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)

A 29-year-old man with congenital protein C deficiency and acute myocardial infarction is reported. Four hours after the onset of chest pain, he was treated intravenously with tissue-type plasminogen activator. Subsequent coronary angiography revealed only slight stenosis of the left anterior descending coronary artery without any atherosclerosis. The propositus, his brother, and his mother, showed low levels of both protein C activity and antigen, while plasma thrombomodulin levels were normal. His grandfather had died from acute myocardial infarction at 38 years of age. We investigated several other risk factors for arterial thrombosis, including factor VII, fibrinogen, heparin cofactor II, lipoprotein (a), and anticardiolipin antibodies. No other haemostatic abnormalities apart from factor VII hyperactivity were detected in this family. To study the effects of protein C and factor VII on procoagulant activity, prothrombin time was measured after the addition of activated protein C and factor VII to protein C-deficient plasma. The prothrombin time ratio decreased along with an increase in the factor VII level. It also decreased with a decrease in the activated protein C level. These findings indicated that the procoagulant activity of factor VII was enhanced by low protein C levels, suggesting that concomitant factor VII hyperactivity may cause acute myocardial infarction in patients with protein C deficiency.
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PMID:Congenital protein C deficiency and myocardial infarction:concomitant factor VII hyperactivity may play a role in the onset of arterial thrombosis. 144 May 17

In the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial, patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and were randomized to either a conservative or an invasive strategy. Within this study, the effects of immediate versus deferred beta-blocker therapy were also assessed in patients eligible for beta-blocker therapy, a group of 1,434 patients of which 720 were randomized to the immediate intravenous group and 714 to the deferred group. In the immediate intravenous group, within 2 hours of initiating rt-PA metoprolol was given (5 mg intravenously at 2-minute intervals over 6 minutes, for a total intravenous dose of 15 mg, followed by 50 mg orally every 12 hours in the first 24 hours and 100 mg orally every 12 hours thereafter). The patients assigned to the deferred group received metoprolol, 50 mg orally twice on day 6, followed by 100 mg orally twice a day thereafter. The therapy was tolerated well in both groups and the primary end point, resting global ejection fraction at hospital discharge, averaged 50.5% and was virtually identical in the two groups. The regional ventricular function was also similar in the two groups. Overall, there was no difference in mortality between the immediate intravenous and deferred groups, but in the subgroup defined as low risk there were no deaths at 6 weeks among those receiving immediate beta-blocker therapy in contrast to seven deaths among those in whom beta-blocker therapy was deferred. These findings for a secondary end point in a subgroup were not considered sufficient to warrant a recommendation regarding clinical use. There was a lower incidence of reinfarction (2.7% versus 5.1%, p = 0.02) and recurrent chest pain (18.8% versus 24.1%, p less than 0.02) at 6 days in the immediate intravenous group. Thus, in appropriate postinfarction patients, beta-blockers are safe when given early after thrombolytic therapy and are associated with decreased myocardial ischemia and reinfarction in the first week but offer no benefit over late administration in improving ventricular function or reducing mortality.
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PMID:Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study. 167 47

Twenty-nine patients with acute myocardial infarction were given recombinant tissue plasminogen activator (tPA) within 6 hr after onset of chest pain (mean: 3.2 hr) with a total dose of 100mg iv drip given within 3hr for thrombolytic therapy. Serial determinations of total FDP, FDP D-Dimer (specific for FbDP), fibrinogen (Fg), PT, APTT, reptilase time (RT), plasminogen, alpha 2-antiplasmin (AAP), euglobulin lysis time (ELT) and antithrombin III (ATIII) were performed before and 1, 2, 4, 6, 12, 24, 48 hr after initiation of tPA injection in the 29 patients in order to evaluate the hemostatic changes after thrombolytic therapy. Decreases of plasminogen, Fg, AAP & ELT were found from 1 hr after therapy and persisted to 24, 12, 24 & 12 hr, respectively, with the maximum decrease usually between 1-4 hr. Increases of FDP, FDP D-dimer, PT, APTT & RT were found from 1, 1, 2, 1 & 1 hr after therapy, respectively, and sustained to 24, 12, 12, 24 & 12 hr, respectively, with maximum increases between 1-4 hr. No significant changes of ATIII were noted during the 48-hr study-period. 4 of these 29 patients (13.79%) had the complication of localized bleeding, 1 of them needed 1 unit of packed red blood cell transfusion. All thrombolysis-related changes recovered within 24 hr after tPA therapy. No parameter we have studied so far could be used for the prediction of the possibility of coronary patency after tPA therapy. But markedly elevated FDP was found to be associated with high risk of bleeding complication. As the coagulation changes persist for 24 hr or longer, careful monitoring of the coagulation tests and close observation of clinical bleeding signs up to 48 hr are necessary in patients treated with tPA.
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PMID:Serial thrombolysis-related changes after thrombolytic therapy with TPA in patients with acute myocardial infarction. 169 93

