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

Adenosine participates in the coupling of cerebral blood flow to oxygen consumption in the brain during such stimuli as hypoxia, ischemia, and seizures. It has been suggested that it also participates in the regulation of cerebral blood flow during somatosensory stimulation, a condition during which cerebral blood flow and oxygen consumption appear to be uncoupled. Interstitial adenosine was estimated by the microdialysis technique and cerebral blood flow was measured by hydrogen clearance in the hindlimb sensory-motor cortex during sciatic nerve stimulation. Cerebral blood flow increased from 102 to 188 ml min-1 100 g-1 (p less than 0.001) in the cortex contralateral to the stimulated leg without an associated increase in interstitial adenosine (baseline 0.624 microM, stimulation 0.583 microM). Infusion of the adenosine antagonist 8-sulfophenyltheophylline failed to block an increase in cerebral blood flow during central sciatic nerve stimulation, but decreased basal cerebral blood flow (69 ml min-1 100 g-1). These results suggest that adenosine does not mediate changes in cerebral blood flow during somatosensory stimulation, but may participate in the regulation of cerebral blood flow in the basal state.
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PMID:Sciatic nerve stimulation does not increase endogenous adenosine production in sensory-motor cortex. 959 50

Oxygen free radicals generated by leukocytes may contribute to tissue injury after central nervous system (CNS) focal ischemia or trauma. Inhibiting oxygen free radicals has improved outcome in experimental models of these conditions and antioxidant therapy appears promising. We evaluated the ability of a novel antioxidant, OPC-14117, to reduce hydrogen peroxide (H2O2) production by stimulated human polymorphonuclear (PMN) leukocytes and monocytes. Stimulated PMN and monocytes were incubated with several concentrations of OPC-14117 for 20 min and H2O2 production, nmol/1 x 10(6) cells/30 min, was measured. OPC-14117 significantly reduced PMN H2O2 production (P less than 0.001) and monocyte H2O2 production (P less than 0.05). A dose response relationship was observed for both leukocytes, as the 100 microM drug concentration was significantly (P less than 0.05) more effective than the 10 microM concentration. These results demonstrate that OPC-14117 inhibits H2O2 generation by stimulated human leukocytes and support further studies of its effects in disorders such as CNS focal ischemia and trauma, conditions where antioxidant therapy may be beneficial.
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PMID:Inhibition of stimulated human leukocyte hydrogen peroxide generation by a novel antioxidant, OPC-14117. 151 59

Hyperglycemia aggravates brain pathologic outcome following middle cerebral artery (MCA) occlusion in cats. We presently determined if hyperglycemia during occlusion leads to high lactic acid accumulations in the ischemic MCA territory. We measured brain metabolite concentrations in 14 MCA territory sites at 0.5 and 4 h following occlusion in hyper- (20 mM) and normoglycemic (5 mM) cats and correlated these results with previous brain pathologic findings. Hyper- versus normoglycemia during MCA occlusion resulted in significantly higher lactate concentrations in the ischemic territory and more numerous loci with lactates greater than 17 mumol/g. At 0.5 h of occlusion, ATP levels were lower in normoglycemic cats, while at 4 h, ATP was similarly reduced (40%) in both glycemia groups. At 4 h, PCr was more reduced in hyperglycemics secondary to a greater brain tissue acidosis. Carbohydrate substrates at 0.5 h were more markedly depleted in normoglycemics, likely limiting lactate accumulation (34.3% versus only 5.0% of sites in hyperglycemics with glucose less than 0.5 mumol/g). Although lactate was markedly elevated at both 0.5 and 4 h in hyperglycemic ischemic territories, clip release at 4 versus 0.5 h yields a significantly poorer brain pathologic outcome. Correspondingly, intracellular pH, calculated from the creatine kinase equilibrium, was more markedly depressed at 4 than at 0.5 h of occlusion, demonstrating a time-dependent dissociation between tissue lactate and hydrogen ion accumulations. The present findings show that following MCA occlusion (a) hyperglycemia increases the magnitude and topographic extent of marked tissue lactic acidosis, (b) infarct size following 0.5 h of clip release correlates more closely with tissue acidosis than with lactate concentrations, (c) ischemic tissue ATP concentrations correlate poorly with infarct size, (d) normoglycemia limits lactate accumulation during focal ischemia because tissue glucose is depleted, and (e) early during ischemia, tissue buffering or antiport mechanisms may prevent marked increases in intracellular hydrogen ion activity.
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PMID:Hyperglycemic versus normoglycemic stroke: topography of brain metabolites, intracellular pH, and infarct size. 154 94

