Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of hypothyroidism on ischemic acute renal failure was studied in rats. Ten days after thyroidectomy with parathyroid reimplantation, rats underwent right uninephrectomy followed by occlusion of the left renal artery for 60 min. Plasma creatinine was lower in thyroidectomized than control rats 24 hr after ischemia; 1.3 +/- 0.5 vs. 3.2 +/- 0.6 mg%; P less than 0.05. Twenty-four hours after ischemia, inulin clearance was higher in thyroidectomized than control animals (0.40 +/- 0.06 vs. 0.17 +/- 0.03 mliter/min; P less than 0.01), despite an initially lower inulin clearance in thyroidectomized animals (0.81 vs. 1.1 +/- 0.07 mliter/min; P less than 0.05). Administration of the antithyroid drug prophylthiouracil for 14 days also resulted in lower plasma creatinine after ischemia. Kidneys from thyroidectomized animals showed less histologic damage 24 hr after ischemia. Renal cortical content of the lipid peroxidation product malondialdehyde was increased less in thyroidectomy than control kidneys after 60 min ischemia plus 15 min reflow (0.08 +/- 0.02 vs. 0.42 +/- 0.1 nmole/mg protein; P less than 0.005). Renal cortical glutathione content was higher in thyroidectomized animals by approximately 36%, 650 +/- 46 vs. 479 +/- 32 nmole/mg protein (P less than 0.02). In normal rats, glutathione infusion also increased renal cortical glutathione content and resulted in lower plasma creatinine 24 hr after renal artery ischemia. Therefore, hypothyroidism resulted in functional and histologic protection against injury after ischemia. Post-ischemic renal lipid peroxidation was reduced in thyroidectomized animals, perhaps the result of increased scavenging of reactive oxygen species (oxygen free radicals and H2O2) by glutathione.
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PMID:Hypothyroidism protects against free radical damage in ischemic acute renal failure. 374 32

The radical anions of molecular oxygen reduction, superoxide (O2), hydrogen peroxide (H2O2), and hydroxyl radical (OH), have been implicated in a number of disease processes, including ischemic bowel injury. This report evaluates the effect of superoxide dismutase (SOD), catalase (CAT), dimethyl sulfoxide (DMSO), selenium treatment, and selenium deficiency on bowel integrity and survival in experimental intestinal ischemia in rats. Ischemic bowel injury was produced in 204 male Sprague-Dawley rats (wt 90 to 100 g) by a one-minute occlusion of the superior mesenteric artery (SMA) with a microaneurysm clip. Experiment I treatment animals (n = 20) received 2.5 mg/kg SOD dissolved in Ringer's lactate, and control animals (n = 71) received Ringer's lactate alone. Experiment II treatment animals (n = 16) received 1 cc of 100% DMSO gavage, and control animals (n = 11) received no treatment. Experiment III treatment animals (n = 17) received 25 mg/kg CAT dissolved in phosphate buffered saline, and control animals (n = 11) received nothing. Experiment IV treatment animals (n = 14) received 300 micrograms of sodium selenate by gavage dissolved in deionized water, and control animals (n = 15) receiving nothing. Experiment V treatment animals (n = 20) were raised from 35 to 50 g size on a selenium deficient diet, and control animals were raised (n = 20) on a normal rat chow diet, until they weighed 100 g when ischemia was induced. At seven days, survival, incidence of bowel perforation or necrosis, and length of survival were compared in each experiment between control and treatment groups using chi 2 analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Superoxide: a critical oxygen-free radical in ischemic bowel injury. 609 60

Evolutionary pressure induced by the release of O2 into the environment has necessitated the development of a group of mechanisms to deal with the toxic free radical byproducts of oxidative metabolism. The complete reduction of O2 to H2O2 involves the addition of four electrons which can occur univalently resulting in a series of toxic intermediates or quadrivalently by the mitochondrial cytochrome oxidase system, which avoids these reactive intermediates. Free radical mechanisms have been associated with a large number of disease states including inflammation, irradiation-induced injury and ischemia. The site of free radical generation, that is whether the generation of radical species is predominantly extracellular or intracellular, may determine to a degree, the types of macromolecular and cellular damage which result. A classification of diseases in which radical generating processes may play a role is presented in the hope that it may aid in the understanding and treatment of these diseases.
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PMID:An approach to free radicals in medicine and biology. 626 28

