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

Although reactive oxygen species are believed to participate in postischemic renal injury, the actual chemical species involved and the role of endogenous scavenging systems in protecting against injury requires additional study. Hydrogen peroxide, which derives from superoxide radical, is toxic and also yields toxic hydroxyl radical. 3-amino-1,2,4-triazole reacts with catalase to form irreversibly inactivated catalase only in the presence of hydrogen peroxide. We made use of this chemical reaction both to determine whether inhibition of the hydrogen peroxide-scavenging enzyme catalase would influence ischemic renal injury and to measure hydrogen peroxide production rates after ischemia. Sprague-Dawley rats were given aminotriazole (100 mg/kg) one hour before 40 min of renal ischemia. Twenty-four h after ischemia GFR had decreased to 300 microL/min in control animals and to 50 microL/min in aminotriazole-treated animals. Histologic evidence of injury was also worse in catalase-inhibited animals. To measure hydrogen peroxide production rates aminotriazole was given 60 min before measurement of renal catalase activity. In control animals, aminotriazole caused a 53.4% decrease in catalase activity. In animals subjected to 40 min of ischemia plus either 10 or 60 min of reflow catalase activity decreased by 33.9 and 49.5% (not significantly different from control). Thus, when measured by this method total renal hydrogen peroxide production was considerable but was not increased by ischemia. However, in isolated proximal tubule segments 60 min of anoxia and 30 min of reoxygenation caused a 42% increase in H2O2 released into the incubation medium. In summary, inhibition of catalase before ischemia led to exacerbation of ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hydrogen peroxide and ischemic renal injury: effect of catalase inhibition. 164 49

The following species; superoxide (O2-.), hydrogen peroxide (H2O2), hydroxyl radical (.OH) and singlet oxygen (1O2), are generally called as reactive oxygen species (ROS). These species have been suggested to play important roles in various diseases caused by oxygen toxicity such as ischemia, carcinogenesis, inflammation, diabetes and aging. During the past two decades, considerable interests have been focused on chemical and biological research of ROS. We have also reported about the research results on ROS, which can be classified as following below; 1) chemical reactivities of O2-., 2) formation and toxicity of 1O2, 3) chemical reactivities of .OH, 4) enzyme mechanism of xanthine oxidase, 5) development of the compounds which induce the formation of O2-. and H2O2 in living cells and 6) development of superoxide dismutase mimics. These studies are reviewed from the standpoint of both chemical and biological interests.
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PMID:[Chemical and biochemical studies on reactivities, formations and toxicities of reactive oxygen species]. 164 54

Hypertonic saline with dextran (HSD) has been recently introduced for prehospital resuscitation of hemorrhagic shock, and is currently undergoing clinical investigation. To determine the effect of clinically relevant amounts of hypertonic saline (7.5% NaCl) and/or 6% dextran 70 on non-ischemic and post-ischemic hearts, we infused rat hearts (Langendorff, 20 minutes global ischemia, 37 degrees, 40 minutes' reperfusion) with: 1) 0.9% NaCl (control); 2) 7.5% NaCl/dextran; 3) 7.5% NaCl; or 4) dextran. We found that 7.5% NaCl alone or with dextran depressed ventricular function (developed pressure, DP; contractility, +dP/dt; and relaxation rate, -dP/dt) in non-ischemic hearts. In contrast, equimolar (2,400 mOsm) sucrose increased myocardial contractility (+dP/dt) of non-ischemic hearts. Coronary flow was unchanged by the addition of 7.5% NaCl, dextran, or sucrose. Treatment of ischemic hearts with 7.5% NaCl/dextran, dextran alone, or sucrose improved recovery of ventricular function compared to 0.9% or 7.5% NaCl. Furthermore, dextran (but not sucrose) with or without 7.5% NaCl reduced myocardial hydrogen peroxide (H2O2) levels during ischemia and reperfusion. We conclude that when given in clinically relevant amounts in the isolated rat heart: 1) 7.5% NaCl directly depresses myocardial function; 2) 7.5% NaCl alone does not improve post-ischemic ventricular function; 3) 7.5% NaCl with dextran or dextran alone improves post-ischemic ventricular function in part by reducing myocardial H2O2; and 4) sucrose equimolar to 7.5% HSD increases ventricular function in non-ischemic and post-ischemic hearts. This investigation suggests that the post-shock benefit of HSD is unrelated to direct myocardial effects of saline but is due in part to toxic oxygen metabolite scavenging by dextran.
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PMID:Hypertonic saline and dextran: impact on cardiac function in the isolated rat heart. 169 95

