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

Oxygen derived free radicals have been shown to be generated during reperfusion of ischemic myocardium by a variety of approaches including spin trap probes. Three levels of injury have been described for the reperfused heart. Periods of ischemia of only several minutes can trigger lethal arrhythmias on reperfusion. Anti-oxidants including SOD and or catalase, as well as iron chelators reduce the incidence of these arrhythmias in both dog and rat. Xanthine oxidase inhibitors are equipotent with SOD in this model suggesting that xanthine oxidase is the source of the radicals. Periods of occlusion lasting 10-15 minutes produce a recoverable defect in contractility termed "stunning". SOD plus catalase has been shown to reduce the incidence of stunning in a variety of models including the xanthine oxidase deficient rabbit. Neither agent on its own seemed to be effective against stunning in either the rabbit or the dog. Stunning is more difficult to demonstrate in the rabbit heart, presumably due to its lack of xanthine oxidase. Periods of ischemia in excess of 20 minutes will result in some irreversible cell death (infarction) with reperfusion. While studies using histochemical methods suggesting that SOD plus catalase given at the time of reperfusion could limit necrosis in the dog model, histological studies reveal that infarct size was not modified but rather, SOD appears to interfere with the ability of tetrazolium to histochemically discriminate between living and dead cells. While PEG SOD with its extended plasma half life was reported to reduce infarct size in the dog, it was unable to protect the reperfused rabbit heart. To date, none of the scavengers have been proven to limit infarction suggesting that free radicals contribute to arrhythmias and stunning, but do not kill cells in the reperfused heart.
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PMID:Superoxide dismutase therapy for myocardial ischemia. 206 Aug 42

This study evaluated the effect of ischemia-reperfusion (I-R) on pulmonary capillary permeability in isolated rabbit lungs and the roles of xanthine oxidase (XO), aldehyde oxidase (AO), and neutrophils (PMN) in producing this lung injury. Effects of XO and AO were studied by inactivation with a tungsten-enriched diet (0.7 g/kg) and inhibition of XO by allopurinol (100 microM) or AO by menadione (3.5 microM). PMN effects were studied by preventing endothelial adhesion with the monoclonal antibody IB4 (10 microM). Vascular permeability was evaluated by determining the capillary filtration coefficient (Kf,c) measured before and after I-R in all experimental conditions. Reperfusion after 2 h of ischemia significantly increased pulmonary capillary permeability (Kf,c changed from 0.096 +/- 0.014 to 0.213 +/- 0.025 ml.min-1. cmH2O-1.100 g-1), and this increase was blocked by the addition of catalase (50,000 U) at reperfusion (baseline Kf,c was 0.125 +/- 0.023 and 0.116 +/- 0.014 ml.min-1.cmH2O-1.100 g-1). XO inactivation with the tungsten-supplemented diet and XO inhibition with allopurinol prevented the Kf,c increase observed after I-R (0.183 +/- 0.030 to 0.185 +/- 0.033 and 0.126 +/- 0.018 to 0.103 +/- 0.005 ml.min-1.cmH2O-1.100 g-1). Inhibition of AO had no effect on I-R injury (Kf,c 0.108 +/- 0.011 to 0.167 +/- 0.014 ml.min-1.cmH2O-1.100 g-1). Preventing PMN adhesion resulted in significant attenuation of the change in Kf,c associated with I-R (0.112 +/- 0.032 to 0.090 +/- 0.065 ml.min-1.cmH2O-1.100 g-1). We conclude that XO and PMN adherence, but not AO, are involved in the increased capillary permeability associated with I-R.
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PMID:Role of xanthine oxidase and neutrophils in ischemia-reperfusion injury in rabbit lung. 207 95

Protective effects of ionol, o-benzoquinone-2 and ascorbic acid, their influence on the activity of antioxidative enzymes, the level of diene conjugates (DC) and of recovered glutathione in the mitochondrial fraction in the case of ischemic and reperfusion injury of the brain have been investigated. An increase in the activity of the antioxidative system enzymes during the post-ischemic period induced probably by the accumulated products of lipid peroxidation is shown: glutathione peroxidase (EC 1.11.1.9)--by 159%, glutathione reductase (EC 1.6.4.2)--by 26%, catalase (EC 1.11.1.6)--by 79%. This effect was not observed after introduction of antioxidants lowering the DC-level. It is concluded that antihypoxic action of the investigated antioxidants providing the survival of animals not only after the 5 min total circulatory ischemia but also after the 15 min one is caused by their antiradical properties and is not connected with stimulation of activity of enzymes supporting peroxidative homeostasis.
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PMID:[Effect of antioxidants on the status of the antioxidative system in cerebral ischemia and reperfusion injury]. 208 87

