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

Using microdialysis, extracellular noradrenaline (NA) levels in the rat cerebral cortex were studied under isoflurane/N2O anaesthesia before, during and for 6 hours following 10 min of forebrain ischemia in a 2-vessel occlusion model. A microdialysis probe was introduced into the parietal cortex and dorsal hippocampus in anaesthetized rats and continuously perfused with Krebs-Ringer-bicarbonate buffer with or without the NA uptake inhibitor desipramine (DMI, 5 microM). Twenty min fractions were collected and the extracellular NA levels were measured in the dialysates using HPLC with electrochemical detection. The basal NA concentration in the dialysate was 10.5 +/- 1.8 (mean +/- SEM) pg/20 min fraction and increased to 39.3 +/- 4.8 pg/20 min fraction after local administration of DMI. During ischemia, NA increased to 38 times the basal level without DMI, and 6 times with DMI included during two hours' perfusion prior to ischemia. After recirculation NA levels returned to, or even transiently decreased below, preischemic values. With DMI present in the dialysis buffer, administration of idazoxan immediately following ischemia delayed the return to preischemic NA levels in the recirculation phase. In the absence of DMI, no effect of idazoxan on postischemic levels of NA was found. Local administration of DMI increases basal extracellular NA levels and reduces the ischemia-induced NA release. The latter effect may be a due to inhibition of the NA uptake system working in a reversed mode, or as a result of decreased synthesis of NA due to activation of presynaptic alpha 2-receptors by the increased synaptic NA levels. Postischemic treatment with the alpha 2-adrenoceptor antagonist idazoxan in combination with DMI prolongs the period of elevated extracellular NA levels, which may be of importance for the protective properties of idazoxan against ischemic cell injury.
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PMID:Extracellular brain cortical levels of noradrenaline in ischemia: effects of desipramine and postischemic administration of idazoxan. 168 52

This study compares the effects of propofol and fentanyl/N2O on spontaneous brain electrical activity, neurologic outcome, and neuronal damage due to incomplete cerebral ischemia in rats. Thirty Sprague-Dawley rats were assigned to one of three groups: group 1 (n = 10) received 70% N2O in O2 plus fentanyl (bolus 10 micrograms.kg-1, infusion 25 micrograms.kg-1.h-1); group 2 (n = 10) received 70% N2 in O2 and propofol (infusion 0.8-1.2 mg.kg-1.min-1) adjusted to maintain EEG burst suppression during ischemia; group 3 (n = 10) was anesthetized with propofol and received 6 ml.kg-1 10% glucose intraperitoneally 15 min before the start of ischemia. Incomplete cerebral ischemia was produced by right common carotid artery occlusion combined with hemorrhagic hypotension (35 mmHg) for 30 min. Arterial blood gases, pH, and rectal temperature were kept constant in all groups. Plasma glucose was lower during ischemia in propofol-anesthetized rats compared to that in fentanyl/N2O- (P = 0.009) and glucose-loaded propofol-treated rats (P = 0.008). Neurologic outcome and brain tissue injury were significantly better in propofol-anesthetized compared to fentanyl/N2O-anesthetized rats (P less than 0.05). Elevated plasma glucose in propofol-treated rats resulted in similar neurologic outcome and histopathologic injury as seen in propofol-anesthetized rats given no glucose. Recovery of EEG theta-alpha activity after ischemia was inversely correlated to neurologic deficit (fentanyl/N2O: r = -0.71; propofol: r = -0.83; P less than 0.01). These results show that propofol improves neurologic outcome and decreases neuronal damage from incomplete cerebral ischemia when compared to fentanyl/N2O. This effect is not dependent on plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of propofol on brain electrical activity, neurologic outcome, and neuronal damage following incomplete ischemia in rats. 173 1

