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

Restoration of coronary blood flow after myocardial ischemia is always a matter of urgency, but the resulting surgical or drug-induced reperfusion of ischemic tissue is often associated with myocardial functional disturbances and tissue injury. The present study was carried out to select experimental conditions under which optimal effects of antioxidants can be observed on the adverse effects of reperfusion of ischemic myocardium. The release of lactate dehydrogenase (LDH) and changes in hemodynamic parameters were compared in two models of cardiac reperfusion injury in rat isolated hearts. LDH release from electrically-stimulated hearts perfused under constant flow and with initial (5 min) reperfusion in calcium-free buffer was greater than that from hearts perfused under constant pressure in which ischemia was induced by reduced flow. Combined SOD+catalase was a weak inhibitor of LDH release in both models, ascorbic acid being more potent under constant pressure than under constant flow conditions. A longer ischemic period enhanced the inhibitory effect of ascorbate. Contractility and ventricular end-diastolic pressure recovered slowly during perfusion under constant flow and brief calcium removal, but remained unphysiological under constant pressure. SOD+catalase had no effect on hemodynamic parameters. Ascorbic acid exacerbated ischemia+reperfusion-induced changes in contractility, ventricular pressure, heart rate and coronary flow under constant pressure, but facilitated recovery of contractility on reperfusion under constant flow and brief calcium removal. In studies on antioxidants, different experimental conditions appear to be necessary to observe beneficial effects on tissue damage on the one hand and on hemodynamics on the other. Mild to moderate ischemia, with sustained pacemaker activity, appears to be the condition under which antioxidants provide hemodynamic improvement. In isolated rat hearts, biochemical parameters of tissue damage may be misleading for the effects of antioxidants.
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PMID:Experimental conditions determine effects of ascorbic acid on reperfusion injury: comparison of tissue damage with hemodynamic parameters in rat isolated hearts. 146 51

The cardioprotective effects of a high dose of ascorbate on ischemia-reperfusion-induced myocardial damage were investigated using open chest anesthetized dogs. Two-hour occlusion of the left anterior descending coronary artery (LAD) induced mitochondrial dysfunction with a depletion of mitochondrial glutathione (GSH) concentration. Two-hour LAD occlusion followed by 1-h reperfusion worsened the ischemia-induced mitochondrial dysfunction together with a marked depletion of mitochondrial GSH concentration. Ascorbate reduced the mitochondrial dysfunction and prevented the depletion of mitochondrial GSH concentration after 2-h LAD occlusion and 1-h reperfusion. Activities of mitochondrial glutathione peroxidase and glutathione reductase did not change significantly in each group. Administration of ascorbate also prevented reperfusion arrhythmias without affecting blood pressure or heart rate. These results suggest that coronary reperfusion induces mitochondrial dysfunction and a depletion of mitochondrial GSH concentration, and that a high dose of ascorbate prevents reperfusion damage.
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PMID:The effects of a high dose of ascorbate on ischemia-reperfusion-induced mitochondrial dysfunction in canine hearts. 158 8

Ascorbate (vitamin C) is believed to act as a neuromodulator that facilitates the release of neurotransmitters and inhibits neurotransmitter binding to receptors, including dopamine and N-methyl-D-aspartate receptors. Extracellular levels of ascorbate are known to reach the low millimolar range after ischemic brain injury. This study shows that treatment of cultured cortical neurons with micromolar to low millimolar ascorbate first inhibits total protein synthesis and then results in late neuronal death. Astrocytes are much less vulnerable to ascorbate than neurons. Ascorbate may exacerbate neuronal and glial damage after brain ischemia, and it may play a pathological role in other neurological diseases.
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PMID:Ascorbate neurotoxicity in cortical cell culture. 159 92

