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

Acute gastric stress ulceration occurs frequently in severely ill patients. Mucosal ischemia is central to the etiology of stress ulceration. The ability of the mucosa to restore continuity when damaged is one of the most important of the local defence mechanisms against injury. The aims of this study were to investigate this restitutive process during stress ulcer formation and to determine the effect of prophylaxis against stress ulceration on gastric mucosal cell kinetics. Nuclear DNA was radiolabeled in vivo with tritiated thymidine, and after autoradiography the position and number of labeled cells along the gastric mucosal gland were determined. Wistar rats were studied immediately and 48 hr after cold restraint stress. The labeling index in the proliferative zone of the gastric mucosa was significantly suppressed immediately after stress (12.58% vs 16.81% for unstressed controls, P < 0.001). This effect persisted for 48 hr after stress (9.89% vs 16.35% for unstressed controls, P < 0.001). Prophylaxis against stress ulceration with cimetidine or allopurinol prevented this suppression of gastric mucosal cell kinetics and promoted early migration of labeled cells towards the surface of the mucosal gland. Allopurinol prophylaxis was associated with migration of mucosal cells immediately following stress greater than that following cimetidine prophylaxis (14.0% vs 9.3% surface layer labeling index, P < 0.01). Allopurinol, a xanthine oxidase inhibitor, reduces oxygen free radical production during ischemia reperfusion injury. These results emphasise the importance of the gastric mucosal defence mechanisms in protection against injury and indicate the role of ischemia in the aetiology of acute gastric stress ulceration.
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PMID:Stress ulceration and gastric mucosal cell kinetics: the influence of prophylaxis against acute stress ulceration. 841 98

We investigated the contribution of scavenging of oxygen free radicals to retinal ion contents during ischemia and reperfusion with the use of superoxide dismutase (SOD, Sigma), allopurinol (Sigma), EGB 761 (extract of Ginkgo biloba, Tanakan, IPSEN, Paris, France) and allopurinol plus EGB 761 in the rat. SOD (15,000 U/kg/day), allopurinol (50 mg/kg/day), EGB 761 (100 mg/kg/day) and allopurinol (50 mg/kg/day) plus EGB 761 (100 mg/kg/day) were administered for 10 days, respectively. Then, the eyes were subjected to 90 min of ischemia followed by 4 and 24 h of reperfusion, respectively. Retinal Na+, K+, Ca2+ and Mg2+ contents were measured by atomic absorption spectrophotometry after the washing out of blood and extracellular fluid from the vasculature. SOD, EGB 761 and the combination of EGB 761 with allopurinol significantly reduced the ischemia/reperfusion-induced Na+ and Ca2+ accumulation and K+ loss in ischemic/reperfused retinal tissue. Allopurinol alone failed to reduce the maldistribution of Na+, Ca2+ and K+ induced by ischemia/reperfusion in the retina. Neither intervention inhibited the cell Mg2+ loss which was observed during ischemia and reperfusion. Despite the responsible mechanisms remaining controversial, many studies confirmed that ischemia/reperfusion could trigger very sudden metabolic, electrophysiologic, morphologic and functional changes. There is general agreement that major ionic shifts are implicated; what triggers these changes is unclear, although many investigators believe that free radicals and oxidant stress may be important.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modification of ischemia/reperfusion-induced ion shifts (Na+, K+, Ca2+ and Mg2+) by free radical scavengers in the rat retina. 844 62

