Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Eighty-nine consecutive Chinese patients (69 males, 20 females) with acute myocardial infarction treated by 100 mg recombinant tissue plasminogen activator (7 intracoronarily, 82 intravenously) at 3.7 +/- 1.0 h after onset, and intravenous heparin or dipyridamole therapy started at 3 h, were studied prospectively. Their mean age was 59.6 +/- 10.6 yr. Forty-six patients (51.7%) had anterior and 39 patients (43.8%) had inferior infarcts. Clinical evidence of reperfusion were seen in 63 patients (70.8%), while new complications included hypotension (5.6%), heart failure (6.7%), cardiac arrhythmias (76.4%) majority of which are related to reperfusion and self-remitting, haematoma around vascular access sites (23.6%), melaena (3.3%) and cerebral infarction (2.2%). Maximal changes in coagulation profiles were seen at 3 h, including a decrease in fibrinogen by 64.2% and an increase in fibrin degradation products by 47 times. The changes in haemostatic variables were not related to body weight or bleeding complications. Nine patients (10.1%) had recurrence of angina and 6 patients (6.9%) died due to pump failure and reinfarction. Angiogram at 14 days confirmed TIMI 2 or 3 patency of infarct-related arteries in 63 out of 73 (86.3%) patients, with a mean global ejection fraction of 52.5 +/- 12.4%. Nearly all survivors could maintain class I-II functional status after discharge. The safety and promise of recombinant tissue plasminogen activator for acute myocardial infarction in the Chinese were confirmed.
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PMID:Recombinant tissue plasminogen activator in acute myocardial infarction in the Chinese in Hong Kong. 151 55

Thrombolytic agents are aimed at restoring arterial patency thus reducing the risk of cerebral infarction in case of arterial occlusion by blood thrombus or embolus. A review of data from the literature is presented, and the authors have tried to answer the following questions: 1) What are the probabilities of early mortality (first 30 days) and of morbidity due to untreated or medically (thrombolysis excluded) treated cerebral infarction? 2) What are the morbidity and mortality rates after systemic thrombolysis or selective intraarterial thrombolysis? 3) Are the results of thrombolysis affected by the site of arterial occlusion (carotid or vertebrobasilar system)? 4) Does thrombolysis increase the risk of cerebral haemorrhage? 5) Can thrombolysis be regarded as an effective treatment and, if so, in which cases? This study of systemic thrombolysis yielded a mean mortality rate of 22.2%, with satisfactory functional outcome in 58.2% of the survivors. The corresponding figures for selective intraarterial thrombolysis were 29.7% and 84.5% respectively. However when the arterial territories occluded were taken into account, they became 10.4% and 84.4% respectively in the carotid system and 61.5% and 85.00% in the vertebrobasilar system. Comparisons between the natural history of cerebral infarctions, as far as it is known, and the results of thrombolysis suggest that thrombolytic agents are: 1) probably justified by the selective intraarterial route when the occlusion lies in the carotid system; 2) not indicated by the systemic route with urokinase or streptokinase but trials with tPA are being performed. These conclusions, however, must be interpreted with caution as they rest on general data leaving out a number of factors that are often neglected in reports particularly the exact site of arterial occlusion, chiefly in the vertebrobasilar system. From 3 limited cohorts it was possible to evaluate at about 14% the mortality rate in thrombolysis for basilar artery occlusion. This figure, compared with the 70-80% estimate found in the literature for untreated occlusions, suggests that the selective intraarterial thrombolysis may perhaps be indicated also in basilar artery occlusions. It must be noted that selective intraarterial thrombolysis is still an exceptional treatment which requires sophisticated techniques, highly qualified neuroradiologists and prompt application i.e. emergency stroke units.
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PMID:[Thrombolytic agents in cerebral infarctions]. 202 56

Thirteen (1.8%) of 708 patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I, II and III trials developed a stroke. Four strokes were hemorrhagic and nine were nonhemorrhagic. Of five prespecified risk factors for intracranial hemorrhage (age greater than 65 years, history of hypertension, history of prior cerebrovascular disease, aspirin use and acute hypertension), two patients had two risk factors and one patient had one risk factor. However, 80% of patients without intracranial hemorrhage had at least one risk factor and 31% had two risk factors. No patient with a prior stroke or transient ischemic attack (all greater than 6 months previously) had an intracranial hemorrhage. Of three prespecified risk factors for nonhemorrhagic stroke (atrial fibrillation, prior cerebrovascular disease and large anterior wall infarction), only the occurrence of a large anterior myocardial infarction (with ejection fraction less than 45%) was a predictor (p = 0.0015). The in-hospital death rate was 25% for patients with hemorrhagic stroke versus 11% for patients with a non-hemorrhagic stroke and 6% for those patients without a stroke. Furthermore, the hospital stay was greater than 50% longer in patients who had a stroke than in those who did not. Thus, intracranial hemorrhage remains an unpredictable risk in patients treated with thrombolytic therapy and cerebral infarction is related to anterior myocardial infarction and poor left ventricular function. Both types of stroke are associated with substantial morbidity and mortality.
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PMID:Stroke and acute myocardial infarction in the thrombolytic era: clinical correlates and long-term prognosis. 220 11

