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

Recently, attention has been drawn to the possibility that excitatory amino acids (EAAs) may play an important role in the pathogenesis of hypoxic-ischemic neuronal injury. Exaggerated release of EAAs and excessive stimulation of N-methyl-D-aspartate (NMDA) receptors and other EAA receptors have been suggested to contribute to neuronal death in ischemia and anoxia. A number of in vitro and in vivo experimental studies have shown that EAA-receptor antagonists exert a protective effect on the brain after cerebral ischemia. Because neurons are in close apposition to small intracerebral vessels, synaptically released EAAs might also regulate small blood vessel function. With the use of quantitative television microscopic observations, in vivo studies were undertaken on pial arterioles of rats. Perivascular administration of cumulative doses (10(-7)-10(-2) M) of L-glycine, L-glutamate, L-aspartate, and NMDA on the pial microvessels resulted in concentration-dependent constriction of pial arterioles (5-30% decreases in diameter) and cerebrovasospasm; the relative order of potency was aspartate > NMDA > glycine > glutamate. High concentrations of EAAs often resulted in rupture of postcapillary venules. No amine or opiate antagonist or cyclooxygenase inhibitor prevented or attenuated the effects of these putative EAAs. EAA-induced constriction and spasm of pial arterioles as well as rupture of venules could, however, be blocked by the noncompetitive NMDA-receptor antagonist MK-801 and by Mg2+. MK-801 also produced a concentration-dependent relaxation on normal pial arterioles. These results are compatible with the idea that a specific NMDA-receptor complex (RC) exists in rat cortical microvessels, which subserves vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of excitatory amino acids in regulation of rat pial microvasculature. 830 37

Post-ischemic metabolism of arachidonic acid by cyclooxygenase results in the elaboration of numerous eicosanoids and in the generation of free radicals. Accordingly, the effect of cyclooxygenase inhibition by ibuprofen on post-ischemic eicosanoid production and delayed neuronal death was evaluated in Wistar-Kyoto rats subjected to incomplete forebrain ischemia. In control (C) and ibuprofen-treated groups (n = 5 each), pre- and post-ischemic eicosanoid production in the caudate nucleus (CN) and dorsal hippocampus (HPC) were evaluated by microdialysis. The ibuprofen-treated animals were given ibuprofen, 15 mg/kg i.v., prior to insertion of microdialysis probes. Forebrain ischemia was induced by bilateral carotid artery occlusion (BCAO) for 10 min with simultaneous hypotension to 35 Torr. The concentrations of thromboxane B2 (TxB2), 6-keto-PGF1 alpha and PGF2 alpha in the microdialysate were measured by radioimmunoassay. In two additional concurrent groups of rats (n = 10 each), neuronal injury in the HPC, CN and cortex (parietal, temporal and entorhinal regions) was evaluated histologically three days after 10 min of forebrain ischemia with and without pre-ischemic ibuprofen administration. In the control microdialysis group, levels of TxB2, 6-keto-PGF1 alpha and PGF2 alpha increased in both CN and HPC after probe insertion. These probe related increases were substantially reduced in the ibuprofen group. After ischemia and reperfusion in the control group, the levels of TxB2 and PGF2 alpha increased in both CN and HPC. Levels of 6-keto-PGF1 alpha increased in the CN but not in the HPC. The administration of ibuprofen substantially reduced post-ischemic TxB2 and PGF2 alpha levels in both CN and HPC and decreased 6-keto-PGF1 alpha levels in the CN. The results of these initial microdialysis studies left the possibility that, in the ibuprofen group, the reduction in eicosanoid levels after probe penetration might have influenced the subsequent post-ischemic eicosanoid production. Therefore, in an additional group of animals (n = 5), ibuprofen was administered after probe insertion. Only PGF2 alpha levels were measured in this group. Increased levels of PGF2 alpha comparable to the original control group were detected after probe penetration. Nonetheless, after ibuprofen administration, the pre- and post-ischemic levels of PGF2 alpha were again significantly reduced. In the histologic evaluation groups, overall neuronal injury was significantly less in the ibuprofen treated animals. This protective effect of ibuprofen was most clearly evident in the CA3 sector of the HPC.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of ibuprofen on regional eicosanoid production and neuronal injury after forebrain ischemia in rats. 834 24

