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

Etomidate and thiopental reduce ischemic neuronal injury but the mechanism by which they do so is not clear. Ischemia-induced release of the excitatory neurotransmitters glutamate and glycine is thought to play a major role in the pathophysiology of ischemic injury. To determine how etomidate and thiopental modulate excitatory transmitter release, their effect on the release of glycine and glutamate during ischemia was evaluated by microdialysis in the hippocampus and cortex of rats. Three groups of Wistar-Kyoto rats (n = 5/group) were studied. In the etomidate and thiopental groups, electroencephalogram (EEG) burst-suppression was achieved and maintained by a continuous infusion of either etomidate (0.6 mg.kg-1.min-1) or thiopental (3 mg.kg-1.min-1) 40 min prior to ischemia. Halothane anesthetized (1 minimum alveolar anesthetic concentration [MAC]) rats served as controls. Ischemia was induced in all three groups by bilateral carotid artery occlusion with simultaneous hypotension to 35 mm Hg for 10 min. Pericranial temperature was controlled at 38 degrees C. Dialysate was collected before, during, and after ischemia. The levels of glutamate and glycine in the dialysate were measured by high-performance liquid chromatography. Within the hippocampus, both glutamate and glycine levels increased significantly in the thiopental and control groups. By contrast, in the etomidate group, glutamate and glycine levels did not increase during ischemia, and peak levels were significantly less than those in the thiopental group. Peak glutamate levels in the thiopental group were significantly larger than in the control group, whereas the peak glycine levels were not different among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Etomidate reduces ischemia-induced glutamate release in the hippocampus in rats subjected to incomplete forebrain ischemia. 772 35

Ischaemia and reperfusion of the myocardium are associated with cellular injuries leading to a decrease of contractile function and the occurrence of arrhythmias. As reperfusion of an ischaemic heart results in an intracellular overload of calcium, a calcium blocking agent pretreatment has been shown to exert a protective effect. By altering myocardial calcium fluxes, volatile anesthetics might also protect the myocardium from ischaemic damage and reperfusion injuries. A beneficial effect of volatile anesthetics on the ischaemic myocardium has been shown in numerous studies. These agents decrease the severity of ischaemia as well as the incidence of reperfusion arrhythmias and improve recovery of myocardial mechanics during reperfusion. They also preserve myocardial energetics and protect from oxygen-derived free radicals injury. However, some studies do not support these protective effects. The wide discrepancy between the various protocols might explain the discrepancy of the results. Enflurane and halothane seem to be more efficient than isoflurane. This cannot only be explained by different cardiovascular effects, but also by a specific effect on myocardial cells. Halothane and enflurane mainly decrease intracellular calcium availability by a direct effect on sarcoplasmic reticulum, while isoflurane only decreases the transsarcolemnal calcium entry. Enflurane and halothane have more beneficial effects than isoflurane on free radicals induced myocardial injuries. In conclusion, despite a wide diversity between the different studies, halothane and enflurane have better protective properties against ischaemia and reperfusion myocardial injuries than isoflurane.
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PMID:[Do halogenated anesthetics protect from ischemic and reperfusion myocardial injuries?]. 773 19

Halothane impact on cerebral blood flow, brain metabolism and its protective effect in ischemia have been assessed in 30 patients operated on for the occlusion of brachiocephalic arteries. The data obtained indicate that additional use of halothane in N2O:O2 anesthesia during reconstructive surgery on brachiocephalic arteries makes it possible to enhance collateral blood flow, increase retrograde pressure, and decrease O2 consumption by the brain, without considerable changes in systemic hemodynamics. In addition, the studies have shown that halothane decreases lipid peroxidation processes.
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PMID:[Effects of halothane on cerebral blood flow and its protective action in ischemia]. 808 Jan 25