Two-dimensional proton magnetic resonance (MR) spectroscopic imaging studies were performed of the distributions of the major hydrogen-1 metabolites of choline, creatine, N-acetyl aspartate (NAA) and lactate in normal (n = 6) and subacutely to chronically infarcted (n = 10) human brain. The two dimensions of phase encoding were applied over a 20-mm-thick section of brain tissue that had been selected with a double spin-echo localization method. Normal brain showed bilaterally symmetric metabolite distributions and no detectable lactate. Nine of 10 studies of brain infarction showed substantial decreases in NAA, creatine, and choline in the infarcted area compared with control areas; averaged for all studies, the decreases were 77% +/- 8, 63% +/- 11, and 54% +/- 12, respectively (mean +/- standard error). The decreased metabolite concentrations are probably due primarily to diminished cell density in the infarct. The decrease in NAA was larger than the decreases in choline and creatine. Findings in all of the studies showed lactate in the infarcted tissue and/or ventricles. The continued presence of lactate in the infarct indicates increased anaerobic glycolysis due to ischemia or other factors.
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PMID:Human brain infarction: proton MR spectroscopy. 158 25

Similar to other methods of organ preservation, "spinoplegia" may protect the spinal cord from the effects of oxygen desaturation during aortic cross-clamping. In porcine experiments, spinal cord O2 saturation was studied during intraoperative localization of the blood supply to the spinal cord using hydrogen; division of arteries not supplying the spinal cord; aortic cross-clamping for 60 minutes; and 60 minutes after unclamping. In 5 animals, 120 mL of cold saline solution with lidocaine (100 mg/dL) was infused into the aorta during aortic cross-clamping. During sequential localization, O2 saturation dropped by 40.02% (standard deviation, 20.16%) for T-14 artery testing versus a decrease of 17.27% (standard deviation, 11.88%; p = 0.0075) for L-5 artery segment testing in the control animals and returned to baseline thereafter. During aortic cross-clamping maximal O2 desaturation was 5% of baseline (15.7%; p less than 0.0001), which improved slightly by 30 minutes after clamping (48% of baseline +/- 37.37%; p = 0.048 versus maximum) and then returned to baseline (97.1% of baseline +/- 41%) with unclamping; 5 minutes later, hyperoxygenation occurred with a progressive decline thereafter (68% of baseline +/- 29.3%; p = 0.025, 45 minutes after unclamping versus baseline). The decrease in spinal motor evoked potentials was significantly less (p less than 0.02) in the treated group. Intraoperative hydrogen testing in 8 patients was demonstrated to be safe. It accurately localized reattached arteries, and O2 saturation of the spinal cord fell by 56% (standard deviation, 29%; p = 0.0025) with aortic cross-clamping. We conclude that spinal cord ischemia occurs with aortic cross-clamping in both animals and humans.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Spinal oxygenation, blood supply localization, cooling, and function with aortic clamping. 161 Feb 58

Focal cerebral ischemia was induced in anesthetized macaque monkeys by unilateral middle cerebral artery occlusion. The effect of blood volume expansion by a colloid agent and subsequent exsanguination to baseline cardiac output (CO) on local cerebral blood flow (CBF) was measured by the hydrogen clearance technique in both ischemic and nonischemic brain regions. Cardiac output was increased to maximum levels (159% +/- 92%, mean +/- standard error of the mean) by blood volume expansion with the colloid agent hetastarch, and was then reduced a similar amount (166% +/- 82%) by exsanguination during the ischemic period. Local CBF in ischemic brain regions varied directly with CO, with a correlation coefficient of 0.89 (% change CBF/% change CO), while CBF in nonischemic brain was not affected by upward or downward manipulations of CO. The difference in these responses between ischemic and nonischemic brain was highly significant (p less than 0.001). The results of this study show a profound loss of regulatory control in ischemic brain in response to alterations in CO, thereby suggesting that blood volume variations may cause significant changes in the intensity of ischemia. It is proposed that CO monitoring and manipulation may be vital for optimum care of patients with acute cerebral ischemia.
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PMID:Loss of cerebral regulation during cardiac output variations in focal cerebral ischemia. 162 14

