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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indomethacin decreases cerebral blood flow. Such an effect in humans might offer the possibility to establish a human model of cerebral ischemia. In the present study the effects of a single oral dose of 100 mg indomethacin were studied in male subjects with quantitative electroencephalography, cerebral blood flow velocity and the memory comparison task as parameters. Twelve healthy male students (age 23.2 +/- 2.6 years) were studied. Before the test day the memory comparison task was performed twice (parallel versions). On the test day baseline recordings of quantitative electroencephalography were obtained, together with measurement of blood flow velocity. Ninety minutes after indomethacin ingestion recordings of quantitative electroencephalography and blood flow velocity were repeated and a parallel version of the memory comparison task was performed. The blood flow velocity decreased to 60% of the initial value; quantitative electroencephalography showed a -0.3 Hz slowing of the alpha peak frequency (p less than 0.01) and a decrease in the relative power of the alpha band (p less than 0.10) without any change in the delta or theta band. The memory comparison task showed an increase of the slope index (p less than 0.05), indicating a deterioration of cognitive functioning.
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PMID:A pharmacological model of cerebral ischemia. The effects of indomethacin on cerebral blood flow velocity, quantitative EEG and cognitive functions. 208 59

Arachidonic acid is liberated from damaged cell membranes during ischemia and is the source of vasoactive prostanoids. In this study, specific drugs that influence AA metabolism were investigated for their effects on brain edema and energy metabolites during ischemia. The agents tested were: methylprednisolone (phospholipase A2 inhibition), indomethacin (cyclooxygenase inhibitor), trapidil (TXA2 synthetase inhibitor), and OP-41483 (prostacyclin derivative). Cerebral ischemia was produced using bilateral common carotid artery occlusion in spontaneously hypertensive rats. Brain water content and concentrations of ATP, pyruvate, and lactate were determined 3 hr after occlusion. Compared with its vehicle, methylprednisolone significantly reduced water content and lactate concentration and maintained high levels of ATP. Indomethacin had no effect on brain water content nor metabolite levels. Trapidil decreased water content and lactate levels and increased levels of ATP and pyruvate. OP-41483 had no effect on water content and lactate, but maintained ATP and pyruvate at high levels. These results indicate that some of the AA metabolites may play an important role in the development of brain edema and in the impairment of energy metabolism.
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PMID:Role of arachidonic acid metabolism on ischemic brain edema and metabolism. 211 11

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.
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PMID:Effect of MCI-186 on brain edema in rats. 250 9

The goal of this study was to determine whether responses of cerebral arterioles to products released by platelets are impaired in stroke-prone spontaneously hypertensive rats (SHRSP). The diameter of pial arterioles was measured during suffusion with adenosine 5'-diphosphate (ADP), serotonin, and the thromboxane analogue U-46619, using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and SHRSP (7-10 months old). Responses of cerebral arterioles to ADP and serotonin were profoundly impaired in SHRSP. ADP (10(-5) M) increased pial arteriolar diameter 17 +/- 3% (mean +/- SE) in WKY and only 4 +/- 1% in SHRSP. Serotonin (10(-5) M) increased pial arteriolar diameter 15 +/- 2% in WKY and, in contrast, reduced the diameter 13 +/- 1% in SHRSP. Nitroglycerin produced a similar dilatation of cerebral arterioles in WKY and SHRSP, suggesting that impairment of dilatation in SHRSP in response to ADP and serotonin was not related to nonspecific impairment of vasodilatation in SHRSP. The thromboxane analogue U-46619 produced a similar constriction of arterioles in WKY and SHRSP. We also examined the possibility that impaired dilator responses of cerebral arterioles in SHRSP in response to ADP and serotonin may be related to production of a cyclooxygenase vasoconstrictor substance. Indomethacin (10 mg/kg i.v.) partially restored dilator responses to ADP and serotonin in SHRSP, without altering responses in WKY. Thus, we speculate that vasoactive substances released by platelets may release a prostanoid constrictor substance from cerebral vessels of SHRSP and thereby predispose SHRSP to cerebral ischemia and, perhaps, stroke.
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PMID:Responses of cerebral arterioles to adenosine 5'-diphosphate, serotonin, and the thromboxane analogue U-46619 during chronic hypertension. 320 60

The effect of indomethacin (3mg/kg IA) preloading on the pathophysiology of a model of acute cerebral ischaemia has been tested. Primates anaesthetised with alpha-chloralose were used. Indomethacin reduced basal blood flow by 39% and reduced CO2 reactivity by 71%. Water content changes of the cerebral cortex and relationships between blood flow and extracellular potassium (Ke), and calcium (Cae) activities have been measured. Indomethacin infusion did not effect the water content of the left side but there was more water in all regions of the right hemisphere which were rendered ischaemic. There water increases were significant for blood flows greater than 5ml/100g/min in exposed areas. There was a significant increase in the flow thresholds for change in Ke and Cae. Possible mechanisms for these changes have been discussed.
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PMID:Modulation of the pathophysiology of primate focal cerebral ischaemia by indomethacin. 706 74

