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

The involvements of arachidonic acid metabolites in the development of ischemic brain edema and cerebral energy metabolism were investigated on the experimental ischemia and reperfusion model. The level of arachidonic acid in brain tissue increases especially on the ischemic insult, which is rapidly converted to prostaglandins and leukotrienes after the reperfusion. The drugs which modify the arachidonic acid metabolism were administrated to clarify the effect on ischemic brain edema and cerebral energy metabolism. Male stroke resistant spontaneously hypertensive rats (SHRSR) were subjected to incomplete ischemia for two hours by occlusion of both common carotid arteries with vascular clips, and reperfused for two hours. The drugs used are dexamethasone, indomethacin, trapidil and OKY-046. Indomethacin inhibits cyclooxygenase. Dexamethasone inhibits phospholipases by the production of lipocortin. OKY-046 inhibits thromboxane A2 synthetase. Trapidil inhibits thromboxane A2 synthetase and increases the level of 6-keto-PGF1 alpha. These drugs were administered 18 hours before, just after clipping on (1/2) and off (1/2). Brain water content, cerebral ATP and lactic acid levels were examined. In the saline treated group, the cerebral water content was increased after the reperfusion and reached its maximal level after two hours of the reperfusion. The development of brain edema was prevented by the administration of dexamethasone or trapidil, but not by indomethacin and OKY-046. Administration of trapidil or dexamethasone was found to prevent the decrease in ATP and the increase of lactic acid. In the indomethacin administrated group, only the increase of lactic acid was prevented. 6-keto-PGF1 alpha was high in the trapidil administrated group and low in the indomethacin administrated group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Involvement of arachidonic acid cascade in brain edema and cerebral energy metabolism after reperfusion]. 359 3

The effect of a selective thromboxane (TX) synthetase inhibitor (OKY-046), alone and in combination with a very low dose of aspirin, on the platelet function was studied in healthy and diseased subjects. A single dose of 100 mg OKY-046 was orally administered to patients with ischemic cerebrovascular disease (CVD) and healthy volunteers. TXB2 generation and platelet aggregation were measured before and at 1, 4, 6 and 8hr after dosing. In addition, after the administration of a very low dose of aspirin (0.1-0.25 mg/kg/day) for at least one month, a single dose of OKY-046 was given to CVD patients. TXB2 generation and platelet aggregation were measured in the same manner as OKY-046 alone. The effect of OKY-046 on platelet aggregation induced by arachidonic acid (AA) was different in each subject whereas platelet TXB2 generation was almost completely inhibited in all of the patients and healthy volunteers. OKY-046 had a slight inhibitory effect on collagen induced aggregation. A combination of OKY-046 with a very low dose of aspirin, on the other hand, produced additional inhibition of the platelet aggregation induced by both AA and collagen. The present results suggest that the accumulation and metabolism of cyclooxygenase products that accumulate when TX synthetase is blocked, differ in each subject, additional inhibition is caused by the combined use of TX synthetase inhibitor and a very low dose of aspirin because the very low dose of aspirin partially reduces the proaggregatory cyclooxygenase products that accumulate when TX synthetase is blocked.(ABSTRACT TRUNCATED AT 250 WORDS)
Stroke
PMID:A new approach to antithrombotic therapy--evaluation of combined therapy of thromboxane synthetase inhibitor and very low dose of aspirin. 393 2

Using the rat middle cerebral artery occlusion model, alterations in the eicosanoid synthetic capacity of brain microvessels following ischemia were studied by radiochromatography. Brain microvessels of normal rats predominantly produced hydroxyacids with relatively small amounts of PGD2 and PGE2 from exogenous arachidonic acid. Confirmation that hydroxyacids and prostaglandins were products respectively of lipoxygenase(s) and cyclooxygenase was obtained by experiments using indomethacin and eicosatetraynoic acid. The eicosanoid synthetic capacity of the brain microvessel, especially of hydroxyacids, was significantly enhanced 24 and 72 hours after the onset of ischemia. Because this is the phase of maximum edema in the present model, enhanced eicosanoid production in the brain microvessel may be involved in the mechanisms that underly ischemic brain edema.
Stroke
PMID:Ischemic brain edema following occlusion of the middle cerebral artery in the rat. II: Alteration of the eicosanoid synthesis profile of brain microvessels. 396 53

Most earlier studies of platelet function in stroke patients have been performed in the acute phase and are hampered by diagnostic insecurity. A sample of totally 67 young adults below the age of 55, with ischemic cerebrovascular disease (TIA and minor stroke) were investigated at a late stage after acute disease and compared to 20 healthy controls. Patients with atherosclerotic signs at cerebral angiography had significantly (p less than 0.05) higher platelet factor 3 availability than angionegative patients. Unexpectedly, female patients compared to male patients had significantly (p less than 0.05) larger ADP-release after stimulation with collagen in vitro. Furthermore, when female patients were compared to female controls a significantly (p less than 0.05) increased platelet factor 3 availability was found. The results indicate that platelets in female patients may have an increased tendency to aggregate in vivo. Patients had significantly (p less than 0.01) shortened platelet cyclooxygenase regeneration half times (PRT). This was correlated to high levels of factor VIII related antigen (r=0.59) and high levels of factor VIII biological activity (r=0.67), indicating that platelets may be consumed by platelet adhesion and mural thrombi formation in abnormal vessel walls. PRT appears to be a reliable method to assess platelet function in vivo and to optimize aspirin dose and dose intervals in the individual.
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PMID:A study of hemostasis in ischemic cerebrovascular disease. II. Abnormalities in platelet ADP release, platelet cyclooxygenase regeneration time and platelet factor 3 availability. 681 Apr 97