Acute ischemic renal failure is of great clinical importance because of its frequent occurrence and the high mortality it causes. Recent observations indicate that reperfusion has its own dangers because of oxygen-derived free radicals. To study this problem, ischemia was evoked in dogs in one kidney, by clamping the left renal artery for 45 min. This was followed by a 90-min period of reperfusion when diuresis, GFR, PAH clearance and sodium and potassium excretion were studied. Besides a control group (n = 6), the following treatment groups were investigated. Allopurinol (n = 7): 50 mg/kg for two days p.o. and 50 mg/kg in physiological saline infusion during the experiment; a small dose of SOD (n = 6): 0.5 mg/kg in infusion, started 1 min before reperfusion and given continuously for 10 min; and a high dose of SOD (n = 7): 5 mg/kg as above. In the first 15 min following reperfusion, the renal functions significantly worsened in all groups. Later on, the renal functions gradually improved and in the last period after reperfusion, GFR in the ischemic kidney was 64%, cPAH 59%, diuresis 60% and sodium and potassium excretion were 65% and 76%, respectively, of the basal values in the control group. Treatment with free radical scavengers did not cause any considerable changes in the renal functions. In some respects, the worst results were observed with low-level SOD treatment (cPAH, diuresis, as well as sodium and potassium excretion). At the end of reperfusion, there was a significant drop in sodium excretion by the right (intact circulation) kidney of the treated animals.
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PMID:Lack of effect of antioxidant therapy during renal ischemia and reperfusion in dogs. 845 8

We determined that treatment of immature rats with allopurinol at 15 min after cerebral hypoxia-ischemia reduces brain damage. Seven-d postnatal rats were subjected to right common carotid artery ligation followed by 2.25 h of hypoxia (8% O2). At 15 min of recovery in room air, the rat pups received either allopurinol (135 mg/kg s.c.) or saline. Some of the rats (n = 65) were killed at 42 h of recovery for measurement of cerebral hemispheric water content. Other animals (n = 63) were killed at 30 d for morphologic assessment of the severity of damage. In separate rats, we measured the levels of allopurinol and its metabolites in serum and in the brain around the time of peak serum levels. We also determined the effect of allopurinol on rat pup body temperature. Allopurinol reduced the increase in right hemisphere water content and markedly reduced atrophy. No cavitary lesions were seen in the 31 allopurinol-treated rats, whereas 15 of 32 saline-treated rats had cavitary cerebral lesions. Histologic examination confirmed that the allopurinol-treated rats had less brain injury. Serum allopurinol and oxypurinol peaked between 0.5 and 1 h after allopurinol injection. Their peak serum concentrations at 0.75 h postinjection combined was between 360 and 510 microM. Allopurinol did not lower rectal temperature more than 0.04 degrees C. In conclusion, high-dose allopurinol administered at 15 min of recovery from cerebral hypoxia-ischemia markedly reduces both acute brain edema and long-term cerebral injury in immature rats.
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PMID:Allopurinol administered after inducing hypoxia-ischemia reduces brain injury in 7-day-old rats. 847 23

The goal of this study was to test the hypothesis that endotoxin-induced bacterial translocation is the result of a selective decrease in intestinal blood flow that causes an oxidant-mediated intestinal mucosal injury. To accomplish this goal, 116 instrumented rats receiving a nonlethal dose of endotoxin (5 mg/kg IP) or saline were studied. Organ blood flow and cardiac output were measured using the microsphere technique and intestinal permeability was measured both by the blood to luminal clearance of 51Cr-EDTA and by horseradish peroxidase. Cardiac output was higher in the endotoxin-treated group than in the saline group (76 +/- 12 versus 95 +/- 17 mL/min; p < 0.05). Although endotoxin induced a hyperdynamic state, blood flow to the distal ileum and cecum was selectively decreased by 35%-50% (p < 0.01), whereas blood flow to the rest of the intestine, spleen, pancreas, and liver was normal. Furthermore, blood flow to the ileal mucosa was decreased to a greater extent than to the remainder of the gut wall (p < 0.05). Small bowel permeability to 51Cr-EDTA was increased at sites of decreased blood flow (ileum) but not at sites of normal (jejunum) blood flow. Allopurinol, a competitive inhibitor of xanthine oxidase, ameliorated the endotoxin-induced decrease in ileal blood flow as well as the increase in ileal permeability. Thus these studies support the hypothesis that endotoxin-induced mucosal injury is the result of an ischemia reperfusion-mediated injury of the distal small intestine and cecum.
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PMID:Mechanisms of endotoxin-induced intestinal injury in a hyperdynamic model of sepsis. 849 2