Although the specific cause(s) of inflammatory bowel diseases (IBD) has not been identified, one theory suggests ischemia as the early event that occurs in IBD and reperfusion causes sustained release of oxyradicals, leading to inflammation and ulceration. In this study, we have confirmed that H2O2 in the concentration seen during ischemia/reperfusion is primarily responsible for cellular membrane damage in the rat colonic fragments in vitro. Hydrogen peroxide caused a time and dose-dependent increase in 6-keto-PGF1 alpha and TXB2 release. Hydrogen peroxide-stimulated 6-keto-PGF1 alpha release was blocked (50%) by phospholipase A2 (PLA2) inhibitors quinacrine and dimethyleicosadienoic acid at 5 min. Hydrogen peroxide-stimulated 6-keto-PGF1 alpha release was completely blocked by indomethacin, significantly blocked (69%) by nordihydroguiaretic acid, and completely blocked by catalase. Superoxide dismutase and uric acid failed to inhibit H2O2-stimulated 6-keto-PGF1 alpha release. Endogenous catalase inhibitors 3-aminotriazole and sodium azide further enhanced the release of 6-keto-PGF1 alpha stimulated by H2O2 by 29% and 73%, respectively. Xanthine-xanthine oxidase also increased 6-keto-PGF1 alpha release from the fragments by 110%. This release was not inhibited by superoxide dismutase and uric acid, but was completely inhibited by catalase. These studies suggest a direct effect of H2O2 on colonic fragments leading to submicroscopic cellular membrane damage and excess prostanoid production utilizing a PLA2/cyclooxygenase and catalase-sensitive pathway without the formation of toxic hydroxyl ions. The quick release of 6-keto-PGF1 alpha also suggests an early manifestation of H2O2-induced damage in rat colonic fragments.
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PMID:Hydrogen peroxide-induced alterations in prostaglandin secretion in the rat colon in vitro. 209 May 84

Reactive oxygen metabolites have been implicated as important mediators of inflammation-induced intestinal injury associated with ischemia (and reperfusion), radiation, and inflammatory bowel disease. Because the colonic mucosa may be subjected to significant oxidant stress during times of acute and chronic inflammation, knowledge of the oxidant defense mechanisms in the colon is of biologic and potential clinical importance. Therefore, the objective of this study was to quantify the specific activities of superoxide dismutase (SOD), catalase, and GSH peroxidase in the normal human colon. We found low, but significant, amounts of all three enzymes in the mucosa, submucosa, and muscularis/serosa of the human colon. However, the mucosal, levels of SOD (3.6 +/- 0.3 units/mg protein), catalase (11 +/- 3 units/mg), and GSH peroxidase (15.2 +/- 0.8 mU/mg) represented only 8%, 4%, and 40%, respectively, of those values determined for human liver. Colonic epithelial cells derived from mucosal biopsies exhibited significantly higher specific activities for SOD (12 +/- 0.5 units/mg) and catalase (26 +/- 6 units/mg) when compared to whole mucosa, suggesting most of the mucosal activity was associated with the epithelial cells and not the lamina propria. In a comparative study, we found that a human colonic carcinoma cell line (CaCo-2) contained significantly lower SOD (6 +/- 0.5 units/mg) and catalase (6 +/- 0.6 units/mg) activities when compared to colonic epithelial cells. Taken together, our data suggest that: (1) the colonic mucosa is relatively deficient in antioxidant enzymes when compared to liver, and (2) most of the protective enzyme activity is localized within the epithelium and not the mucosal interstitium.
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PMID:Oxidant defense mechanisms in the human colon. 209 May 86

The influence of different drugs on ischemia induced oxygen free radical damage was examined in intestinal tissue of rats by determination of thiobarbituric acid reactive substances (TBARS). Some methodical aspects of this method were considered. Experiments were done with and without the use of polymerized stromafree hemoglobin (PHb) as an additional oxygen carrier. Reversible total occlusion of the superior mesenteric artery was performed for 90 min, reperfusion time was 2.5 hours. Despite higher O2 availability PHb did not increase the TBARS level any further. Superoxide dismutase with catalase; allopurinol; ciprofloxacin; and deferoxamine produced a highly significant reduction of TBARS, even if used together with PHb.
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PMID:Severity of oxygen free radical effects after ischemia and reperfusion in intestinal tissue and the influence of different drugs. 209 68