Rats were subjected to severe incomplete cerebral ischemia followed by recirculation. The levels of several of the cyclooxygenase products of arachidonic acid were measured at 5 and 15 minutes of ischemia and at 30 minutes of recirculation following 15 minutes of ischemia, PGE2 accumulated during the first 5 min. of ischemia and its level declined at 15 min. and returned to control level at 30 min. of recirculation. TXB2, on the other hand, increased during the whole time course of the experiment and at the end of the post ischemic period its level was 5 times higher than control. Treatment of the animals with indomethacin (4 mg/Kg, i.v.) prior to ischemia reduced the levels of these products without altering the pattern of their changes. During the ischemic period the EEG was isoelectric and the mean recovery time of electrical cortical activity after 15 min. of ischemia was 10.4 +/- 3.5 min. in the control rats. The rats which received indomethacin recovered faster (43. +/- 0.9 min) and were more resistant to the induction of ischemia. We suggest that the reversibility of cortical activity may be correlated to the accumulation of TXB2 during ischemia and recirculation, and inhibition of its synthesis might improve the post-ischemic reflow.
Stroke
PMID:The effect of incomplete cerebral ischemia on prostaglandin levels in rat brain. 689 89

Compressed and enteric-coated acetylsalicylate (ASA) tablets have been compared in normal healthy subjects. Plasma ASA and salicylate (SA) were measured by high pressure liquid chromatography (HPLC). Platelet cyclooxygenase activity in vitro was studied by a radiometric technique. Following ingestion of 650 mg of ASA in the form of compressed tablets, cyclooxygenase activity was inhibited 95% within 45 min. Enzyme activity was observed to increase within 8 h and reached 10% of control level by 24 h. The pattern suggests that only circulating platelets are affected by ASA ingestion. Following the administration of 650 mg of ASA as enteric-coated tablets comparable inhibition of cyclooxygenase activity was observed, although the effect was delayed, reflecting the delayed appearance of ASA in the plasma. Return to control levels followed a pattern similar to that observed with the compressed tablet.
Stroke
PMID:Plasma acetylsalicylate and salicylate and platelet cyclooxygenase activity following plain and enteric-coated aspirin. 735 37

We investigated mechanisms by which hypoxia produces relaxation of the aorta and tested the hypothesis that these mechanisms are altered during chronic hypertension. Tension of thoracic aortae from normotensive Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) was measured in an organ bath under control conditions and at two levels of hypoxia. In WKY rats, mild and severe hypoxia produced relaxation of the aortae (precontracted with phenylephrine) by 33 +/- 4% and 82 +/- 3%, respectively (mean +/- SEM). Removal of endothelium or administration of NG-nitro-L-arginine (10(-4) mol/L), an inhibitor of nitric oxide synthase, abolished relaxation of the aortae in response to mild hypoxia but did not affect relaxation during severe hypoxia. Glibenclamide (10(-6) mol/L), an inhibitor of potassium channels, attenuated relaxation of the aortae during mild and severe hypoxia by 49 +/- 16% and 74 +/- 4%, respectively. In SHRSP, mild hypoxia produced little relaxation of the aortae (3 +/- 4%, P < .05 compared with WKY). Indomethacin did not increase relaxation to mild hypoxia in SHRSP, which suggests that a cyclooxygenase-derived contracting factor does not contribute to impaired relaxation. Severe hypoxia relaxed the aortae by 86 +/- 4% in SHRSP, and glibenclamide inhibited this response by 60 +/- 9%. These findings suggest that relaxation of the aorta in response to mild hypoxia in WKY rats is mediated primarily by endothelium-derived relaxing factor, and the response to mild hypoxia is markedly impaired in SHRSP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relaxation of the aorta during hypoxia is impaired in chronically hypertensive rats. 753 13

