Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 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 (rt-PA) (7 intracoronarily, 82 intravenously) at 3.7 +/- 1.0 hours after onset, and intravenous heparin or dipyridamole therapy started at 3 hours, were studied prospectively. Their mean age was 59.6 +/- 10.6 years. Forty-six patients (51.7%) had anterior and 39 patients (43.8%) had inferior infarcts. Clinical evidence of reperfusion was seen in 63 patients (72.8%), while new complications included hypotension (5.6%), heart failure (6.7%), cardiac arrhythmias (76.4%), hematoma around vascular access sites (23.6%), melena (2.2%) and cerebral infarction (2.2%). Maximal changes in coagulation profiles were seen at 3 hours, including a decrease in fibrinogen (by 64.2%), an increase in FDP by 11.7 times and D-dimers by 4.4 times. Nine patients (10.1%) had recurrence of angina and 6 patients (6.9%) died due to pump failure (5) and reinfarction (1). Angiogram at 14 days confirmed TIMI (2 or 3) patency of infarct related arteries in 62/81 (76.5%) 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 promises of rt-PA for acute myocardial infarction in the Chinese were confirmed.
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PMID:Recombinant tissue-plasminogen activator (rt-PA) in acute myocardial infarction in the Chinese in Hong Kong. 149 66

Tissue-type plasminogen activator (t-PA) is thought to be a promising fibrinolytic agent because of its high affinity to fibrin without evidence of significant systemic fibrinolysis. The feasibility of t-PA and urokinase (UK) in local fibrinolytic therapy was investigated in a canine common carotid artery thrombus model. After the screening of coagulation-fibrinolytic activities, autologous blood clot was injected into the segment of intimal injured common carotid artery. The fibrinolytic agent was locally applied from the origin of the common carotid artery under temporary flow arrest with a double lumen balloon catheter. T-PA used in this study was produced by the cell culture technique of normal human cells. Its activity was-expressed by AK units (AKU), namely, the fibrinolytic area of the fibrin-agar plate induced by 10 AKU/ml of t-PA solution corresponds to that of 10 IU/ml of UK solution. The doses of t-PA required to produce angiographical recanalization were 600-1,200 AKU/kg (approximately 0.015-0.03 mg/kg) of t-PA, while 24,000 IU/kg was necessary for UK. In these doses, t-PA evoked no adverse effects on the plasma coagulation-fibrinolytic system, while UK produced significant decrease in plasma fibrinogen and alpha-2 plasmin inhibitor levels. Thus, t-PA may be considered to have higher fibrinolytic ability and lower adverse effect on the plasma coagulation-fibrinolytic system than UK. Local fibrinolytic therapy for acute cerebral infarction using t-PA is considered to be a promising intravascular therapeutic procedure with less systemic fibrinolytic complications such as hemorrhagic infarction.
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PMID:[An experimental study of local fibrinolysis using tissue plasminogen activator and urokinase in a canine common carotid artery thrombus model]. 211 1

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

Plasma levels of thrombin-antithrombin III complex (TAT), plasmin-alpha 2-plasmin inhibitor complex (PAP), von Willebrand factor antigen (vWF:Ag) plasminogen activator antigen (PA) and plasminogen activator inhibitor-1 antigen (PAI-1), were determined in 110 patients with arterial thromboembolic diseases within 4 weeks after attack (Th; 41 cases with myocardial infarction and 69 with cerebral infarction), 67 patients with various types of carcinoma (Ca; 31 cases without metastasis and 36 with metastasis) and 50 age-matched healthy individuals (Co). The following results were obtained: 1) Mean plasma levels of TAT, PAP, vWF:Ag, PA and PAI-1 were significantly higher in Th than Co. 2) Mean plasma levels of TAT, PA and PAI-1 were significantly higher in Ca than Co regardless of metastasis but those of PAP and vWF:Ag were significantly higher only in Ca with metastasis than Co. 3) Significant relationship was observed between plasma levels of TAT and PAP both in Th and Ca. 4) Significant relationship was also observed between plasma levels of TAT and vWF:Ag, PA or PAI-1 in Th, but not in Ca. It is suggested from these results that the coagulopathies observed in these patients result from the activation of intravascular blood coagulation and fibrinolysis, and that vascular endothelial cell damage may play an important role in the activation in Th.
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PMID:Studies on the pathogenesis of coagulopathy in patients with arterial thromboembolism and malignancy. 214 28

