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)

To determine whether pharmacologic reperfusion to Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow during acute myocardial infarction confers the same clinical benefit as restoration of TIMI 3 flow, in-hospital clinical and angiographic outcomes in 1,229 patients prospectively enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction trials were analyzed. Patients were treated with intravenous tissue plasminogen activator or urokinase, or both. Angiography of the infarct-related artery 90 minutes after initiation of thrombolytic therapy demonstrated TIMI grades 0, 1, 2, or 3 flow in 20%, 7%, 17%, and 55% of vessels, respectively. Rescue or adjunctive coronary angioplasty was performed in 80%, 27%, and 16% of patients with TIMI 0/1, 2, or 3 flow, respectively. Predischarge angiography was performed in 963 patients. A significant gradient of increasing mortality was seen in patients with lower TIMI flow (4.3%, 6.1%, and 10.1% with TIMI 3, 2, and 0/1 flow, respectively, p = 0.002). The incidence of congestive heart failure and recurrent ischemia was significantly higher in patients with TIMI 2 than with TIMI 3 perfusion (26% vs 19% for heart failure, p = 0.03; 23% vs 17% for recurrent ischemia, p = 0.05). Acute left ventricular ejection fraction and infarct zone regional wall motion were also significantly improved in patients with TIMI 3 than with TIMI 2 flow, with trends toward better improvement in global and regional function in the TIMI 3 group. These findings were not affected by the use of acute coronary angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Significance of a coronary artery with thrombolysis in myocardial infarction grade 2 flow "patency" (outcome in the thrombolysis and angioplasty in myocardial infarction trials). Thrombolysis and Angioplasty in Myocardial Infarction Study Group. 773 92

The effect of thrombolytic therapy is well-documented in acute myocardial infarction. In acute cerebral infarction, thrombolytic therapy has been evaluated in small series of patients. The point of thrombolytic therapy is to avoid or reduce ischemic damage of neuronal tissue by rapid arterial recanalization. In thrombolytic therapy of cerebral vascular occlusion, the pathophysiology of reperfusion needs further investigation and documentation. This review describes studies of thrombolysis in embolic stroke using animals embolized by intracarotid injections of blood clots. Vascular occlusion was demonstrated by angiography and measurement of cerebral blood flow. Thrombolytic therapy with recombinant tissue-type plasminogen activator was initiated after varying periods of time. Reperfusion, cellular function, and brain damage were examined by angiography and by clinical and pathoanatomical examination. Based mainly on results from our own investigations, the following theses concerning ischemic stroke were made: (a) Cerebral infarction caused by arterial occlusion is due to delayed, incomplete, or no reperfusion. Spasms, or hemodynamic mechanisms, seem to be of only minor importance. (b) Early thrombolytic therapy in animal models increases the degree of reperfusion and reduces brain damage, clinical deficits, and mortality. (c) Early arterial reperfusion reduces cerebral infarction and related edema. With early reperfusion, the extent of brain damage correlates to the length of the delay from onset of ischemia. (d) Cerebral stunning is caused by arterial occlusion followed by very early spontaneous or induced reperfusion, as neurons temporarily lose their functional capabilities without dying. (e) Multiple embolic microclots in experimental stroke result in more brain damage than a single macroclot, and with clots the extent of brain damage is dependent on the structural composition and volume of emboli. (f) The ability to recanalization in experimental embolic stroke is related to the amount of red cells in the emboli and inversely related to the volume of emboli and to the fibrin content and density of the clots. (g) Infarct-limiting effects in experimental stroke can be obtained by ischemic neuroprotectants or by hypothermia, either alone or with thrombolytic therapy, which then reduces brain damage further.
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PMID:Thrombolytic therapy in experimental embolic stroke. 781 66

Neutrophil accumulation and free radical release are implicated in the genesis of reperfusion injury. However, little is known about the changes in myocardial lipid peroxidation and antioxidant activity in relation to coronary artery thrombosis and thrombolysis. To investigate this issue, 18 dogs with electrically induced occlusive thrombus in the left anterior descending (LAD) coronary artery were given tissue-type plasminogen activator (TPA). Sustained reflow (lasting > 120 min) occurred in 4 dogs, reocclusion after initial thrombolysis (transient reflow, duration of reflow 5 to 25 min) occurred in 7 dogs, and no reperfusion was evident in 7 dogs. Myocardial neutrophil infiltration was determined by measuring myeloperoxidase (MPO) activity, lipid peroxidation by malondialdehyde (MDA) levels and antioxidant activity by superoxide dismutase (SOD) activity in the myocardial regions supplied by the nonischemic left circumflex (Cx) and the ischemic LAD coronary arteries. In dogs with ischemia alone (no reperfusion), MPO activity and MDA levels in the LAD-supplied myocardium were modestly higher and SOD activity modestly lower than in the corresponding Cx-supplied myocardium. In dogs with sustained reperfusion there was a marked increase in MPO and MDA and a marked reduction in SOD activity in the reperfused myocardium. The MPO and MDA values in the myocardium of dogs with transient reperfusion, although much higher than the corresponding normal myocardial values, were less marked than in the myocardium of dogs with sustained reperfusion, and the SOD activity was preserved in the transiently reperfused regions. Myocardial shortening fraction in the LAD region was worse in dogs with sustained reperfusion than in those with sustained ischemia or transient reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial neutrophil infiltration, lipid peroxidation, and antioxidant activity after coronary artery thrombosis and thrombolysis. 783 91

