Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.9.3.1 (cytochrome oxidase)
8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cat stroke model was used to evaluate the efficacy of Dextran-40 (DEX) or Fluosol-DA 20% (FDA) in the treatment of focal cerebral ischemia. The animals were assigned randomly to one of three treatment groups: control, isovolemic hemodilution with DEX or isovolemic hemodilution with FDA. The oxidation state of cytochrome aa3 was measured in-vivo using near infrared reflectance spectrophotometry. The cerebral edema was measured by magnetic resonance imaging (MRI). The MRI edema indices for the three groups revealed that the FDA group had less edema (p less than 0.05), approaching that of non-stroke controls. The relative oxidation state of aa3 for the DEX group declined both during and after hemodilution. At the ninth hour post stroke the FDA group was better (aa3 more oxidized. p less than 0.025). Changes in blood and plasma components were reflective of the extent of hemodilution. Whole blood viscosity analysis revealed a difference (p less than 0.05) at the lower shear rates comparing DEX to FDA with FDA being higher than DEX. Two animals in each of the groups were allowed to awaken at the end of the procedure for functional assessment. These observations suggest that hemodilution with FDA following stroke significantly reduces early post-ischemic cerebral edema, improves oxidation in the peri-infarct area and appears to minimize functional deficits.
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PMID:Treatment of cerebral ischemia with Dextran-40 or Fluosol DA 20%. 138 45

Electron microscopic examination of muscle specimens taken at biopsy in 6 patients with complex I deficiency and 1 patient with an unknown primary chemical defect who had the clinical characteristics of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) revealed striking abnormalities in blood vessels in 5. Abnormalities consisted of an increased number of enlarged mitochondria with complicated cristae in the pericytes of capillaries, endothelial cells, and smooth muscle cells of the small arteries, including terminal arterioles and precapillary sphincters, predominantly in smooth muscle cells. On statistical analysis, the number of mitochondria and the ratio of mitochondrial area to the total area of the smooth muscle cells were increased approximately tenfold (p less than 0.001). Although stroke-like episodes were not present, similar mitochondrial abnormalities in blood vessels were found in 1 patient who had the encephalomyopathic form of complex IV deficiency and in 2 patients in whom the primary chemical defects could not be clearly defined. Such abnormalities in small arteries might be responsible for the occasional occurrence of transient cerebral ischemia causing stroke-like episodes and progressive mental deterioration.
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PMID:Vascular involvement in mitochondrial myopathy. 250 Aug 89

Cerebral blood volume, hemoglobin saturation and the cytochrome a, a3 redox state were monitored simultaneously by using three wavelengths of light in the near infrared portion of the spectrum for transillumination of the intact skull of rats. The changes in these parameters following incomplete cerebral ischemia were assessed in Wistar and Long-Evans rats submitted to carotid ligation. Another group of Wistar rats was submitted to vertebral + carotid occlusion. The experiments, performed under N2O/O2 anesthesia, showed that in all three groups carotid occlusion induced a decrease in blood volume, Hb saturation and a reduction of cyt. a, a3. However, the cytochrome redox state tended to normalize during ischemia as a consequence of higher O2 extraction from blood. The primary finding of this study was the marked hyperoxidation of cyt. a, a3 which occurred after reestablishing of the carotid blood supply, in spite of a secondary post-ischemic hypoperfusion of the brain. Although uncoupling of oxidative phosphorylation cannot be excluded the dissociation between blood supply and metabolism could well be due to ischemia-induced hypermetabolism of the central nervous tissue. In view of the marked oxidation of cyt. a, a3 during the reperfusion period as compared with the small extent of its reduction during the ischemic episode, the data also support the hypothesis that under steady state conditions in vivo, cytochrome oxidase is mainly reduced.
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PMID:Incomplete cerebral ischemia in the rat: vascular and metabolic changes as measured by infrared transillumination in vivo. 631 78

The effect of reperfusion following 30 min of cerebral ischaemia on brain mitochondrial respiratory chain activity has been studied in the gerbil. The state 3 respiration rates with both FAD- and NAD-linked substrates were reduced after ischaemia. After 5 min of reperfusion, state 3 respiration with FAD-linked substrates was restored, but levels of NAD-linked substrates did not return to control values until 30 min of reperfusion. By 120 min of reperfusion state 3 respiration decreased relative to control values with all substrates studied. Measurement of the individual respiratory chain complexes showed that complex I, complex II-III, and complex V activities were reduced after ischaemia. By 5 min of reperfusion complex II-III activity was restored, but the activities of complexes I and V did not return to control values until 30 min of reperfusion. In contrast, complex IV activity was unaffected by ischaemia or 5 and 30 min of reperfusion but was significantly reduced after 120 min of reperfusion, possibly owing to free radical production and lipid peroxidation.
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PMID:Effect of reperfusion following cerebral ischaemia on the activity of the mitochondrial respiratory chain in the gerbil brain. 756 67

