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

The ability of low-dose aspirin to irreversibly inhibit platelet-dependent cyclooxygenase provides a biologic mechanism to explain why this drug may decrease the risk of thrombotic cardiovascular events. Observational epidemiologic studies, both case-control and cohort, have suggested that aspirin might reduce the risk of cardiovascular disease by approximately 20 to 30%. An overview of 25 randomized trials of aspirin among individuals with a history of prior cardiovascular disease demonstrated that those receiving aspirin experienced a significant 25% reduction in the occurrence of "important vascular events," an endpoint that combines nonfatal myocardial infarction (MI), nonfatal stroke, and cardiovascular death. There were also significant 32% reductions in subsequent nonfatal MI, 27% reductions in nonfatal stroke, and 15% reductions in vascular mortality. Thus, individuals with a history of MI, stroke, transient ischemic attack, or unstable angina clearly benefit from aspirin. The Second International Study of Infarct Survival (ISIS-2) sought to determine if benefits would accrue if aspirin was given within the first 24 hours of suspected evolving MI. The aspirin group experienced a significant 23% reduction in 5-week vascular mortality compared with those receiving placebo. Aspirin was also associated with significantly fewer reinfarctions and strokes. Thus, among those with suspected evolving MI, aspirin significantly reduces the risk of reinfarction, stroke, and vascular mortality. These analyses indicate that aspirin is of proven value in the therapy of most patients who have survived MI, stroke, or unstable angina, as well as those evolving a suspected MI.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aspirin in chronic cardiovascular disease and acute myocardial infarction. 218 44

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

Prostaglandin manipulation has been shown to improve pulmonary dysfunction in animal models of acute respiratory distress syndrome. Using our previously reported porcine model of Pseudomonas-induced respiratory failure, we examined the therapeutic effects of a vasodilating prostaglandin, PGE1, and a reversible cyclooxygenase inhibitor, ibuprofen. Forty-two animals were randomized to seven groups: I--ibuprofen; II--PGE1; III--ibuprofen + PGE1; IV--Pseudomonas + ibuprofen; V--Pseudomonas + PGE1; VI--Pseudomonas + ibuprofen + PGE1; VII--Pseudomonas. Ibuprofen significantly improved pulmonary vasoconstriction, pulmonary hypertension, and hypoxemia, as well as increased survival slightly. PGE1 had no effect on pulmonary dysfunction, but prevented the rise in systemic vascular resistance that occurred in untreated, infected animals and animals treated with ibuprofen alone. Combination therapy improved stroke volume index, a measure of nonpulmonary organ function.
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PMID:Ibuprofen plus prostaglandin E1 in a septic porcine model of adult respiratory distress syndrome. 249 56

Cerebral microvessels isolated from perfused, adult murine brain produce a compound with the chromatographic properties of a monohydroxyeicosatetraenoic acid when incubated with arachidonic acid or stimulated with calcium ionophore A23187. The formation of this arachidonic acid metabolite is not reduced in the presence of the cyclooxygenase inhibitor ibuprofen, but it is abolished by the lipoxygenase inhibitor nordihydroguaiaretic acid. Analysis by gas chromatography combined with chemical ionization and electron impact mass spectrometry of reduced and nonreduced derivatives of the metabolite, indicate that the compound is 12-hydroxyeicosatetraenoic acid. Fractions of isolated microvessels enriched with capillaries produce 2.1 times more 12-hydroxyeicosatetraenoic acid per microgram of protein than do fractions of microvessels enriched with arterioles. These studies confirm that brain microvessels can produce 12-hydroxyeicosatetraenoic acid and strongly suggest that cerebral endothelia are the primary source of microvessel-derived 12-hydroxyeicosatetraenoic acid. They further suggest that in brain injury, the liberation and accumulation of arachidonic acid in cerebral tissues may lead to the production of 12-hydroxyeicosatetraenoic acid within microvessels. The 12-hydroxyeicosatetraenoic acid formed in this way may mediate some of the blood-brain barrier and cerebrovascular dysfunction that occurs following stroke, brain trauma, or seizures.
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PMID:Brain microvessels produce 12-hydroxyeicosatetraenoic acid. 250 50

The purpose of our study was to examine whether cyclooxygenase and lipoxygenase inhibitors ameliorate delayed neuronal death in the hippocampal CA1 sector in Mongolian gerbils after 5 minutes of forebrain ischemia. Gerbils were injected intraperitoneally with cyclooxygenase inhibitors piroxicam and flurbiprofen or with lipoxygenase inhibitors AA-861 and BW-755C. Seven days after ischemic insult, the animals were perfusion-fixed, and the neuronal density in the hippocampal CA1 sector was estimated. The average neuronal density in unoperated normal gerbils was 247 +/- 9/mm (mean +/- SEM). In ischemic gerbils with vehicle administration, the average neuronal densities were 13 +/- 2, 14 +/- 2, 13 +/- 2, and 13 +/- 1 for piroxicam, flurbiprofen, AA-861, and BW-755C, respectively. The average neuronal densities in ischemic gerbils treated with 1.5 and 10 mg/kg piroxicam and 1.5 and 10 mg/kg flurbiprofen were 13 +/- 2, 194 +/- 9, 19 +/- 5, and 143 +/- 12, respectively. In ischemic gerbils treated with 15 and 100 mg/kg AA-861 and 30 mg/kg BW-755C, the average neuronal densities were 12 +/- 1, 13 +/- 1, and 14 +/- 2, respectively. At their higher doses, both piroxicam and flurbiprofen significantly (p less than 0.01) ameliorated delayed neuronal death in the hippocampal CA1 sector. Our results suggest that cyclooxygenase products play an important role in the development of delayed neuronal injury after cerebral ischemia.
Stroke 1989 Jul
PMID:Effect of cyclooxygenase and lipoxygenase inhibitors on delayed neuronal death in the gerbil hippocampus. 250 15

