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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, several large randomized trials have clarified the role of various interventions in acute myocardial infarction. There is clear evidence that thrombolytic therapy, aspirin, and beta-blockers reduce mortality. Both aspirin and beta-blockers also reduce reinfarction and stroke. Of the thrombolytic agents, comparative trials have established that tissue plasminogen activator and streptokinase have similar effects on mortality, morbidity, and left ventricular function. There appears to be an increased risk of cerebral hemorrhage with tissue plasminogen activator. The benefits of heparin in conjunction with aspirin and a thrombolytic agent are unclear and, at best, are likely to be modest. Heparin increases the risk of hemorrhagic complications twofold. Although trials of vasodilators conducted before the widespread use of thrombolytic therapy and aspirin have been promising, newer trials are needed to evaluate their effects among patients receiving these agents. The aggregate of all trials of the routine use of calcium antagonists or antiarrhythmic agents indicates that these agents do not improve survival.
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PMID:Routine medical management of acute myocardial infarction. Lessons from overviews of recent randomized controlled trials. 197 22

The effect of an intravenous infusion of recombinant tissue plasminogen activator on hemorrhagic transformation early after middle cerebral artery territory ischemia was studied in an established awake nonhuman primate (baboon) model. Following 3 hours' occlusion of the middle cerebral artery and 30 minutes' reperfusion in each of 30 baboons, a 60-minute infusion of recombinant tissue plasminogen activator (at three doses: Group A, 0.3 mg/kg, n = 6; Group B, 1.5 mg/kg, n = 6; Group C, 10 mg/kg, n = 6) or normal saline (n = 12) was undertaken. The frequency and volume of intracerebral hemorrhage, the volume of infarction, and clinical alterations were determined by computed tomography at 24 hours and 10 days, neuropathology at 14 days, and serial daily neurologic evaluations, respectively. Peripheral (nonintracranial) hemorrhage (Group A, p = 0.46; Group B, p = 0.015; Group C, p = 0.002) and peak plasma tissue plasminogen activator levels varied directly with the dose of recombinant tissue plasminogen activator. Petechial hemorrhagic infarction was a common finding among the 30 baboons. No significant differences in the incidences or volumes of infarction-related hemorrhage were apparent in any group compared with the respective saline-treated baboons. In pooled data, no significant relation between the volume of hemorrhage and the volume of infarction could be established. We conclude that the incidence and severity of hemorrhagic transformation are not related to infarction size and that recombinant tissue plasminogen activator does not increase the incidence or severity (volume) of hemorrhage when given early (less than or equal to 3.5 hours) after the onset of focal cerebral ischemia in this model.
Stroke 1990 Apr
PMID:Hemorrhagic transformation following tissue plasminogen activator in experimental cerebral infarction. 210 75

Fibrinolytic therapy may be effective in the treatment of ischemic stroke, and clinical trials are under way. We evaluated two fibrinolytic agents, an analogue of tissue plasminogen activator (Fb-Fb-CF, the catalytic fragment of the tissue plasminogen activator molecule with a prolonged serum half-life, n = 10) and streptokinase (n = 7), in a rabbit model of embolic stroke. Both agents were given 3 hours after stroke onset, a time relevant to the clinical setting. Fb-Fb-CF was significantly better (p less than 0.04) than saline (n = 7) in restoring blood flow to previously occluded intracranial arteries, but streptokinase was ineffective. Neither fibrinolytic agent was associated with a substantial risk for intracerebral hemorrhagic side effects. Our study demonstrates that Fb-Fb-CF can safely and effectively reperfuse rabbit intracranial arteries 3 hours after occlusion, while streptokinase does not.
Stroke 1990 Apr
PMID:Delayed treatment with a t-PA analogue and streptokinase in a rabbit embolic stroke model. 210 76

We studied thrombolysis in an animal model of embolic stroke to determine the safety of tissue plasminogen activator and streptokinase. We occluded the middle cerebral arteries of 137 rabbits with radiolabeled blood clots and administered tissue plasminogen activator (n = 49), streptokinase (n = 40), or saline (n = 48) at various times after embolization. We assessed the rate of thrombolysis and cerebral hemorrhage 24 hours later. Both drugs were very effective in producing thrombolysis. Compared with saline, streptokinase caused a significant increase in the rate of cerebral hemorrhage (p less than 0.05), but tissue plasminogen activator did not. We conclude that thrombolytic therapy for acute stroke should be safer with tissue plasminogen activator than with streptokinase.
Stroke 1990 Nov
PMID:Incidence of cerebral hemorrhage after treatment with tissue plasminogen activator or streptokinase following embolic stroke in rabbits [corrected]. 212 52

