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

Three trials of thrombolytic therapy in myocardial infarction (MI) up to 12 hours after symptom onset were conducted to measure the mean time from onset of chest pain to hospital arrival, and mean time to therapy. The trials, using intracoronary streptokinase, intravenous streptokinase and tissue plasminogen activator (t-PA), indicated a progressive shortening of time between symptom onset and hospital arrival. The Seattle Myocardial Infarction, Triage and Intervention (MITI) trial is evaluating the safety and efficacy of thrombolytic therapy initiated by paramedics in the prehospital setting. Phase I of the trial indicates that one-half of the patients would receive prehospital therapy in the field within the first hour of symptoms, substantially sooner than what can be achieved in the hospital. Phase II of MITI, in a nonrandomized trial, will compare the use of intravenous t-PA in the field with t-PA administered in the emergency department.
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PMID:Potential use of thrombolytic therapy before hospitalization. 250 Aug 39

In some patients with acute myocardial infarction, low-amplitude potentials that prolong the QRS complex, termed "late potentials," can be recorded on a signal-averaged electrocardiogram. The presence of these late potentials is known to be associated with an increase in the risk of ventricular tachycardia and sudden death. Because patients with acute myocardial infarction who receive thrombolytic therapy have a reduced incidence of ventricular tachyarrhythmia and sudden death, we sought to determine whether such patients also have a decreased incidence of late potentials. We studied 106 patients less than 75 years of age who were admitted with a first myocardial infarction and in whom a signal-averaged electrocardiogram was recorded within 48 hours of admission. Within four hours of the onset of chest pain, tissue plasminogen activator (t-PA) was given to 44 patients, and 62 were treated conventionally. In the t-PA group, late potentials were recorded in 2 of 44 patients (5 percent), as compared with 14 of 62 (23 percent) in the conventionally treated group (P = 0.01). Furthermore, among the patients treated with t-PA, continued occlusion of the infarct-related artery was related to the presence of late potentials. In the t-PA group, late potentials were recorded within 24 hours of angiography in 2 of the 6 patients with an occluded infarct-related artery, as compared with none of the 38 patients with a patient infarct-related artery. Our data suggest that successful thrombolytic therapy is associated with a marked reduction in the incidence of late potentials on the signal-averaged electrocardiogram. Long-term follow-up will be required to determine whether this finding predicts a reduced incidence of subsequent ventricular tachyarrhythmia and sudden death.
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PMID:Decreased incidence of ventricular late potentials after successful thrombolytic therapy for acute myocardial infarction. 250 75

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

Although the search for the ideal thrombolytic agent continues, recombinant tissue plasminogen activator (t-PA) has proven to be a more potent clot-specific thrombolytic agent than streptokinase. Because t-PA binds directly to the fibrin-plasminogen complex, its effect on circulating fibrinogen is minimized. The development of persistent antibodies or direct induction of hypotension has not been reported, nor has significant activation of the complement system. Unlike streptokinase, urokinase, or anisoylated plasminogen streptokinase activator complex (APSAC), t-PA shows a consistent recanalization rate over time, even as late as 9 hours following onset of chest pain. A number of clinical trials have shown that t-PA is superior in terms of average coronary artery patency rates and survival rates, but bleeding complications with t-PA are similar to those of the other thrombolytic agents. Studies of combinations of t-PA and recombinant prourokinase, as well as of various mutants and hybrids of t-PA, are now underway. The search for viable third-generation thrombolytic agents will have to consider the precarious balance between increasing patency and increasing bleeding complications.
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PMID:Recombinant tissue plasminogen activator: implications in therapy. 250 27

