Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arachidonic acid is metabolized in endothelial cells to antiaggregatory, vasodilatory prostacyclin (PGI2), and in platelets to aggregatory, vasoconstrictory thromboxane A2 (TxA2). The balance of these two prostanoids is supposed to be involved with thrombogenesis and atherogenesis. Acetylsalicylic acid (ASA) inhibits irreversibly the key enzyme of the synthesis of these prostanoids, i.e. cyclo-oxygenase. Platelets do not synthetize new protein, but endothelial cells do. Because of this, and certain pharmacokinetic characteristics of ASA, it should be possible to shift the balance between PGI2 and TxA2 to the dominance of the former with the proper dose of this drug. Altogether more than 50,000 subjects have volunteered for studies on the effect of ASA in the primary or secondary prevention of myocardial infarction or ischemic stroke. The results show that it is possible to reduce vascular attacks by ASA. Furthermore, ASA has also found to prevent pre-eclampsia. Conclusions on the effect of ASA on the PGI2/TxA2-balance are hampered by uncertainties concerning the measurement PGI2 and TxA2 productions in vivo. It is, however, evident that the doses of ASA used in most trials have been high enough to inhibit partly also the production of PGI2. Whether smaller doses or less frequent administration would be more efficient, remains to be studied.
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PMID:Acetylsalicylic acid and the balance between prostacyclin and thromboxane A2. 224 78

Sudden fissuring of an atherosclerotic plaque has been suggested as the primary trigger of transient spontaneous ischemia in both the coronary and cerebral circulation. Measurements of urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2, as well as results of Aspirin trials, have suggested that episodic platelet activation at the site of this acute vascular lesion is mediated, at least partly, by enhanced thromboxane (TX) A2 biosynthesis. Thus, episodic increases in metabolite excretion have been detected in unstable angina. Aspirin (75-325 mg/day) prevents about one third of all fatal and nonfatal thrombotic events in this setting. That a similar "dynamic" thrombotic process occurs during the early phase of acute myocardial infarction is suggested by thromboxane metabolite measurements and by the results of the ISIS-2 trial showing a similar impact of short-term Aspirin therapy to that seen in unstable angina. Percutaneous transluminal coronary angioplasty is associated with transiently enhanced TXA2 biosynthesis and Aspirin-suppressable periprocedural thrombotic complications. On the other hand, both non-insulin-dependent diabetes mellitus and type IIa hypercholesterolemia are associated with a relatively reproducible and persisting abnormality of TXA2-dependent platelet function. This association is likely to reflect a systemic rather than localized stimulus to platelet activation and a continuous rather than episodic alteration. Low-dose (50 mg/day) Aspirin can largely suppress thromboxane metabolite excretion in both diseases. Thus, low-dose Aspirin and/or selective prostaglandin H2/TXA2-receptor antagonists may be important tools to test the hypothesis that TXA2-dependent platelet activation represents an important transducer of the enhanced thrombotic risk associated with these metabolic abnormalities.
Stroke 1990 Dec
PMID:Thromboxane biosynthesis in cardiovascular diseases. 226 Jan 37

We analyzed the effect of Aspirin on the growth of experimentally induced vascular thickenings in rat carotid arteries. Vascular thickenings were induced by denudation of the endothelium in the left carotid artery with a balloon catheter. Administration of Aspirin-rich food (17.4 g/kg body wt/day) was started 1 week before and continued 2 weeks after injury. Nine rats were used. A control group of equal size received normal food. Sizes of the tunica media, the neointima, and the open vessel lumen were measured on cross sections of carotid segments with the aid of a videomorphometry system. The results show that in the Aspirin group, neointimal lesions are significantly smaller than in the control group (0.14 mm2 versus 0.23 mm2; p less than 0.5). Thickenings of the tunica media are also reduced (0.11 mm2 versus 0.12 mm2; p less than 0.5). It is suggested that Aspirin reduces both medial hypertrophy and neointimal outgrowth in injury-induced atherosclerosis.
Stroke 1990 Dec
PMID:Aspirin reduces the growth of medial and neointimal thickenings in balloon-injured rat carotid arteries. 226 Jan 48

