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

Certain rheological disorders such as enhanced aggregation and reduced deformability of erythrocytes are closely associated with microcirculatory disturbances, decreased tissue oxygen supply and represent a major problem in severely burnt patients [1-4]. Vitamin E (alpha-tocopherol) and vitamin A (retinol) exert an important plasma antioxidant properties against free radical-induced damage [11,12]. They possess chain-breaking properties and act as synergists [13]. Plasma antioxidant capacity may be decreased in severely burnt patients as a result of the enhanced consumption and inadequate restoration of antioxidants in the conditions of activated peroxidative process [14]. Treatment with alpha-tocopherol suppresses lipid peroxidation in blood and therefore improves erythrocyte rheology [15]. Perfluorocarbon emulsions improve microcirculation and rheological blood properties [16-18] and preserve the structure and function of endothelial cells [19]. The very small particle size, low viscosity and high oxygen carrying capacity ensure their penetration into the microvasculature even under conditions of ischemia and acidosis [20, 21]. Perfluorocarbons have been reported to inhibit leukocyte activation and superoxide radical production [22]. The aim of the present study was to examine the antioxidant capacity, free radical mediated damage and erythrocyte aggregation in plasma of rats with thermal skin injury in the early postburn period and to evaluate the effect of treatment with alpha-tocopherol and FC-43 perfluorocarbon emulsion alone and in combination. We might conclude that thermal skin injury in rats reduces the antioxidant capacity, enhances free radical mediated damage and erythrocyte aggregation on the third hour after injury. The combined application of alpha-tocopherol and FC-43 perfluorocarbon emulsion immediately after thermal skin injury in rats increases plasma antioxidant capacity, decreases free radical mediated damage of erythrocytes and suppresses their aggregation on the third hour after the injury.
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PMID:Increased antioxidant capacity, suppression of free radical damage and erythrocyte aggrerability after combined application of alpha-tocopherol and FC-43 perfluorocarbon emulsion in early postburn period in rats. 892 32

Brain ischemia reperfusion causes increased formation of reactive oxygen species (ROS). Activity of the mitochondrial enzyme pyruvate dehydrogenase (PDH) has been shown to undergo a significant decrease following reperfusion of the ischemic tissue. We have examined the effect of a superoxide radical-generating system (xanthine oxidase/hypoxanthine, XO/HX) on the activity of this enzyme. Incubation of PDH in the presence of XO/HX resulted in its inactivation. The degree of the inactivation was dependent on the amount of XO present, which correlated linearly with the concentration of superoxide radical generated by this system. The activity of lactate dehydrogenase, an enzyme resistant to inactivation by ischemia reperfusion, was not affected by this system. Superoxide dismutase partially prevented and catalase exerted a nearly complete protective effect against the inactivation of PDH. Deferoxamine was partially protective. The sulfhydryl protective reagents, dithiothreitol and glutathione, prevented the inactivation of PDH, even though to varying degrees, which implicates sulfhydryl oxidation. A hydroxyl radical-generating system (hydrogen peroxide irradiated with ultraviolet radiation) effectively inactivated PDH. These results demonstrate that PDH is susceptible to damage and inactivation by ROS and point to the involvement of Fenton chemistry and hydroxyl radicals formed through it in PDH inactivation by XO/HX. A similar mechanism may be responsible for the PDH inactivation during ischemia/reperfusion.
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PMID:Reactive oxygen species-mediated inactivation of pyruvate dehydrogenase. 895 77

