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)

Effects of thrombotic coronary occlusion followed by thrombolytic reperfusion with recombinant tissue-type plasminogen activator (rt-PA) on infarct size and left ventricular function were studied in anesthetized closed chest dogs. After thrombotic occlusion of the left anterior descending coronary artery was produced by a copper coil technique, 74 dogs were randomly alloted to three groups; dogs treated with rt-PA at 90 min (n = 23) (group I) and at 180 min (n = 25) (group II) of the thrombotic occlusion, and 26 dogs treated with saline solution (permanent thrombotic occlusion, group III). The loading dose of intravenous rt-PA was 8,160 IU/kg body weight per min at the initial 60 min and the maintenance dose was 2,450 IU/kg per min continuously infused for 24 h. Thrombolytic recanalization was achieved at 15 +/- 4 and 18 +/- 6 min after rt-PA infusion in groups I and II, respectively. Infarct size and area at risk were determined by triphenyltetrazolium chloride staining and postmortem angiography; infarct size/area at risk ratio was 10 +/- 3% (n = 10), 33 +/- 7% (n = 9) and 63 +/- 3% (n = 10) in groups I, II and III, respectively (difference significant among groups). To examine whether infarct size and left ventricular function after thrombolytic reperfusion differ from those after mechanical reperfusion, 39 other dogs (group IV) underwent mechanical coronary occlusion for 106 +/- 1 min (occlusion period comparable with that of group I) and reperfusion using a balloon catheter.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recombinant tissue-type plasminogen activator ameliorates ischemic derangements induced by thrombotic occlusion in closed chest anesthetized dogs. 160 29

Regional wall motion was examined by angiography after 3 weeks in 154 patients taking part in the Thrombolysis in Coronary Occlusion (TICO) Trial. Coronary patency rate was greater after administration of recombinant tissue plasminogen activator, (rt-PA 62/77pts 81%) than after a placebo (P 49/77pts 64% P = 0.02), particularly for the left anterior descending artery compared with the right coronary artery (LAD 27/28 96% vs RCA 28/40 70% P = 0.006). Left ventricular ejection fraction (LVEF) was preserved after rt-PA (rt-PA 59 +/- 14% vs P 53 +/- 15% P = 0.01), predominantly because of more effective non-infarct zone contraction (rt-PA 0.52 +/- 1.16 SD/cord vs P 1.01 +/- 1.07 SD/cord P = 0.008). Infarct zone scores differed little (rt-PA 2.88 +/- 0.95 SD/cord vs P 3.16 +/- 1.11 SD/cord P = 0.09). Left ventricular ejection fraction and non-infarct zone function were best preserved after rt-PA compared with the placebo, particularly in patients with single vessel disease and in patients in whom the infarct-related artery was the left anterior descending vessel.
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PMID:Thrombolysis and coronary occlusion: effects upon the non-infarct zone. 162 65

The efficacy and safety of intravenous administration of recombinant tissue-type plasminogen activator (rt-PA, made by Boehringer Ingelheim Corp.) was investigated in 10 patients with acute myocardial infarction (AMI). The rt-PA was given as a bolus dose of 10 mg followed by an infusion of 50 mg, 20 mg and 20 mg in successive hours. Heparin and aspirin were given to all the patients. The time interval from the onset of chest pain to thrombolysis was from 2.3 to 6.1 h with mean of 3.9 h. Coronary angiography, performed before administration of rt-PA and every 30 minutes thereafter, demonstrated total coronary occlusion (grade O) in 9 patients and grade 1 in 1 at baseline study. The infarct-related coronary artery were LAD in 5, RCA in 3 and LCX in 2. At 90 minutes after infusion of rt-PA reperfusion of the infarct-related artery was observed in 7 patients, the success rate was 70%. In one case the infarct-related LCX was not opened at 90 minutes, but it was reperfused at 170 minutes, after intracoronary administration of 10 mg of rt-PA. The total dose in this case was 130 mg. During 30 days of hospitalization death occurred in only one case with cardiogenic shock, in whom the infarct-related RCA was not reperfused by rt-PA but was successfully recanalized by PTCA. The patient died from rupture of the left ventricle on the 4th day. No patient had clinical evidence of reinfarction. Follow-up angiography in 2 patients showed that the arteries reperfused initially were patent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Intravenous recombinant tissue-type plasminogen activator in acute myocardial infarction]. 181 88

