recombinant deoxyribonucleic acid (DNA) technology, amenable to large scale production of pharmaceutical agents and hence widespread availability. Initial clinical trials conducted with t-PA have demonstrated opening rates of completely occluded, infarct-related coronary arteries of approximately 75% without marked depletion of fibrinogen. The focus of research in progress includes: noninvasive delineation of recanalization and estimation of the extent of myocardium salvaged by initial recanalization, development of alternative routes of administration of thrombolytic agents potentially exploitable by paramedical personnel and, perhaps, high risk patients themselves, and definitive elucidation of the extent to which benefits conferred by thrombolysis can be enhanced with adjunctive pharmacologic interventions as well as early angioplasty or surgery.
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PMID:Coronary thrombolysis with tissue-type plasminogen activator (t-PA): emerging strategies. 309 55


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