Present study was performed to confirm the protective effect of megadose methylprednisolone therapy for the posttraumatic spinal cord ischemia. Seventeen Wistar-King rats weighing 215-330 g were divided into four groups which were normal group (n = 5), injury group treated by saline (control group, n = 4), treated by methylprednisolone (MP) 30 mg/kg (n = 4) and treated by MP 60 mg/kg (n = 4). Animals were anesthetized aspirating 1.5% Halothane and made epidural clipping injury (140 g for 3 seconds) at Th7/8 after laminectomy of Th7,8. Saline or MP of which total volume was 1 ml was injected intravenously 30 minutes after injury and spinal cord blood flow (SCBF) was measured 2 hours after injury by using 14C-iodoantipyrine autoradiography technique. As for normal value of spinal cord blood flow, its gray matter is 96.0 +/- 1.5 ml/100 g/min (mean +/- SE), and white matter is 22.9 +/- 1.8 ml/100 g/min. In the gray matter, SCBF severely decreased in all injury groups as it closed to the injury site, and there was no significant difference among these three groups. In the white matter, SCBF decreased at the injury site in all injury groups and there was no significant difference. From rostral to caudal of the injury site SCBF decreased in MP groups, but in the saline group SCBF showed not so much decrease as MP groups at adjacent to the injury site and at more than 3 mm caudal to the injury site increase of SCBF (hyperemia) was observed. And decrease of white matter SCBF was observed in the rostral rather than in the caudal to the injury site in all injury groups. SCBF of the white matter adjacent to the injury site was not decreased, but preserved within normal range or rather slightly hyperemic. These condition may cause the secondary damage in the adjacent spinal cord. It is considered that megadose of methylprednisolone, if it is effective for the spinal cord injury, would suppress the SCBF of white matter of adjacent to the injury site at the acute phase and prevent the progression of secondary damage.
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PMID:[Effects of megadose methylprednisolone therapy on acute spinal cord injury in rats]. 815 49

We studied the effect of halothane on regional myocardial function during acute ischemia and reperfusion in an open-chest pig model. Anesthesia was induced with thiopental and fentanyl and maintained with an intravenous (IV) infusion of pentobarbital and fentanyl. Regional myocardial function was studied with microsonometers placed in the subendocardium supplied by the left anterior descending coronary (LAD) and circumflex coronary artery (LX). Systolic function was evaluated with reference to the end-systolic pressure-length relationship (ESPLR) and regional systolic shortening. Diastolic dysfunction was studied with postsystolic shortening (PSS). Ischemia was induced with 15 min of total occlusion of the LAD artery, and thereafter reperfusion was allowed for 120 min. Five groups were studied: one group received only pentobarbital and fentanyl (n = 10); the other groups received halothane 0.2% (n = 5), 0.4% (n = 7), 0.6% (n = 5), and 0.8% (n = 5). The pentobarbital and fentanyl infusion was adjusted in the halothane groups in an effort to maintain arterial blood pressure and heart rate within specified limits (when possible). Results indicate that regional dysfunction during acute ischemia was equal among all the groups. However, on reperfusion, halothane significantly reduced the incidence of ventricular arrhythmias. Halothane (0.6% and 0.8%) was associated with less regional postischemic systolic dysfunction during reperfusion when compared to the other groups. Hearts subjected to 0.6% and 0.8% halothane also were less stiff at the end of systole (i.e., the extrapolated ventricular volume at zero ventricular pressure was less) after 120 min reperfusion compared to animals receiving less halothane. However, diastolic dysfunction was equal among the groups during reperfusion. We conclude that, in this model, administration of halothane is associated with improved recovery of regional systolic function and potentially beneficial pressure-length relations at the end of systole after acute severe myocardial ischemia and reperfusion. Furthermore, administration of halothane was associated with fewer reperfusion arrhythmias compared to animals not receiving halothane.
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PMID:Halothane and the reperfusion injury in the intact animal model. 846 9

To address the importance of nitric oxide or its reaction products as mediators of neurotoxicity in brain, tissue injury was assessed after transient global ischemia in mice rendered mutant in the gene for neuronal nitric oxide synthase. Halothane-anesthetized wild type and mutant mice were subjected to temporary occlusion of the basilar plus both carotid arteries for 5 or 10 min followed by three days of reperfusion. Hippocampal injury, assessed both by qualitative grading and by cell counting in the CA1 subregion, was significantly less in the mutant mice group after 5 or 10 min of ischemia. Mutant mice exhibited a lower mortality (P < 0.01), less weight loss, more normal grooming and spontaneous motor activity and better grasping in the 10 min group. There were no obvious differences in cerebrovascular anatomy or hemodynamics between wild type and mutant mice. The data suggest that a deficiency of neuronal nitric oxide synthase confers increased resistance to transient global cerebral ischemia, and support the suggestion that selective neuronal nitric oxide synthase inhibitors might reduce tissue injury associated with global cerebral ischemia.
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PMID:Attenuated hippocampal damage after global cerebral ischemia in mice mutant in neuronal nitric oxide synthase. 873 5