Leukotriene C4 (LTC4) and prostaglandin E2 (PGE2) are the 5-lipoxygenase and cyclooxygenase metabolites of arachidonic acid (AA). They constrict blood vessels and enhance vascular permeability inducing vasogenic edema that may hurt the ischemic penumbra after cerebral ischemia and reperfusion. Nordihydroguaiaretic acid (NDGA) is known as the most potent inhibitor of 5-lipoxygenase in different tissues. Furthermore, it has considerable inhibitory activity against cyclooxygenase. In this study, after developing a global ischemic model in the rat, the levels of LTC4 and PGE2 in the forebrain were measured, following different reperfusion periods after 10 min ischemia including 8 rats for each reperfused group. Sham operations were performed for each corresponding control group (n = 8). AA metabolites were then correlated with neuropathological findings. In the combined reperfused groups both metabolites increased significantly when compared with 10 min, ischemic group (P < 0.05). In the 8 min reperfused group, PGE2 and LTC4 increased significantly compared with each corresponding control group (P < 0.005). These mediators also increased to high levels compared with the 4 min reperfused group (P < 0.05, P < 0.005). PGE2 and LTC4 were reduced significantly at the 15th and 60th min of reperfusion compared with the 8 min reperfused group (P < 0.05, P < 0.005). NDGA (0.1 mg/kg) reduced both metabolites in the 8 min reperfused group significantly (P < 0.05). Brain cortex specimens were taken for light and electromicroscopical investigations. No significant differences were noted between the structural changes in the 4, 8 and 15 min of reperfusion and NDGA administered groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of nordihydroguaiaretic acid on leukotriene C4 and prostaglandin E2 production following different reperfusion periods in rat brain after forebrain ischemia correlated with morphological changes. 841 14

During the last decade intensive work on the relationships between the liver and the arachidonic acid cascade has greatly expanded our knowledge of this area of research. The liver has emerged as the major organ participating in the degradation and elimination of arachidonate products of systemic origin. The synthesis in the liver of arachidonate products derived from the cyclooxygenase, lipoxygenase and cytochrome P450 system pathways has been demonstrated. The participation of leukotriene B4 and cysteinyl-leukotrienes as mediators of liver damage and the possible therapeutic usefulness of prostaglandins (PGs) in acute liver injury has attracted the interest of clinicians. This article reviews the essential features regarding the role of arachidonate metabolites in liver disease and specially focuses on the cytoprotective effects on the liver displayed by PGE2, PGE1, PGI2 and synthetic PG analogs in experimental models of liver damage induced by ischemia-reperfusion injury, carbon tetrachloride, bacterial lipopolysaccharide and viral hepatitis and on the possible mechanisms underlying liver cytoprotection in these experimental models. The therapeutic usefulness of PGs in clinical practice is critically analyzed on the basis of available evidence in patients with fulminant hepatic failure and primary graft nonfunction following liver transplantation.
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PMID:Liver cytoprotection by prostaglandins. 841 74