Tissue plasminogen activator is an endogenous fibrin-specific serine protease with potent thrombolytic activity. We investigated the efficacy of tissue plasminogen activator in reducing cerebral infarct size after thromboembolic stroke in a rabbit model. Seventeen rabbits were randomized to receive either tissue plasminogen activator (2.5 mg/kg, n = 6) or vehicle control (n = 11). We controlled mean arterial pressure, hematocrit, and arterial blood gases before and after the intracarotid embolization of an autologous clot. Cerebral blood flow (cm3/100 g/min) (mean +/- SEM) was immediately reduced from 55.2 +/- 7.7 to 8.5 +/- 2.5 in the control group and from 61.8 +/- 14.8 to 10.0 +/- 3.5 in the treated group after embolization. Cerebral blood flow recovered significantly within 60 minutes of thrombolytic therapy and attained a value of 59.6 +/- 10.0 cm3/100 g/min 4 hours after embolization, whereas cerebral blood flow in control animals demonstrated only a minimal recovery to 15.3 +/- 8.9 cm3/100 g/min. Cerebral infarct size (percent of hemisphere) was reduced from 34.4 +/- 5.6% in control animals to 8.8 +/- 5.6% in treated animals (mean +/- SEM, p less than 0.01). These results suggest that tissue plasminogen activator may be efficacious in restoring cerebral blood flow and thus limiting infarct size in acute thromboembolic stroke.
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PMID:Tissue plasminogen activator reduces brain injury in a rabbit model of thromboembolic stroke. 212 36

The mean levels of fibrinopeptide A (FPA), thrombin-antithrombin complex (TAT), and soluble fibrin (tPA method) in cancer patients (n = 32) were intermediate between those of patients with cerebral infarction and pancreatitis who had the most abnormal results and patients with myocardial infarction and pneumonia who had the least abnormal results. Patients with disseminated malignancies (n = 16) had significantly higher mean levels of FPA (10.6 vs. 5.3 nmol/l) and TAT (11.0 vs. 4.4 pmol/l) than patients with limited malignancies (n = 16). The difference in soluble fibrin (fibrin monomer, FM; 22.1 vs. 18.0 nmol/l) was not significant. The values of FPA, FM, and TAT in the patient population correlated significantly. There was a negative correlation between the level of antithrombin and test results for FPA (-0.69), FM (-0.48), and TAT (-0.38) in the cancer patients. Even cancer patients with locally limited disease may have elevated FPA, FM, and TAT test results, indicating a state of definite hypercoagulation.
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PMID:Indices of hypercoagulation in cancer as compared with those in acute inflammation and acute infarction. 228 6

In an effort to determine the value of tissue-type plasminogen activator (TPA) in the treatment of embolic stroke, 17 rabbits were subjected to a model of embolic stroke in which 2-hour-old, tin-impregnated, autologous clots were embolized to the bifurcation of the internal carotid artery at the circle of Willis via retrograde injection into the cannulated external carotid artery. High-resolution digital subtraction radiography was used to localize clots intracranially at the carotid bifurcation. Circulation through the internal carotid artery and intracranial vessels was monitored with serial digital subtraction angiography before and after embolization and during treatment. Disappearance of the tin marker on the digital subtraction radiograph indicated dissolution of clot and was associated with reestablishment of circulation on the digital subtraction angiogram. Experimental animals were treated with human-specific recombinant TPA 30 minutes, 2 hours, or 4 hours after clot embolization. TPA was administered as an intravenous bolus of 0.5 mg/kg followed by an infusion of 1 mg/kg/h for 2 hours. Digital subtraction angiograms were performed every 30 minutes. All clots dissolved, and cerebral circulation was reestablished within 120 minutes of treatment. In control animals treated with saline, embolized clots were stable, and the internal carotid artery remained occluded. At the completion of each study, the animal was perfused with freshly prepared, buffered 2,3,5-triphenyltetrazolium chloride (TTC) for demarcation of cerebral infarction. Control animals demonstrated infarction of 50 +/- 3.6% of the ipsilateral cerebral hemisphere, with an infarct weight of 2.1 +/- 0.2 g.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of recombinant tissue plasminogen activator in embolic stroke. 249 63