This study tests the hypothesis that adenosine A2 receptor activation reduces reperfusion injury by inhibiting neutrophils in a canine model of ischemia and reperfusion. In 16 anesthetized, open-chest dogs, the left anterior descending coronary artery was ligated for 60 min and reperfused for 3 hr. An intracoronary infusion of either the selective adenosine A2 agonist CGS-21680 at 0.2 microgram/kg/min (n = 8) or vehicle (n = 8) was started 5 min before reperfusion and discontinued after 60 min. The area at risk was comparable between vehicle-treated and CGS-21680-treated groups (39.6 +/- 4.1 vs. 37.1 +/- 2.5% of left ventricle). Infarction size, determined with triphenyltetrazolium chloride, was smaller in the CGS-21680-treated group than in the vehicle-treated group (15.4 +/- 2.9 vs. 29.8 +/- 2.3% of area at risk, P < .05 vs. vehicle-treated group). CGS-21680 significantly reduced neutrophil accumulation (myeloperoxidase activity) in the nonnecrotic area at risk tissue, compared with the vehicle-treated group (2.12 +/- 0.5 vs. 6.47 +/- 0.6 U/g of tissue, P < .05 vs. vehicle-treated group). In in vitro studies, CGS-21680 reduced platelet-activating factor (PAF)-activated canine neutrophil adherence to the endothelial surface of normal homologous coronary artery segments. Compared with PAF-stimulated neutrophils (188.4 +/- 9.4 adhered neutrophils/mm2), CGS-21680 reduced adherence close to base-line levels (46.6 +/- 5.8 adhered neutrophils/mm2) at concentrations of 10 microM (65.6 +/- 8.2 adhered neutrophils/mm2, P < .05 vs. PAF-stimulated group) and 50 microM (56.6 +/- 4.6 adhered neutrophils/mm2, P < .05 vs. PAF-stimulated group). Superoxide anion production (cytochrome c reduction) by activated neutrophils was reduced by CGS-21680 from 33.8 +/- 5.0 to 8.9 +/- 3.6 nmol/5 min/5 x 10(5) cells (P < .05 vs. PAF-stimulated group). We conclude that specific A2 receptor stimulation with CGS-21680 at reflow reduces reperfusion injury by inhibiting neutrophil-related processes.
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PMID:Adenosine A2 receptor activation attenuates reperfusion injury by inhibiting neutrophil accumulation, superoxide generation and coronary endothelial adherence. 899 10

Although the formation of oxygen-derived free radicals (or reactive oxygen species; ROS) and the release of endogenous opioid peptides (EOP) have been independently reported to be the major arrhythmogenic factors in ischemic hearts, possible relations between these two factors have seldom been investigated. Thus, we studied whether the ROS and EOP were related in the progression of ischemia-induced arrhythmias. Isolated rat hearts perfused in the Langendorff mode were treated with dynorphin A1-13 (kappa EOP receptor agonist), and/or allopurinol (xanthine oxidase inhibitor), before the onset of ischemia induced by ligating the left coronary arteries. Ischemic period lasted for 30 min, during which cardiac rhythms were recorded. At the end of ischemia, hearts were analyzed for the glutathione and ascorbate levels. Allopurinol (100 nmoles/heart) was effective in reducing the severity of arrhythmia (arrhythmia score: Mean +/- SEM 3.00 +/- 0.80 for allopurinol, 5.75 +/- 0.41 for placebo, p < 0.01), while dynorphin (10 micrograms/heart) potentiated the arrhythmia (6.71 +/- 0.52, p < 0.05 vs. placebo). Coadministration of allopurinol and dynorphin was capable of reducing arrhythmia (5.57 +/- 0.65) when compared with the administration of dynorphin alone (6.71 +/- 0.52, p < 0.05). Tissue oxidative stress was evaluated by the concentrations of glutathione (GSH) and ascorbate. Allopurinol did not significantly elevate tissue GSH concentrations (1.46 +/- 0.05 mumoles/g wet wt) in ischemic hearts, while dynorphin alone significantly decreased the GSH concentrations (0.96 +/- 0.08, p < 0.05) when compared with the placebo (1.32 +/- 0.03). The dynorphin-induced GSH decrease cannot be reversed by coadministration with allopurinol (0.90 +/- 0.104). Allopurinol significantly elevated tissue ascorbate levels (0.16 +/- 0.01) when compared with placebo (0.10 +/- 0.01, p < 0.05). Interestingly, dynorphin alone also elevated the tissue ascorbate concentrations (0.16 +/- 0.02). Coadministration of allopurinol and dynorphin further spiked the ascorbate levels (0.28 +/- 0.05, p < 0.01). In conclusion, the results suggested that ischemia-induced arrhythmia mechanisms might involve the formation of superoxide and other ROS, which were probably generated from the release of EOP (or EOP/EOP receptor interactions). Superoxide, the formation of which can be inhibited by allopurinol that exerted antiarrhythmic effect, was probably scavenged by ascorbate in myocardial ischemia. The ROS resulting from EOP/EOP receptor interactions were probably scavenged by glutathione system. Elevated ascorbate levels in dynorphin-treated hearts might result from the compensatory synthesis induced by decreased glutathione levels.
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PMID:The roles of reactive oxygen species and endogenous opioid peptides in ischemia-induced arrhythmia of isolated rat hearts. 910 Dec 52

