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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 formation of hydroxyl radical in the post-ischemic reperfused heart was measured with high performance liquid chromatography and ultraviolet detection using salicylic acid. Hydroxyl radicals react with salicylic acid yielding 2,3- and 2,5-dihydroxybenzoic acid, which can be separated by the liquid chromatography. Isolated rat hearts were perfused with 1 mM salicylic acid and were subjected to 30 mins of global ischemia followed by aerobic or anaerobic reperfusion at 37 degrees C. The effluent from the hearts was collected at various intervals, extracted with ether, and injected into the high performance liquid chromatography unit. 2,5-dihydroxybenzoic acid was present only after aerobic reperfusion and was not detected before ischemia. The liquid chromatography peak of 2,3-dihydroxybenzoic acid was too small for quantitation. The concentration of 2,5-dihydroxybenzoic acid was the highest within 300 s of reperfusion. 2,5-dihydroxybenzoic acid was not detected in the ischemic hearts during anaerobic reperfusion. In ischemic hearts perfused with mannitol, the amount of 2,5-dihydroxybenzoic acid after reperfusion was reduced. These data suggest that hydroxyl radicals are produced in the post-ischemic reperfused heart and that the present method is useful and reliable for the measurement of hydroxyl radicals in the heart.
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PMID:Detection of hydroxyl radicals in the post-ischemic reperfused heart using salicylate as a trapping agent. 165 47

Salicylic acid was used as a probe for .OH formed during reperfusion of the ischemic myocardium. .OH adds to the phenolic ring of salicylate to yield dihydroxybenzoic acid species. The two principal dihydroxybenzoic acids formed are the 2,3- and 2,5-derivatives and can be isolated and quantitated using HPLC combined with electrochemical detection. In these experiments, dihydroxybenzoic acids were detectable in the f molar range. Rat hearts were perfused in the Langendorff mode with Krebs-Henseleit buffer containing 100 microM salicylate. Following 20 min of global ischemia a 173% increase in tissue content of 2,5-dihydroxybenzoic acid was detected after 2.5 min of reperfusion. The duration of ischemia did not significantly affect tissue content of 2,5-dihydroxybenzoic acid peaked at 250 to 300% of control within 2.5 min of reperfusion. The inclusion of 100 microM salicylate in the perfusion buffer had no effect on myocardial function during the duration of the experiments. The results indicate that salicylate can be used as a very sensitive probe for .OH in the isolated ischemic heart.
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PMID:Use of salicylate as a probe for .OH formation in isolated ischemic rat hearts. 217 99

To obtain direct evidence of oxygen radical activity in the course of cerebral ischemia under different intraischemic temperatures, we used a method based on the chemical trapping of hydroxyl radical in the form of the stable adducts 2,3- and 2,5-dihydroxybenzoic acid (DHBA) following salicylate administration. Wistar rats were subjected to 20 min of global forebrain ischemia by two-vessel occlusion plus systemic hypotension (50 mm Hg). Intraischemic striatal temperature was maintained as normothermic (37 degrees C), hypothermic (30 degrees C), or hyperthermic (39 degrees C) but was held at 37 degrees C before and following ischemia. Salicylate was administered either systemically (200 mg/kg, i.p.) or by continuous infusion (5 mM) through a microdialysis probe implanted in the striatum. Striatal extracellular fluid was sampled at regular intervals before, during, and after ischemia, and levels of 2,3- and 2,5-DHBA were assayed by HPLC with electrochemical detection. Following systemic administration of salicylate, stable baseline levels of 2,3- and 2,5-DHBA were observed before ischemia. During 20 min of normothermic ischemia, a 50% reduction in mean levels of both DHBAs was documented, suggesting a baseline level of hydroxyl radical that was diminished during ischemia, presumably owing to oxygen restriction to tissue at that time. During recirculation, 2,3- and 2,5-DHBA levels increased by 2.5- and 2.8-fold, respectively. Levels of 2,3-DHBA remained elevated during 1 h of reperfusion, whereas the increase in 2,5-DHBA persisted for 2 h. The increases in 2,3- and 2,5-DHBA levels observed following hyperthermic ischemia were significantly higher (3.8- and fivefold, respectively). In contrast, no significant changes in DHBA levels were observed following hypothermic ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of free radical activity during transient global ischemia and recirculation: effects of intraischemic brain temperature modulation. 764 4

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

We applied in vivo microdialysis techniques in examining the relation between norepinephrine and free radical generation on myocardial ischemic injury. We designed the microdialysis probe holding system, which includes loose fixation of the tube and synchronization of the movement of the heart and the probe. The heart was subjected to myocardiac ischemia for 15 min by occlusion of rat left anterior descending coronary artery. We confirmed typical changes in the electrocardiogram. The hydroxyl free radical (.OH) reacts with salicylate and generates 2, 3- and 2,5-dihydroxybenzoic acid (DHBA), which can be measured electrochemically in picomole quantity by a high-performance liquid chromatographic-electrochemical procedure. After probe implantation, the norepinephrine concentration of dialysate decreased over the first 120 min and then reached an almost steady-state level of 0.15 +/- 0.02 nmol/ml. However, when the heart was reperfused, the levels of norepinephrine and 2,3- and 2,5-DHBA were elevated. In vivo microdialysis techniques permit monitoring of norepinephrine levels and free radical generation in myocardial ischemic injury.
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PMID:In vivo monitoring of norepinephrine and .OH generation on myocardial ischemic injury by dialysis technique. 816 Aug 38

The formation of hydroxyl radical in the extracellular fluid in striatum of rats subjected to 4-vessel occlusion during ischemia and reperfusion was measured by HPLC with UV detector using salicylic acid as a trapping agent. Hydroxyl radicals react with salicylic acid yielding 2,3- and 2,5-dihydroxybenzoic acids which can be separated by liquid chromatography. The striatum was perfused with artificial cerebrospinal fluid containing 0.5 mmol.L-1 salicylic acid at a flow rate of 2.5 microliters.min-1. The results indicate that the concentration of 2,5-dihydroxybenzoic acid in the perfusates was highest during 25 min reperfusion and no change was found during ischemia. Vit E at 30, 60 and 120 mg.kg-1 i.p. 20 min before ischemia was shown to dose dependently suppress the rise of 2,5-dihydroxybenzoic acid after reperfusion. The results suggest that the HPLC method is useful and reliable for the measurement of hydroxy radical in global ischemia in vivo.
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PMID:[HPLC--detection of hydroxyl radicals in striatum extracellular fluid in rats subjected to reperfusion after cerebral ischemia and the action of vitamin E]. 823 77

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


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