This paper reports the immediate effects of thrombolysis and their subsequent influence on revascularisation procedures and clinical outcome over the subsequent twelve months. Coronary arteriography was performed at 21 days on 131 of 145 patients who received recombinant tissue plasminogen activator (n = 68) or placebo (n = 63) within 2.5 hours of symptom onset after primary coronary occlusion. Patency rates (TIMI grades 2 and 3) of the infarct-related artery were 81% with plasminogen activator and 63% with placebo (P = 0.02). Early (within 21 days) angiography for recurrent ischaemia was necessary in 31 (21%) patients (20 plasminogen activator, 11 placebo NS) and definite reinfarction occurred in 8 (5%) patients (4 plasminogen activator, 4 placebo). During one year follow-up without planned secondary intervention, coronary artery bypass grafting was more frequent in patients who had received thrombolytic therapy (23% plasminogen activator, 4% placebo P = 0.001); coronary angioplasty procedures were similar in both groups (12% plasminogen activator, 11% placebo NS). Mortality at 21 days was 5% (4 plasminogen activator, 4 placebo) and at one year was 7% (5 plasminogen activator, 5 placebo). Logistic regression analysis identified models comprising characteristics predictive of subsequent bypass grafting (plasminogen activator, multivessel disease, occluded infarct-related artery) and coronary angioplasty (non-q wave infarction, severe (91-99%) residual stenosis, left anterior descending infarct-related artery). Initial non-q wave infarction was the only predictor of early recurrent ischemia (odds ratio 4, P = 0.02) irrespective of residual stenosis severity.
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PMID:Determinants of recurrent ischaemia and revascularisation procedures after thrombolysis with recombinant tissue plasminogen activator in primary coronary occlusion. 189 9

Recent studies of interventional therapy by way of the coronary venous system have demonstrated that it can protect acutely ischemic myocardium. To evaluate the efficacy of coronary venous retroinfusion compared with systemic intravenous administration of recombinant tissue-type plasminogen activator (rt-PA), 14 dogs were studied with a copper coil-induced thrombus in the left anterior descending coronary artery. The rt-PA (24,000 fluorescence units/kg) was administered continuously, either intravenously (n = 8) or retrogradely (n = 6), for 30 min beginning 60 min after coronary occlusion. Thrombolysis was determined by repetitive coronary angiography. All dogs were killed 3 h after termination of rt-PA infusion and infarct size was measured by the triphenyltetrazolium chloride staining technique. Complete thrombolysis occurred in five of the six dogs in the retroinfusion group and four of the eight dogs in the systemic intravenous infusion group. Partial lysis was achieved in two dogs treated by intravenous infusion. Lysis did not occur in one dog treated with retroinfusion and in two dogs treated with intravenous infusion. Time to thrombolysis was 13.4 +/- 2.3 min in the retroinfusion group versus 27.8 +/- 4.8 min in the intravenous group (p less than 0.001). Myocardial functional recovery in the ischemic zone measured by two-dimensional echocardiography 60 min after reperfusion was significant only in the retroinfusion group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Retrograde coronary venous administration of recombinant tissue-type plasminogen activator: a unique and effective approach to coronary artery thrombolysis. 190 6