The most common type of cerebrovascular disease is ischaemia or infarction from atherothrombosis or cardiac embolism. Antithrombotic treatment with an antiplatelet agent or anticoagulant assumes a prior clinical classification into categories of transient ischaemic attack (TIA) or minor stroke, acute partial stable stroke, stroke-in-progression, and completed stroke. Aspirin reduces the risk of stroke, myocardial infarction, and death after TIA or minor stroke secondary to atherothrombosis. Aspirin is effective in both sexes at a dose of 300 or 1200 mg/day. Ticlopidine (500 mg/day), a new antiplatelet agent, is more effective than aspirin in preventing stroke and death in patients with TIA or minor stroke. Ticlopidine (500 mg/day) is effective in preventing recurrent stroke, myocardial infarction, or vascular death in patients with completed stroke. Aspirin has not been directly shown to be effective after completed stroke. No clear evidence exists for the use of anticoagulants in atherothrombotic cerebral vascular disease in patients presenting with TIA or minor stroke, acute partial stable stroke, stroke-in-progression, or completed stroke. Anticoagulation for rheumatic valvular heart disease is effective in preventing recurrent embolism. Long-term anticoagulation of patients with mechanical prosthetic valves protects against initial embolism and prevents recurrent embolism. The addition of aspirin (500-1000 mg/day) to warfarin reduces the rate of cerebral embolism from mechanical prosthetic heart valves but is associated with increased bleeding. The addition of dipyridamole (400 mg/day) to warfarin may be more effective than aspirin in reducing the rate of cerebral embolism from mechanical prosthetic heart valves and has fewer bleeding side-effects. Anticoagulation during the hospital phase of myocardial infarction reduces the incidence of systemic embolism/stroke. Long-term anticoagulation of patients after the hospital phase of myocardial infarction reduces the incidence of systemic embolism/stroke, recurrent myocardial infarction and death. Prophylactic anticoagulant treatment of patients with non-valvular atrial fibrillation reduces the incidence of embolism, but the optimal duration of treatment is not known. Immediate anticoagulation of patients with completed cardioembolic stroke is safe and effective in preventing recurrent embolism.
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PMID:Antithrombotic treatment of cerebrovascular disease. 227 90

Thromboxane B2 (TXB2) levels in bleeding time blood and in serum were measured in 13 elderly patients with cardiovascular disease, seven of whom were receiving continuous treatment with low dose acetylsalicylic acid (ASA, 125 mg every second day--250 mg daily) for prevention of stroke. Blood sampling was performed openly, but assays of TXB2 were performed by a blinded investigator. In patients treated with ASA, median serum TXB2-levels were 4% and TXB2-levels in bleeding-time blood were less than 16% of the corresponding levels in patients without ASA (P less than 0.01). The results show that in elderly atherosclerotic patients very low doses of ASA substantially suppress TXB2 formation, not only in serum but also at the site of local haemostasis. The extent of suppression is comparable to that previously reported from young healthy subjects.
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PMID:Low dose acetylsalicylic acid and thromboxane release at the site of plug formation in vivo in elderly patients with cardiovascular disease. 231 26

Aspirin, which is an effective anti-platelet agent, given in the low dosage of 60 to 100 mg per day appears to be beneficial for patients with a history of unstable angina, myocardial infarction, transient ischaemic attacks and stroke.
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PMID:Aspirin and coronary heart disease. Clinical applications. 232 88

Three hundred and thirty one carotid endarterectomies were performed on 279 patients during a period of twenty years from 1965 to 1984. The indication for surgery was transient ischemic attack in 67.4%, stroke in 22.7% and asymptomatic carotid stenosis in 10.0% of the operations. The overall major cerebral complication rate attending the operation was 9.6%. During the last four years' period from 1981 to 1984 the procedure morbidity was 3.6% and there was no mortality. Postoperative complications comprised 31 ipsilateral strokes and one contralateral stroke; the complications occurred during the first 24 hours in 28 cases and on the fourth or fifth day in four cases. Of these patients 11 succumbed to internal carotid thrombosis, one to cerebral infarction without thrombosis and one to intracerebral hemorrhage. The associated factors for major complications were analyzed retrospectively in the light of 32 parameters. Patients of advanced age, patients with type II diabetes mellitus, elevated serum triglycerides, high-grade stenosis or occlusion of the contralateral carotid artery, negative smoking history and those undergoing a second operation proved to be at high risk of early postoperative cerebral complications. These complications can be reduced by intraoperative use of heparin, preoperative ASA treatment and a short clamping time. Also peroperative use of shunt is obviously of benefit.
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PMID:Early cerebral complications in carotid endarterectomy: risk factors. 234 71

