Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant tissue plasminogen activator (t-PA) is a synthetic fibrinolytic protein which activates plasminogen or converts plasminogen to plasmin specifically in the presence of fibrin. With its "clot-selectivity", t-PA is capable of lysing clots without having a significant effect on circulating plasminogen. In contrast, activation by streptokinase and urokinase is non-specific and affects circulating as well as thrombus plasminogen. These agents, therefore, have a greater potential to induce bleeding than does t-PA. Plasma levels of t-PA following intravenous administration are generally proportional to the dose, but there can be significant interpatient variation. The drug is eliminated primarily by hepatic metabolism and is then excreted in the urine. Half-life of circulating t-PA ranges from 2-8 minutes. Most clinical trials of t-PA have evaluated its use in acute myocardial infarction. Indeed, its current indication is for thrombolysis in evolving MI. Short-term benefits of t-PA administration include a prompt reperfusion and restoration of coronary artery patency in patients with total coronary artery occlusion. The degree to which the heart benefits from thrombolysis is unknown, but electrocardiographic changes, changes in cardiac enzymes and alterations in the pattern of chest pain indicate that rapid reperfusion may limit the size of the infarct. Overall, t-PA appears to be a relatively safe thrombolytic agent. Bleeding is the most significant adverse effect reported with t-PA administration. In most cases, however, bleeding has been minor. Other reported adverse effects include reperfusion arrhythmias, bradycardia, and chest pain. Allergic reactions were not observed in clinical trials.
 ...
PMID:Tissue plasminogen activator: an evaluation of clinical efficacy in acute myocardial infarction. 312 Jan 60

Forty-two patients with acute myocardial infarction received 150-mg recombinant human tissue-type plasminogen activator (rt-PA) at 2.3 +/- 1.2 hours after the onset of chest pain. After a 40 U/kg bolus of heparin, rt-PA was given as a 10-mg bolus followed by a 2-hour continuous infusion of 90 mg in the first hour and 50 mg in the second hour. Nonangiographic signs of reperfusion occurred during treatment (41 +/- 21 minutes) in 35 patients and in 1 other patient about 30 minutes after rt-PA. Three patients had discordant nonangiographic signs of reperfusion, 2 patients had no evidence of reperfusion and 1 patient in cardiogenic shock died before completion of the rt-PA infusion and before reperfusion status could be ascertained. Clinical signs of early reocclusion occurred in 4 of the 36 patients with evidence of reperfusion, 3 of whom were retreated with rt-PA with clinical success in 2. Coronary angiography 10 +/- 8 hours later revealed a patent artery of infarction in 35 patients: 32 with nonangiographic signs of sustained reperfusion, both patients with successfully treated reocclusion and 1 of 3 patients with discordant signs of reperfusion. Angiography revealed evidence of partial reperfusion in the remaining 2 patients with discordant signs, and an occluded artery was found in both patients without any evidence of reperfusion and in both patients with clinical signs of persistent reocclusion. Hemorrhagic complications occurred in 9 patients, 7 were related to procedural trauma and 2 patients required a blood transfusion. Four patients died, each of a cardiac cause: 3 in hospital and 1 at home.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Efficacy of a two-hour infusion of 150-mg tissue plasminogen activator in acute myocardial infarction. 312 May 67