Neuroanatomical methods have been used to study selective vulnerability after global brain ischemia. A consistent pattern of ischemic neuronal damage is found in the rodent hippocampus with loss of CA1 neurons and of some cells in the hilus of the dentate gyrus. Very little is known about plastic changes that would be expected in ischemia-resistant areas such as CA3 neurons and granule cells. Neuronal plasticity after lesions may be indicated by changes in labeling with antibodies to the growth-associated protein 43 (GAP-43). Expression of GAP-43 as a marker for neuronal plasticity was studied here in the hippocampus after global brain ischemia. Halothane-anesthetized rats were subjected to 20 min of transient forebrain ischemia using four-vessel occlusion. In situ hybridization was used to study GAP-43 mRNA at 1, 3, 6, and 12 h and at 1, 3, and 7 days after ischemia. Immunostaining was carried out with two different antibodies to GAP-43 in brains which were perfusion-fixed after 1, 2, 4, and 7/8 days. In the control hippocampus, GAP-43 mRNA was localized to CA1-CA3 and the hilus. Moderate increases in cellular signals were seen in hilar cells and granule cells early after ischemia, and some changes occurred in CA3 at late stages. Hybridization was lost in CA1 due to cell death. With immunostaining, GAP-43 was not seen in the cytoplasm of neurons, whereas dense labeling occurred in a differentiated pattern in the axonal and dendritic layers. At 1 day after ischemia, neurons in the hilus of the dentate gyrus and in the stratum pyramidale and lucidum of CA3 showed strong cytoplasmic labeling for GAP-43. Few cells were labeled in these regions at 2 days, and none at later stages. Pyramidal cells in CA1 and CA3 areas and granule cells were never labeled. These studies demonstrate a transient expression of GAP-43 mRNA and protein in a subset of vulnerable neurons after transient brain ischemia. The cytoplasmic localization in hilar neurons could be due to increased synthesis of GAP-43 or to changes in axoplasmic transport. It is suggested that axonal damage occurs in hilar cells which stimulates GAP-43 expression. The increased production of trophic factors after ischemia in granule cells could also cause plastic changes in hilar cells. Since hilar neurons are in a strategic position to control the excitability of the dentate area, increased expression of GAP-43 may indicate an important pathophysiological process. In seizure experiments, strong expression of GAP-43 mRNA in granule cells was associated with abnormal mossy fiber sprouting and development of chronic epilepsy. The relevance of the minor GAP-43 mRNA upregulation after ischemia must be considered. The changes in CA3 neurons at several days after ischemia might represent a plastic response to a loss of CA1 neurons.
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PMID:Transient expression of GAP-43 within the hippocampus after global brain ischemia in rat. 908 58

Genetically engineered mice deficient in the expression of type III nitric oxide synthase (NOS) [endothelial NOS (eNOS)] were used to decipher the importance of nitric oxide (NO)-dependent augmentation of regional cerebral blood flow (rCBF) to infarct volume reduction following basic fibroblast growth factor (bFGF) infusion during acute middle cerebral artery (MCA) occlusion. We have shown previously that intravenously administered bFGF reduces infarct volume following MCA occlusion in rats and that bFGF dilates cerebral pial arterioles by NO-dependent mechanisms. Halothane-anesthetized eNOS knockout and wild-type mice were subjected to permanent MCA occlusion by intraluminal filament for 24 h. bFGF (100 microg x kg(-1) x h(-1)) was infused intravenously for 2 h, beginning 15 min after the onset of occlusion. Infarct volume was reduced from 119 +/- 8 to 93 +/- 4 mm3 (22% reduction, P < 0.05) or from 102 +/- 9 to 77 +/- 6 mm3 (24% reduction, P < 0.05) in eNOS knockout or wild-type mice, respectively (means +/- SE; n = 10 per group), and neurological deficits were also significantly reduced. Although bFGF infusion caused a 27% increase in rCBF and a 17% reduction in vascular resistance in the infarct margin of wild-type animals as measured by laser Doppler flowmetry, bFGF did not enhance rCBF in the infarct margin of eNOS mutant mice. These data indicate that intravenous bFGF reduces infarct volume following focal ischemia by mechanisms that are largely blood flow independent.
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PMID:bFGF ameliorates focal ischemic injury by blood flow-independent mechanisms in eNOS mutant mice. 908 17