The effects of pretreatment with mannitol on local cerebral blood flow (CBF) after permanent or temporary global cerebral ischemia were evaluated with 14C-iodoantipyrine autoradiography in rats under halothane-N2O endotracheal anesthesia. Blood pressure, pulse rate, arterial blood gas levels, and electroencephalographic (EEG) tracings were monitored throughout the experiments. After permanent occlusion of the basilar artery and both external carotid and pterygopalatine arteries, severe global ischemia was induced by permanent occlusion of the common carotid arteries (CCA's) or by a 30-minute temporary CCA occlusion followed by 5 minutes of reperfusion. Intravenous mannitol (25%, 1 gm/kg) or saline solution was administered 5 minutes before occlusion of the CCA's. Cerebral blood flow was measured in 24 anatomical regions. The EEG tracings flattened within 2 to 3 minutes after the onset of ischemia, and no recovery was observed during reperfusion. In the mannitol-treated rats and the saline-treated controls, autoradiographic studies after permanent occlusion showed no CBF in the forebrain or cerebellum, although brain-stem and spinal cord CBF values were normal. After 5 minutes of reperfusion, CBF in the cortex, basal ganglia, and white matter was 100% to 200% higher in mannitol-treated rats and 50% to 100% higher in saline-injected rats than in the nonischemic anesthetized control group. Heterogeneously distributed areas of no-reflow were seen in all saline-injected rats but were observed in none of the mannitol-treated rats. Pretreatment with mannitol prevented postischemic obstruction of the microcirculation during 5 minutes of recirculation after 30 minutes of severe temporary ischemia, but the EEG signals did not recover. Further studies of the functional and morphological responses to longer periods of postischemic recirculation are needed to verify the extent to which these mannitol-induced effects are protective.
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PMID:Effect of mannitol on local cerebral blood flow after temporary complete cerebral ischemia in rats. 173 31

Clonidine decreases central sympathetic activity and anesthetic requirement. We tested whether clonidine improves outcome from incomplete ischemia of the brain in rats. Control rats were anesthetized with 25 micrograms.kg-1.h-1 of intravenous fentanyl and inhalation of 70% nitrous oxide (N2O). Clonidine-treated rats received fentanyl/N2O and 10 micrograms/kg of intravenous clonidine 10 min before ischemia, which was produced by right carotid ligation combined with hemorrhagic hypotension to 35 mm Hg for 30 min. Clonidine increased plasma glucose before ischemia and decreased blood catecholamine concentrations during ischemia compared with the control group. Neurologic outcome was evaluated daily for 3 days after ischemia and histopathology was performed at the end of this period. Clonidine significantly improved neurologic outcome on each of the 3 days after ischemia. Histopathology was severe in the control group but not enough rats survived in this group for statistical analysis. The authors conclude that clonidine decreases sympathetic activity during ischemia and that this is associated with an improvement in outcome from incomplete ischemia.
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PMID:Clonidine decreases plasma catecholamines and improves outcome from incomplete ischemia in the rat. 189 70

A new model of temporary complete cerebral ischemia was developed and tested in 64 rats. With use of microsurgical techniques, both pterygopalatine and external carotid arteries were occluded and the basilar artery was coagulated to reduce potential collateral CBF during ischemia. After this preliminary five-vessel occlusion, temporary global ischemia was induced by occluding the common carotid arteries (CCAs) with microclips. To validate the method, CBF was measured autoradiographically in 24 anatomical regions at death after 5 min of ischemia or after 15 min of ischemia followed by 5 min of reperfusion. Mean arterial blood pressure and arterial blood gases remained stable under controlled endotracheal ventilation and anesthesia (halothane, 70% N2O, and 30% O2) throughout the CBF experiments, except for a 10-15% increase in mean arterial blood pressure for 1-5 min after bilateral CCA occlusion. After the initial five-vessel occlusion, the EEG did not change, and local CBF levels were comparable to those in anesthetized non-surgical controls. When the CCAs were occluded, the EEG flattened rapidly; after 5 min of ischemia, autoradiography showed no detectable blood flow in the forebrain and cerebellum. The local CBF levels measured after 15 min of temporary global ischemia and 5 min of reperfusion demonstrated relatively homogeneous postischemic hyperperfusion; only two of eight rats had several 1- to 3-mm areas of no-reflow. Survival studies showed increasing motor impairment after 10, 15, 30, and 60 min of temporary CCA occlusion. Ischemic neuronal damage was observed histologically in the hippocampus and basal ganglia 24 h after 10 min of temporary ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A new method for producing temporary complete cerebral ischemia in rats. 193 88