Extracellular concentrations of ascorbic acid, glutathione, cysteine, uric acid, tyrosine, and tryptophan were monitored using intracerebral microdialysis in the left frontoparietal cortex of spontaneous hypertensive rats before, and for 3 h after, either focal ischemia [left middle cerebral artery occlusion (MCAO)] or sham operation. The size of the ischemic area and the position of the microdialysis probe were checked using the enzyme histotopochemical acid phosphatase reaction. The probe was always located in the cortex inside the stained area. Ascorbic acid levels rose immediately after MCAO and remained at about 12-fold for 3 h. There was a transient release of glutathione during 1-1.5 h. Uric acid concentrations were also increased but the differences did not reach significance. The levels of the amino acids tyrosine and tryptophan increased steadily after MCAO. The increases in cysteine were variable but significant. In some experiments, the pH of the dialysate was measured online. The parameters ascorbic acid, glutathione, cysteine, and pH are suitable for the early detection of cortical ischemic events by microdialysis.
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PMID:Extracellular antioxidants and amino acids in the cortex of the rat: monitoring by microdialysis of early ischemic changes. 172 46

It has been proposed that free radical reactions are involved in ischemic brain damage. Since irreversible pathological changes occurs very early phase of the focal ischemia and the ischemic brain edema reaches its peak at about 2 days of ischemia, the free radical reactions must take place before these changes. Superoxide dismutase is a famous enzyme that dismutase superoxide anion, which is believed to be one of the initiator of the free radical reactions. If superoxide anion plays a pivotal role in the genesis of pathological ischemic brain damage and edema, the activity of the enzyme may decrease in the early phase of ischemia. Ascorbic acid is also known to be a scavenger of superoxide anion, and brain tissue contains it in a high concentration. We investigated the changes in superoxide dismutase activity and concentration of reduced ascorbate in focal ischemia. Focal ischemia was produced in rats by permanent occlusion of the left middle cerebral artery. The animals were decapitated 30 minutes, 4, 24, and 48 hours after the operation. Middle cerebral artery territory of each cerebral hemisphere was homogenized and centrifuged with phosphate buffer. The supernatant was divided into two aliquots; one was dialyzed to remove ascorbate and the other was not. The SOD activity was measured by electron-spin-resonance (ESR) spin trapping method, and the ascorbic acid concentration was measured by high performance liquid chromatography with electrochemical detection (HPLC-ECD). Protein concentration was measured by Lowry's method. The enzyme activity was expressed as unit/mg protein, and the ascorbic acid concentration was expressed as microgram/g tissue. The SOD activity decreased markedly by dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Temporal profile of the superoxide dismutase and the ascorbic acid in focal cerebral ischemia]. 179 14

Ascorbic acid, cysteine, glutathione, uric acid, tyrosine and tryptophan were quantified in samples of frontoparietal cortex, striatum, hippocampus and cerebellum from both sides of rat brain 0.5 h, 4 h and 24 h after focal ischemia. Cysteine, tyrosine and tryptophan were increased in cortex and striatum at 0.5 h, returning afterwards to normal. Uric acid was increased, whereas ascorbic acid and glutathione were correspondingly decreased. Although changes can be explained primarily by energy failure they are also consistent with free radical activity during early stages of ischemia.
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PMID:Levels of low molecular weight scavengers in the rat brain during focal ischemia. 181 35

Reflectance spectroscopy was utilized to monitor the oxidation states of myoglobin (Mb) in isolated, buffer-perfused rat hearts. Hearts were subjected to 30 min global, no-flow ischemia, followed by reperfusion under anoxic conditions. The addition of Na2S to the buffer at reperfusion permitted the detection of ferryl myoglobin (MbIV) as its sulfmyoglobin derivative. The accumulation of MbIV was prevented by addition of ascorbic acid (1 mM), ergothioneine (2 mM), or desferal (1 mM) to the buffer prior to ischemia. Ascorbate and other agents have been previously shown to serve as one-electron reductants of MbIV. We propose that during the early phases of ischemia, deoxymyoglobin is oxidized to MbIV by residual H2O2. It also seems reasonable that the peroxidative activity of Mb(IV), during oxygenated reperfusion, might lead to cellular damage if this hypervalent form of Mb is not reduced.
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PMID:Detection of ferryl myoglobin in the isolated ischemic rat heart. 207 31