The mechanisms of hepatic ischemia/reperfusion injury are complicated and multifactorial. This study was designed to examine superoxide generation and neutrophil accumulation in cold ischemic-reperfused rat livers after elimination of Kupffer cells and to determine the role of superoxide/tumor necrosis factor (TNF) interactions. Rat Kupffer cells were eliminated by liposome-encapsulated dichloromethylene diphosphonate injected intravenously. Livers from control and treated rats were isolated and preserved in University of Wisconsin solution (4 degrees C) for 0, 12, and 24 hours and then perfused for 60 minutes with oxygenated Krebs-Henseleit bicarbonate buffer (37 degrees C) by adding neutrophils into the perfusate. Superoxide generation was measured by using real-time chemiluminescence (CL) during perfusion, and neutrophil accumulation was assessed by measuring myeloperoxidase activity in the liver tissue. In the control livers, CL intensity markedly increased on reoxygenation, and after neutrophil infusion it increased again with a lag period of 10 minutes. Total CL intensity and myeloperoxidase activity increased with the duration of cold preservation. TNF release into the effluent perfusate was detectable only after 24 hours of preservation, and lactate dehydrogenase release was high. Elimination of Kupffer cells attenuated CL intensity and TNF and lactate dehydrogenase release and resulted in reduced myeloperoxidase activity. Electron microscopy revealed amelioration of hepatocyte swelling and endothelial cell disruption when Kupffer cells were eliminated. After 24 hours of preservation, superoxide generation was inhibited in the control livers by anti-TNF antiserum, whereas TNF release was not inhibited by superoxide dismutase. These results suggest that TNF induces superoxide generation by Kupffer cells, which mediates neutrophil accumulation and causes cellular injury in the initial phase of reperfusion.
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PMID:Tumor necrosis factor-induced, superoxide-mediated neutrophil accumulation in cold ischemic/reperfused rat liver. 921 59

This study tests the hypothesis that cardioprotection exerted by adenosine A2-receptor activation and neutrophil-related events involves stimulation of ATP-sensitive potassium (K(ATP)) channels on neutrophils during reperfusion. The adenosine A2 agonist CGS-21680 (CGS) inhibited superoxide radical generation from isolated rabbit polymorphonuclear neutrophils (PMNs) in a dose-dependent manner from 17.7 +/- 2.1 to 7.4 +/- 1.3 nmol/5 x 10(6) PMNs (P < 0.05). Pinacidil, a K(ATP)-channel opener, partially inhibited superoxide radical production, which was completely reversed by glibenclamide (Glib). Incremental doses of Glib in combination with CGS (1 microM) did not alter CGS-induced inhibition of superoxide radical generation. CGS significantly reduced PMN adherence to the endothelial surface of aortic segments in a dose-dependent manner from 189 +/- 8 to 50 +/- 6 PMNs/mm2 (P < 0.05), which was also not altered by incremental doses of Glib. Infusion of CGS (0.025 mg/kg) before reperfusion reduced infarct size from 29 +/- 2% in the Vehicle group to 15 +/- 1% in rabbits undergoing 30 min of ischemia and 120 min of reperfusion (P < 0.05). Glib (0.3 mg/kg) did not change the infarct size (28 +/- 2%) vs. the Vehicle group and did not attenuate infarct size reduction by CGS (16 +/- 1%). Glib did not change blood glucose levels. Cardiac myeloperoxidase activity was decreased in the ischemic tissue of the CGS group (0.15 +/- 0.03 U/100 mg tissue) compared with the Vehicle group (0.37 +/- 0.05 U/100 mg tissue; P < 0.05). We conclude that adenosine A2 activation before reperfusion partially reduces infarct size by inhibiting neutrophil activity and that this effect does not involve K(ATP)-channel stimulation.
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PMID:Adenosine inhibition of neutrophil damage during reperfusion does not involve K(ATP)-channel activation. 936 30

Oxygen free radicals may contribute to tissue injury processes in the central nervous system following ischemia or trauma. Recent studies have suggested that inhibition of free radicals improves the outcome in experimental models involving such conditions, and antioxidant therapy appears promising. In the present study, behavioral changes and edema formation in rat cortical contusion model were investigated, and the effects of a superoxide radical scavenger, OPC-14117, were tested. Wistar rats were anesthetized with halothane inhalation. Cortical contusion was induced in the parietal cortex employing a controlled cortical impact device. Immediately following injury induction, OPC-14117 was administered (300 mg/kg, p.o.). Edema formation was assessed in the center and peripheral areas of the contusion by the specific gravity method. Behavioral changes were evaluated by the Morris water maze test and the habituation of exploratory activity. The results revealed that the vehicle-administered control showed progressive edema formation and behavioral deficits following the injury. These changes were significantly attenuated by the OPC-14117 treatment (p < 0.05). Further, OPC-14117 reduced the size of contusional necrosis (p < 0.05). These findings suggest that superoxide free radicals are involved in contusion-induced edema formation, necrosis formation, and behavioral deficits, and that OPC-14117 has a therapeutic potential to prevent secondary cell damage following traumatic brain injury.
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PMID:Antioxidant, OPC-14117, attenuates edema formation and behavioral deficits following cortical contusion in rats. 941 19