Mesenteric ischemia reflexly activates the cardiovascular system. In addition, mesenteric ischemia and reperfusion generate reactive oxygen species. However, the ability of these short-lived reactive oxygen species to generate cardiovascular reflexes is unknown. We therefore investigated cardiovascular reflexes induced by serosal application of hydrogen peroxide (H2O2) to the gallbladder, stomach, or duodenum in anesthetized cats. Serosal application of hydrogen peroxide (44 mumols) to the gallbladder (n = 14) significantly (p less than 0.05) increased mean arterial blood pressure (MAP) by 37 +/- 6 mm Hg, left ventricular dP/dt by 1,893 +/- 416 mm Hg/sec, heart rate by 6 +/- 1 beats per minute, and systemic vascular resistance from 0.34 +/- 0.01 to 0.42 +/- 0.04 peripheral resistance units. The cardiovascular effects were dose-dependent over a range of 0.4 pmol to 132 mumols H2O2. Celiac and superior mesenteric ganglionectomy abolished H2O2-induced cardiovascular effects. Dimethylthiourea (10 mg/kg), a reactive oxygen species scavenger, significantly (p less than 0.05) attenuated 44 mumols H2O2-induced increases in MAP from 36 +/- 3 to 2 +/- 2 mm Hg. Deferoxamine (10 mg/kg) also significantly attenuated 44 mumols H2O2-induced increases in MAP from 40 +/- 7 to 19 +/- 10 mm Hg, but iron-loaded deferoxamine did not. Aspirin (50 mg/kg) did not attenuate H2O2-induced excitation of the cardiovascular system. These data suggest that H2O2 activates abdominal visceral afferents to reflexly stimulate the cardiovascular system by a mechanism involving hydroxyl radicals. Thus, reactive oxygen species could modulate systemic vascular tone by stimulating abdominal visceral afferents during mesenteric ischemia and reperfusion.
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PMID:Hydrogen peroxide-induced cardiovascular reflexes. Role of hydroxyl radicals. 162 88

The effect of ulinastatin on postischemic brain edema was investigated in adult mongrel cats. Focal brain ischemia was produced by occlusion of the left middle cerebral artery (MCA) through the transorbital approach. Following two hours of occlusion, the brain was reperfused for two hours. In all seven animals of the ulinastatin-treated group, ulinastatin was administered intravenously at a dose of 50000 U/kg before and after occlusion. In the control group, six animals were given only vehicle. Measurements of regional cerebral blood flow (rCBF) were performed before MCA occlusion by the hydrogen clearance method, and then repeated every 30 minutes during and after occlusion. Following two-hour reperfusion, the animals were sacrificed by intravenous KCl injection. Specific gravity of the cortex, where rCBF was measured, was determined by microgravimetric method. In the analysis of specific gravity of the cortex, in which mean rCBF during ischemia was above 15ml/100g/min, no significant difference was found between the ulinastatin-treated and control groups. In the specimen with mean rCBF below 15ml/100g/min during ischemia, cortical specific gravity was reduced remarkably in the control group, while not decreased in the ulinastatin-treated group. The difference was statistically significant between two groups (p less than 0.001). These findings suggest antiedema effect of ulinastatin.
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PMID:[Effect of ulinastatin on postischemic brain edema in cats]. 163 31

To determine the contribution of oxygen-derived free radicals to the changes in microvascular structure and function which follow reperfusion of ischemic myocardium, isolated perfused rat hearts were subjected to 15 or 45 min of global ischemia followed by 5 min of oxygenated reperfusion. Hearts were then fixed by perfusion with glutaraldehyde and perfused with nuclear track photographic emulsion to identify competent capillaries in scanning and transmission electron micrographs. Reperfusion after 15 min caused a significant reduction in the density of competent capillaries in the subendocardial third of the left ventricle, but this reduction was lessened but not eliminated by the addition of 0.61 mmole/liter desferrioxamine, but not by 60,000 U/liter superoxide dismutase plus 60,000 U/liter catalase, to the perfusate. After 45 min of ischemia both interventions prevented the myocyte swelling, endothelial cell changes, bleb formation, and reduction in microvascular lumina characteristic of unprotected reperfusion, but only desferrioxamine significantly improved microvascular competence. This suggests that the hydroxyl radical rather than superoxide and/or hydrogen peroxide has a pathogenic role, although desferrioxamine may have other effects as nonspecific chelator. Postischemic reductions in capillary function also occur in reversibly injured myocardium in the absence of structural abnormality. Preventing postischemic microvascular incompetence has the potential to minimize ischemic cell injury and to enhance repair following myocardial infarction, but it also may increase the risk of hemorrhage from venules.
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PMID:Anti-oxidant therapy improves microvascular ultrastructure and perfusion in postischemic myocardium. 163 71

The role of the intracellular generation of reactive oxygen species in the pathogenesis of ischemia-reperfusion damage of the liver was investigated in two in vivo rat models. Global hepatic ischemia was produced in the left and median lobes for 90 min followed by 60 min reperfusion to the total organ (model A) or only to the ischemic lobes (model B). Although both regimens caused significant rises in serum transaminases, this rise was higher in model B. In neither model was intracellular hydrogen peroxide production nor increased glutathione disulfide in bile found. The activities of various antioxidant enzymes were not affected by ischemia or ischemia-reperfusion. In conclusion, oxygen-free radicals are unlikely to be produced in the cells of rat liver during ischemia-reperfusion.
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PMID:No evidence of intracellular oxidative stress during ischemia-reperfusion damage in rat liver in vivo. 164 74


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