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)

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 risk of arterial reocclusion or recurrent ischemia after acute intervention in myocardial infarction, we analyzed the results of coronary arteriography performed acutely and at 1 week in 50 consecutive patients who received acute intervention. Successful recanalization of the infarct vessel was achieved in 46 (92%) patients after therapy with intravenous tissue plasminogen activator, percutaneous coronary angioplasty, or both. Follow-up angiography in 44 showed early reocclusion in 10 patients (23%). Intermittent patency during acute arteriography was always associated with reocclusion; suboptimal (Thrombolysis in Myocardial Infarction [TIMI] class 2) flow was associated with a 50% rate of reocclusion. Although residual stenosis of greater than 50% alone was not predictive of rethrombosis, 90% of all reocclusions were associated with either stenosis greater than 50%, TIMI 2 flow, or intermittent patency. Absence of these angiographic risk factors predicted a 95% patency rate at follow-up. In-hospital cardiac complications occurred in 17 of 23 (74%) patients with residual stenosis of greater than 50% (death in four, ischemia in 13), and late revascularization was required in 53% of survivors. Only 15% of the group with less than 50% stenosis had an in-hospital ischemic event (p less than 0.001). Thus, after acute intervention, an infarct vessel with intermittent patency or suboptimal flow is associated with a high rate of reocclusion. Residual stenosis greater than or equal to 50% appears to predict a high incidence of negative in-hospital clinical outcomes and the need for subsequent revascularization.
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PMID:Infarct vessel status after intravenous tissue plasminogen activator and acute coronary angioplasty: prediction of clinical outcome. 296 78

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

Early experience with the use of tissue plasminogen activator (tPA) in acute myocardial infarction is reviewed, including comparisons with other thrombolytic agents, a summary of hemorrhagic complications associated with its use, and the rationale for adjunctive therapeutic strategies. The use of tPA has been associated with improvement in left ventricular function, a lower mortality, and a decrease in congestive heart failure signs and symptoms. A protocol for evaluation of patients with possible myocardial infarction for thrombolytic therapy is presented. Consideration must be given to other possible diagnoses, and the ECG must be evaluated carefully to ensure that appropriate criteria are met. Risk factors for hemorrhagic complications include recent trauma, surgery, gastrointestinal and genitourinary bleeding, stroke, and focal neurologic findings. Greater benefit of therapy is expected in patients with larger infarcts who have more marked ST segment changes or evidence of hemodynamic compromise, especially when they are treated early after the onset of symptoms (within the first several hours). Adjunctive measures that can be considered in the emergency department include prophylactic lidocaine, IV nitroglycerin, beta blockade, aspirin, volume replacement and monitoring for dysrhythmias, bleeding, and recurrent ischemia. A comprehensive understanding of these rapidly evolving concepts will assist the emergency physician in the evaluation and management of patients with acute myocardial infarction.
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PMID:Experience with the use of tPA in the treatment of acute myocardial infarction. 297 70

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

Defibrotide (D) is a natural polydeoxyribonucleotide from mammalian lungs with profibrinolytic and antithrombotic activities. D also has PGI2-stimulating and tissue plasminogen activator (TPA)-releasing activities, but has no anticoagulant properties. The protective effects of D were demonstrated very recently in a model for non-lethal ischemia in the cat. In the experiments reported here Defibrotide was tested in a model for acute myocardial ischemia leading to ventricular fibrillation (VF) and death of the cat. Occlusion of the coronary artery (LAD) at its origin induced VF and death in 17 of 20 control cats. When cats were treated with D (32 mg Kg-1, bolus i.v., + 32 mg Kg-1 h-1, i.v., after LAD occlusion) 19 of 20 animals survived until the end of experiments. D also prevented changes in plasma and myocardial CPK, hemodynamics and ECG. D was compared with a variety of pharmacological agents which are used clinically for specific cardiovascular diseases. The ability of D to promote considerable generation of PGI2 from vascular walls plus its ability to prevent the decreases in CPK-activity and ATP in the myocardial tissue may have roles in its beneficial effects against ischemic heart in the cat. However, the mechanism/s of the substantial protective effect of D against cardiac death has still to be clarified.
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PMID:Protective activity of defibrotide against lethal acute myocardial ischemia in the cat. 308 10

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

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.
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PMID:Streptokinase, urokinase, and tissue plasminogen activator: pharmacokinetics, relative advantages, and methods for maximizing rates and consistency of lysis. 310 38

Thrombolytic agents may be useful in the treatment of cerebral ischemia caused by arterial thrombosis or embolic occlusion. A trial of intravenous human tissue-type plasminogen activator (rt-PA) was carried out in seven male Sprague-Dawley rats subjected to embolic cerebral ischemia, with eight control animals. One-hour-old autogenous blood clot was injected into the internal carotid artery. A 30-minute infusion of 10 micrograms/kg/minute of rt-PA or saline followed. Areas of ischemia at two hours post-embolization were assessed by digital image processing of serial iodo-14C-antipyrine autoradiographic images. The volumes of "no-flow" (NF) and "low-flow" (LF) regions were calculated. One animal in each group suffered no detectable ischemia; the remainder had well-defined regions of middle and posterior cerebral artery ischemia. No animal sustained a hemorrhagic lesion. Treatment produced no noticeable effect on the patency of cervical vessels. Total NF and LF volumes were less for the treated group but did not reach statistical significance by t-test. In middle cerebral distribution sections, however, LF volume was significantly less (p less than 0.05) for treated animals (150 vs. 191 mm3), primarily due to a more significant decrease in LF volume in the anterior-middle cerebral overlap zone (47 vs. 90 mm3; p less than 0.025). Fibrinogen levels were not altered by drug treatment (p greater than 0.30).
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PMID:The effect of intravenous tissue-type plasminogen activator in a rat model of embolic cerebral ischemia. 311 Nov 8

The use of fibrinolytic agents to control the fibrinolytic enzyme system and lyse pathologic fibrin deposits or thrombus has now assumed a position with anticoagulants and vascular surgery in the physician's therapeutic armamentarium. The principal exogenous activators that are used clinically are streptokinase, urokinase, and tissue plasminogen activator. Acute arterial occlusions are more likely than chronic occlusions to respond to thrombolytic therapy, especially if treatment is instituted within a few hours of onset of symptoms and if the disease is due to embolic material rather than in situ thrombosis. Since the duration of drug infusion necessary to lyse arterial thrombus cannot be predicted, patients in whom tissue viability cannot be determined or in whom ischemia cannot be tolerated during the drug infusion interval are not candidates for intraarterial fibrinolytic drug infusion. In treating patients with venous occlusion, thrombolytic therapy is more effective against proximal clots than in calf thrombosis. No protective effect from pulmonary embolism has been noted in trials comparing heparin with streptokinase. Fifty percent of patients with an initial episode of deep venous thrombosis treated within 72 hours of onset will have complete resolution of thrombus with preservation of valve function.
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PMID:Application of thrombolytic therapy in vascular occlusive disease. A surgical view. 311 28


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