The objective of this study was to assess the relationship between the changes in the redox state of cytochrome oxidase (Cyt. ox.) and those of spontaneous EEG activity and cellular energy state during cerebral ischemia and recirculation. We induced 5-min forebrain ischemia by occluding the bilateral common carotid arteries in anesthetized gerbils. Redox changes of Cyt. ox. were monitored with near-infrared spectroscopy (NIRS) through the experiments. Cortical energy metabolites, ATP, ADP, and AMP, were also measured with high performance liquid chromatography (HPLC) during ischemia and recirculation. Ischemia immediately caused a rapid reduction of Cyt. ox., which paralleled to deterioration of spontaneous EEG activity and preceded significant changes in cellular energy state. Re-oxygenation of Cyt. ox. was observed just after recirculation, and paralleled to the recovery of cellular energy state. Spontaneous EEG activity did not recover even when all other NIRS parameters almost recovered during recirculation after 5-min ischemia. During clamping of the carotid artery, NIRS findings also correlated with those of somatosensory evoked potential (SEP). We concluded that, by means of monitoring redox changes of Cyt. ox., NIRS can detect non-invasively critical neuronal hypoxia prior to a significant impariment of cellular energy state caused by cerebral ischemia, and that NIRS can also detect recovery of oxidative phosphorylation during recirculation, which cannot be observed on EEG.
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PMID:[Near-infrared monitoring of cerebral oxygenation during cerebral ischemia]. 759 May 92

In this study we have examined (1) the integrated function of the mitochondrial respiratory chain by polarographic measurements and (2) the activities of the respiratory chain complexes I, II-III, and IV as well as the ATP synthase (complex V) in free mitochondria and synaptosomes isolated from gerbil brain, after a 30-min period of graded cerebral ischaemia. These data have been correlated with cerebral blood flow (CBF) values as measured by the hydrogen clearance technique. Integrated functioning of the mitochondrial respiratory chain, using both NAD-linked and FAD-linked substrates, was initially affected at CBF values of approximately 35 ml 100 g-1 min-1, and declined further as the CBF was reduced. The individual mitochondrial respiratory chain complexes, however, showed differences in sensitivity to graded cerebral ischaemia. Complex I activities decreased sharply at blood flows below approximately 30 ml 100 g-1 min-1 (mitochondria and synaptosomes) and complex II-III activities decreased at blood flows below 20 ml 100 g-1 min-1 (mitochondria) and 35-30 ml 100 g-1 min-1 (synaptosomes). Activities declined further as CBF was reduced below these levels. Complex V activity was significantly affected only when the blood flow was reduced below 15-10 ml 100 g-1 min-1 (mitochondria and synaptosomes). In contrast, complex IV activity was unaffected by graded cerebral ischaemia, even at very low CBF levels.
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PMID:Changes of respiratory chain activity in mitochondrial and synaptosomal fractions isolated from the gerbil brain after graded ischaemia. 772 7

The study investigated the hypothesis that delayed cerebral injury after transient cerebral ischemia is associated with vasoconstriction and decreased cerebral oxygenation. Eight chronically instrumented, late gestation fetal sheep were subjected to 30 min of cerebral ischemia in utero. Cortical impedance (CI) and electrocorticogram (ECoG) were recorded to determine the time course of cellular dysfunction. Histologic outcome was assessed 4 d postischemia. Changes in cerebral vascular tone and oxygenation were observed during and for 4 d after the insult using near infrared spectroscopy to measure changes in total cerebral Hb ([tHb]), oxyhemoglobin ([Hbo2]), and oxidized cytochrome aa3 ([Cyto2]). Results are expressed as mean +/- SEM. CI increased transiently during ischemia; then a delayed increase commenced 17.5 +/- 2.3 h postischemia and peaked at 42.3 +/- 2.4 h. ECoG was depressed during and after the insult. Seizures started 13.6 +/- 3.0 h postinsult and persisted for 25.4 +/- 3.2 h. Increases in [tHb] indicated two periods of cerebral vasodilation: immediately after early reperfusion, lasting 2.3 +/- 0.4 h and peaking to 20 +/- 2.0 mumol.L-1; and a later phase, commencing 12.8 +/- 2.0 h postischemia, peaking to 43 +/- 4.0 mumol.L-1 and lasting 43.1 +/- 5.2 h. [Hbo2] was relatively elevated (18 +/- 3.0 mumol.L-1) during d 4 postischemia, demonstrating a delayed increase in mean cerebral oxygen saturation. [Cyto2] fell during the insult (-0.7 +/- 0.2 mumol.L-1); and, commencing at 28-30 h postischemia, fell progressively to reach a minimum of -5.0 +/- 2.8 mumol.L-1 at 78-80 h postischemia. A greater fall in [Cyto2] was related to worse cerebral injury (p < 0.05). Delayed cerebral injury is accompanied by vasodilation and increased mean cerebral oxygen saturation, although a progressive fall in [Cyto2] might indicate a fall in mitochondrial oxygenation, cell loss, or changes in tissue optical characteristics.
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PMID:Delayed vasodilation and altered oxygenation after cerebral ischemia in fetal sheep. 882 85