The incidence of intracoronary thrombus and the effects of thrombolytic therapy were studied in 41 patients with unstable angina. All patients underwent coronary angiography 2 to 69 h (mean 19) after their last attack of chest pain. Immediately after angiography, 21 patients received intracoronary streptokinase (250,000 IU in 45 min) and were retrospectively analyzed. Twenty patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) (100 mg in 3 h) and were involved in a prospective study. Eleven of the 21 patients from the streptokinase group and 11 of the 20 patients from the rt-PA group showed a decrease in the severity of the coronary stenosis on repeat angiography 1 day later. A decrease in coronary obstruction was primarily observed in 10 of 13 patients with a complete stenosis and in 6 of 9 patients with a subtotal stenosis and markedly diminished coronary flow. Improvement in coronary anatomy was not determined by the clinical characteristics of the patients. Twenty-eight of the 41 patients had angiographic evidence of intracoronary thrombus formation before and 16 had such evidence after thrombolytic treatment. Nine patients developed a small increase in serum cardiac enzymes before or during treatment. Ischemic symptoms and the incidence of surgical or angioplastic intervention were not different in patients with or without a reduction in coronary artery stenosis after fibrinolytic therapy. These observations suggest a high incidence of coronary thrombosis in patients with unstable angina. The data do not permit assessment of the clinical therapeutic efficacy of thrombolytic therapy. Better risk stratification and placebo-controlled prospective studies are required to obtain information on the risk/benefit ratio of such therapy in unstable angina.
 ...
PMID:Effects of thrombolytic therapy in unstable angina: clinical and angiographic results. 313 80

Sixty-eight patients with acute "transmural" myocardial infarction presenting within 6 hours (range, 1.3-5.8 hours) of onset of chest pain were given intravenous recombinant tissue-type plasminogen activator (rt-PA) at a dosage of 1 mg/kg during 90 minutes. Coronary angiography at 90 minutes revealed a patent infarct-related coronary artery in 52 patients (76%). These patients were randomized either to treatment by continuous infusion of heparin alone (27 patients) or to treatment by heparin and a maintenance infusion of rt-PA at a dosage of 0.8 mg/kg during 4 hours (25 patients). Coronary angiography was repeated 60 minutes after the start of the maintenance infusion and again after 8-14 days. Acute symptomatic reocclusion of the infarct-related artery occurred during the 1-hour observation period in five (19%) patients treated with heparin alone but in none of the patients treated with rt-PA (p = 0.05). The measured residual stenosis of the patent infarct-related coronary artery was similar in the heparin-treated and the rt-PA-treated groups at 90 minutes infusion: 66 +/- 14% versus 68 +/- 13% diameter stenosis, respectively (mean +/- SD) and 1.1 +/- 1.1 mm2 versus 0.82 +/- 0.7 mm2 area (p = 0.35). At 8-14 days after infusion, residual stenosis was unchanged in the heparin-treated group, but it improved to 55 +/- 17% (p = 0.001) and 1.6 +/- 1.2 mm2 (p = 0.003) in the rt-PA-treated group. At 90 minutes of infusion, residual intraluminal thrombus was observed in 29 of the 52 patients (56%) with a comparably measured distribution in the two groups (p = 0.43). At 150 minutes, however, the extent of intraluminal thrombus was significantly reduced in the rt-PA-treated group as compared with the heparin-treated group (p = 0.03). In-hospital ischemic events (symptomatic reocclusion, unstable angina, or cardiovascular death) occurred in 12 patients of the heparin-treated group but only in three patients of the rt-PA-treated group (p = 0.03). Fibrinogen levels decreased to 65 +/- 21% of baseline at 90 minutes of rt-PA infusion. During the rt-PA maintenance infusion, fibrinogen fell slightly from 63 +/- 26 to 57 +/- 28% (p = 0.18). This study shows that after successful reperfusion with 1 mg/kg rt-PA during 90 minutes, a maintenance infusion of 0.8 mg/kg rt-PA during 4 hours prevents acute symptomatic coronary artery reocclusion, and it reduces the frequency of ischemic events and the severity of residual coronary artery stenosis at hospital discharge.
 ...
PMID:Prevention of coronary artery reocclusion and reduction in late coronary artery stenosis after thrombolytic therapy in patients with acute myocardial infarction. A randomized study of maintenance infusion of recombinant human tissue-type plasminogen activator. 313 53