We conducted a randomized, blinded controlled trial to test the efficacy of fibrinolytic therapy with tissue plasminogen activator and urokinase in the treatment of acute embolic stroke. Embolic stroke was simulated in rabbits by injecting three 0.5 x 0.5 mm fragments of autologous arterial thrombus harvested from a traumatized auricular artery. Thirty minutes after embolization the rabbits were blindly treated with tissue plasminogen activator (n = 21), urokinase (n = 20), or 0.9% saline (n = 20). At 6 hours the rabbits were sacrificed, and the cerebral vasculature was inspected for the location and number of emboli. The brain was then cut into 0.5-cm-thick coronal sections and stained with triphenyltetrazolium chloride to define areas of infarction. Treatment with either tissue plasminogen activator or urokinase significantly reduced the number of emboli present in the cerebral circulation (p less than 0.05). The area of ischemic injury was also significantly reduced (p less than 0.05) by acute fibrinolytic therapy with either tissue plasminogen activator or urokinase. However, only treatment with tissue plasminogen activator significantly reduced (p less than 0.05) the incidence of infarction. There was no evidence of intracerebral hemorrhage in any rabbit. Early fibrinolytic therapy improved outcome in this model of acute embolic stroke.
Stroke 1990 Nov
PMID:Effect of intra-arterial tissue plasminogen activator and urokinase on autologous arterial emboli in the cerebral circulation of rabbits [corrected]. 212 53

The frequency of stroke among patients in six recent placebo-controlled trials of thrombolytic therapy for acute myocardial infarction is reviewed. Three trials used streptokinase and three used tissue plasminogen activator as the thrombolytic agent. While thrombolytic therapy greatly reduces the morbidity and mortality of acute myocardial infarction, it increases the rate of intracerebral hemorrhage.
Stroke 1990 Nov
PMID:Stroke in patients treated with thrombolytic therapy for acute myocardial infarction. The thrombosis in myocardial infarction clinical trial and a review of placebo-controlled trials. 212 57

Sixteen clinical centers in two countries have undertaken a prospective open angiography- and computed tomography scan-based safety and efficacy dose-rate finding study of recombinant (two-chain) tissue plasminogen activator (rt-PA) in acute thrombotic and thromboembolic stroke. Preliminary experience with 71 rt-PA treated patients in seven dose-rate groups has demonstrated both partial and complete recanalization, documented by angiography, although a dose response has not yet been achieved. Hemorrhagic infarction has been documented at all dose rates, and dose-rate independent cerebral hematomas have been observed. The study continues at higher dose rates while still remaining within the safety guidelines.
Stroke 1990 Dec
PMID:An open, multicenter trial of recombinant tissue plasminogen activator in acute stroke. A progress report. The rt-PA Acute Stroke Study Group. 212 86

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.
Stroke 1990 Dec
PMID:Tissue plasminogen activator reduces brain injury in a rabbit model of thromboembolic stroke. 212 36

Thrombolytic therapy has become an established procedure in patients with acute myocardial infarction (AMI). However, the aftercare of such patients is still uncertain. A meta-analysis of twenty trials of intravenous or subcutaneous heparin in AMI performed during the prethrombolysis period indicated a significant reduction in mortality, reinfarction, and stroke in treated patients. More recently, a study (SCATI) aimed at investigating the clinical effects of subcutaneous heparin (12.500 U two times daily) in the setting of thrombolytic therapeutical strategy in AMI, showed a lower in-hospital mortality, a trend towards lesser transient ischemic episodes in patients given streptokinase, and no difference in recurrent infarction rate. Ventricular thrombi were markedly reduced by heparin. Anti-platelet drugs were not permitted in the SCATI. In both GISSI 2 (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico) and International tissue plasminogen activator/streptokinase trials, aspirin was a recommended treatment, and subcutaneous heparin was randomized. No difference in mortality was noted in patients given heparin. In GISSI 2 recurrent ischemic episodes were also similar in treated and control groups, whereas embolic events were reduced by heparin. Major bleedings were rare in all trials. In conclusion, subcutaneous heparin is beneficial in AMI: however, the association with aspirin does not add consistent benefits. Heparin is effective in preventing thrombus formation and embolic complications - such effects are not shared by aspirin.
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PMID:Heparin in acute myocardial infarction. 215 Jun 62

The oral administration of the thrombolytic agent urokinase was studied. Its intestinal absorption was demonstrated in dogs by the observation of a prolonged urokinase activity in plasma with a concomitant lytic effect on artificial thrombi after intraduodenal administration. In situ intestine-liver perfusion experiments in dogs revealed that a plasminogen activator, distinct from the administered urokinase--thus presumed to be a tissue plasminogen activator--was liberated into the circulation in association with intestinal absorption of urokinase. Its absorption in men was demonstrated in a cross-over double blind study of oral urokinase on healthy subjects. On the basis of these results a double blind clinical trial of oral urokinase was performed on 101 patients with cerebral thrombosis. The results showed the usefulness of urokinase treatment, particularly in the early phase after the onset of stroke. The clinical effect was influenced by the plasma plasminogen level.
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PMID:Oral urokinase: absorption, mechanisms of fibrinolytic enhancement and clinical effect on cerebral thrombosis. 242 93


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