Coronary artery disease pathophysiology and platelet physiology are summarized, and the use of antiplatelet drugs in coronary artery disease is reviewed. Aspirin, sulfinpyrazone, and most other nonsteroidal anti-inflammatory agents alter platelet function by inhibiting the activity of cyclooxygenase, an enzyme necessary for the production of prostaglandins. Drugs that inhibit thromboxane synthetase or antagonize thromboxane A2 at the receptor level are under investigation. Prostacyclin and dipyridamole inhibit platelet function by elevating the concentration of cyclic AMP in platelets, but proof of their efficacy is limited. Most clinical trials of antiplatelet drugs in coronary artery disease have been small and of short duration; many have demonstrated short-term benefits, but long-term benefits are less obvious. Retrospective studies of patients before initial myocardial infarction suggest that regular aspirin ingestion may reduce the occurrence of cardiovascular complications. In prospective trials, the benefit of aspirin therapy for primary prevention of coronary artery disease was balanced by an increased likelihood of stroke. For secondary--after initial infarction--prevention of cardiovascular complications, the administration of aspirin and other antiplatelet agents has consistently decreased the rate of nonfatal myocardial infarction, overall mortality, or both. In the Second International Study of Infarct Survival, patients treated with streptokinase plus aspirin showed the greatest reduction in mortality, while each drug alone was associated with significantly lower mortality than placebo. Aspirin may improve clinical outcome in patients with or without previous myocardial infarction or with unstable angina pectoris. The daily dose should not exceed 325 mg. Antiplatelet therapy should not be used in patients at high risk for bleeding.
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PMID:Antiplatelet agents in coronary artery disease. 240 21

Inhibitors of thrombocyte aggregation are generally accepted in the therapy and prophylaxis of ischemic cerebrovascular disease. The frequency of re-infarction, morbidity and mortality after TIA, PRIND and minor stroke is influenced favourably. There are controversial opinions, however, about the usefulness for patients suffering from completed strokes. In patients with progressive stroke, cerebral embolism of cardiac source, or non-infective thrombosis of sinuses or cerebral veins, inhibitors of thrombocyte aggregation are used if anticoagulation therapy is not possible. Additionally, they are applied in cases of infective thrombosis of sinuses or cerebral veins, after termination of anticoagulation therapy, after cardiac valve replacement, and after surgical reconstructions of craniocervical vessels. Acetylsalicylic acid is the clinically best examined substance; its effect--especially in males--was proven by numerous prospective trials. A combined treatment with dipyridamole, sulfinpyrazone or other drugs seems to be unnecessary. A daily dose of not more than 300 to 325 mg acetylsalicylic acid is recommended for prophylaxis after ischemic cerebral events; in connection with that dose severe gastrointestinal side effects are hardly to be expected. Whether even lower doses would yield the same prophylactic effects will have to be clarified by further studies.
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PMID:[Clinical aspects of treatment and preventive treatment with thrombocyte aggregation inhibitors in cerebrovascular diseases]. 251 54

Aspirin inhibits thromboxane and prostaglandin formation in platelets and in vascular cells. It prevents platelet aggregation by irreversible acetylation of cyclooxygenase, a key enzyme in arachidonic acid metabolism. On the basis of its antiplatelet effect, aspirin has been assessed during the past two decades in patients with a history of myocardial infarction, stroke, transient ischemic attack or unstable angina. A meta-analysis of randomized controlled trials of long-term aspirin treatment for the secondary prevention of vascular disease indicated that aspirin (300-1500 mg daily) significantly reduced fatal and non-fatal vascular events. More recently aspirin (160 mg daily) produced a significant reduction in hospital vascular mortality and in non-fatal events in patients with suspected acute myocardial infarction. The combination of aspirin and streptokinase was significantly better than either drug alone. On the other hand, two primary prevention trials of aspirin in healthy doctors did not show any modification of vascular mortality despite an overall reduction of non-fatal myocardial infarction. Resolution of some problems related to the mechanism of action of aspirin and to selection of trial populations will possibly increase the benefit/risk ratio of aspirin treatment for the prevention of vascular disease.
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PMID:Aspirin, platelets and prevention of vascular disease. 251 99


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