Isovolumically perfused control and chronic diabetic rat hearts were subjected to 20 min of global ischemia plus 30 min of reperfusion at preischemic flow rates. Recoveries of contractile function during reperfusion were similar in both groups. Addition of arachidonic acid produced profound postischemic dysfunction in nondiabetic hearts (isovolumic minute work = 19 +/- 8 vs. 86 +/- 10% of preischemic levels after 30 min), whereas arachidonic acid had no detrimental effect in diabetic hearts. Arachidonic acid also augmented endogenous prostacyclin release in control hearts (untreated 2.28 +/- 0.23 ng/ml; arachidonic acid 4.07 +/- 0.22 ng/ml) but failed to alter postischemic prostacyclin release in diabetic hearts. The arachidonic acid-induced postischemic dysfunction was significantly attenuated by coadministration of the oxygen free radical scavengers, superoxide dismutase plus catalase, but not by indomethacin. Thus arachidonic acid-induced dysfunction in normal hearts appears to be related, in part, to free radical production. The intrinsic capacity of the heart to synthesize prostacyclin as a result of ischemia and reperfusion does not appear to be impaired by diabetes. In contrast, the arachidonic acid-induced increase in prostacyclin following ischemia is blunted in the diabetic heart. Although chronic diabetic hearts showed increased tolerance to arachidonic acid-induced dysfunction during reperfusion, a defect in prostacyclin stimulation may place the diabetic at greater risk of complications of ischemic reperfusion in vivo by reducing the capacity to adequately respond to the aggregatory and vasospastic actions of increased circulating thromboxane consequent to myocardial ischemia and reperfusion.
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PMID:Arachidonic acid causes postischemic dysfunction in control but not diabetic hearts. 210 41

We hypothesized that xanthine oxidase (XO)-derived hydrogen peroxide (H2O2) contributes to ischemic skeletal muscle injury during reperfusion. We found that after ischemia (3 h) and then reperfusion (4 h) rat gastrocnemius muscles had decreased contractile function following direct stimulation. Three lines of investigation suggested that XO-derived H2O2 contributes to reperfusion injury of ischemic skeletal muscle. First, treatment with dimethylthiurea (DMTU), a highly permeant O2 metabolite scavenger, but not urea, just before reperfusion improved muscle function in legs subjected to ischemia and then reperfusion. Second, gastrocnemius muscles from rats fed tungsten or allopurinol had negligible XO activities and increased muscle function after ischemia and reperfusion. Third, as assessed by measurement of skeletal muscle catalase activity in the presence of aminotriazole, H2O2 was measured during reperfusion of ischemic muscles from untreated or urea-treated rats but not during reperfusion of muscles from rats treated with DMTU, tungsten, or allopurinol.
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PMID:Xanthine oxidase-derived H2O2 contributes to reperfusion injury of ischemic skeletal muscle. 211 Jul 80

The perfused isolated kidney is a partial ischemic system that is characterised by glomerular proteinuria and release of glomerular heparan sulfate. Metabolic changes associated with the levels of glutathione, xanthine oxidase and glyceraldehyde 3-dehydrogenase indicated that oxygen radical metabolites were being produced during the perfusion. We have demonstrated that a mixture of oxygen metabolite scavengers containing mannitol, superoxide dismutase and catalase included in the perfusion medium significantly reduced protein excretion. Similar results were obtained with the administration of allopurinol to the rat 24h prior to kidney removal and allopurinol in the perfusion medium. [35S]Heparan sulfate loss from the glomerulus was totally inhibited by the scavenger mixture. These results suggest that reactive oxygen metabolites may be involved in damage to renal capillaries, specifically to heparan sulfate proteoglycan, which leads to proteinuria as a result of partial ischemia produced during perfusion.
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PMID:The inhibitory action of oxygen radical scavengers on proteinuria and glomerular heparan sulphate loss in the isolated perfused kidney. 214 Dec 55

The objective of this study was to determine whether hydrogen peroxide, iron, and/or hydroxyl radicals play a role in ischemia/reperfusion (I/R)-induced granulocyte infiltration in the feline small intestine and whether a chemoattractant is formed when superoxide or hydrogen peroxide reacts with feline extracellular fluid. In vivo determinations of granulocyte infiltration consisted of measurements of tissue myeloperoxidase activity in either the intestinal mucosa (I/R studies) or dermis (chemotaxis studies), whereas in vitro measurements of granulocyte migration were obtained using a Boyden chamber. Treatment with either catalase or the iron chelator deferoxamine significantly attenuated granulocyte infiltration into the mucosa induced by reperfusion of the ischemic intestine. Two hydroxyl radical scavengers, dimethyl sulfoxide (DMSO) and dimethylthiourea (DMTU), were also evaluated for their ability to modulate I/R-induced granulocyte infiltration. DMTU significantly attenuated the I/R-induced granulocyte accumulation, whereas DMSO had no effect. In other experiments, we were unable to stimulate granulocyte migration with feline plasma exposed to superoxide-generating systems using both in vitro and in vivo models of leukocyte chemotaxis. However, hydrogen peroxide in the presence of either ferrous iron or hemoglobin did significantly increase the chemotactic activity of cat plasma. The results obtained from our studies suggest that either hydrogen peroxide or radical species derived from the interaction of superoxide and hydrogen peroxide with iron elicit I/R-induced granulocyte infiltration in the intestine.
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PMID:Role of oxidants in ischemia/reperfusion-induced granulocyte infiltration. 215 38


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