We studied the effects of acetylcholine and calcium ionophore A23187 on human basilar artery rings. Among 11 arteries, both agents produced significant relaxations in five, A23187 but not acetylcholine caused a response in six, and neither agent was effective in four. After rubbing off the endothelium, the relaxations induced by both agents were significantly attenuated. Indomethacin (a cyclooxygenase inhibitor) and AA861 (a specific inhibitor of 5-lipoxygenase) did not but SKF525A (an inhibitor of cytochrome P450-dependent monooxygenase) did significantly inhibit the acetylcholine-induced relaxation in human basilar arteries. On the other hand, AA861 inhibited while neither indomethacin nor SKF525A had any effect on the A23187-induced relaxation. Our results suggest that different mechanisms may be involved in acetylcholine and A23187-induced relaxations in human basilar arteries.
Stroke 1989 Sep
PMID:Endothelium-dependent relaxation of human basilar arteries. 250 8

We induced brain edema in 72 rats by injecting 5 microliters of 3.0% wt:vol polyvinyl acetate into the left internal carotid artery, producing permanent embolization in the left cerebral hemisphere, which developed ipsilateral brain edema reproducibly. Edema was assessed 24 hours after embolization by determining the brain water content and the sodium and potassium concentrations. In this model, the free radical scavenger MCI-186 at 1.0 and 3.0 mg/kg i.v. prevented brain edema in a dose-dependent manner. At 3.0 mg/kg i.v., MCI-186 significantly reduced water content by 1.5% and improved the sodium-potassium balance to within the normal range in the embolized left hemisphere. Dexamethasone at 1.0 mg/kg i.v. did but at 3.0 mg/kg i.v. did not significantly inhibit the development of brain edema. Indomethacin at 4.0 mg/kg i.p. had no effect on brain edema. We suggest that the cyclooxygenase metabolites of arachidonic acid liberated from neuronal cell membrane phospholipids are not likely to be involved in the pathogenesis of permanent brain edema induced by polyvinyl acetate. Our results suggest that MCI-186 attenuates brain edema by suppressing the production of lipoxygenase metabolites, including free radicals or lipid peroxides, and that it may prove valuable for the treatment of brain edema associated with cerebral ischemia.
Stroke 1989 Sep
PMID:Effect of MCI-186 on brain edema in rats. 250 9

Pial arterioles on the surface of the mouse brain were observed in vivo under a chamber with a glass window. When placed under the window, calcium ionophore, acetylcholine, and previously acidified sodium nitrite each dilated the arterioles. If the cyclooxygenase inhibitors indomethacin or acetylsalicylic acid were first placed in the chamber, subsequent dilation of the arterioles by calcium ionophore was reduced to essentially zero. Similar blockade of cyclooxygenase failed to significantly reduce dilation by acetylcholine or sodium nitrite. We have previously shown that dilations by calcium ionophore and acetylcholine were endothelium dependent. Our present experiments show that the endothelium-dependent mechanism for dilation by calcium ionophore is cyclooxygenase dependent, while that for acetylcholine is not. This implies that, in pial arterioles, the endothelium-derived relaxing factor for acetylcholine differs from that for calcium ionophore. This agrees with data from other microvascular beds.
Stroke 1989 Oct
PMID:Calcium ionophore and acetylcholine dilate arterioles on the mouse brain by different mechanisms. 250 75

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

Platelet activating factor, a potent inducer of in vivo platelet activation and thrombosis, has been shown to be excessively active in acute ischemic stroke patients. Therefore, we studied the effect of aspirin/dipyridamole therapy in inhibiting platelet activating factor-induced platelet activation in acute ischemic stroke patients, 23 taking aspirin/dipyridamole and 21 untreated. Aspirin/dipyridamole-treated patients failed to show suppression of platelet activating factor-induced platelet aggregation even though collagen-induced activation was inhibited, suggesting that platelet activating factor acts by cyclooxygenase-independent mechanisms. Failure to suppress cyclooxygenase-independent mechanisms of platelet activation may explain the limited usefulness of current antiplatelet therapy, aspirin in particular, in stroke prevention. The role of selective platelet activating factor antagonists both in isolation and combined with aspirin needs to be investigated for their usefulness in the treatment and prevention of ischemic stroke.
Stroke 1989 May
PMID:Effect of therapy on platelet activating factor-induced aggregation in acute stroke. 271


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