The authors investigated the effects of nitrous oxide (N2O), ganglionic blockade, and combined infusion of epinephrine and norepinephrine (0.1 microgram.kg-1.min-1 each) on neurologic outcome and brain histopathology in a model of incomplete cerebral ischemia in the rat. Thirty-eight Sprague-Dawley rats were assigned to one of four groups: group 1 (n = 10) received 70% N2O in O2; group 2 (n = 12) received 70% N2O in O2, plus ganglionic blockade; and group 3 (n = 10) received 70% N2O in O2, plus ganglionic blockade and catecholamine infusion. In groups 1-3, ischemia was produced by right carotid occlusion combined with hemorrhagic hypotension (35 mmHg) for 30 min. Group 4 (n = 6) received 70% N2O in O2 and hemorrhagic hypotension without carotid occlusion for 30 min. At the end of ischemic and nonischemic hypotension, the carotid artery was unclamped and the blood slowly reinfused. Neurologic outcome was evaluated for a 5-day period with a graded deficit score (0 = normal to 39 = stroke-related death). Brain histopathology was evaluated in coronal section at the level of the caudate nucleus according to a 6-point scale, from 0 = normal to 5 = total hemispheric infarction. Arterial blood gases, pH, and body temperature were kept constant in all groups. Compared to N2O alone (group 1), treatment with ganglionic blockade (group 2) decreased plasma catecholamines by 75% and significantly improved neurologic outcome from incomplete cerebral ischemia (P less than 0.05). Administration of exogenous epinephrine and norepinephrine in the presence of N2O and ganglionic blockade (group 3) worsened neurologic outcome compared to group 2 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ganglionic blockade improves neurologic outcome from incomplete ischemia in rats: partial reversal by exogenous catecholamines. 197 17

To determine whether nitrous oxide (N2O) worsens myocardial ischemia by diminishing coronary pressure, we performed two sets of experiments using an acutely instrumented swine model of regional coronary ischemia. In constant pressure experiments (n = 11), coronary pressure and heart rate were kept constant as N2O (77%-79%) was substituted for N2 in the inspired gas. Nitrous oxide decreased systolic shortening, measured by sonomicrometry, from 68.0% to 63.6% (P less than 0.05) of preischemic control values in the ischemic zone and from 116.2% to 103.2% (P less than 0.05) of control values in the adjacent normal myocardium. There was no disproportionate effect of N2O on ischemic myocardium, and the N2O-induced depression of contractile function was fully reversible. In a series of constant external stenosis experiments (n = 13), the effects of N2O on heart rate, mean arterial pressure, and the coronary stenosis itself were not controlled. In these experiments, substitution of N2O for N2 induced deterioration in both the ischemic zone (systolic shortening decreased from 68.7% to 58.4% of preischemic control values, P less than 0.05) and in the adjacent normal myocardium (systolic shortening decreased from 113% to 102.9% of preischemic control, P less than 0.05). Nitrous-oxide-induced ischemic zone contractile dysfunction was often not reversible. The pressure gradient across the coronary stenosis did not increase and peripheral coronary pressure did not decrease because of N2O. Diffusion hypoxia was also excluded. This study confirms that N2O has a significant but mild depressant effect on the performance of both normal and ischemic myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of nitrous oxide on coronary pressure and regional contractile function in experimental myocardial ischemia. 201 16