The effects of flavone (2-phenyl-1,4-benzopyrone), a modulator of the cytochrome P-450 monooxygenase system, on myocardial postischemic reperfusion recovery were examined in the present study. Left ventricular functional recovery was evaluated in isolated, crystalloid-perfused rabbit hearts after 2 hours of modestly hypothermic (34 degrees C) global ischemia. Four groups (n = 8 in each group) were studied and compared: a vehicle control group, a second group pretreated with flavone (8 x 10(-6) mol/L) before ischemia, a third group pretreated with flavone followed by SKF 525-A (1.7 x 10(-5) mol/L), an inhibitor of cytochrome P-450, and a fourth group pretreated with flavone followed by indomethacin (1 x 10(-6) mol/L), an inhibitor of cyclooxygenase. At 15, 30, and 45 minutes after reperfusion, recovery of left ventricular developed pressure in the control group averaged (mean +/- standard deviation) only 2.60% +/- 12.7%, 35.5% +/- 15.0%, and 42.9% +/- 13.5% of baseline, respectively. In the flavone-treated group, recovery was significantly better, averaging 67.7% +/- 10.7%, 73.9% +/- 9.3%, and 73.6% +/- 7.6% of baseline at the same time periods. Recovery of peak positive rate of pressure rise in the control group averaged 27.4% +/- 15.2%, 38.6% +/- 19.2%, and 45.4% +/- 18.6% of baseline at 15, 30, and 45 minutes of reperfusion, respectively. In the flavone-treated group recovery values were significantly higher, averaging 67.8% +/- 9.6%, 77.3% +/- 8.5%, and 77.0% +/- 9.0% of baseline. End-diastolic pressures were significantly lower in the flavone-treated group compared with the control group at all reperfusion time points. Myocardial oxygen consumption was significantly higher in the flavone-treated group at 30 and 45 minutes of reperfusion, as well. The improvement resulting from flavone infusion was abolished completely by SKF 525-A, providing support for the interpretation that the effects of flavone were mediated through the cytochrome P-450 system. The cyclooxygenase inhibitor indomethacin midly attenuated the effects of flavone pretreatment, suggesting that the effects of flavone were only minimally related to metabolites of cyclooxygenase. We conclude that pretreatment with flavone represents a promising approach to myocardial protection that may be due to modulation of the myocardial cytochrome P-450 system.
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PMID:Flavone improves functional recovery after ischemia in isolated reperfused rabbit hearts. 844 32

The susceptibility to ventricular arrhythmias under the conditions of cardiac ischemia and reperfusion was investigated in the Langendorff heart preparation of rats fed for eight weeks a standard chow enriched with 2% of pulverized wild garlic leaves. The isolated hearts were perfused with a modified Krebs-Henseleit solution. The incidence of ventricular fibrillation (VF) during 20 min occlusion of the descending branch of the left coronary artery (LAD) was significantly reduced in the wild garlic group as compared to untreated controls (20% vs 88%). The same holds for the size of the ischemic zone (33.6% vs 40.9% of heart weight). In the reperfusion experiments (5 min after 10 min ischemia), ventricular tachycardia (VT) occurred in 70% of the wild garlic group vs 100% in untreated controls and VF in 50% vs 90%. The time until occurrence of extrasystoles, VT or VR was prolonged. No significant alterations in cardiac fatty acid composition could be observed. Although the prostacyclin production was slightly increased in hearts of the wild garlic group, inhibition of cyclooxygenase by acetylsalicylic acid (ASA; aspirin) could not completely prevent the cardioprotective effects suggesting that the prostaglandin system does not play a decisive role in the cardioprotective action of wild garlic. Furthermore, a moderate angiotensin converting enzyme (ACE) inhibiting action of wild garlic was found in vitro as well as in vivo that could contribute to the cardioprotective and blood pressure lowering action of wild garlic. Whether a free radical scavenging activity of wild garlic is involved in its cardioprotective effects remains to be established.
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PMID:Cardioprotective actions of wild garlic (allium ursinum) in ischemia and reperfusion. 845 76

The influence of an intake of garlic powder (1%--corresponding to Kwai/Sapec--added to a standard chow for a 10-week period) on the susceptibility to ventricular arrhythmias under ischemia and reperfusion was investigated in the isolated rat heart (Langendorff preparation) perfused with a modified Krebs-Henseleit solution. The incidence of ventricular tachycardia (VT) and fibrillation (VF) after ligation of the descending branch of the left coronary artery (LAD) (20 min) was significantly reduced in the garlic group as compared to untreated controls (VT: 0% vs. 35.5%; VF: 50% vs. 88%). The size of the ischemic zone was significantly smaller (31.7% vs. 40.9% of total heart tissue). The reperfusion experiments (5 min after 10 min ischemia) revealed similar results (VT: 50% vs. 100%; VF: 30% vs. 90%). The time until occurrence of extrasystoles and VT or VF was prolonged in most cases, and the duration of arrhythmias was abbreviated. No significant alterations in cardiac membrane fatty acid composition could be found. Inhibition of cyclooxygenase by acetylsalicylic acid (ASA) caused a moderate increase in arrhythmias and ischemic zone in the garlic group as well as in untreated controls under the conditions of the present experiments. Thus, it seems that the prostaglandin system does not play a predominant role in the cardioprotective action of garlic. The significance of free radical scavenging activity of garlic for its antiarrhythmic effects has to be established.
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PMID:Cardioprotective actions of garlic (Allium sativum). 845 43