The concentrations of the arachidonic acid metabolites, PGD2, PGF2 alpha and 6-keto-PGF1 alpha, were measured in the cerebral hemispheres of gerbils subjected to unilateral carotid occlusion. Approximately 37 percent of the animals with occlusion had symptoms of cerebral ischemia. In those animals PGD2 and PGF2 alpha levels were elevated in both hemispheres. The levels of 6-keto-PGF1 alpha increased only slightly. There was no change of prostaglandin levels in asymptomatic animals. Indomethacin inhibited the increase in the levels of these arachidonic acid metabolites but did not alter brain swelling as judged by a decrease in specific gravity after 6 hours occlusion.
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PMID:Effect of unilateral common carotid artery occlusion on levels of prostaglandins D2, F2 alpha and 6-keto-prostaglandin F1 alpha in gerbil brain. 721 72

A 10-min cerebral ischemia was induced in rabbits by a combination of vascular occlusion (carotid and vertebral arteries) and systemic hypotension. Cerebral cortex blood flow, cortical pO2, arterial pH, arterial blood gases, arterial pressure and electrocorticogram were recorded before, during and for 4 h after ischemia. Indomethacin (4 mg . kg-1 i.v.) was administered 45 min before or immediately after ischemia. Pretreatment with indomethacin improved cortical reperfusion but did not influence cortical pO2 and electrocorticographic activity. Post-ischemic treatment did not affect the different measurements. Water and electrolyte contents remained unchanged.
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PMID:Recovery from global cerebral ischemia in rabbits: influence of indomethacin. 726 22

Sixty-three mongrel dogs were exposed to 8-10 min. of complete cerebral ischemia with Aortic occlusion balloon catheter and followed by 120 min. of recirculation. The degree and distribution of post-ischemic reperfusion in 11 different cerebral regions were then assessed using radioactive labelled microspheres (15 +/- 3 micrometers). The animals were divided into 3 groups by the administration of drugs as follows: 1) no additional drugs; 2) Indomethacin (selective inhibitor of cyclooxygenase) 4 mg/kg 5 min. after ischemia; 3) Pyridine deriv. (OKY-1580 Na-salt, selective inhibitor of thromboxane synthetase) infusion 100 gamma/kg/min. beginning 5 min. after ischemia. Animals receiving no additional drugs had low cerebral blood flow rates at 120 min. after ischemia especially in basal ganglia and cerebral cortex. Animals receiving Indomethacin did not differ significantly from the no additional drug group. The significant enhancement and redistribution of post-ischemic reperfusion at 120 min. after ischemia occurred in animals receiving Pyridine deriv. with reversal of the state of poor reperfusion. These observations implicate an imbalance of prostaglandin pathways in platelets and blood vessel walls in the genesis of impaired post-ischemic reflow and suggest the usefulness of Pyridine deriv. in the treatment of local vasoconstriction of the brain after total cerebral ischemia.
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PMID:[Cerebral blood flow after total cerebral ischemia in dog (author's transl)]. 733 24

This study was carried out to evaluate the effects of perioperative indomethacin on intracranial pressure (ICP), cerebral blood flow (CBF), and cerebral metabolism. Twenty patients subjected to craniotomy for supratentorial cerebral tumors were anesthetized with thiopental, fentanyl, nitrous oxide, and isoflurane. A PaCO2 level averaging 4.8 kPa (median) was achieved. The patients were randomized to intravenous indomethacin 50 mg or placebo administrated after exposure of the dura. ICP was measured continuously subdurally with a 22-gauge canula connected to a transducer. CBF and the arteriovenous difference of oxygen (AVDO2) were measured twice, before and after indomethacin/placebo administration. A significant decrease in ICP from 6.5 to 1.5 mm Hg (median) was found after indomethacin administration. This decrease was caused by a significant decrease in CBF associated with a significant increase in AVDO2. Indomethacin did not affect the cerebral metabolic rate of oxygen, the arteriovenous difference of lactate, or the lactate/oxygen index, suggesting that indomethacin did not provoke global cerebral ischemia. In the indomethacin group, dura was sufficiently relaxed in eight of nine patients and dura was opened without the occurrence of cerebral swelling. In one patient, mannitol treatment was necessary to prevent dural tightness. In the placebo group, mannitol supplemented with hypocapnia was applied in five patients. These findings suggest that perioperative treatment with indomethacin is an excellent treatment of intracranial hypertension during normocapnic isoflurane anesthesia for craniotomy.
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PMID:Effects of perioperative indomethacin on intracranial pressure, cerebral blood flow, and cerebral metabolism in patients subjected to craniotomy for cerebral tumors. 888 23

Twenty patients subjected to craniotomy for supratentorial cerebral tumours were anaesthetized with thiopental, fentanyl, nitrous oxide, and isoflurane. A PaCO2 level averaging 4.8 kPa was achieved. The patients were randomized to intravenous indomethacin 50 mg or placebo administrated after exposure of the dura. A significant decrease in intracranial pressure from 6.5 to 1.5 mmHg (medians) was found after indomethacin administration. This decrease was caused by a significant decrease in cerebral blood flow associated with a significant increase in the arterio-venous oxygen difference. Indomethacin did not affect cerebral oxygen uptake, arteriovenous difference in lactate or the lactate/oxygen index, suggesting that indomethacin did not provoke global cerebral ischaemia. In the indomethacin group, dura was sufficiently relaxed in eight of nine patients, and dura was opened without the occurrence of cerebral swelling. In the placebo group, mannitol supplemented with hypocapnia was applied in five patients. These findings suggest that perioperative treatment with indomethacin is an excellent treatment of intracranial hypertension during normocapnic isoflurane anaesthesia for craniotomy.
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PMID:[Effect of indomethacin on the intracranial pressure]. 922 82


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