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

Systemic thrombolysis is an effective therapy for acute myocardial infarction, since it restores coronary flow and contributes to preserve left ventricular function. We analyze our experience with intravenous thrombolytic therapy in 45 cases with acute myocardial infarction treated within 6 hours of onset of symptoms. 28 patients had anterior and 17 inferior myocardial infarction. We treated 38 patients with streptokinase 1 to 1.5 million units infused during a 30 to 60 minute period and 7 patients with tissue plasminogen activator factor, 100 mg infused during 2 hours. Regression of chest pain and ST segment elevation and early CPK peaking (less than 4 hours) were utilized as criteria for reperfusion. Accordingly 29 patients (64%) met these criteria. Coronary angiogram was performed within 7 days in 38 patients. It disclosed a patent coronary artery in the infarcted area in 28 cases (74%). Transient hypotension with thrombolytic therapy was observed in 17 patients (38%) and bleeding complications in 3 cases (7%). Two patients (4%) died early after therapeutic failure. In summary we have confirmed that intravenous thrombolytic therapy is safe and effective in the early period of myocardial infarction and that is associated with a high incidence of clinical and angiographic reperfusion.
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PMID:[Early systemic thrombolysis in acute myocardial infarction: clinical and angiographic results]. 182 39

This investigation was designed to determine if acute ischemic cardiac injury causes the release of the 98 amino acid (aa) N-terminus of the 126 aa atrial natriuretic factor prohormone (pro ANF). Seventeen patients with acute myocardial infarction, but without clinical evidence of congestive heart failure, had their circulating concentrations of the whole N-terminus (ie, pro ANF 1-98), the midportion of the N-terminus of the ANF prohormone (consisting of aa 31-67; pro ANF 31-67) and creatine phosphokinase (CPK) monitored daily for 14 days. All seventeen patients had elevated plasma pro ANF 1-98 and pro ANF 31-67 concentrations at the time of presentation. Maximal increase on day three post-infarction correlated with the size of infarction estimated by the maximal CPK (r = 0.675; p less than 0.05) but did not correlate with the amount of left ventricular dysfunction. Another three patients with acute myocardial infarction were treated with tissue plasminogen activator (tPA). The measured pro ANF 1-98 and pro ANF 31-67 levels in these patients were within our normal range and significantly lower (p less than 0.001) than seen in patients with acute myocardial infarction not given thrombolytic therapy. Six patients with unstable angina, likewise, had normal circulating pro ANFs 1-98 and 31-67 concentrations during prolonged episodes of chest pain. These data suggest that myocardial necrosis but not ischemia triggers the release of the entire 126 aa prohormone.
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PMID:Acute and sustained release of the atrial natriuretic factor prohormone N-terminus with acute myocardial infarction. 182 42

Unstable angina is a clinical syndrome of recurrent myocardial ischemia. In some cases, this reflects episodic platelet activation and coronary thrombosis. Thus, the biosynthesis of thromboxane A2, which is largely derived from activated platelets, is increased, often coincident with chest pain. The major role of platelets in unstable angina may influence the response to plasminogen activators. Platelets increase the resistance of thrombi to lysis, by inducing clot retraction and cross-linking and by releasing inhibitors. Thus, coronary thrombi in unstable angina may be resistant to lysis. Furthermore, both t-PA and streptokinase cause platelet activation and thrombin formation in vivo, possibly via plasmin. Plasmin can activate platelets and factor V directly. These prothrombotic effects of plasminogen activators may limit their activity in unstable angina. At the very least, their therapeutic efficacy may be highly dependent on the coadministration of potent antiplatelet agents and anticoagulants.
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PMID:Platelet activation in the pathogenesis of unstable angina: importance in determining the response to plasminogen activators. 189 67