The impact of age on hospital mortality, incidence of major hemorrhagic events and transfusion requirements was examined in 756 patients with acute myocardial infarction enrolled in the Thrombolysis in Myocardial Infarction (TIMI) Phase I, open label studies and the TIMI Phase II pilot study. The mortality rate significantly increased with age and was 3.5%, 11.5% and 12% in patients less than 65, 65 to 69 and 70 to 76 years of age, respectively (p less than 0.001). Logistic regression analyses selected female gender, diabetes mellitus, extensive coronary artery disease, history of congestive heart failure, continuing chest pain immediately after recombinant tissue-type plasminogen activator (rt-PA) administration, low systolic blood pressure at the time of admission and advanced age as variables predictive of in-hospital death. The incidence of major hemorrhagic events among patients not undergoing cardiac surgery during hospitalization was 8.7%, 14.5% and 24.7% in patients aged less than 65, 65 to 69 and greater than or equal to 70 years, respectively (p less than 0.001). The majority of hemorrhages were secondary to cardiac catheterization or puncture wounds. Variables related to a major hemorrhagic event included protocol, age, rt-PA dose/kg body weight and elevated diastolic blood pressure on admission. Of five intracranial bleeding events, three occurred in patients greater than 65 years. Transfusion requirements significantly increased with age (p less than 0.001). Reperfusion status at 90 min in the TIMI Phase I and open label studies A to C was similar in the three age groups studied and ranged from 60% to 71%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The use of tissue-type plasminogen activator for acute myocardial infarction in the elderly: results from thrombolysis in myocardial infarction Phase I, open label studies and the Thrombolysis in Myocardial Infarction Phase II pilot study. The TIMI Investigators. 250 28

Forty six patients admitted for precordial chest pain were included in this study. The clinical, electrocardiographic, enzymatic and angiographic features allowed retrospective identification of 6 subgroups (nos 1 to 6): all transmural myocardial infarction (Q-MI) (Group 1), Q-MI without intracoronary thrombus (Group 2), Q-MI with intracoronary thrombus (Group 3), acute non-Q wave infarction (non Q-MI) (Group 4), unstable angina (Group 5) and atypical chest pain (Group 6). Several blood clotting factors were studied; von Willebrand factor (VWF), fibrinogen, tissue plasminogen activator (t-PA) and its inhibitor (PAI-1) and factor VII. There was no significant difference in the fibrinogen, t-PA, PAI-1 or factor VII levels between the 6 groups. On the other hand, the VWF was increased in the all transmural myocardial infarction (Q-MI) groups (n. 1). In Group 3 with visible intracoronary thrombus the VWF was high or very high in all patients, attaining three times the normal values. The values were lower in Group 5 (unstable angina) patients in whom no thrombus was observed on coronary angiography. The differences between Group 1 and Groups 4, 5 and 6 were statistically significant (p less than 0.05). The VWF was higher in the Q-MI group with intracoronary thrombus than in the group without thrombus, but the difference was not statistically different. In conclusion, the VWF may be considered to be a marker for thrombus and/or endothelial activation but a larger study population would be required to identify more accurately the subgroups with thrombosis or risk of thrombosis.
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PMID:[Relation of an increase of von Willebrand factor in the blood, acute myocardial infarction, unstable angina and coronary thrombosis]. 251 33

232 consecutive patients with acute myocardial infarction were treated either with 2 x 10(6) IU urokinase as an intravenous bolus injection, or 250,000 IU streptokinase intracoronary, or 60 mg recombinant tissue-type plasminogen activator (rt-PA) over 90 min. All patients enrolled had chest pain for more than 30 min and less than 3 h before admission and a typical electrocardiogram. Contra-indications to thrombolytic treatment were absent. All bleeding complications occurring within 24 h after admission were assumed to be due to thrombolytic therapy. Bleeding complications occurred in 14 patients (6.5%). Only seven patients received a blood transfusion (3%). No correlation was evident between previous hypertension, diabetes mellitus, smoking, sex, age, fibrinogen level before and 24 h after thrombolytic therapy and bleeding complications. The risk of bleeding was not significantly different between the different thrombolytic regimens despite marked differences in the fall of the fibrinogen level. The decrease of fibrinogen following thrombolytic therapy did not influence the patency rate of the infarct vessel. Thrombolytic therapy in acute myocardial infarction is a safe treatment even among patients advanced in years and with medically controlled hypertension and diabetes mellitus, irrespective of the kind of thrombolytic treatment.
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PMID:Bleeding after thrombolysis in acute myocardial infarction. 270 62