It is now becoming increasingly clear that free radicals contribute to brain damage in several conditions, such as hyperoxia and trauma. It has been more difficult to prove that free radical production mediates ischemic brain damage, but it has often been suggested that it may be a major contributor to reperfusion damage, observed following transient ischemia. Recent results demonstrate that cerebral ischemia of long duration, particularly when followed by reperfusion, leads to enhanced production of partially reduced oxygen species, notably hydrogen peroxide (H2O2). It has also been suggested that postischemic hyperoxia, e.g. an increased oxygen tension during the recirculation period, adversely affects recovery following transient ischemia. Other data support the notion that brain damage caused by permanent ischemia (stroke) is significantly influenced by production of free radicals. The present study, however, fails to show that recirculation following brief periods of ischemia (15 min) leads to an enhanced H2O2 production, and that hyperoxia aggravates the ischemic damage. This study was undertaken to reveal whether variations in oxygen supply in the postischemic period following forebrain ischemia in rats affect free radical production and the brain damage incurred. To that end, rats ventilated on N2O/O2 (70:30) were subjected to 15 min of transient ischemia. Normoxic animals were ventilated with the N2O/O2 mixture, hyperoxic animals with 100% O2, and hypoxic ones with about 10% O2 (balance either N2O/N2 or N2) during the recirculation. At the end of this period, the animals were decapitated for assessment of H2O2 production with the aminotriazole/catalase method. This method is based on the notion that aminotriazole interacts with H2O2 to inactivate catalase; thus, the rate of inactivation of catalase in aminotriazole treated animals reflects H2O2 production. In a parallel series, animals ventilated with one of the three gas mixtures in the early recirculation period, respectively, were allowed to recover for 7 days, with subsequent perfusion-fixation of brain tissues and light microscopical evaluation of the brain damage. Animals given aminotriazole, whether rendered ischemic or not, showed a reduced tissue catalase activity, reflecting H2O2 production in the brain. Hyperoxic animals failed to show increased tissue H2O2 production, while hypoxic ones showed a tendency towards decreased production. However, all three groups (hypo, normo- and hyperoxic) had similar density and distribution of neuronal damage. These results suggest that although postischemic oxygen tensions may determine the rates of H2O2 production, variations in oxygen tensions do not influence the final brain damage incurred.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Free radical production and ischemic brain damage: influence of postischemic oxygen tension. 205 15

Postischemic events cause exacerbation of brain injury, not only in the postischemic area but also in the area originally free from the ischemic insult. The present study was performed in rats. After the animals were anesthetized with a mixture of 70% N2O, 0.5% halothane, a focal ischemia was induced by occlusion of the right MCA by means of a silicone rubber cylinder introduced from the internal carotid artery. Three hours after the MCA occlusion, the embolus was pulling out from the artery by an attached nylon surgical thread. Three hours after the recanalization, animals were decapitated to acquire water content of the brain, local CBF, or local CMRgl. After recirculation, water content markedly increased in the MCA area whereas the CBF returned near normal. However, the CMRgl decreased below half of the normal value. In the neighboring, originally nonischemic area, water content remained within the normal limit although the CBF markedly decreased and the CMRgl increased. Deductions from these data were as follows: (a) If the brain tissue cannot recover from the ischemic-induced injury, restored blood flow may exacerbate the brain edema; and (b) the edematous brain tissue affects the neighboring area with lowering blood flow and rising glucose consumption.
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PMID:Uncoupling of blood flow and glucose metabolism in the neighboring postischemic edematous brain area. 214 97

This experiment was designed to determine if nitrous oxide alters neurologic and pathologic outcome from temporary focal cerebral ischemia in spontaneously hypertensive rats deeply anesthetized with a barbiturate. Two groups of rats were given intravenous methohexital such that a stable EEG pattern of burst suppression was achieved. In one group of rats (n = 11), the lungs were mechanically ventilated with 70% N2O/30% O2, and in the other group (n = 10), ventilation was done with 70% nitrogen/30% O2. The middle cerebral artery was then occluded for 2 h, during which time mean arterial pressure, blood gases, hematocrit, plasma glucose, and head temperature were held constant between groups. The total doses of methohexital administered were similar in both groups as were the plasma methohexital concentrations immediately prior to onset of ischemia. After reperfusion of the middle cerebral artery, the animals were allowed to awaken. Neurologic evaluations were performed prior to ischemia and at 24 and 96 h postischemia. Cerebral infarct volume was measured at 96 h postischemia using triphenyl tetrazolium chloride staining and computer imaging techniques. There were no neurologic differences between the N2O and nitrogen groups at any experimental interval although both groups exhibited deficits at both 24 and 96 h postischemia relative to preischemic values. The two groups also had nearly identical cerebral infarct volumes (N2O = 231 +/- 97 mm3; nitrogen = 226 +/- 75 mm3; mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitrous oxide does not alter infarct volume in rats undergoing reversible middle cerebral artery occlusion. 222 37


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