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

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

In diseases associated with thrombotic or thromboembolic complications, a reduction in the fibrinolytic potential may contribute to the risk to develop thrombosis. To investigate whether juvenile cerebral infarction is associated with a permanent defect of the fibrinolytic system we measured the main components of the fibrinolytic system, tissue plasminogen activator (t-PA) and its fast acting inhibitor (PAI) in plasma samples of 21 patients (aged 21-44 years) 3-24 months after the acute event. The data obtained were compared to those from thirteen healthy young volunteers (22-46 years). A direct effect of known risk factors on the fibrinolytic system could be excluded because patients avoided their risk factors immediately after the ischemic cerebral attack. Hypertension and the combination of oral contraceptives and smoking had been the most striking original risk factors. Levels of t-PA antigen and t-PA activity before and after venous occlusion, or PAI activity were not different between patients and controls suggesting that at least a permanent decrease in the activity of the fibrinolytic system does not exist in these patients. However, our findings do not exclude that a temporary defect in fibrinolysis might have contributed to the acute onset of the thrombotic cerebral event possibly induced by the risk factors originally present.
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PMID:[Persistent changes in tissue-type plasminogen activator and plasminogen activator inhibitor fibrinolytic parameters in patients following juvenile ischemic cerebral infarct]. 314 88

Parenchymatous intracerebral hemorrhage (ICH) is a serious, infrequent complication of thrombolytic therapy for acute myocardial infarction. We studied the clinical and radiologic features, manner of presentation, associated factors, and temporal course in 23 patients with ICH associated with 150 mg or 100 mg recombinant tissue-type plasminogen activator (rt-PA) and heparin therapy for acute myocardial infarction in the Thrombolysis in Myocardial Infarction (TIMI) II Pilot and Randomized Clinical Trial. In TIMI II, 13 of the 23 ICH patients developed or maintained systolic blood pressure > or = 160 mm Hg or diastolic blood pressure > or = 90 mm Hg during the rt-PA infusion and before the onset of neurologic symptoms. Six patients (26%) had life-threatening ventricular arrhythmias, five before onset of neurologic symptoms. A decreased level of consciousness was the earliest neurologic abnormality in 15 (65%) and the most common initial physical finding (in 19, or 82%). Onset was usually gradual (70%), but time to maximal deficit was frequently (61%) within 6 hours of onset. The locations of the primary ICH sites were lobar in 16 (70%), thalamic in four (17%), and brainstem-cerebellum in three (13%), but the putamen was never the primary site. Multiple lobar hemorrhages occurred in six cases (26%). The timing and size of ICH was similar among patients treated with 150 mg rt-PA and 100 mg rt-PA. Brain CT demonstrated an arteriovenous malformation in one case. Four patients had hypofibrinogenemia, which was profound in three patients. Pathologic findings were available for five patients. Of these, three patients had cerebral amyloid angiopathy, and one had hemorrhagic transformation of an ischemic cerebral infarction found at autopsy. We conclude that ICH following rt-PA and heparin therapy for acute myocardial infarction presents as a distinctive clinical syndrome. Intracerebral bleeding after combined thrombolytic and antithrombotic therapy may be associated with cerebral amyloid angiopathy and other vascular lesions. Acute or persistent hypertension before or during rt-PA infusion, life-threatening ventricular arrhythmias, and hypofibrinogenemia, either alone or in combination, may play roles in some cases. Care should be exercised when considering thrombolytic therapy for patients with risk factors for ICH.
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PMID:Clinical features and pathogenesis of intracerebral hemorrhage after rt-PA and heparin therapy for acute myocardial infarction: the Thrombolysis in Myocardial Infarction (TIMI) II Pilot and Randomized Clinical Trial combined experience. 772 50