In ischemic organs, arachidonic acid (AA) metabolites and mostly prostaglandins (PGs) have been found to be released in high amounts. The mechanism for this AA metabolism activation and its physiological implications are not clear. Because endothelial cells are an important source of PGs and because they seem to be very rapidly affected by ischemia, we developed an in vitro model where human endothelial cells were submitted to hypoxia. An important specific activation of phospholipase A2 was observed during hypoxia, which was concomitant with a rise in cytosolic calcium concentration. Endothelial cells synthetize in normal conditions as a mean 1.42, 1.00, 7.69, and 26.92 ng/mg proteins of, respectively, PGE2, PGD2, PGF2 alpha, PGI2. An important increase of about five- to ninefold in the synthesis of the four PGs was observed during hypoxia, which followed the same kinetics as the PLA2 activation. This increase in PG synthesis was sensitive to cyclooxygenase inhibitors. During reoxygenation, PG synthesis decreased back to the basal level of resting cells, suggesting that cells were able to recover their homeostasis after hypoxia. These observations indicate that endothelial cells exposed to oxygen deprivation are a major source of PGs and could contribute to the high amounts of PG released in vivo in ischemic organs.
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PMID:Stimulation of prostaglandin synthesis by human endothelial cells exposed to hypoxia. 847 19

The effect of 2-mercaptopropionylglycine (MPG), a potent free radical scavenger, on ischemia/reperfusion-induced tissue oxidation in isolated perfused rat lung was investigated. The isolated lung, continuously ventilated with 95% oxygen, was subjected to 1 h global ischemia followed by 1 h reperfusion with or without the presence of an antioxidant. In ischemic/reperfused lungs, there was a significant increase in protein oxidation (carbonyl formation) and lipid peroxidation (thiobarbituric acid reactive substances) to 10.7 nmol/mg protein and 176 pmol/mg protein, respectively, at the end of reperfusion. MPG administered at 6 mg/kg body wt intravenously to the rats prior to isolation of lung reduced protein oxidation by 65% and lipid peroxidation by 40%. An additional effect was noted when MPG was also added to the perfusate (0.275 mg/ml) during reperfusion. Pretreatment with dimethylthiourea (DMTU) or addition of desferal to the perfusate also significantly reduced the protein oxidation of lung ischemia/reperfusion. The addition of DMTU or desferal with MPG showed no additive effect. However, eicosatetraynoic acid (100 microM), a cyclooxygenase and lipoxygenase inhibitor, added with MPG reduced ischemia/reperfusion-induced lipid peroxidation by 80%, which was significantly greater than the protective effect exhibited by MPG alone. The oxidative stress on the lung tissue components was also demonstrated by a decrease in the sulfhydryl content of "end ischemic" lungs; MPG pretreatment maintained the sulfhydryl level at the control level in ischemic lungs. The results indicate that MPG at relatively low and non-toxic concentrations can markedly inhibit the oxidation of tissue sulfhydryls, soluble protein, and lipids associated with ischemia/reperfusion injury of the lung.
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PMID:Inhibition of lung tissue oxidation during ischemia/reperfusion by 2-mercaptopropionylglycine. 851 17

Despite the known effectiveness of anti-inflammatory therapy in reducing reperfusion injury, no studies to date involve the use of anti-inflammatory therapy in reducing ischemia-reperfusion injury in fasciocutaneous flaps. Dexamethasone (a phospholipase A2 inhibitor) and specific cyclooxygenase and lipoxygenase inhibitors (indomethacin and BW755C) were administered to rats with ischemic island groin (fasciocutaneous) flaps. Significant improvement in ischemic flap survival was found with dexamethasone and BW755C. The mode of action of dexamethasone was not specifically investigated in our study; however, it may suppress neutrophil function and reduce ischemia-reperfusion injury in its shared ability with BW755C to reduce the formation of leukotrienes. Dexamethasone could be applied in the clinical setting to reduce ischemic flap loss by attenuating the systemic inflammatory response to reperfused ischemic-damaged tissue.
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PMID:Reducing ischemia-reperfusion injury in rat island groin flaps by dexamethasone and BW755C. 852 85


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