We retrospectively evaluated 66 patients younger than 40 years of age who presented with acute nonhemorrhagic cerebral infarction (n = 63) or transient ischemic attacks (n = 3) to determine the possible etiology and long-term outcome at a mean follow-up interval of 3 years after initial presentation. A probable cause for the stroke was identified in 24 patients (36%); this group included one woman with a history of recurrent spontaneous abortions and a positive test for the presence of the lupus anticoagulant. We performed detailed hemostatic investigations at follow-up in 38 (90%) of the remaining 42 patients in whom the cause of the stroke was unknown or uncertain; results of the basic hemostatic screening tests (including that for fibrinogen) were uniformly normal. All 38 patients demonstrated a normal fibrinolytic response as measured by tissue plasminogen activator release to a standard venous occlusion stress test; concentration of the inhibitor of tissue plasminogen activator was not increased. No abnormalities in the concentrations of the inhibitory proteins C or S or antithrombin III were identified, and none of the 38 patients had evidence of a lupus anticoagulant. Neurologic recovery was complete or the residual disability mild in 46 of 59 (78%) patients. Overall prognosis was excellent and independent of whether a precipitating factor for the stroke could be identified.
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PMID:Etiology, prognosis, and hemostatic function after cerebral infarction in young adults. 249 81

To test the safety of a large intrathecal dose of human recombinant tissue plasminogen activator (rt-PA), 6 cynomolgous monkeys were given 10 mg of rt-PA (mean, 2.7 mg/kg) through an Ommaya reservoir after craniectomy and dissection of the basal cisterns. Bleeding occurred briefly at the incision in 2 animals; otherwise the clinical condition of all 6 remained normal throughout the postoperative period. Systemic fibrinolysis did not occur, and gross and microscopic examination of the brain and meninges revealed no abnormality. Next, we evaluated the efficacy of unilateral administration of rt-PA suspension (0.5 mg) plus slow-release gel rt-PA (1.25 mg) in lysing a bilateral subarachnoid clot and preventing vasospasm in a randomized, placebo-controlled trial. Sixteen monkeys were divided randomly into 2 equal groups, each of which underwent baseline cerebral angiography, followed by frontotemporal craniectomy and induction of subarachnoid hemorrhage on the left side and then on the right. Before closure on the right side either rt-PA or an equal volume of placebo was injected into the subarachnoid space. On day 7 angiography was repeated, and the animals were killed under anesthesia for necropsy. One of the animals in the placebo group developed a cerebral infarction on day 5. In the placebo group significant vasospasm occurred in all major right and left-sided anterior cerebral vessels (P less than 0.01). No vasospasm occurred in the rt-PA-treated animals. Whereas gross subarachnoid clot was found in all animals in the placebo group (mean clot weight 1.13 g), only a small fragment of clot was found in a single rt-PA-treated animal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Safety and efficacy of intrathecal thrombolytic therapy in a primate model of cerebral vasospasm. 249 28

Recent success with thrombolytic therapy for acute myocardial infarction has stimulated interest in its use for stroke. To determine the hemorrhagic potential of thrombolytic therapy in experimental cerebral infarction, we compared a group of tissue plasminogen activator-treated rabbits (n = 4) with 2 groups of streptokinase-treated rabbits (n = 6 in each), as well as with 3 groups of heparin-treated rabbits (n = 5 in each) and untreated controls (n = 12). Focal cerebral infarction was produced in rabbits by occlusion of the right common carotid and middle cerebral arteries coupled with 2 hours of halothane-induced hypotension. Treatment with heparin or thrombolytic agents began 24 hours after occlusion. One additional group was treated with streptokinase 1 hour after occlusion (n = 6) to determine the hemorrhagic potential of thrombolytic agents in evolving infarction. Rabbits were killed 29-33 hours after occlusion, and brain sections were examined using light microscopy. The results demonstrate that microscopic hemorrhage is frequently present in infarcted tissue irrespective of treatment. Gross cerebral hemorrhage did not occur in untreated rabbits or in rabbits treated with streptokinase 1 hour after occlusion. Only rabbits treated with streptokinase, tissue plasminogen activator, or excessive doses of heparin 24 hours after occlusion, at a time when cerebral infarction was well established, exhibited gross hemorrhage in the area of infarction. These data suggest that treatment of ischemic stroke with thrombolytic agents carries an increased risk of cerebral hemorrhage unless the agents are given early after the onset of symptoms.
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PMID:Hemorrhagic complications of thrombolytic therapy in experimental stroke. 312 Mar 60

Thrombolysis with tissue plasminogen activator (tPA) has been used to treat myocardial infarction and pulmonary embolism in humans. This plasminogen activator may also be useful in treating certain strokes. We infused tPA or saline in rabbits 15 minutes after selective internal carotid artery embolization with 18-hour aged autologous clot. By serial angiography, the tPA-treated group demonstrated rapid angiographic reperfusion of the occluded vascular territory in 7 of 8 animals, whereas none of 6 saline controls did. None of the animals in either group developed macroscopic cerebral hemorrhage. Both groups showed cerebral infarction, predominantly in the territory of the occluded vessel; the extent of infarction did not differ between tPA-treated animals and controls. Early tPA therapy can allow reperfusion of occluded cerebral arteries safely and effectively in a rabbit cerebral embolization model.
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PMID:The safety and angiographic efficacy of tissue plasminogen activator in a cerebral embolization model. 313 92


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