Hydrogen peroxide produces marked antigonadotropic and lytic actions in luteal cells, but the effects of superoxide, the archetypal oxygen radical, are unknown. Xanthine oxidase generates superoxide, and the activity of this enzyme, and purine substrate, are increased under ischemia, such as that seen at luteal regression. We therefore examined the actions of xanthine oxidase on luteal cells to assess the effects of this enzyme and the superoxide anion on luteal function. Xanthine oxidase, in the presence of hypoxanthine (50 microM), produced marked inhibition of LH-sensitive cAMP and progesterone production with complete inhibition at 25 mU/ml and half-maximal inhibition at about 5 mU/ml. These antigonadotropic actions of xanthine oxidase were rapid with maximal effects within 5 min, followed several minutes later by substantial depletion of ATP. Heat, superoxide dismutase, and catalase or catalase alone abolished the actions of xanthine oxidase. While depletion of ATP by xanthine oxidase was prevented by 3-amino-benzamide, an inhibitor of DNA repair, inhibition of cAMP and progesterone production was still evident. Xanthine oxidase also inhibited progesterone synthesis stimulated by 8-bromo-cAMP. Isobutylmethylxanthine, a cAMP phosphodiesterase inhibitor, did not reverse the inhibition of cAMP accumulation by xanthine oxidase, and the enzyme had no effect on LH receptor binding activity. Since catalase reversed the effects of xanthine oxidase, we conclude that superoxide was rapidly dismuted to hydrogen peroxide and mediated the antigonadotropic and antisteroidogenic actions of xanthine oxidase in luteal cells. The sensitivity of luteal cells to xanthine oxidase raises the possibility that this enzyme may serve as a significant source of hydrogen peroxide in the corpus luteum.
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PMID:Inhibition of gonadotropin action and progesterone synthesis by xanthine oxidase in rat luteal cells. 170 32

A number of scavengers of reactive oxygen metabolites reduce myocardial injury when given before ischemia and reperfusion, but few, if any, have proven to be effective when given near the onset of reperfusion. This is particularly true when infarct size is measured after at least 48 hours of reperfusion, when the full extent of myocardial damage has become apparent. Dimethylthiourea (DMTU) is an extremely diffusible, potent scavenger of hydroxyl radical, hydrogen peroxide, and hypochlorous acid, with a long half-life of 43 hours. Sixteen chloralose-anesthetized dogs underwent 90 minutes of left anterior descending coronary artery (LAD) occlusion followed by 48 hours of reperfusion. Collateral flow was measured by radioactive microspheres. Infarct size and risk area were measured by a postmortem dual-perfusion technique using triphenyl tetrazolium chloride and Evan's blue dye. In eight dogs, therapy with DMTU (500 mg/kg i.v.) was given during the last 15 minutes of ischemia and the first 15 minutes of reperfusion. In eight control dogs, the same volume of 0.9% saline was given during the last 15 minutes of ischemia through the first 15 minutes of reperfusion. Infarct size as a percent of risk area was reduced in the DMTU-treated group compared with the saline-treated controls (DMTU = 42 +/- 4% versus saline = 59 +/- 4%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduction of canine myocardial infarct size by a diffusible reactive oxygen metabolite scavenger. Efficacy of dimethylthiourea given at the onset of reperfusion. 170 40

Reactive oxygen intermediates (ROI) play a major role in the mucosal damage developing during the reperfusion period following intestinal ischemia. We have shown previously that histamine (H) release is related to the ROI generated by xanthine oxidase during intestinal ischemia-reperfusion. The present study sought to determine the possible chain of events leading to H liberation. The artery supplying a segment of the ileum was occluded for 2 hr in 51 anesthetized dogs, and plasma levels of H were determined radioenzymatically in the venous effluent. Catalase was applied to scavenge hydrogen peroxide; dimethylsulfoxide and mannitol were used as hydroxyl radical scavengers; the role of catalytically active iron was assessed by using desferrioxamine. Pretreatment with either catalase or desferrioxamine, but not with dimethyl sulfoxide or mannitol, was effective in reducing the postocclusive H release. The results provide further in vivo evidence that ROI are causative agents in H liberation during reperfusion of the ischemic gut. Hydrogen peroxide can interact with catalytically active iron and generate highly reactive oxidants, which in turn are responsible for H release. The exact nature of these oxidants is still uncertain.
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PMID:Histamine release during intestinal ischemia-reperfusion: role of iron ions and hydrogen peroxide. 172 54