The purpose of this study was to determine whether short-term exposure of resistance arterioles to lipopolysaccharide in situ is associated with changes in vasomotor tone. Using intravital microscopy, we found that suffusion of Escherichia coli lipopolysaccharide (3 micrograms/ml) over hamster cheek pouch arterioles for 1 h was associated with a significant immediate biphasic response: vasoconstriction followed by vasodilation (p < 0.05). The former was attenuated by indomethacin, and the latter by SK&F 108566, a selective, non-peptide angiotension II receptor antagonist (p < 0.05). The nitric oxide synthase inhibitor, NG-L-nitro arginine, had no significant effects on lipopolysaccharide-induced responses. Allopurinol, a scavenger of reactive oxygen species, significantly attenuated lipopolysaccharide-induced vasodilation. Acetylcholine- and nitroglycerin-induced vasodilation were significantly potentiated after lipopolysaccharide. These responses were recorded in the absence of any significant changes in systemic arterial blood pressure. Collectively, these data suggest that short-term exposure of the peripheral microcirculation to lipopolysaccharide in situ is associated with an ischemia-reperfusion-like injury. These changes may contribute to end organ failure observed several hours after exposure to lipopolysaccharide.
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PMID:Short-term exposure to lipopolysaccharide is associated with microvascular contractile dysfunction in vivo. 861 41

Glutathione is a low molecular weight tripeptide that is a major intracellular antioxidant, modulates DNA synthesis, and may regulate signal transduction mechanisms. Our previous studies in rats suggested that intracellular stores of glutathione were sensitive to skin ischemia and, therefore, may regulate the early temporal course of wound healing. A 4-cm incision was placed on a rat's back and in vivo wound strength was measured over time. Animals were depleted of glutathione using L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of the enzyme gamma-glutamylcysteine synthetase. Some animals were treated in combination with allopurinol/BSO or with allopurinol alone. The data demonstrated at 4 days that BSO treatment produced a fourfold reduction in glutathione (3.51 +/- 1.78) over baseline (16.15 +/- 2.18) levels and twofold reduction (5.0 +/- 1.1) over untreated sham controls (11.1 +/- 2.3) (P < 0.05). Allopurinol provided no protection to glutathione levels. BSO treatment alone reduced wound burst strength compared to the other groups (P < 0.05). Allopurinol treatment enhanced wound strength over sham controls and BSO groups at 9 days after wounding (P < 0.05). Hydroxyproline content in wounds accumulated faster by Day 4 in the BSO-treatment groups compared to sham controls (P < 0.05), whereas the BSO-treatment groups had lower hydroxyproline levels measured at Day 6 (P < 0.05). These data provide the first evidence that wound healing is related to the temporal course of glutathione metabolism. The effect may not be related to oxidant stress since allopurinol provided enhanced wound burst strength without protecting wound glutathione levels.
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PMID:Delayed repair: the role of glutathione in a rat incisional wound model. 863 33

This study determined the role that oxygen-derived free radicals played in the production of gastric injury in rats challenged orally with concentrated ethanol or subjected to vascular compromise. In the ethanol study, rats were pretreated with a variety of free radical scavengers or enzyme inhibitors prior to exposing the stomach to 100% ethanol. At sacrifice, the degree of macroscopic damage to the glandular gastric mucosa was quantified. In separate studies, the effects of ethanol on gastric mucosal levels of enaldehydes (malondialdehyde and 4-hydroxynonenal) were examined as an index of lipid peroxidation. Superoxide dismutase and catalase pretreatment were without benefit in reducing injury in our ethanol model, excluding potential contributory roles for the superoxide anion or hydrogen peroxide, respectively. Dimethyl sulfoxide and desferoxamine were likewise without protective capabilities, eliminating a role for the hydroxyl radical. Allopurinol, a xanthine oxidase inhibitor, provided no protection under acute conditions, even though partial protection was noted when administered chronically. Further, enaldehyde levels were not increased over control levels in alcohol-exposed mucosa, indicating no enhanced lipid peroxide formation. In contrast, in animals in which ischemia to the stomach was induced followed by reperfusion, marked gastric injury was observed in combination with enhanced enaldehyde levels. Prevention of enaldehyde formation by a 21-aminosteroid concomitantly prevented injury induced by ischemia-reperfusion. These findings support the conclusion that ischemia-reperfusion injury to the stomach is an oxygen-derived free radical process whereas ethanol-induced injury clearly involved some other process. Although allopurinal was partially protective against ethanol damage when administered chronically, observations in other models of injury suggest that this action is independent of its inhibitory effect on xanthine oxidase.
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PMID:Gastric injury induced by ethanol and ischemia-reperfusion in the rat. Differing roles for lipid peroxidation and oxygen radicals. 865 47

