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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Focal brain ischemia was induced in rats by inserting a silicone rubber cylinder attached to a nylon surgical thread from the common carotid artery into the middle cerebral artery bifurcation. Reperfusion was achieved by removing the cylinder. In the ischemic area, free fatty acids were measured. Arachidonic acid lipoxygenase metabolites: leukotriene C4 (LTC4), and cyclooxygenase metabolites: thromboxane B2 (TXB2), prostaglandin E2 (PGE2) and 6-keto-prostaglandin-F1 alpha (6-keto-PGF1 alpha) were measured during ischemia and after reperfusion. There were five ischemia groups. The rats in these groups were killed 1, 2, 3, 4 or 6 hours after occlusion. In the reperfusion group, rats exposed to 1, 2, 3 and 4 hours of ischemia were killed 5, 4, 3 and 2 hours after reperfusion, respectively. The free fatty acids, which had increased due to occlusion, decreased after reperfusion from 1 hour of ischemia. With 2 or more hours of ischemia, however, the free fatty acids increased after reperfusion, indicating cell membrane destruction. Eicosanoids showed almost the same changes in all groups. The eicosanoid level was high only after 1 hour of ischemia and it stayed low if the ischemia time exceeded 2 hours and after reperfusion. Therefore, we suggested that eicosanoids are not a main cause of tissue damage in the ischemic area after 2 or more hours of ischemia.
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PMID:[Effect of occlusion and reperfusion on free fatty acid levels and eicosanoid metabolism in a rat model of focal ischemia]. 179 94

Content of 5-, 8-, 11-, 12- and 15-monohydroxyeicosatetraenoic acids was markedly increased in blood of patients with cerebral atherosclerosis accompanied by discirculatory encephalopathy and brain infarction. These values were lower in the patients with infarction as compared with healthy people. After tourniquet ischemia of limbs concentration of the eicosatetraenoic acids was altered in blood of patients: in one group the concentration of all the lipoxygenase metabolites of arachidonic acid was increased, in the other group of patients it was decreased. Development of atherosclerosis appears to be related to activation of lipoxygenases and production of monohydroxyeicosatetraenoic acids.
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PMID:[Level of monohydroxyeicosatetraenoic acid in the blood of patients with cerebral blood circulation disorders]. 194 87

Leukotrienes and prostaglandins are formed from arachidonic acid by activation of local phospholipases in pathological conditions such as cerebral ischemia, subarachnoid hemorrhage, cerebral tumors and seizures. These mediators, especially leukotrienes have a very potent vasoconstrictor effect on cerebral arteries. Experimental studies have shown that this effect, by increasing vascular permeability causes vasogenic edema that contributes to the ischemic penumbra. In this study, after developing an experimental animal model simulating the concept of ischemic penumbra in the rat, the levels of leukotriene C and prostaglandin E2 produced in the forebrain were measured and the effects of these mediators in prolonged ischemia were investigated. The results, in the first 4 min of ischemia, showed that the arachidonic acid metabolites, particularly, leukotriene C4, reached a peak in the ischemic cerebral tissue in association with leukocyte accumulation. Later in the 15th min, significant decreases in leukotriene C4 and prostaglandin E2 levels were seen. In the 1st and 4th h, probably due to the stimulation of the relevant enzymes by free oxygen radicals in the ischemic tissue; the levels increase again, returning to control values by the 12th h. It is concluded that the use of lipoxygenase inhibitors and free radical scavengers may be helpful to limit the infarct area in the first 4 h of ischemia.
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PMID:The alterations of leukotriene C4 and prostaglandin E2 levels following different ischemic periods in rat brain tissue. 201 13

The activation and accumulation of leukocytes during inflammatory processes such as that initiated by myocardial ischemia and reflow appear to be major determinants of irreversible tissue injury. Myocardial salvage by dual cyclooxygenase/lipoxygenase inhibitors and selective 5-lipoxygenase inhibitors has suggested a role for lipoxygenase (LOX) products, such as the potent chemotactic factor leukotriene B4, in ischemia-reflow injury. However, many LOX inhibitors are antioxidants and several have been shown to directly inhibit neutrophil function in vitro, thereby questioning the role of LOX products in reperfusion injury. To clarify further the protective mechanism of lipoxygenase inhibitors, we have examined the effects of two nonantioxidant inhibitors, SK&F 86002 and REV-5901, on human neutrophil activation and function in vitro. The antioxidant LOX inhibitor nordihydroguiaretic acid, which served as a positive control, exhibited a concentration-dependent inhibition of N-formyl-methionyl-leucyl-phenylalanine (fMLP) and recombinant C5a-induced neutrophil bipolarization, fMLP-induced upregulation of the adherence glycoprotein Mac-1 (CD11b/CD18), fMLP-induced aggregation and neutrophil adherence to and migration through interleukin-1-stimulated human endothelial monolayers. In contrast, neither SK&F 86002 nor REV-5901 (in concentrations up to 50 microM) had any effect on these functions, nor did they inhibit neutrophil oxidative metabolism (phorbol myristate acetate-induced chemiluminescence). Inasmuch as both of these agents have been observed to reduce myocardial ischemia-reflow injury in vivo, their failure to directly inhibit neutrophil function further supports an important role for chemotactic LOX products in the pathogenesis of reperfusion injury.
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PMID:Comparison of antioxidant and nonantioxidant lipoxygenase inhibitors on neutrophil function. Implications for pathogenesis of myocardial reperfusion injury. 215 49