The effect of nitrendipine, an antihypertensive calcium antagonist, on the impairment of cerebral blood flow and EEG observed after 10-min complete cerebral ischemia in anesthetized rabbits was compared with those of nicardipine. The ischemia was produced by neck tourniquet in combination with hypotension (50-60 mmHg). Blood flow was measured by hydrogen-clearance method. Transient reactive hyperemia was observed immediately after the cessation of ischemic procedure, and was followed by a decrease in blood flow in the range of 58-73% of corresponding basal values in the total brain, cortex and thalamus. The postischemic decrease in blood flow was suppressed when nitrendipine (0.3-1 mg/kg) or nicardipine (3-10 mg/kg) was given intraduodenally before ischemia. The postischemic decrease in total intensity and frequency index in EEG recovered rapidly when nitrendipine was pretreated, whereas the recovery of EEG parameters was not obtained by the nicardipine pretreatment. These results suggest that the effect of nitrendipine and nicardipine on the postischemic cerebral blood flow may be due to the inhibition of calcium-induced contraction in cerebral vessels, whereas the discrepancy between the effects of these agents on EEG may not be due solely to the improvement in cerebral circulation. Furthermore, the improvement in postischemic cerebral energy metabolism was confirmed by nitrendipine pretreatment (0.3 mg/kg).
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PMID:Nitrendipine facilitates recovery of cerebral blood flow, EEG and metabolites following cerebral ischemia in anesthetized rabbits. 179 73

Previously in our laboratory, nimodipine was effective in reversing posttraumatic ischemia and promoting electrophysiologic recovery in a rat spinal cord injury (SCI) model. However, these beneficial effects were achieved when nimodipine was combined with adjuvant therapy to reverse posttraumatic hypotension, by either volume expansion or vasopressor therapy. The present experiments determined if nimodipine alone can increase spinal cord blood flow (SCBF) and improve function after SCI. The hydrogen clearance technique was used to measure SCBF, and motor and somatosensory evoked potentials (MEP and SSEP) were used to quantitate electrophysiologic function. SCBF, MEP, and SSEP were recorded before and after a 52 g clip compression injury at the T1 segment and then repeated after a 35 minute infusion of nimodipine. Twenty-five rats were allocated randomly to five equal groups, each of which received 35 minute infusions of one of the following doses of nimodipine: (1) 0 mg/kg, (2) 0.005 mg/kg, (3) 0.01 mg/kg, (4) 0.025 mg/kg, or (5) 0.05 mg/kg. SCBF decreased after injury in all groups, and there was no increase in SCBF after nimodipine infusion in any group. MEP and SSEP were abolished by the injury in all rats, and there was no recovery of the evoked potentials in any group. It is concluded that adjuvant therapy for posttraumatic hypotension may be necessary for nimodipine to improve SCBF and promote recovery of function in the injured spinal cord.
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PMID:Further studies of nimodipine in experimental spinal cord injury in the rat. 180 31

Free radicals have recently been proposed to play a role in the development of diabetic retinopathy. Ischaemia and hyperglycaemia followed by recirculation have been suggested to initiate free radical production in other tissues and the aim of the present study was to examine whether this could also be the case in the retina. The present study showed retinal cell damage, as measured by pycnotic cells, to be more pronounced when ischaemia was combined with hyperglycaemia than when combined with normoglycaemia. As an indication of free radical production, catalase activity was measured, reflecting the production of hydrogen peroxide (H2O2). Small amounts of H2O2 were found to be generated in the normal retina, but did not increase during ischaemia and hyperglycaemia followed by recirculation. It thus seems, as if hyperglycaemia aggravates the harmful effects of ischaemia, but with the methods used, there does not seem to be any increase in free radical production (as measured by H2O2 production) in normal rat retina during ischaemic and hyperglycaemic conditions.
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PMID:Hydrogen peroxide production in ischaemic retina: influence of hyperglycaemia and postischaemic oxygen tension. 181 95

Interventional studies yielded conflicting results on reperfusion injury. They are unable to discriminate between lesions due to ischemia or to additional damage during reoxygenation. Since reactive oxygen metabolites have been implicated as a major cause of reperfusion injury, 375 nmol/min of hydrogen peroxide was infused in a Langendorff rat heart preparation as a model of oxidant stress without previous ischemic contractile dysfunction. Impaired endogenous defense was remodeled, using selenium-deficient hearts with reduced glutathione peroxidase activity. Measurements of hemodynamic parameters demonstrate increased myocardial susceptibility to oxidant stress in hearts with decreased antioxidant defense. Defined concentrations of hydrogen peroxide produce isolated impairment of active and passive diastolic properties of the ventricle in this model.
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PMID:Selenium as a protector of diastolic function during oxidant stress. 182 15


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