Smokers with acute myocardial infarction appear to have a better outcome after thrombolysis than do nonsmokers. To identify factors that could contribute to this curious finding, we analyzed data from the Thrombolysis in Myocardial Infarction (TIMI-4) trial, in which 382 patients with acute myocardial infarction were randomized to tissue plasminogen activator, anistreplase, or both. Coronary angiography was performed 90 minutes and 18 to 36 hours after randomization, a myocardial perfusion scan was performed at 18 to 36 hours and before discharge, and a radionuclide ventriculogram was obtained before discharge. Angiographic and clinical outcome variables were determined in current smokers, ex-smokers, and nonsmokers, and regression analysis was used to correct for differences in baseline characteristics. The in-hospital mortality of current smokers was lower than that of ex-smokers and nonsmokers: 2.3% versus 5.2% versus 7.0%, respectively (p = 0.04 by paired comparison, current vs nonsmokers). Ninety minutes after randomization, the incidence of TIMI grade 3 flow was significantly higher in smokers than in ex-smokers and nonsmokers (55% vs 43% and 45%, p = 0.02); this difference was no longer observed at the second angiogram, nor did smokers differ from nonsmokers with respect to residual stenosis, thrombus grade, infarct size, ejection fraction, or recurrent ischemia. Because a strong inverse relation exists between TIMI grade 3 flow at 90 minutes and mortality, our findings suggest that the lower mortality of current smokers after thrombolytic therapy may be related to a higher incidence of early, complete reperfusion.
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PMID:How do smokers differ from nonsmokers in their response to thrombolysis? (the TIMI-4 trial) 783 39

Among patients with recent-onset unstable angina and evidence of ischemia or coronary artery disease, the incidence of subsequent cardiovascular events is high. The aim of this study was to investigate, in this high-risk population, whether unstable angina was associated with abnormalities of tissue-type plasminogen activator (t-PA) or plasminogen activator inhibitor (PAI) activities and whether, in a prospective study, any of these parameters would identify patients with an adverse cardiovascular prognosis. A group of 22 high-risk patients with unstable angina (64% event rate at 3 months) was studied prospectively for 12 weeks, and the fibrinolytic parameters measured at presentation were related to subsequent cardiovascular progress. A group of 20 age- and sex-matched healthy subjects acted as control subjects. Patients who had subsequent cardiovascular events (acute myocardial infarction or severe recurrent angina +/- intervention) had significantly elevated PAI activity at presentation compared with both those who remained event-free (p < 0.05) or with control subjects (p < 0.02). In addition, basal activation of fibrinolysis was demonstrated in unstable angina at presentation; this persisted at 9 weeks in patients with a favorable outcome (p < 0.02 vs control subjects), whereas it was no longer evident in those who developed cardiac events. These findings suggest that measurements of t-PA/PAI activity may reflect the underlying pathophysiologic state and relate to subsequent cardiovascular events in unstable angina.
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PMID:Tissue-type plasminogen activator and plasminogen activator inhibitor activities as predictors of adverse events in unstable angina. 805 19

From July 1990 to July 1993, we performed 41 percutaneous intra-arterial thrombolysis procedures for the treatment of obstructed infra-inguinal bypass grafts in 32 patients. There were 27 men and five women with a mean age of 63 +/- 17 years (range 21 to 83 years). The symptoms of occlusion were intermittent claudication in three cases, rest pain in 12 cases, severe ischemia without sensitive-motor loss in 26 cases. Bypasses were achieved using a prosthesis in 18 cases (43.9%), a saphenous vein in 10 cases (24.4%), an arterial allograft in nine cases (21.9%), and a composite prosthesis-vein graft in four cases (9.8%) (table I). The distal anastomosis of the bypass graft was located on the popliteal artery in 26 cases (63.4%) and a crural artery in 15 cases (36.6%). The mean duration of the occlusion was 4.9 +/- 3.4 days (range 1 to 15 days). The percutaneous approach was through the contralateral common femoral artery in 26 cases (63.4%), through the ipsilateral common femoral artery in seven cases (17.1%), through the left humeral artery in eight cases (19.5%). In all cases the thrombolytic agent was the recombinant tissue-type plasminogen activator (rt-PA). Each procedure began with the injection of a five milligram bolus of rt-PA into or onto the thrombus followed by infusion of rt-PA into the thrombus at a dose of 0.05 mg/kg/h. Intravenous heparin was simultaneously administered. Serum fibrinogen, prothrombin time, and partial thromboplastin time (PTT) were measured every three hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Intra-arterial thrombolysis using rt-PA for the treatment of occluded infra-inguinal bypasses]. 807 60