The Thrombolysis in Myocardial Infarction (TIMI) Study Group is investigating whether percutaneous transluminal coronary angioplasty or intravenous beta-receptor blockers, or both, are useful adjuncts to recombinant tissue-type plasminogen activator (rt-PA) in the treatment of patients with acute myocardial infarction (TIMI II study). A total of 317 patients with acute myocardial infarction were treated an average of 2.7 hours after the onset of chest pain during the course of a nonrandomized pilot investigation with 150 mg of rt-PA given over 6 hours. This dose of rt-PA resulted in a high rate of infarct-related coronary artery patency (82 and 87% of patients catheterized an average of either 1 or 32 hours after entry, respectively) and a low 21 day mortality rate of 4.4%. Coronary angioplasty was performed successfully in greater than 90% of patients with appropriate anatomy and in greater than 50% of those treated with rt-PA. In 75 patients treated within 2 hours of the onset of chest pain only 2 (2.7%) were dead by 6 weeks. However, five cases of intracranial hemorrhage were noted, and the rt-PA dose was subsequently reduced to 100 mg given over 6 hours. The TIMI II design and the results of the TIMI II pilot study are discussed.
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PMID:The Thrombolysis in Myocardial Infarction (TIMI) phase II pilot study: tissue plasminogen activator followed by percutaneous transluminal coronary angioplasty. 288 58

Two dosing schedules of intravenous tissue plasminogen activator (t-PA) for acute myocardial infarction were compared in a multicenter trial. At 2.95 +/- 1.1 hours from onset of chest pain, 386 patients received 150 mg of intravenous t-PA. For the first 178 patients (group A), 60 mg were given in the first-hour dose and the remaining 90 mg were infused over 7 hours. In the subsequent 208 patients (group B), the first-hour dose was 1.0 mg/kg and the remaining 150 mg were given over 5 hours. At initial angiography 94 +/- 30 minutes into therapy, the infarct vessel patency was 64% in group A versus 75% in group B (p = 0.02). By final angiography with up to 4 selective contrast injections, patency was 68% versus 77%, respectively (p = 0.06). Repeat angiography at 7 to 10 days demonstrated reocclusion in 17% of group A and 13% of group B patients (p = 0.35). There was no difference in fibrinogen nadir or mean hematocrit drop between the 2 groups: 120 mg/dl and 11 points, respectively, in group A compared with 120 mg/dl and 10 points in group B. However, bleeding was reduced in group B patients as evident by a decrease in requirement for greater than or equal to 2 units of packed red blood cell transfusion (group A 36%, group B 27%, p = 0.05) and lower incidence of gastrointestinal bleeding (group A 12%, group B 4%, p = 0.002). To further study the importance of weight adjustment, patients were divided into 2 groups according to weight (less than or equal to 90 kg versus greater than 90 kg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of two dose regimens of intravenous tissue plasminogen activator for acute myocardial infarction. 296 4

Twenty-four patients with unstable angina pectoris, defined as chest pain at rest with transient ST segment deviation of at least 1 mm, were randomly assigned to blinded treatment with either placebo or intravenous recombinant human tissue-type plasminogen activator (rt-PA). Before randomization, all patients were treated with oral beta-blockers, calcium antagonists, nitrates, and continuous intravenous heparin for a monitoring period of 12 to 28 hr. After this monitoring period the 24 patients were randomly assigned to receive either placebo or 1.75 mg/kg intravenous rt-PA given over 12 hr at a rate of 0.75 mg/kg over 1 hr, 0.5 mg/kg over 4 hr, and 0.5 mg/kg over 7 hr. One patient, assigned to receive placebo, developed acute myocardial infarction after randomization but before receiving the study drug. Ischemic events were recorded during a hospital follow-up period of at least 4 days unless a further intervention was indicated or the coronary angiogram was normal. The follow-up period was 7 +/- 5 days (mean +/- SD) after the placebo infusion and 8 +/- 4 days after the infusion of rt-PA. Unstable angina pectoris persisted after the completion of the infusion in six of 11 patients receiving placebo and only one of 12 patients receiving rt-PA (p less than .03). Coronary angiography, performed 38 +/- 19 hr after the infusion, demonstrated subocclusive thrombus in eight of 11 patients receiving placebo but in none of 11 patients treated with rt-PA (p less than .002). One patient on rt-PA refused coronary angiography.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A randomized, blinded, placebo-controlled trial of recombinant human tissue-type plasminogen activator in patients with unstable angina pectoris. 310 13


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