Although the efficacy of tissue-type plasminogen activator (t-PA) for coronary thrombolysis is well established, its direct cardioprotective effect - independent of its thrombolytic effect - is still controversial. In addition, the potentiation of t-PA's direct cardioprotective effect by thromboxane A2 synthetase inhibitor has recently been reported. In this study, the authors examined whether t-PA alone or in combination with DP1904, a thromboxane A2 synthetase inhibitor, is able to salvage ischemic myocardium via a direct action on myocardium. In addition, the effect of these interventions on intramyocardial hemorrhage in reperfused infarcts was assessed. A branch of the coronary artery of the rabbit was occluded for 30 mins and then reperfused for 72 h. Myocardial infarct size and 'area at risk' were determined by histology and fluorescent particles, respectively. The extent of intramyocardial hemorrhage was graded using scores. Rabbits were divided into three groups: control, t-PA and DP1904 plus t-PA. The t-PA was administered intravenously at 500 iu/kg/min for 30 mins starting 5 mins prior to reperfusion. DP1904 was injected intravenously at a dosage of 10 mg/kg every 24 h starting 2 hr prior to coronary occlusion. Mortality was similar and hemodynamic parameters and area at risk were comparable between all three groups. The myocardial infarct size as a percentage of area at risk was 44.5 +/- 3.8% (mean +/- standard error) (n = 9) in the control group, 41.6 +/- 4.6% in the t-PA group (n = 8) and 51.3 +/- 5.2% in DP1904 plus t-PA group (n = 8), not significantly different (ANOVA). Neither were the hemorrhage scores significantly different between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tissue-type plasminogen activator alone or in combination with thromboxane A2 synthetase inhibitor for ischemic myocardium. 212 35

Technetium-99m (Tc-99m) sestamibi has been used to evaluate the efficacy of thrombolytic therapy. Improved image quality due to the higher photon energy of Tc-99m and the increased allowable doses of this radiopharmaceutical along with its lack of redistribution makes Tc-99m sestamibi an acceptable imaging agent for such studies. This imaging agent was used for serial quantitative planar and tomographic imaging to assess the initial risk area of infarction, its change over time and the relation to infarct-related artery patency in patients with a first acute myocardial infarction. Twenty-three of 30 patients were treated with recombinant tissue-type plasminogen activator (rt-PA) within 4 hours after onset of acute chest pain. Seven patients were treated in the conventional manner and did not receive thrombolytic therapy. The initial area at risk varied greatly both in patients treated with rt-PA and in those who received conventional therapy. Patients with successful thrombolysis and patient infarct arteries had a significantly greater reduction of Tc-99m sestamibi defect size than patients who had persistent coronary occlusion. Serial imaging with Tc-99m sestamibi could find important application in future clinical research evaluating the efficacy of new thrombolytic agents. Direct measurements of the amount of hypoperfused myocardium before and after thrombolysis could provide rapid and unequivocal results using fewer patients and avoiding the use of "mortality" as an end point. This approach has not yet been widely tested in the clinical arena.
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PMID:Thrombolytic therapy for myocardial infarction: assessment of efficacy by myocardial perfusion imaging with technetium-99m sestamibi. 214 44

Technetium-99m isonitrile is a new myocardial perfusion imaging agent that accumulates according to the distribution of myocardial blood flow. However, unlike thallium-201, it does not redistribute over time. This imaging agent was used with serial quantitative planar imaging to assess the initial risk area of infarction, its change over time and the relation to infarct-related artery patency in 30 patients with a first acute myocardial infarction. Twenty-three of 30 patients were treated with recombinant tissue-type plasminogen activator (rt-PA) within 4 h after the onset of chest pain. Seven patients were treated in the conventional manner without thrombolytic therapy. Technetium-99m isonitrile was injected before or at the initiation of thrombolytic therapy, and imaging was performed several hours later. These initial images demonstrated the area at risk. Repeat imaging was performed 18 to 48 h later and at 6 to 14 days after the onset of myocardial infarction to visualize the ultimate extent of infarction. The initial area at risk varied greatly (range defect integral 2 to 61) both in patients treated with rt-PA and in those who received conventional treatment. For the total group, the initial imaging defect decreased in size in 20 patients and was unchanged or larger in 10 patients. Patients with a patent infarct-related artery had a significantly greater decrease in defect size than did patients with persistent coronary occlusion (-51 +/- 38% versus -1 +/- 26%, p = 0.0001). All patients with a decrease in defect size greater than 30% had a patent infarct-related artery. In 12 patients who also had predischarge quantitative exercise thallium-201 imaging, good agreement existed between the extent and severity of myocardial perfusion defect on the last technetium-99m isonitrile study before discharge and that noted on delayed thallium-201 imaging. It is concluded that serial planar technetium-99m isonitrile myocardial imaging in patients with acute myocardial infarction undergoing thrombolytic therapy offers a new quantitative noninvasive approach for assessment of the initial risk zone as well as the success of reperfusion.
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PMID:Serial quantitative planar technetium-99m isonitrile imaging in acute myocardial infarction: efficacy for noninvasive assessment of thrombolytic therapy. 250 12