Previous studies have demonstrated that reactive oxygen species are involved in ischemic injury. The present work was undertaken to determine in vivo the role of xanthine oxidase in the oxygen free radical production during rat liver ischemia and to examine the activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) during the same period. Our results indicate a 4-fold increase in xanthine oxidase activity between 2 and 3 hours of normothermic ischemia, in parallel with a decrease in cell viability. Moderate hypothermia delays both events. Under the same conditions, the activity of oxygen radical scavenging enzymes remains unchanged. Moreover, we have compared in vitro the susceptibility of isolated liver cells to an oxidative stress induced by O2.-, H2O2 and .OH. Our results reveal that endothelial cells are much more susceptible to reactive oxygen species than hepatocytes, probably because they lack H2O2-detoxifying enzymes. These findings suggest that xanthine oxidase might play a major role in the ischemic injury mainly at the level of the sinusoidal space where most endothelial cells are located.
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PMID:Deleterious effects of xanthine oxidase on rat liver endothelial cells after ischemia/reperfusion. 748 47

Activation of cardiac sympathetic afferents leads to excitatory cardiovascular reflexes and pain during myocardial ischemia. We hypothesized that cardiac sympathetic afferents are activated by reactive oxygen species produced during ischemia and reperfusion. Single-unit nerve activity of 55 afferents was recorded from the left paravertebral sympathetic chain (T1-T4) in cats anesthetized with alpha-chloralose. Receptive fields of all afferents were located on the right or left ventricle. Mechanical and chemical sensitivities of each afferent ending were evaluated by von Frey hairs, cardiac distension, and local application of bradykinin (BK, 142 pmol) or H2O2 (7.5-15 mumol) to the receptive field. Thirty-one afferents (56%) were responsive to bradykinin (BK), H2O2, and ischemia (2 or 10 min). Deferoxamine (Def, 10-100 mg/kg), dimethylthiourea (DMTU, 10-100 mg/kg), or iron-loaded Def (10 mg/kg) were employed to evaluate the role of H2O2 and hydroxyl radicals (.OH) in activating these afferents (10A delta and 21C fibers) during ischemia and reperfusion. Treatment with the nonspecific scavenger DMTU (n = 10) significantly diminished the increase in discharge activity evoked by ischemia and reperfusion. Treatment with Def also significantly attenuated the responses during ischemia and reperfusion. Thus reactive oxygen species, particularly .OH, activate a group of cardiac sympathetic A delta- and C-fiber afferents during myocardial ischemia and reperfusion and may play an important role in mediating cardiovascular sympathetic reflex responses and/or pain transmission.
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PMID:Ischemia- and reperfusion-sensitive cardiac sympathetic afferents: influence of H2O2 and hydroxyl radicals. 757 32