Ischemia and reperfusion lead to eicosanoid- and neutrophil (PMN)-dependent injury. This study tests the role of ischemia-induced lipoxygenase activity in mediating PMN activation and diapedesis. Anesthetized rabbits (n = 8) underwent 3 hours of bilateral hindlimb ischemia. At 10 minutes of reperfusion, leukotriene B4 (LTB4) levels in femoral venous effluent were 0.49 +/- 0.05 ng/ml compared with 0.04 +/- 0.07 ng/ml in sham-treated animals (n = 10) (p less than 0.05). Intracellular H2O2 production of circulating PMNs assayed flow cytometrically by dichlorofluorescein (DCF) oxidation, increased from a preischemic value of 74 +/- 14 femtomoles DCF/cell to 135 +/- 8 fmol DCF/cell (p less than 0.05). PMNs were treated with phorbol myristate acetate (PMA), 10(-7) mol/L. In contrast to a 162% increase in H2O2 production before ischemia, PMNs at 10 minutes of reperfusion had an enhanced response to PMA of 336% (p less than 0.05). Addition of authentic LTB4 (0.5 ng/ml) to PMN from sham-treated animals led to their activation, manifest by an oxidative burst, 127 +/- 12 fmol DCF/cell, and an enhanced response of 337% to PMA stimulation. To study diapedesis, plasma collected at 10 minutes of reperfusion was introduced into plastic chambers taped atop skin abrasions in rabbits (n = 8). After 3 hours, 1610 +/- 246 PMN/mm3 accumulated and LTB4 levels in blister fluid were 0.83 +/- 0.03 ng/ml, higher than values of 44 +/- 23 PMN/mm3 (p less than 0.05) and 0.04 +/- 0.03 ng LTB4/ml (p less than 0.05) with saline solution and 68 +/- 16 PMN/mm3 (p less than 0.05) and 0.19 +/- 0.02 ng/ml (p less than 0.05) with nonischemic plasma. The introduction of LTB4, 3.3 ng/ml, into the chambers resulted in an accumulation of 536 +/- 352 PMN/mm3 (p less than 0.05). Pretreatment of animals before hindlimb ischemia (n = 5) with the lipoxygenase inhibitor diethylcarbamazine abolished PMN activation (51 +/- 12 fmol DCF/cell) and ischemic plasma-induced diapedesis into the plastic chamber (38 +/- 18 PMN/mm3). Pretreatment of nonischemic animals (n = 13) used for the dermabrasion bioassay with diethylcarbamazine abolished diapedesis into the plastic chambers induced by ischemic plasma (n = 5) (32 +/- 24 PMN/mm3) or LTB4 (n = 3) (36 +/- 28 PMN/mm3). These data indicate that PMN activation after reperfusion of ischemic tissue is mediated by a lipoxygenase product, perhaps LTB4, and that both reperfusion plasma and authentic LTB4 induce diapedesis by stimulating de novo lipoxygenase activity.
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PMID:Ischemia-induced neutrophil activation and diapedesis is lipoxygenase dependent. 215

Several studies have demonstrated that granulocytes accumulate in the intestinal mucosa following ischemia/reperfusion. It has been suggested that leukotriene B4 may be released during ischemia/reperfusion and consequently may promote granulocyte infiltration into the mucosa. The objectives of this study were to determine whether (a) leukotriene B4 is produced in the gut mucosa during ischemia and reperfusion, and (b) inhibition of leukotriene B4 attenuates granulocyte infiltration into the postischemic intestinal mucosa. Isolated segments of cat intestine were subjected to 3 hours of ischemia and 1 hour of reperfusion. Mucosal samples were obtained during baseline, ischemia at 3 hours and reperfusion at 1 hour. Leukotriene B4 production was determined by radioimmunoassay. Tissue-associated myeloperoxidase activity was used to quantitate granulocyte accumulation in the mucosal samples. In untreated animals, mucosal leukotriene B4 concentration was higher at reperfusion compared with baseline levels. The reperfusion-induced increase in mucosal leukotriene B4 was entirely prevented by pretreatment with either nordihydroguaiaretic acid (Sigma Chemical Co., St. Louis, MO) or L663,536 (Merck-Frosst, Montreal, Quebec, Canada), two potent lipoxygenase inhibitors. Both lipoxygenase inhibitors, as well as leukotriene B4 antagonist (SC-41930) significantly attenuated the reperfusion-induced infiltration of granulocytes. These results indicate that leukotriene B4 plays an important role in mediating the granulocyte accumulation elicited by reperfusion of the ischemic bowel.
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PMID:Role of leukotriene B4 in granulocyte infiltration into the postischemic feline intestine. 217 Feb 22