A model was designed to examine the relations between incremental costs and benefits of coronary thrombolysis/reperfusion therapy. The model allows for the study of intravenous and intracoronary streptokinase, intravenous tissue plasminogen activator and primary angioplasty. Three strategies for the management of reocclusion are also compared. It was found that each of the following four variables can be responsible for a 2- to 15-fold variation in the costs per additional survivor: 1) the quantity of jeopardized myocardium, 2) the duration of coronary occlusion before the onset of therapy, 3) the time required from the onset of therapy until reperfusion is achieved, and 4) the reocclusion management strategy. Therapeutic strategies involving intravenous administration of thrombolytic agents were found to be consistently more cost effective than were strategies involving intracoronary administration of thrombolytic agents and primary angioplasty. In patients with a large or moderate-sized infarct, proper selection of intravenous protocols and reocclusion management strategies leads to costs of $7,000 to $100,000/additional survivor, costs that are similar to those of many generally accepted medical practices. Substantially higher costs per additional survivor are incurred with the routine use of thrombolytic therapy in patients with a small infarct or the routine use of coronary artery bypass surgery to reduce the risk of reocclusion after successful thrombolytic therapy. Decisions regarding which patients should receive thrombolysis/reperfusion therapy depend on society's willingness to pay for its incremental benefits.
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PMID:A cost-effectiveness model for coronary thrombolysis/reperfusion therapy. 295 18

The efficacy and safety of a 3 hr, 80 mg intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA) were investigated in 47 patients with acute myocardial infarction. Coronary angiography, performed before the administration of rt-PA and for 90 min thereafter, demonstrated that 37 patients had total coronary occlusion before therapy. After 90 min of rt-PA (50 mg), reperfusion of the infarct-related artery was observed in 25 patients (68%). Continuous infusions of heparin for anticoagulation were administered for 8 to 10 days. Of 36 patients who underwent follow-up coronary cineangiography, 21 had initially presented with total occlusion and had experienced reperfusion at 90 min. Sustained perfusion of the infarct-related artery was observed in 14 (67%) of these 21 initially reperfused patients. Late angiography was performed in nine patients who initially demonstrated subtotal occlusion of the infarct-related artery; sustained perfusion was observed in eight (89%). Significant bleeding was observed in 15 patients (32%). A hematoma at the site of the acute catheterization accounted for most instances of significant bleeding (11/15, 73%). Administration of rt-PA resulted in a significant decline in fibrinogen and plasminogen while amounts of fibrin(ogen) degradation products rose. In no patient, however, did fibrinogen levels decline to less than 140 mg/dl. Thus, rt-PA, administered as a brief 80 mg intravenous infusion, is capable of restoring blood flow in a high proportion of patients with acute myocardial infarction due to total coronary obstruction. Declines in plasma fibrinogen and plasminogen are observed. If combined with heparin anticoagulation and invasive vascular procedures, significant bleeding is a common complication.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intravenous recombinant tissue-type plasminogen activator in patients with acute myocardial infarction: a report from the NHLBI thrombolysis in myocardial infarction trial. 308 Feb 61


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