Coronary atherosclerosis is the process underlying virtually all the clinical manifestations of ischemic heart disease. When ulcer or fissure in the fibrous cap of the atheroma occur, platelet adhesion to subendothelium, aggregation and further platelet recruitment culminate in thrombus formation. These mechanisms are known to be responsible for most cases of acute events in patients with ischemic heart disease. Inside platelets, aspirin blocks the synthesis of thromboxane A2 by irreversibly inhibiting cyclooxygenase. Aspirin is recommended not only for treatment of patients with acute coronary syndromes (unstable angina, acute myocardial infarction), but also for secondary prevention of vascular events in chronic coronary syndromes. Aspirin prevents myocardial infarction in patients with chronic stable angina and reduces mortality, reinfarction and stroke in survivors of an acute myocardial infarction. Aspirin, alone or in combination with dipyridamole, prevents early and late occlusion of aortocoronary vein grafts. It is useful also in patients undergoing coronary angioplasty. Such benefits extend to all patients regardless of age, sex, history of hypertension or diabetes. Higher daily doses (900-1500 mg) are not more effective than lower doses (75-325 mg). Other antiplatelet drugs are not more effective than aspirin, which has the best risk-to-benefit and cost-to-benefit ratios. Ticlopidine is a reasonable alternative for use in preventing vascular events among patients intolerant to aspirin. Warfarin is an effective antithrombotic alternative to aspirin for secondary prevention after a myocardial infarction. However aspirin is easier to administer and follow-up when compared with warfarin. Warfarin should be preferred in high risk patients with left ventricular dysfunction with or without a mural thrombus, and those with associated atrial fibrillation.
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PMID:[Low-dose aspirin in the long-term treatment of the patient with ischemic heart disease]. 763 59

The carotid sinuses, one of the major sites of baroreceptor innervation, are also a common site of atherosclerotic lesions and platelet aggregation. The goal of the present study was to determine whether platelet activation in carotid sinuses causes reflex-mediated changes in renal sympathetic nerve activity and arterial pressure. Rabbit platelets were isolated, resuspended in Krebs' buffer, and activated by thrombin. Injection of activated platelets (3 x 10(8) platelets/mL) into the vascularly isolated carotid sinuses of anesthetized rabbits essentially eliminated sympathetic nerve activity and acutely decreased mean arterial pressure from 126 +/- 5 to 53 +/- 4 mm Hg (n=16; P < .05). Sympathetic activity and arterial pressure returned to control levels over a period of minutes despite sustained exposure to activated platelets. Injection of U-46619, a thromboxane analogue and vasoconstrictor, into carotid sinuses did not alter sympathetic activity or arterial pressure. However, serotonin (5-hydroxytryptamine [5-HT]), which is known to be released from activated platelets, and the 5-HT3 receptor agonist phenylbiguanide mimicked the effect of platelets. Furthermore, the platelet-induced reflex inhibition of sympathetic activity and hypotension were not altered by the cyclooxygenase inhibitor indomethacin but were attenuated significantly by 5-HT receptor antagonists. Platelet activation inhibited sympathetic activity to 5 +/- 2% of control in the absence of antagonists but to only 35 +/- 11 and 76 +/- 4% of control after selective blockade of 5-HT2 and 5-HT3 receptors with ketanserin and MDL-72222, respectively. The results indicate that (1) platelet activation in carotid sinuses triggers reflex inhibition of sympathetic nerve activity and hypotension; (2) the reflex is not caused by carotid vasoconstriction and is not mediated by prostanoids; and (3) the reflex is mediated by 5-HT acting primarily on 5-HT3 and to a lesser extent on 5-HT2 receptors. We speculate that this reflex may contribute to arterial pressure lability and susceptibility to stroke in patients with carotid atherosclerotic disease.
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PMID:Platelet activation in carotid sinuses triggers reflex sympathoinhibition and hypotension. 861 8

Using the acute cranial window technique in rabbits under surgical anesthesia, we tested the vasoactivity of acetylcholine (ACh, 10(-8)-10(-5) M), bradykinin (BK, 10(-8)-10(-5) M), and asphyxia (10% O2, 9% CO2, balance N2) after subchronic pretreatment with cocaine. After repeated administration of cocaine (20 mg.kg-1.day-1 sc x 7 days), the BK-induced dilation of pial arterioles was reduced by 51%. Previous work showed that BK produces dilation of pial arterioles by a cyclooxygenase-dependent oxygen radical-mediated mechanism and that in rabbits the BK-induced dilation is dependent on both vascular and nonvascular cyclooxygenase. Selective blockade of vascular cyclooxygenase, in addition to cocaine treatment, did not produce any greater inhibition of the BK-induced dilation. The dilation in response to ACh and asphyxia was unaltered by cocaine. Levels of cerebrospinal fluid prostaglandins suggest cocaine pretreatment may inhibit cerebral vascular prostaglandin production. Together, cerebrospinal fluid prostaglandin and vasoreactivity data indicate cocaine pretreatment selectively inhibits the vascular cyclooxygenase-dependent mechanism mediating the BK-induced dilation. This decreased response to BK in cocaine-treated rabbits may result from decreased oxygen radical production concomitant with decreased vascular prostaglandin production. Alternatively, oxygen radical scavenging may be increased after cocaine treatment. We speculate that cocaine-induced alterations in cerebrovascular function and metabolism may be related to the increased incidence of stroke reported to occur in human cocaine users.
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PMID:Repeated cocaine administration reduces bradykinin-induced dilation of pial arterioles. 889 54


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