To determine whether there are differences in responses to thrombolytic therapy in certain populations, the data for the Thrombolysis and Angioplasty in Myocardial Infarction (phase 1) study were analyzed for black and white patients. Baseline variables including risk factors and extent of coronary artery disease were similar in the 352 white and 24 black patients. The time from onset of chest pain to recombinant tissue-type plasminogen activator (rt-PA) therapy and rt-PA dosing regimens were the same in the two groups. The patency rate of the infarct-related artery at 90 minutes was 91% for blacks and was 72% for whites (p = 0.051). Blacks displayed significantly lower nadir fibrinogen levels (0.57 +/- 0.62 versus 1.3 +/- 0.76 g/l, p less than 0.0001), greater delta fibrinogen (baseline-nadir) (2.7 +/- 1.1 versus 1.7 +/- 1.1 g/l, p less than 0.0001), and increased peak levels of fibrin(ogen) degradation products (837 +/- 865 versus 245 +/- 475 micrograms/ml, p less than 0.0001). rt-PA antigen levels tended to be higher in blacks than in whites (2.8 +/- 2.2 versus 2.2 +/- 3.2 micrograms/ml [p = 0.10] at the peak and 1.6 +/- 1.3 versus 0.99 +/- 1.4 micrograms/ml [p = 0.06] at the end of the maintenance infusion). Major clinical outcomes including survival until time of hospital discharge (92% black versus 93% white, p = 0.68) were not significantly different. However, despite undergoing fewer angioplasty procedures (25% versus 46.3%, p = 0.047), blacks received more transfusions (58.8% versus 19.5% were administered greater than or equal to 2 units packed erythrocytes, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Racial differences in responses to thrombolytic therapy with recombinant tissue-type plasminogen activator. Increased fibrin(ogen)olysis in blacks. The Thrombolysis and Angioplasty in Myocardial Infarction Study Group. 193 93

Intravenous thrombolytic therapy improves left ventricular function and reduces mortality in patients with acute myocardial infarction (AMI). In European and Middle Eastern trials, prehospital delivery of thrombolytic agents by physician-directed mobile intensive care units has been successful. This report describes two independently conceived and performed trials that used cellular telephone transmission of 12-lead ECGs to deliver recombinant tissue plasminogen activator (r-tPA) in the field to patients with AMI. In the Nashville Prehospital TPA Trial, 85 patients with chest pain were evaluated in the field for possible administration of r-tPA over a 6-month period. Three of 85 patients (3.5%) were found to be actual candidates for r-tPA treatment in the field. In phase II (dry-run phase) of the Cincinnati Heart Project, 374 patients were evaluated in the field with 14 documented cases of AMI (3.7%) before r-tPA was placed in ambulances for administration by paramedics. In phase III (active with r-TPA in ambulances), over a 1-year period 103 patients were evaluated with six (5.8%) documented cases of AMI. Three of five r-tPA field treatment decisions by emergency physicians using transmitted 12-lead ECGs were accurate (60%). When patients in phases II and III were combined, only 20 of 477 total patients (4.2%) were documented to have AMI. A decline in paramedic skills was noted because of the infrequent administration of the thrombolytic agent. Combining the Nashville and Cincinnati experiences, only 27 of 562 total patients with chest pain (4.8%) were candidates for prehospital thrombolysis. We conclude that few patients evaluated in the prehospital setting are actual candidates for thrombolytic therapy. Substantial allocation of financial and human resources for prehospital delivery of intravenous thrombolytic therapy does not appear warranted.
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PMID:Prehospital diagnosis and treatment of acute myocardial infarction: a north-south perspective. The Cincinnati Heart Project and the Nashville Prehospital TPA Trial. 189 78

In a randomized, double-blind study, in which recombinant tissue plasminogen activator (rt-PA) administered at an early stage was compared with placebo in patients with suspected acute myocardial infarction (AMI), the effects on pain were studied in 312 patients. Inclusion criteria were as follows: (a) chest pain of duration less than 2 h and 45 min; and (b) age less than 75 years. Chest pain was estimated subjectively by the patients, using a 10-point numerical rating scale, at hourly intervals for the first 24 h, and by the requirement for narcotic analgesics. Compared with placebo, rt-PA treatment resulted in a 43% reduction in mean total pain score (P less than 0.0001), a 26% reduction in pain duration (P less than 0.01), and a 33% reduction in morphine requirement (P = 0.01). Fifty-seven per cent of all patients developed a confirmed AMI. In these subjects rt-PA reduced the pain score by 46% (P less than 0.001). Among patients without confirmed AMI, a 37% reduction in pain score was observed (P = 0.05). The effect on pain was most marked in patients with ST-elevation on the initial ECG. We conclude that early treatment with rt-PA in suspected AMI reduces chest pain considerably. The effect is most marked in patients with ST-elevation on the initial ECG.
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PMID:Effects on chest pain of early thrombolytic treatment in suspected acute myocardial infarction: results from the TEAHAT Study. 190 9


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