The effects of several concentrations of amines and reducing agents on the activity of creatine (CK) and adenylate (AK) kinases were determined in homogenates of the brain of the rat at 0 and 37 degrees C. The order of decreasing irreversible inhibition of the enzymes was peroxide, 6-hydroxydopamine, dopamine, norepinephrine, 5-hydroxytryptamine. At 37 degrees C, approx. 50% of the activity of creatine kinase was lost in 30 min in the presence of 20 microM dopamine. 5-Hydroxytryptamine was several orders of magnitude less toxic. The action of dopamine was not prevented by inhibition of monoamine oxidase, chelation of metals or the addition of a catalase, indicating that formation of peroxide by monoamine oxidase was not the primary cause of the loss of enzyme. Although auto-oxidation of dopamine to a toxic quinone was considered, the degree of inhibition of creatine kinase was not affected when auto-oxidation was prevented under anaerobic conditions. Glutathione (GSH), present during the incubation, protected the enzymes but could not restore activity after exposure to amine. Concentrations of glutathione above 5 mM and of oxidized glutathione as low as 10 microM inhibited creatine kinase. Ascorbate protected the enzymes even when present at a concentration much less than that of the amine, but ascorbate was itself toxic. The findings indicate that dopamine, at concentrations attained after drug-induced release or ischemia, can be toxic to a metabolic enzyme present in the synaptosomal membrane.
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PMID:Amine-mediated toxicity. The effects of dopamine, norepinephrine, 5-hydroxytryptamine, 6-hydroxydopamine, ascorbate, glutathione and peroxide on the in vitro activities of creatine and adenylate kinases in the brain of the rat. 300 2

Ascorbate and glutathione (GSH) are the primary water-soluble antioxidants in the CNS. Oxidative stress, sometimes indicated by loss of these antioxidants, has been linked to several clinical and experimental conditions, including cerebral ischemia. These conditions are also gender-linked, with greater incidence or severity in males than females. To test whether there are gender differences in oxidant/antioxidant regulation, we determined basal levels of ascorbate and GSH in rat brain and their loss after 1 h decapitation ischemia. We found that ascorbate levels in male rat brain were 7-10% higher than in females, depending on region, whereas GSH levels were gender-independent. Significant ascorbate loss (up to 12%) occurred in males during ischemia, with a regional pattern of cerebellum > hippocampus > prefrontal cortex. Loss of ascorbate in females was not significant in any region. By contrast, loss of GSH was significant in both males and females. Greater loss of GSH than ascorbate was in agreement with previous studies and was consistent with loss from enzymatic degradation, as well as oxidation. The significant gender difference in ascorbate loss, as a marker of oxidative stress, supports the hypothesis that inherent differences in oxidant/antioxidant regulation contribute to gender differences in response to ischemia and other pathological conditions.
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PMID:Gender differences in cerebral ascorbate levels and ascorbate loss in ischemia. 757 30

The polymorphonuclear neutrophilic granulocyte (PMN) has been implicated as one possible cause of the no-reflow phenomenon seen upon reperfusion after ischemia, by, for instance, the release of toxic substances and/or microvascular flow obstruction. In the present study we studied the effects of ascorbate (an antioxidant) and fucoidin (an inhibitor of leukocyte rolling in microvessels) on the rat gastric mucosal and submucosal PMN content and vascular patency (the latter assessed as the surface density of perfused vessels) in connection with hemorrhagic shock (15 min) and retransfusion (5 or 10 min). The effect of fucoidin on the leukocyte rolling in small venules was studied separately with vital microscopy in the rat mesentery. As found in earlier studies, shock and retransfusion led to a decrease in the surface density of perfused vessels, whereas the number of PMNs in the mucosa or the submucosa was not affected by shock and retransfusion. Ascorbate improved vascular patency without affecting the PMN content. In the mesentery, fucoidin caused a 76% reduction in the number of rolling PMNs and it reduced significantly the number of PMNs in the mucosa, but not in the submucosa, after 10 min of retransfusion. Fucoidin had no effect on the vascular patency at that or any other time point. On the basis of these experiments it is concluded that PMN accumulation cannot be singled out as the cause of no-reflow in the rat gastric mucosa after shock and retransfusion of the degree and duration analyzed in this investigation.
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PMID:Blocking of endothelial-leukocyte interaction (rolling) does not improve reflow in the rat gastric mucosa after hemorrhagic shock and retransfusion. 775 17


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