Microcirculatory impairments have theoretically been proposed as a potential factor in the development of ischemic injury, but few attempts have been made to directly assess microvascular patency following stroke. To address this issue we investigated the temporal changes in microvascular perfusion induced by permanent focal ischemia. Halothane-anesthetized spontaneously hypertensive rats were subjected to middle cerebral artery occlusion (MCAO) of 5 min to 4 h duration. Two fluorescent tracers (FITC-dextran and Evans blue) were then sequentially administered i.v. and allowed to circulate for 10 and 5 s respectively. Tissue sections were examined by fluorescent microscopy, and the mean number of perfused microvessels/mm2 calculated for cortical areas representing non-ischemic (Region A), perifocal/penumbral (Region B) and core ischemic (Region C) regions. For sham-operated controls, virtually all microvessels perfused with tracer within 5 s. In contrast MCAO induced significant reductions in the number of perfused microvessels in Regions B and C. The most marked impairments in perfusion were observed in core MCA territory (e.g. 2-10% of control values for 5 s circulation period) while, initially, the deficit was less severe in penumbral cortex. However, a secondary perfusion impairment developed over time in the perifocal/penumbral region, so that the deficit was greater 4 h after MCAO than at earlier time points (e.g. 72%, 71% and 22% of control value for 0.5, 1 and 4 h MCAO respectively; 10 s circulation period). In conclusion, MCAO induced severe impairments in microcirculatory perfusion within the core ischemic region, and to a lesser extent in the penumbra. However, the development of a more severe perfusion deficit in the penumbra within 4 h of MCAO supports the hypothesis that microcirculatory failure in this region contributes to its recruitment to the ischemic infarct.
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PMID:Temporal impairment of microcirculatory perfusion following focal cerebral ischemia in the spontaneously hypertensive rat. 913 19

Halothane is a strong inhibitor of potassium evoked spreading depression (SD) in cats. In the current study, we investigate halothane effects on induction of perifocal SD-like depolarizations, CBF, and infarct evolution in focal ischemia. Calomel and platinum electrodes measured cortical direct current potential and CBF in ectosylvian, suprasylvian, and marginal gyri. Left middle cerebral artery occlusion (MCAO) induced permanent focal ischemia for 16 hours in artificially ventilated cats (30% oxygen, 70% nitrous oxide) under halothane (0.75%, n = 8) or alpha-chloralose anesthesia (60 mg/kg intravenously, n = 7). Under alpha-chloralose, MCAO induced severe ischemia in ectosylvian and suprasylvian gyri(mean CBF < 10 mL/100 g/min), and direct current potentials turned immediately into terminal depolarization. In marginal gyri, CBF reduction was mild (more than 20 mL/100 g/min), and in six of seven animals, frequent SD-like depolarizations turned into terminal depolarization at a later stage of the experiments. Under halothane, MCAO induced severe ischemia (less than 10 mL/100 g/min) and immediate terminal depolarization only in ectosylvian gyrus. In suprasylvian gyrus, residual CBF remained significantly higher (more than 10 mL/100 g/min) than under alpha-chloralose, whereas in marginal gyri, CBF did not differ between groups. Compared with chloralose, the number of transient depolarizations was significantly reduced in marginal gyrus, and in suprasylvian gyrus transient but significantly longer depolarizations than in marginal gyrus were recorded. Except for one animal, transient depolarizations did not turn into terminal depolarization under halothane, and infarct volume reduction was particularly seen in suprasylvian gyrus. We conclude that halothane, the most commonly used anesthetic in studies of experimental brain ischemia, has protective properties, which may depend on both cerebrovascular and electrophysiologic influences.
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PMID:Reduction of infarct volume by halothane: effect on cerebral blood flow or perifocal spreading depression-like depolarizations. 929 May 83


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