The anti-ischemic effects of nafazatrom (10 mg/kg intraduodenally) have been studied in a canine model of myocardial infarction. Nafazatrom was given 30 min before and 2 h after occlusion of the left anterior descending coronary artery (LAD). Effects were compared with those after intravenous indomethacin (10 mg/kg) treatment. Infarct size was measured at 6 h of coronary occlusion by postmortem tetrazolium staining. Myocardial ischemia was reduced after nafazatrom administration, whether related to total left ventricle (18 +/- 3.3 vs. 30.7 +/- 4.8%; p less than 0.05) or to the LAD vessel area at risk for infarction (51.4 +/- 4.0 vs. 82.5 +/- 4.5%; p less than 0.01). Salvage with nafazatrom occurred in the subepicardial and endomural tissues without lateral protection. Indomethacin had no effects on infarction. The LAD occlusion-induced hemodynamic consequences were reduced at 15 min by nafazatrom and remained unchanged by indomethacin. During the following experimental course, no differences were noted between the groups. At 6 h, blood flow in the nonoccluded circumflex artery increased by 12.6 +/- 3.2 ml/min (p less than 0.05) following nafazatrom treatment. Thus, nafazatrom reduced ischemia by a mechanism unrelated to changes in hemodynamics. Most likely, this was due to 5-lipoxygenase inhibition. This may shift arachidonic acid metabolism to cyclooxygenase products and prevent release of deleterious lipoxygenase products by neutrophils during ischemic injury.
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PMID:Effects of nafazatrom and indomethacin on experimental myocardial ischemia in the anesthetized dog. 241 12

Arachidonic acid metabolites are postulated to play a role in the pathogenesis of cerebral ischemia. In order to test the development of lipoxygenase metabolites of arachidonic acid in cerebral ischemia, we measured free arachidonic acid and slow reacting substance of anaphylaxis (SRS-A) and leukotriene C4 in the brain tissue. Moreover, we studied the influence of inhibitor of SRS-A release on postischemic cerebral edema. Severe forebrain ischemia in rats was induced by the modification of the method described by Pulsinelli and Brierley. Both vertebral arteries were electrocauterized through the alar foramen and then bilateral common carotid arteries were clamped by aneurysmal clips and mean arterial pressure was reduced to 80-90 mmHg. EEG activity was isoelectric throughout the period of carotid clamping. After forebrain ischemia had been maintained for 30 minutes, recirculation was started by removal of the arterial clamps and by increasing blood pressure to the preischemic level. Following the desired ischemic or postischemic periods, the brains were frozen in situ with liquid nitrogen. The brains were then chiselled out during irrigation with liquid nitrogen and stored at -80 degrees C until analysis. The brain extracts were analysed by high performance liquid chromatography for free arachidonic acid, by bioassay using the ileum of guinea pig for SRS-A and by radioimmunoassay for leukotriene C4. Brain water content was calculated with dry weight method. Inhibitor of SRS-A release, tranilast, was given intraperitoneally, 100 mg/kg 30 minutes before induction of ischemia and 50 mg/kg immediately before recirculation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Brain tissue leukotrienes in cerebral ischemia and the effect of inhibitor of SRS-A release on postischemic cerebral edema]. 246 14

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.
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PMID:Effect of cyclooxygenase and lipoxygenase inhibitors on delayed neuronal death in the gerbil hippocampus. 250 15

The aim of our study was to investigate the changes of various biochemical parameters (concentrations of lactate, free arachidonate, cyclo- and lipoxygenase products) in rat brain after ischemia and reperfusion and the effects of pretreatment with the ganglioside derivative GM1-lactone on the same parameters. Ischemia was induced by reversible occlusion of common carotid arteries for 20 min, which included a final 5 min of respiration of 5% oxygen in nitrogen. Reperfusion was obtained by removing the occlusion. Pre-ischemic conditions were obtained on sham-operated animals. Animals were killed by microwave irradiation of their heads. Brain levels of lactate and of free arachidonate were markedly increased after ischemia and returned to normal values at 5 min of reperfusion. Levels of the cyclooxygenase metabolites prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2 were increased after ischemia, whereas levels of the lipoxygenase metabolite leukotriene C4 (LTC4) did not change. After reperfusion, a very marked increase of the cyclooxygenase products occurred but not of LTC4. Treatment with GM1-lactone prevented the elevation of cyclo- and lipoxygenase metabolites especially during reperfusion, with limited effects on lactate and free arachidonate levels.
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PMID:Accumulation of arachidonic acid cyclo- and lipoxygenase products in rat brain during ischemia and reperfusion: effects of treatment with GM1-lactone. 250 87


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