Pyruvate (PYR) supplementation protects myocardium from ischemia reperfusion injury. This study was designed to characterize and quantify the mechanism underlying this protection: specifically whether this ability resides in PYR's metabolic effect or in its antioxidant effect. Isolated perfused rat hearts (n = 6/group) were subjected to 15 min of equilibration (EQ), 25 min of ischemia, and 10 min of reperfusion (RP). Glucose was the sole metabolic substrate (Control) or was supplemented with PYR (5 mM) during (a) EQ only (PYREQ group), (b) RP only (PYRRP group), or (c) EQ and RP (PYREQ-RP group). Left ventricular developed pressure (DP) and +/- dP/dt were recorded throughout the experiment. ATP concentrations and intracellular pH were determined by 31P NMR spectroscopy. Myocardial creatinine kinase (CK) activity was assayed at end EQ and end RP. In vitro, purified CK was assayed and, after exposure to H2O2 (200 microM) and increasing concentrations of PYR (0-6 mM) for 10 min, reassayed to determine the antioxidant effect of PYR. In all cases PYR improved recovery of mechanical function at end RP (DP: Control, 11 +/- 1%; PRYRP, 23 +/- 6%; PYREQ, 34 +/- 8%; PRYEQ&RP, 53 +/- 7%; P < 0.05 between all groups and Control). Ischemic contracture was delayed in hearts that received PYR during EQ (PYREQ and PYREQ&RP: 17.8 +/- 0.2 vs 12.5 +/- 0.3 min, P < 0.001). PYR during EQ (PYREQ and PYREQ&RP) led to higher end ischemic ATP levels (32 +/- 4% vs 14 +/- 3%, P < 0.001) and a more acidic end ischemic pH (5.92 +/- 0.02 vs 5.98 +/- 0.03 in Control and PYRRP, P < 0.05). PYREQ&RP showed the highest end reperfusion ATP levels (55 +/- 7% vs 38 +/- 4%, P < 0.05 vs other groups).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The cumulative nature of pyruvate's dual mechanism for myocardial protection. 763 Jan 28

Active oxygen species including hydrogen peroxide (H2O2) play a major role in ischemia-reperfusion injury. In the present study, changes in myocardial H2O2 content as well as its subcellular distribution were examined in rat hearts subjected to ischemia-reperfusion. Isolated perfused rat hearts were made globally ischemic for 20 or 30 minutes and were reperfused for different durations. H2O2 content in these hearts was studied biochemically and changes were correlated with the recovery of function. These hearts were also analyzed for subcellular distribution of H2O2. Optimal conditions of tissue processing as well as incubation medium were established for reacting cerium chloride with H2O2 to form cerium perhydroxide, an insoluble electron-dense product. The chemical composition of these deposits was confirmed by x-ray micro-analysis. Global ischemia caused complete contractile failure in minutes and after 30 minutes of ischemia, these was a > 250% increase in the myocardial H2O2 content. Depressed contractile function recovery in the early phase of reperfusion was accompanied by approximately a 600% increase in the myocardial H2O2 content. Brief pre-fixation with low concentrations of glutaraldehyde, inhibition of alkaline phosphatase, glutathione peroxidase, and catalase, post-fixation but no post-osmication, and no counterstaining yielded the best cytochemical definition of H2O2. In normal hearts, extremely small amounts of cerium hydroperoxide precipitates were located on the endothelial cells. X-ray microanalysis confirmed the presence of cerium in the reaction product. Ischemia resulted in a stronger reaction, particularly on the sarcolemma as well as abluminal side of the endothelial cells; and upon reperfusion, cerium precipitate reaction at these sites was more intense. In the reperfused hearts, the reaction product also appeared within mitochondria between the cristae as well as on the myofibrils, but Z-lines were devoid of any precipitate. The data support a significant increase in myocardial H2O2 during both the phase of ischemia and the first few minutes of reperfusion. A stronger reaction on the sarcolemma and abluminal side of endothelial cells may also indicate enhanced H2O2 accumulation as well as vulnerability of these sites to oxidative stress injury.
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PMID:Hydrogen peroxide changes in ischemic and reperfused heart. Cytochemistry and biochemical and X-ray microanalysis. 767 88