A decrease in the fibrinolytic potential, mainly due to an elevation of plasminogen activator inhibitor (PAI), has been described in patients with stable coronary artery disease and a previous myocardial infarction. We investigated plasma levels of PAI and tissue plasminogen activator (t-PA) and their possible circadian variations in patients with unstable coronary artery disease (CAD). Sixty-three patients were studied for at least 2 consecutive days during their stay at the coronary care unit (CCU). Diurnal plasma fluctuations in PAI and t-PA and onset of further myocardial ischemic episodes were monitored. As controls we used 22 age-matched patients submitted to the clinic because of non cardiac chest pain or valvular disease who revealed no evidence of CAD. PAI levels were significantly elevated in patients with unstable CAD (p less than 0.0001) but were not influenced by the extent of underlying CAD, history of previous myocardial infarction, known risk factors for CAD, or by extent of myocardial damage. The circadian variation of PAI levels with peak values between midnight and 6 A.M. found in controls was still present in patients but at a higher level. Preservation of circadian pattern in PAI plasma levels despite myocardial ischemic attacks indicates that elevation of PAI is rather not caused by a reactive phenomenon. On the other hand, elevated PAI levels and episodes of severe myocardial ischemia exhibiting a median time of onset at 10 A.M. seem to be closely related.
 ...
PMID:Circadian fluctuations of plasminogen activator inhibitor and tissue plasminogen activator levels in plasma of patients with unstable coronary artery disease and acute myocardial infarction. 314 44

To evaluate functional recovery in 20 consecutive patients with acute myocardial infarction who received recombinant tissue-type plasminogen activator, serial two-dimensional echocardiograms were performed before and immediately after tissue plasminogen activator administration and at 1 and 10 days postinfarction. Tissue plasminogen activator was administered intravenously (17 patients) or by intracoronary infusion (3 patients) after angiographic confirmation of total occlusion. Reperfusion, documented by angiography, occurred in 13 of the 20 patients. The mean time from onset of chest pain to thrombolysis was 5.1 +/- 1.1 hours. Echocardiograms were evaluated for regional function with a visual semiquantitative scoring system by two independent observers who had no knowledge of patient identity, temporal sequence, therapy or effect of therapy. There was no immediate or 24 hour improvement in wall motion. At day 10 compared with pretreatment, 28 of 33 reperfused infarct zone segments versus 6 of 20 nonreperfused infarct segments demonstrated improved wall motion (p = 0.01). This improvement did not relate to time from onset of chest pain to successful thrombolysis. Of reperfused infarct zone segments in the distribution of coronary artery balloon dilation, 19 of 23 segments exhibited improvement versus 7 of 17 (reperfused, no angioplasty) and 6 of 20 (nonreperfused, no angioplasty) segments (p = 0.001). Infarct zone segments reperfused at the time of ongoing chest pain demonstrated functional recovery compared with segments reperfused in the absence of chest pain (18 of 23 versus 10 of 20, respectively; p = 0.05). Thus, in this uncontrolled series, there was echocardiographically detectable improvement in function of reperfused infarct segments 10 days after coronary thrombolysis with recombinant tissue plasminogen activator.
 ...
PMID:Regional wall motion improvement after coronary thrombolysis with recombinant tissue plasminogen activator: importance of coronary angioplasty. 316 Jul 57

Clinical assessment of patients with evolving acute myocardial infarction may suggest recanalization of the infarct coronary artery if chest pain, electrocardiographic ST-segment elevation and reperfusion arrhythmia are diminished. These 3 criteria, however, have not been correlated with immediate coronary angiography. Determination of which patients will achieve myocardial reperfusion after intravenous fibrinolytic therapy would allow for appropriate triage; those in whom it fails may be considered for mechanical or surgical recanalization. Fifty-six patients were studied: 28 received intravenous streptokinase and 28 intravenous recombinant tissue-type plasminogen activator. None of these clinical criteria, considered separately, was predictive of infarct artery recanalization status. Using the presence or absence of all 3 criteria, the specificity and predictive value increased to 100%. However, only 9% of patients in the series had all 3 criteria present (all had a patent infarct artery) and 34% had no criteria present (all had an occluded vessel). Noninvasive clinical markers are simple and practical, but only concordance of all 3 major criteria, when present, accurately predicts results of thrombolytic therapy.
 ...
PMID:Prediction of infarct coronary artery recanalization after intravenous thrombolytic therapy. 382 86

