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

To elucidate the pathophysiological role of the hydroxyl radical (.OH) during the postischemic reperfusion of the heart, we measured the .OH product in the coronary effluent from isolated perfused rat heart during a 30-minute reperfusion period after various ischemic intervals of 5, 10, 15, 20, 30, and 60 minutes. Salicylic acid was used as the probe for .OH, and its derivative, 2,5-dihydroxybenzoic acid (2,5-DHBA), was quantified using high-performance liquid chromatography with ultraviolet detection. 2,5-DHBA was negligible in the effluent from nonischemic hearts, but a significant amount was detected from the hearts rendered ischemic for 10 minutes or longer. The peak of 2,5-DHBA was seen within 90 seconds after the onset of reperfusion in every group. The accumulated amount of 2,5-DHBA was maximal in the group with 15-minute ischemia (6.73 +/- 1.04 nmol/g wet heart wt after 30 minutes of reperfusion); it decreased as the ischemic time was prolonged and was 2.38 +/- 0.84 nmol/g wet wt after 30 minutes of reperfusion in the group with 60-minute ischemia. In the model of 15-minute ischemia/30-minute reperfusion, there was no correlation between the accumulated amount of 2,5-DHBA and functional recovery (+/- dP/dt, heart rate, and coronary flow), lactate dehydrogenase release, and morphological damage. Although treatment with 0.5 mM deferoxamine, an iron chelator, significantly decreased 2,5-DHBA (from 6.73 +/- 1.04 to 2.29 +/- 0.80 nmol/g wet wt after 30 minutes of reperfusion, p less than 0.01), it failed to reduce the postischemic myocardial injury in the group with 15-minute ischemia. The results suggest that .OH production is influenced by the preceding ischemic interval and that .OH does not exert an immediate direct effect on postischemic damage during early reperfusion in the isolated perfused rat heart, although a possibility remains that the small portion of .OH trapped by salicylic acid may not be intimately associated with myocardial injury.
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PMID:Quantification of hydroxyl radical and its lack of relevance to myocardial injury during early reperfusion after graded ischemia in rat hearts. 131 98

To elucidate the significance of hydroxyl radical (.OH) in postischemic reperfusion injury, we measured the .OH production in the coronary effluent collected from isolated perfused rat hearts during reperfusion period of 15 minutes after various ischemic intervals ranging from 5 to 60 minutes. Salicylic acid was used as a probe for .OH formation, and its derivative, 2,5-dihydroxybenzoic acid (2,5-DHBA), was quantified using high performance liquid chromatography. A significant amount of 2,5-DHBA was detected from the hearts rendered ischemic for 10 minutes and longer. The peak of 2,5-DHBA was seen within 90 seconds after the onset of reperfusion in every group, and the accumulated amount of 2,5-DHBA was maximal in 15 minutes ischemia group (3.97 +/- 0.49 nmol/g/15 minutes reperfusion) in contrast to 1.22 +/- 0.30 nmol/g/15 minute in 60 minutes ischemia. This study demonstrated an ischemic time-dependent .OH production during reperfusion, and no direct effect of .OH was observed on the post-ischemic injury related to myocardial function.
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PMID:Hydroxyl radical production during early reperfusion after different periods of ischemia in rat hearts and its effect on myocardial function. .OH in postischemic heart. 132 89

The concentration of glutamate as well as the hydroxylation of salicylate, as an index of hydroxyl free radical formation, has been determined in the abdominal aorta and heart of gerbils undergoing an ischemia/reperfusion insult (IRI) and compared to control sham-operated gerbils. The amount of glutamate and hydroxylated salicylate (dihydroxybenzoic acid, DHBA) was significantly increased in both the aorta and heart of IRI-treated gerbils as compared to the aorta and in the heart of sham-operated gerbils. Vitamin E (90 mg/kg at 24 and 1 h prior to an IRI) pretreatment prevented the increase of both glutamate and DHBA in both the aorta and heart of IRI-lesioned gerbils. The results suggest that increases in glutamate, perhaps due to the decreased activities of glutamine synthetase, are correlated with increased oxygen free radical formation during an ischemia/reperfusion insult to the heart.
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PMID:Glutamate accumulation and increased hydroxyl free radical formation in the abdominal aorta and heart of gerbil after ischemia/reperfusion insult. 135 62

The mongolian gerbil was introduced as a stroke model because of its incomplete circle of Willis. Unilateral carotid ligation ischemia produced in such a fashion was not effective in all gerbils. We have selected gerbils by examination of the ocular fundus to study the level of amino acids and hydroxyl free radicals (OH0 formation of DHBA, dihydroxybenzoic acid, from salicylate) in gerbil cerebral ischemia. Only gerbils with absence of retinal blood after ligation were selected as sensitive. One group (sham operated) served as control. The other group was subjected to unilateral left carotid occlusion with a clip during 30 minutes and classified as sensitive and non sensitive. Sixty minutes after release of the clip, levels of aspartate, glutamate, GABA were quantified in left hippocampus and in left retina. Levels of 2,5 DHBA (2,5 dihydroxybenzoic acid) were quantified in left retina and in left hemisphere. Compared to sham operated group, levels of aspartate (greater than 371%), glutamate (greater than 318%), GABA (greater than 122%) and 2,5 DHBA (greater than 385%) significantly increased in the group subjected to carotid occlusion. The determination of concentrations of amino acids and 2,5 DHBA in sensitive gerbils was a suitable method to study cerebral and retinal ischemia.
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PMID:Accumulation of amino acids and hydroxyl free radicals in brain and retina of gerbil after transient ischemia. 191 70