We evaluated the effect of antibodies directed against a leukocyte adhesion molecule (ICAM-1) in an embolic model of stroke followed by thrombolysis with tissue plasminogen activator (tPA). To test whether reperfusion injury after ischemia was related to white cell adhesion, microclots were injected into carotid circulation. The conditions examined were control, alpha-ICAM 5 min following ischemia, tPA 30 min after ischemia, and the combination of alpha-ICAM and tPA. alpha-ICAM and tPA both increased the amount of clot necessary to produce permanent neurological damage. Combined therapy was no more effective than either substance alone. A similar outcome was obtained when tPA was delayed until 90 min postischemia. When thrombolysis was delayed 3 h following embolism, neither tPA nor the tPA/alpha-ICAM combination reduced neurological damage. Thus, the alpha-ICAM antibody and tPA each effectively reduced neurological damage but the interaction was not significant.
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PMID:Monoclonal antibody to the ICAM-1 adhesion site reduces neurological damage in a rabbit cerebral embolism stroke model. 809 42

A thrombotic etiology has been suggested as the cause of idiopathic avascular necrosis of the hip, although the underlying pathophysiological mechanisms are unknown. Transient osteoporosis of the hip has also been suggested to represent bone marrow edema that may be related to ischemia. We evaluated four patients with idiopathic avascular necrosis and one patient with transient osteoporosis of the hip for thrombotic potential placing a special emphasis on the fibrinolytic system. All five patients had identifiable abnormalities of fibrinolysis. Four patients had elevated levels of plasminogen activator inhibitor (PAI-1) and one patient had an inadequate increase in tissue plasminogen activator (tPA) post venous occlusion. Serum triglycerides were increased in three of the patients. These findings suggest an association between decreased fibrinolytic potential and the subsequent development of avascular necrosis and transient osteoporosis of the hip. These patients should have an evaluation of the fibrinolytic system with tPA and PAI-1 levels as well as a lipid profile.
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PMID:Decreased fibrinolytic potential in patients with idiopathic avascular necrosis and transient osteoporosis of the hip. 823 94

Proper understanding of the pathologic process of a ruptured plaque followed by thrombus formation, with acute assessment of the deranged pathophysiology of the coronary circulation as a sequel, remains the basis for rational therapy of cardiac ischemia. With the advent of better thrombolytic regimens, improved direct reperfusion via angioplasty, and streamlined recognition/admission procedures, therapeutic strategies for dealing with acute myocardial infarction have once more turned to the options for early therapy. From recent studies of out-of-hospital thrombolysis or immediate percutaneous transluminal coronary angioplasty, the position is reinforced that "early" means the first 100 minutes. It is hoped that the large Global Utilization of Streptokinase and t-PA for Occluded Arteries (GUSTO) study, which specifically analyses the effect of early reperfusion by optimal alteplase and actilyse (recombinant tissue-type plasminogen activator [rt-PA]) versus streptokinase regimens will confirm this essential concept once and for all. Thus, when appropriate therapy--depending in the local availability of facilities--is promptly given, further reductions in myocardial infarction size and ventricular dysfunction can be achieved, resulting in mortality rates < 5%, at substantial savings in ever more expensive healthcare resources. "Early is < 100 minutes; later may be too late or too costly."
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PMID:Expanding indications for thrombolytic therapy in acute myocardial infarction. How late is too late, and how early is early: the clinician's view of the first 100 minutes. 827 56

A patient undergoing surgery within 24 hours of aneurysm rupture was administered recombinant tissue plasminogen activator (rt-PA) directly into the basal subarachnoid cisterns after aneurysm clipping. Preoperatively, the patient had diffuse thick subarachnoid blood clots on CT. The rt-PA was given as a single injection of 10 mg. Postoperatively the patient was evaluated by serial CT scans and daily transcranial Doppler (TCD) examinations. An almost complete clot clearance was demonstrated on CT scans carried out on day 2 and day 4 after surgery. TCD studies failed to show any acceleration of blood flow velocity indicative of vasospasm. The postoperative curse was uneventful, without any clinical indication of delayed ischemia and no evidence of progressive hydrocephalus. Considering the data of the literature, as well as our initial experience, it appears that intracisternal thrombolysis with rt-PA can be achieved with relative safety and is effective for large-volume subarachnoid blood collections removal and vasospasm prevention. Results from open trials recently published suggest that a substantial advance in the management of an important subgroup of patients with aneurysmal subarachnoid hemorrhage (SAH) may be in the offing. However, randomized, placebo-controlled trials are still needed to confirm that there is a well-definite clinical benefit from the use of rt-PA. These considerations now call for a nation-wide multicentric italian trial which should be also addressed to evaluate other dose regimens and modalities of application.
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PMID:Intracisternal rt-PA during early surgery for aneurysmal subarachnoid hemorrhage: an Italian report. 830 73


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