We were interested to investigate if a combination of a modified tissue-type plasminogen activator, SUN9216, which is constructed by modifying a single amino acid (Asn117-Gln117) to yield a tissue-type plasminogen activator lacking finger and growth factor domains with a long half-life in blood, and an endothelin receptor antagonist, FR139317, (R)2-[(R)-2-[(S)-2[[1-(hexahydro-1H-azepinyl)]carbonyl]amino-4- methyl-pentanoyl]amino-3-[3-(1-methyl-1H-indolyl)]propionyl)amino-3- (2-pyridyl)propionic acid, has greater thrombolytic efficacy than a thrombolytic agent alone in reducing the size of cerebral infarction. The thrombotic occlusion of the rat middle cerebral artery was induced by a photochemical reaction between rose bengal and green light, which causes endothelial injury followed by platelet adhesion and formation of a platelet-rich thrombus. SUN9216 (1 mg/kg) was injected intravenously 30 min after the middle cerebral artery occlusion and the time for reopening of the middle cerebral artery by SUN9216 was monitored for a 60-min period under an operating microscope. In the rats in which thrombolysis was achieved with SUN9216, the size of the cerebral infarction was significantly (P < 0.05) reduced as compared with that in the rats treated with saline and was comparable to the reduction produced by the combination doses. It is concluded that, under the present experimental conditions, endothelin may not be involved in the impaired local cerebral blood flow after thrombolysis.
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PMID:Effect of combination of a tissue-type plasminogen activator and an endothelin receptor antagonist, FR139317, in the rat cerebral infarction model. 777 58

The effect of thrombolytic therapy is well-documented in acute myocardial infarction. In acute cerebral infarction, thrombolytic therapy has been evaluated in small series of patients. The point of thrombolytic therapy is to avoid or reduce ischemic damage of neuronal tissue by rapid arterial recanalization. In thrombolytic therapy of cerebral vascular occlusion, the pathophysiology of reperfusion needs further investigation and documentation. This review describes studies of thrombolysis in embolic stroke using animals embolized by intracarotid injections of blood clots. Vascular occlusion was demonstrated by angiography and measurement of cerebral blood flow. Thrombolytic therapy with recombinant tissue-type plasminogen activator was initiated after varying periods of time. Reperfusion, cellular function, and brain damage were examined by angiography and by clinical and pathoanatomical examination. Based mainly on results from our own investigations, the following theses concerning ischemic stroke were made: (a) Cerebral infarction caused by arterial occlusion is due to delayed, incomplete, or no reperfusion. Spasms, or hemodynamic mechanisms, seem to be of only minor importance. (b) Early thrombolytic therapy in animal models increases the degree of reperfusion and reduces brain damage, clinical deficits, and mortality. (c) Early arterial reperfusion reduces cerebral infarction and related edema. With early reperfusion, the extent of brain damage correlates to the length of the delay from onset of ischemia. (d) Cerebral stunning is caused by arterial occlusion followed by very early spontaneous or induced reperfusion, as neurons temporarily lose their functional capabilities without dying. (e) Multiple embolic microclots in experimental stroke result in more brain damage than a single macroclot, and with clots the extent of brain damage is dependent on the structural composition and volume of emboli. (f) The ability to recanalization in experimental embolic stroke is related to the amount of red cells in the emboli and inversely related to the volume of emboli and to the fibrin content and density of the clots. (g) Infarct-limiting effects in experimental stroke can be obtained by ischemic neuroprotectants or by hypothermia, either alone or with thrombolytic therapy, which then reduces brain damage further.
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PMID:Thrombolytic therapy in experimental embolic stroke. 781 66


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