Transient global ischemia may lead to persistent production of reactive oxygen species in selected brain regions thereby contributing to selective vulnerability to ischemia. Using cerebral microdialysis, we assessed the production of the highly reactive hydroxyl radical (OH.) in rat hippocampus during global ischemia and reperfusion (IR). During IR, perfusate containing salicylic acid was collected and analyzed for non-enzymatic hydroxylation of salicylate to 2,3-DHBA. Since 21-aminosteroids can attenuate excitatory amino acid-mediated OH. production in the brain, we repeated the experiments after administration of the 21-aminosteroid, U-74389G. The data indicate that 2,3-DHBA level increased progressively between 15 and 60 min after reperfusion, reaching values nearly three times the baseline value at 60 min. U-74389G, given 30 min before ischemia, greatly attenuated the increase in 2,3-DHBA during reperfusion. This is the first evidence for prolonged OH. production in the hippocampus after reperfusion in vivo which can be prevented by 21-aminosteroids.
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PMID:Prolonged production of hydroxyl radical in rat hippocampus after brain ischemia-reperfusion is decreased by 21-aminosteroids. 782 63

The difficulty in direct detection of oxygen-derived free radicals (OFR) in the intact kidney has left uncertain the role of OFR in renal hypoperfusion injury. Salicylate hydroxylation was used as a sensitive method of estimating the extent of production of highly reactive hydroxyl radicals in renal ischaemia-reperfusion injury in the intact rat kidney perfused with recirculating cell-free medium. The reaction products were detected and quantified by HPLC with electrochemical detection. Hydroxyl radicals were detected as 2,5-dihydroxybenzoic acid (2,5-DHBA). Ischaemia for 15 min followed by reperfusion for 15 min caused more than a twofold increase in 2,5-DHBA concentration (to 2279 +/- 225 pg/g tissue weight) compared to controls (933 +/- 103, P < 0.001). Addition of 15 mM dimethylthiourea (DMTU) before induction of ischaemia prevented this increase. Induction of hypoxia for 15 min with continued perfusion (as a model of low-flow ischaemia) had no significant effect on hydroxyl radical formation. We conclude that significant quantities of hydroxyl radicals form in the absence of circulating leucocytes during reperfusion following ischaemia, but not during hypoxia in the perfused rat kidney.
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PMID:Hydroxyl radical generation following ischaemia-reperfusion in cell-free perfused rat kidney. 787 60

Cerebrolysin (FPF1070) is an extract from pig brain obtained after enzymic digestion, containing free amino acids (85%) and low-molecular weight amino acid sequences (15%). We studied FPF 1070 to determine its ability to protect against delayed neuronal death in the gerbil when administered before and after ischemia. Transient forebrain ischemia was produced by occluding both common carotid arteries. Morphological changes in the CA1 sector of the hippocampus were evaluated 4 days after 5 min. occlusion. The formation of hydroxyl radicals in the postischemic (15 min. occlusion) reperfused (2 min.) brain was measured with HPLC using salicylate (SA). SA reacts with hydroxyl radicals and yields 2,3- and 2,5-dihydroxybenzoic acid (2,3- and 2,5-DHBA), which can be detected by HPLC-ECD. Gerbils treated with FPF 1070 revealed significant protection of CA1 neurons when it was applied 2 hrs before the occlusion. In contrast, no clear beneficial effects were observed when FPF 1070 was administered immediately after the recirculation. Concentrations of 2,3- and 2,5-DHBA after reperfusion increased significantly compared to the basal levels both in the hippocampus and cerebral cortex. The 2,5-DHBA contents in the postischemic reperfused brain was significantly reduced when FPF 1070 was administered 2 hr. before the occlusion. The administration of dimethylsulfoxide (DMSO), a hydroxyl radical scavenger, prevented ischemia-reperfusion-induced delayed neuronal death, and significantly reduced the 2,5-DHBA content after reperfusion. The results indicated that hydroxyl radicals are produced in the postischemic-reperfused brain and that hydroxyl radical scavenging action of FPF 1070 played an important role in preventing delayed neuronal death.
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PMID:[Protective effect of FPF 1070 (cerebrolysin) on delayed neuronal death in the gerbil--detection of hydroxyl radicals with salicylic acid]. 833 17