The human red blood cell (RBC) is known to be susceptible to oxidant damage, with both structural and functional properties altered consequent to oxidant attack. Such oxidant-related alterations may lead to changes of RBC rheologic behavior (i.e., deformability, aggregability). Two different models of oxidant stress were used in this study to generate superoxide anions either internal or external to the RBC. Our results indicate that generation of superoxide within the RBC by phenazine methosulfate decreases RBC deformability without effects on cell aggregation. Conversely, superoxide generated externally by the xanthine oxidase-hypoxanthine system primarily affects RBC aggregability: the shear rate necessary to disaggregate RBC was markedly increased while the extent of aggregation decreased slightly. Increased disaggregation shear rate (i.e., greater aggregate strength) as a result of superoxide radical damage may adversely affect the dynamics of blood flow in low-shear portions of the circulation, and may also play a role in the no-reflow phenomena encountered after ischemia-reperfusion.
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PMID:Effect of superoxide anions on red blood cell rheologic properties. 943 19

Oxidant injury is considered to be an important mechanism in the pathophysiology of acute renal failure. It has been thought that decrease in extracellular and intracellular fluid and endotoxemia seen in obstructive jaundice may cause an increase in production of oxygen free radicals and impairment in antioxidant defense mechanism. This study is designed to investigate the possible role of oxidant injury in renal failure seen in jaundiced patients. In this study, 28 rats were divided into four groups: Control (C)(N = 7); Renal ischemia (RI)(N = 7); Obstructive jaundice+renal ischemia (OJ+RI)(N = 7); Obstructive jaundice (OJ)(N = 7). All groups were compared with each other according to renal failure findings and enzyme activities, such as Xanthine oxidase (XOD), Superoxide Dismutase (SOD) and Catalase in renal cortex and Glutathione Peroxidase (GSH-Px), in blood at 3rd day after ischemia and reperfusion. Renal failure findings monitored by blood urea and creatinine levels, seemed more evident in OJ+RI than RI group (p < 0.05). When compared with RI, in OJ+RI group, increase in XOD activity at 3rd day was statistically significant [0.259 +/- 0.01 U/g (tissue) and 0.362 +/- 0.03 U/g (tissue) respectively] (p < 0.05). SOD and GSH-Px activities of each ischemic group at 3rd day were decreased compared to non-ischemic groups. This fall was significant (p < 0.05). But there was no statistical difference between jaundiced and non-jaundiced groups. Alterations in catalase activities also had no statistical significance. These findings may suggest that the injury induced by oxygen free radicals at re-oxygenation of tissue after ischemia may also play a role in the pathogenesis of acute renal failure developed in obstructive jaundice.
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PMID:The role of oxygen free radicals in acute renal failure complicating obstructive jaundice: an experimental study. 951 37

Nitric oxide (NO) generation in the rat gastric mucosa during ischemia-reperfusion was measured using an NO-sensitive electrode. Under pentobarbital sodium anesthesia, an electrode was inserted into the submucosa from the serous membrane side in the fundus. After steady-state baseline recording, the celiac artery was clamped for 30 min, and then ischemia-reperfusion was achieved by removing the clamp. The clamping of the celiac artery caused a decrease in blood flow and an increase in NO level in the gastric tissue. Just after the removal of the clamp, the NO level rapidly fell and returned to the baseline level. Administration of NG-nitro-L-arginine methyl ester (an NO synthase inhibitor, 30 mg/kg i.p.) before ischemia significantly attenuated both the increase in NO level during ischemia and the formation of acute gastric mucosal lesions observed after 60 min reperfusion. Administration of superoxide dismutase (a superoxide radical scavenger, 10,000 U/kg i.v.) at the end of ischemia inhibited both the rapid decrease in NO level during the reperfusion and the gastric mucosal erosions. Because NO and superoxide radical produce a highly reactive peroxynitrite, it can be argued that NO has an important pathological role in acute gastric mucosal injury induced by ischemia-reperfusion. Our conclusion was strongly supported by immunohistochemical staining of nitrotyrosine residues, an indication of peroxynitrite formation.
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PMID:Direct measurement of nitric oxide release in gastric mucosa during ischemia-reperfusion in rats. 953 Jan 46


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