Clinical and pathological findings in 15 autopsy cases, 13 males and 2 females, confirming cardiac free wall rupture after AMI were reported. The incidence is 30.6% of all autopsy cases of AMI in Chinese PLA General Hospital from 1958 to 1979. The ages ranged from 46 to 79 years, 10 being above 60 years. For 73.3% it was the first AMI and 66.7% of the patients had a history of hypertension. Thirteen of the 15 patients died within 5 days after the onset of AMI and another 2 within 7 days. When the cardiac rupture occurred, the ECG generally showed bradycardia, AV-junctional rhythm, III degrees AV block or isorhythmic ventricular rhythm and cardiac arrest. Both the gross and microscopic AMI were examined in 13 cases. All of them had a septal infarct, but only 2 had an ECG diagnosis. Of the 6 patients with inferior MI on ECG, 5 had right and left coronary lesions worse than grade III. The effective prevention of cardiac rupture consists of early diagnosis, control of chest pain and vomiting, prevention or treatment of hypertension or hypotension and 1 to 2 weeks of bed rest after the onset of AMI.
 ...
PMID:Cardiac free wall rupture after acute myocardial infarction. Clinical and pathological analysis. 383 11

The aim of this study was to evaluate the impact of concurrent nitroglycerin administration on the thrombolytic efficacy of recombinant tissue-type plasminogen activator (rTPA) in patients with acute anterior myocardial infarction (AMI). Sixty patients (53 men, 7 women; mean age 54 +/- 7 years) with AMI entered the study. Thirty-three patients were randomized to receive rTPA alone (100 mg in 3 hours) (group A) and 27 to receive rTPA plus nitroglycerin (100 micrograms/min) (group B). Time from the onset of chest pain and delivery of rTPA was similar in the two groups of patients. Patients in group A had signs of reperfusion more often than the patients in group B (25 of 33 or 75.7% vs 15 of 27 or 55.5%, p < 0.05). Time to reperfusion was also shorter in group A than in group B (19.6 +/- 9.4 minutes vs 37.8 +/- 5.9 minutes, p < 0.05). Group B had a greater incidence of in-hospital adverse events (9 of 27 vs 5 of 33, p < 0.05) and a higher incidence of coronary artery reocclusion (8 of 15 or 53.3% vs 6 of 25 or 24%, p < 0.05). Peak plasma levels of rTPA antigen were higher in group A compared with group B (1427 +/- 679 vs 512 +/- 312 ng/ml, p < 0.01). In conclusion, concurrent nitroglycerin administration reduces the thrombolytic efficacy of rTPA in patients with AMI probably by lowering the plasma levels of rTPA antigen. The diminished efficacy of rTPA is associated with an adverse outcome.
 ...
PMID:Concurrent nitroglycerin administration reduces the efficacy of recombinant tissue-type plasminogen activator in patients with acute anterior wall myocardial infarction. 920 Apr 1

Spontaneous coronary artery dissection is a rare cause of acute myocardial infarction. It usually occurs in relatively young patients and is frequently found at autopsy. Because of the low incidence, the treatment of choice for spontaneous coronary artery dissection is still not settled. Here the authors report a sixty-six-year-old woman with coronary lesions judged as spontaneous coronary artery dissection. She presented with chest pain. Under diagnosis of acute inferior myocardial infarction, she was treated with recombinant tissue-type plasminogen activator. Coronary arteriography performed two weeks later revealed a dissection involving a long segment of right coronary artery. The left coronary arteries and uninvolved portion of right coronary artery were smooth and patent. She suffered no hypertension and gave no definite history of trauma. This patient was treated medically with aspirin, isosorbide dinitrate, and metoprolol and remained in stable condition after a follow-up period of six months.
 ...
PMID:Spontaneous coronary artery dissection in an elderly woman with acute inferior myocardial infarction. A case report. 766 90


<< Previous 1 2 3 4 5 6 7 8 Next >>