The salicylate trapping method was used to investigate the changes in hydroxyl radical (.OH) levels in the selectively vulnerable hippocampus compared to the cerebral cortex of gerbils subjected to a 10 min period of near complete forebrain ischemia. Salicylate-derived 2,5-dihydroxybenzoic acid (2,5-DHBA) was measured in sham-operated animals and at 1, 5, and 15 min of reperfusion. A basal level of 2,5-DHBA was also seen in non-ischemic gerbil brain, both in the hippocampus and cortex. The hippocampal basal level was 160% higher than in the cortex (P < .01). Treatment with the cytochrome P450 inhibitor SKF-525A (50 mg/kg s.c. 30 min before measurement) did not affect this basal level in either hippocampus or cortex, which argues against a contribution of metabolic salicylate hydroxylation as its source. In contrast, pretreatment with the arachidonic acid cyclo-oxygenase inhibitor ibuprofen (20 mg/kg s.c.) decreased (-68.8%) the level of salicylate hydroxylation in the hippocampus, but not the cortex. In animals subjected to 10 min of forebrain ischemia, a selective increase in 2,5-DHBA was observed in the hippocampus at 1 min of reperfusion which subsided by 5 min. No increase in salicylate hydroxylation was apparent in the cortex within the same time frame. The increase in .OH in the hippocampus at 1 min of reperfusion was accompanied by a significant decrease (-15.7%; P < .03) in the hippocampal levels of vitamin E. No loss of vitamin E was observed in the cortex at the same time.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hydroxyl radical production and lipid peroxidation parallels selective post-ischemic vulnerability in gerbil brain. 838 Aug 74

Selective neuronal cell death in the CA1 pyramidal cells of the hippocampus and neurons of the dorsolateral striatum as a consequence of brain ischemia/reperfusion (IR) can be ameliorated with brain hypothermia. Since postischemic injury is mediated partially by chemical production of reactive oxygen species (ROS), decreased ROS production may be one of the mechanisms responsible for cerebral protection by hypothermia. To determine if ischemic brain temperature alters ROS production, reversible IR was produced in rats by occlusion of both carotid arteries with hemorrhagic hypotension. After 15 min of ischemia, circulation was restored for 60 min. Brain temperature was maintained during ischemia at either 30, 36, or 39 degrees C and kept at 36-37 degrees C after reperfusion. Using cerebral microdialysis, we measured nonenzymatic hydroxylation of salicylate by HPLC with electrochemical detection in the hippocampus. CBF was also compared among the groups during IR. The results were that normothermic animals during reperfusion had persistently increased levels of the salicylate hydroxylation product, 2,3-dihydroxybenzoic acid (2,3-DHBA), reaching 251% of control at 60 min. This increase in 2,3-DHBA production was potentiated after 60 min of reperfusion (406% of control) with ischemic hyperthermia. In hypothermic ischemia, 2,3-DHBA production at 60 min was attenuated to 160% of control. CBF decreased to approximately 5% of baseline value during ischemia, but increased three- to four-fold relative to control in all three groups. Therefore, the effects of ischemic brain temperature on 2,3-DHBA production did not correlate with changes in CBF during IR. We conclude that brain-temperature-related changes in OH.production are readily detected in the rat and decreased ROS generation may contribute to cerebral protection afforded by hypothermia during brain ischemia.
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PMID:Brain temperature alters hydroxyl radical production during cerebral ischemia/reperfusion in rats. 853 May 42

An in vivo rat model of isolated intestinal ischemia-perfusion was developed. This is used to compare the effects of crosslinked hemoglobin (PolyHb) versus crosslinked hemolobin-superoxide dismutase-catalase (PolyHb-SOD-CAT) on free radical generation in ischemia-reperfusion. Fasted, anesthetized male Sprague Dawley rats underwent midline laparotomy with cannulation of the abdominal aorta and inferior vena cava. Ligation was carried out at the renal pedicles bilaterally and the aorta and vena cava proximally at the diaphragm and distally above the femoral bifurcation. The system was flushed of blood with 20 ml of lactated Ringer's solution. The portal vein was then cannulated with distal clamping at the porta hepatis so that isolated intestinal perfusion could be achieved with the aorta as the inlet and the portal vein as the outlet. Following a 90 minute ischemic time, perfusates containing modified hemoglobin (5 g/dl) and 4-hydroxybenzoate (5 mM) were infused at 0.8 ml/min for 10 min. Portal vein effluent samples were collected at 2.5 minute intervals. Hydroxyl radical generation was assessed by an aromatic hydroxylation technique with 4-hydroxybenzoate (4HB). Reaction of hydroxyl radical with 4HB produces 3,4 dihydroxybenzoate (3,4 DHBA). In the PolyHb group, the levels of 3,4-DHBA increased 10.75-13.58 x-fold above pre-perfusion values compared to 2.25-3.75 x-fold in PolyHb-SOD-CAT group. This indicates that PolyHb-SOD-CAT is effective in reducing in vivo hydroxyl radical generation following reperfusion. Since free radicals may play a major role in the pathogenesis of ischemia-reperfusion injury, this suggests a role for PolyHb-SOD-CAT as a possible protective perfusate in intestinal reperfusion injury.
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PMID:Crosslinked hemoglobin-superoxide dismutase-catalase scavenges free radicals in a rat model of intestinal ischemia-reperfusion injury. 908 38


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