Using a gerbil model of severe, temporary focal ischemia (3 h unilateral carotid occlusion), preliminary experiments identified an involvement of neutrophils in the reperfusion injury to the ischemic hemisphere. The present experiments were designed to (1) quantitate the temporal accumulation of neutrophils in the gerbil model, (2) determine if cyclophosphamide-induced neutropenia provided cytoprotection to the ischemic hemisphere, and (3) attempt to correlate the cytoprotective efficacy of tirilazad mesylate with possible effects on postischemic neutrophil accumulation. Following 3 h of unilateral carotid occlusion, animals were collected at increasing times of reperfusion and the CA1 region of the hippocampus and the lateral cortex were assessed for postischemic neuronal damage using a semiquantitative index (N.D.I.) of 0 (no damage) to 4 (>75% neuronal loss). The extent of neutrophil accumulation was determined by counting intensely cytochrome oxidase-positive cells. Minimal neuronal death was evident after 2 h of reperfusion, mean N.D.I. = 0.36. However, between 2 and 4 h of reperfusion, neuronal death did not increase. By 6 h of reperfusion, the neuronal death began to proceed at an accelerated rate, N.D.I. = 0.78. By 12 h, the N.D.I. reached 3.20. The accelerated neuronal death coincided with parenchymal invasion of neutrophils. Cyclophosphamide administration delayed neuronal death in the hippocampus, but exhibited a more sustained protective effect in the lateral cortex. Administration of tirilazad mesylate also resulted in a significant reduction in neutrophil accumulation and significant neuronal protection in both brain areas. Thus, in this gerbil model of transient, but prolonged focal cerebral ischemia, neutrophils appear to play an active role in the reperfusion injury to brain tissue. Our experiments confirm the previously demonstrated neuroprotective efficacy of tirilazad mesylate in this model and provide evidence for a similar protective effect of cyclophosphamide. Although other effects of this antioxidant are also thought to contribute to the overall efficacy, the data are consistent with the hypothesis that one mechanism by which tirilazad acts involves limiting the ability of neutrophils to participate in the reperfusion phase of ischemic cerebral injury.
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PMID:Cyclophosphamide is neuroprotective in a gerbil model of transient severe focal cerebral ischemia: correlation with effects of tirilazad mesylate (U-74006F). 909 81

Inspired oxygen (FiO2) was manipulated during the early reperfusion period after global cerebral ischemia (four-vessel occlusion of 20 or 30 min duration) in anesthetized rats. The goal was to determine whether oxygen availability during the early reperfusion period alters recovery of mitochondrial redox state and evoked electrical activity. The effectiveness of post-ischemic oxygen treatment was monitored at the tissue level with oxygen sensitive microelectrodes, and at the mitochondrial level by reflection spectrophotometry of the redox state of cytochrome oxidase. Transiently decreasing FiO2 from 0.3 to 0.15 limited reperfusion-induced hyperoxygenation and post-ischemic mitochondrial hyperoxidation (PIMHo). Evoked potential recovery was improved by this treatment after 20 min ischemia but not after 30 min ischemia. Increasing FiO2 from 0.3 to 1.0 exacerbated PIMHo and tissue hyperoxygenation. Transient elevation of tissue oxygen tension after 30 min of global ischemia inhibited recovery of evoked potentials. These data suggest that a period of heightened vulnerability to oxidative stress occurs within the first 10 min of reperfusion after global ischemia. This period is characterized by tissue hyperoxygenation and mitochondrial hyperoxidation. Limiting oxygen availability during this period may improve the outcome while conversely elevating oxygenation may be detrimental.
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PMID:Oxygen sensitivity of mitochondrial redox status and evoked potential recovery early during reperfusion in post-ischemic rat brain. 966 36

In order to test the effect of hypothermia on mitochondrial function damage following cerebral ischaemia/reperfusion, Mongolian gerbils were submitted to 30 min bilateral carotid occlusion and 2 h of reperfusion at 37 degreesC or 30 degreesC. After normothermic (37 degreesC) ischaemia/reperfusion, significant decreases in mitochondrial state 3 (+ADP) oxygen consumption (-42.2%), complex II-III activity in synaptosomes (-31.7%) and complex IV were measured, in both free mitochondria and synaptosomes (-30.3% and -27. 8% respectively). However, following hypothermic (30 degreesC) reperfusion, both respiration rates and all enzyme activities remained at levels not significantly different from those in the sham operated controls.
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PMID:Effect of postischaemic hypothermia on the mitochondrial damage induced by ischaemia and reperfusion in the gerbil. 988 78


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