We tested the hypothesis that gram-negative bacteremia (GNB) and brief (30 min) reductions in the hepatic O2 supply by low-flow ischemia differentially modulate tumor necrosis factor-alpha (TNF-alpha) gene expression owing to sequence-specific activation of cyclooxygenase vs. complement (C) pathways. Buffer-perfused Sprague-Dawley rat livers (n = 82) were studied over 180 min after intraportal 10(9) live E. coli serotype 055:B5 (EC) or 0.9% NaCl (NS) at t = 0. Compared with EC and NS controls receiving constant-flow perfusion, sequential GNB and ischemia/reperfusion (I/R) were studied in EC + 30 I/R and NS + 30 I/R livers, in which 30 min of ischemia (I) beginning 0.5 h after EC or NS was followed by 120 min of reperfusion (R). This sequence was reversed in 30 I/R + EC and 30 I/R + NS groups. Bacterial clearance, bioactive and antigenic TNF-alpha, prostaglandin E2 (PGE2), and hepatic O2 uptake and performance were serially assessed. Venous TNF-alpha increased in EC controls to peak at 155 +/- 29 U/ml after 180 min (P < 0.001 vs. NS controls) as did hepatic TNF-alpha mRNA. Both TNF-alpha transcripts and protein levels were markedly attenuated in EC + 30 I/R (P < 0.001 vs. EC) despite equivalent EC clearance by Kupffer cells. Indomethacin (10(-5) M) decreased I/R-induced PGE2 secretion and restored TNF-alpha to control levels. In contrast, TNF-alpha levels in 30 I/R + EC perfusates exceeded those of EC + 30 I/R livers (P < 0.05) and were indistinguishable from EC controls. Allopurinol pretreatment but not heat inactivation of C or infusion of soluble human complement receptor type 1 inhibited TNF-alpha production in 30 I/R + EC organs. These results identify a novel sequence-dependent interaction whereby hepatic O2 deprivation after GNB downregulates TNF-alpha via generation of cyclooxygenase metabolites, whereas ischemia preceding GNB increases cytokine expression via reactive O2 species but not C activation.
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PMID:Bidirectional effects of hepatic ischemia/reperfusion on E. coli-induced TNF-alpha gene expression. 876 13

One of the most important mechanisms in the production of ischemic damage after replantation surgery is the rise of oxygen free radicals during revascularization of ischemic tissues. Free radicals produce damage in the cell membranes (lipoperoxydation). This occurs not only in muscle tissue, but also in endothelial cells, with a consequent increase of local edema and the risk of compartment syndrome. This study attempted to interrupt the ischemic-reperfusion injury process in ischemic rat hindlimbs. Complete ischemia was induced for different numbers of hours (3, 6, 9, 12 hr) in four groups of rats (24 animals in each group). Allopurinol, an oxygen free radical scavenger, was tested in solution, 12.5 mg/kg b.w., in half the studied animals (n = 12). Collected data showed an increase (mean value: 0.60 nM/mg 3 hri 0.90 nM/mg at 6 hr; 0.80 nM/mg at 9 hr; 0.89 nM/mg at 12 hr; mean value in nonischemic muscle = 0.526 nM/mg) in lipoperoxides (NS between treated/untreated groups, p > 0.05) and high tissue pressure values in the posterior compartment of the ischemic rat hindlimbs. Allopurinol reduced the pressure values (p < 0.05 in Groups 1-3; p < 0.1 in Group 4), but was not effective in reducing lipoperoxides in skeletal muscle.
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PMID:The role of allopurinol in preventing oxygen free radical injury to skeletal muscle and endothelial cells after ischemia-reperfusion. 890 44


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