Current methods of experimental infarct size measurement require tissue analysis several hours after the ischemic event. Electron microscopy identifies irreversibly injured myocytes early after ischemia, but cannot be used to measure myocardial infarct size. Horseradish peroxidase (HRP), a tracer protein that permeates the disrupted sarcolemma of injured myocytes, was used to determine infarct size. New Zealand White rabbits (n = 15) were subjected to 30 min coronary artery occlusion and 24 h reperfusion. Prior to euthanasia, HRP was administered intravenously. The hearts were excised, perfused with triphenyl tetrazolium chloride (TTC), and perfusion fixed. A frozen section was cut from left ventricular slices, and the brown HRP reaction product was developed with 3,3'-diaminobenzidine tetrahydrochloride and H2O2. The areas delineated by intramyocyte HRP (as a percent of the left ventricle) closely correlated with infarct size determined by conventional hematoxylin-eosin (H&E) stain and TTC (means +/- S.E.M.): 29.5 +/- 3.0% vs 27.6 +/- 2.9% vs 28.6 +/- 2.6%, respectively. The coefficient of correlation between HRP and H&E was 0.94. This method was tested for early infarct detection in rabbits subjected to 30 min coronary occlusion followed by intravenous injection of HRP and sacrifice. HRP-delineated infarcts measured 21.4 +/- 3.7% of the left ventricle, and electron microscopic examination from ischemic and non-ischemic areas was used to confirm that cells containing HRP were irreversibly injured. Thus, HRP can be used to accurately measure myocardial infarct size in experimental coronary artery occlusion and reperfusion in infarcts as early as 30 min after coronary occlusion or following 24 h of reperfusion.
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PMID:Early detection and measurement of experimental myocardial infarcts with horseradish peroxidase. 768 52

We wished to determine whether histidine scavenges hydroxyl radical, H2O2, and superoxide anion in vitro and to investigate the protective effect of histidine on isolated perfused rat hearts after global ischemia (40 min) and reperfusion (30 min) (I/R). Left ventricular (LV) function was recorded and coronary effluent was collected for measurement of lactate dehydrogenase (LDH) before ischemia and at 5, 10, 15, and 30 min of reperfusion. At the end of the experiment, a portion of the LV wall was fixed with 2% glutaraldehyde for morphological analysis; the remaining heart was immediately frozen in liquid nitrogen for determination of adenine nucleotides. Histidine effectively quenched hydroxyl radicals and H2O2, but not superoxide anions, in in vitro and in vivo conditions. Hearts treated with histidine exhibited significantly greater functional recovery during reperfusion as compared with nontreated hearts (p < 0.05). Cell morphology was well preserved, and enzyme release was significantly attenuated by histidine treatment (p < 0.05). Histidine raised the ATP level to 73% and the creatine phosphate level to 68% of normal control during reperfusion. Total adenine nucleotide pool and energy charge rate in histidine-treated hearts significantly increased as compared with those in nontreated hearts (p < 0.05), but no effect on ATP and creatine phosphate was noted during ischemia, Histidine prevents postischemic reperfusion injury in isolated heart by inhibiting reactive O2 species and preserving high-energy phosphates (HEP).
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PMID:Antioxidative properties of histidine and its effect on myocardial injury during ischemia/reperfusion in isolated rat heart. 772 45

Electron transport and production of O2-/H2O2 by the NADH dehydrogenase flavin-semiquinone (FMNH.) and ubisemiquinone (UQH.) were studied in a model of in vivo ischemia-reperfusion in rat kidney. H2O2 production rates were assessed in isolated mitochondria using either succinate, with and without antimycin, or malate-glutamate, with and without rotenone. Respiratory activities of isolated mitochondria and activity of NADH- and succinate-cytochrome c reductase and of NADH- and succinate-dehydrogenase in submitochondrial particles were measured to evaluate the electron flux throughout respiratory carriers. The mitochondrial H2O2 production rate was approximately 1.5- and 4-times increased in ischemic and ischemic-reperfused kidneys, respectively. Ischemia caused a marked decrease in the electron transport throughout the NADH-UQ segment with no significant changes either in the NADH dehydrogenase activity or in the electron flux trough the succinate-cytochrome oxidase segment. Reperfusion did not further affect the NADH-ubiquinone segment but markedly inhibited the succinate-supported oxygen consumption, succinate-cytochrome c reductase and succinate dehydrogenase activity. Our results show a redistribution of the electron flux with an increased rate of superoxide anion/hydrogen peroxide production at NADH dehydrogenase in mitochondria subjected to ischemia only. After 10 min reperfusion an impairment of the electron flow at succinate-cytochrome c segment is established and hydrogen peroxide production by UQH. increases up to maximal values becoming the major source of superoxide anion/hydrogen peroxide.
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PMID:Mitochondrial sites of hydrogen peroxide production in reperfused rat kidney cortex. 772 10


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