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Anesth Analg 2003;97:1155-1161
© 2003 International Anesthesia Research Society

NEUROSURGICAL ANESTHESIA

The Effect of Sevoflurane and Propofol on Cerebral Neurotransmitter Concentrations During Cerebral Ischemia in Rats

Kristin Engelhard, MD*, Christian Werner, MD*, William E. Hoffman, PhD{ddagger}, Bianca Matthes, BS{dagger}, Manfred Blobner, MD*, and Eberhard Kochs, MD*

*Klinik für Anaesthesiologie and {dagger}Institut für klinische Chemie und Pathobiochemie, Technische Universität München, Klinikum rechts der Isar, Munich, Germany; and {ddagger}Department of Anesthesiology, University of Illinois at Chicago

Address correspondence and reprint requests to Kristin Engelhard, MD, Klinik für Anaesthesiologie, Technische Universität München, Klinikum rechts der Isar, Ismaninger Straße 22, 81675 MÜNCHEN, Germany. Address e-mail to k.engelhard{at}lrz.tu-muenchen.de


   Abstract
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 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Sevoflurane and propofol are neuroprotective possibly by attenuating central or peripheral catecholamines. We evaluated the effect of these anesthetics on circulating catecholamines and brain neurotransmitters during ischemia in rats. Forty male Sprague-Dawley rats were randomly assigned to one of the following treatment groups: fentanyl and N2O/O2 (control), 2.0% sevoflurane, 0.8–1.2 mg · kg-1 · min-1 of propofol, and sham-operated rats with fentanyl and N2O/O2. Ischemia (30 min) was produced by unilateral common carotid artery occlusion plus hemorrhagic hypotension to a mean arterial blood pressure of 32 ± 2 mm Hg. Pericranial temperature, arterial blood gases, and pH value were maintained constant. Cerebral catecholamine and glutamate concentrations, sampled by microdialysis, and plasma catecholamine concentrations were analyzed using high-pressure liquid chromatography. During ischemia, circulating catecholamines were almost completely suppressed by propofol but only modestly decreased with sevoflurane. Sevoflurane and propofol suppressed brain norepinephrine concentration increases by 75% and 58%, respectively, compared with controls. Intra-ischemia cerebral glutamate concentration was decreased by 60% with both sevoflurane and propofol. These results question a role of circulating catecholamines as a common mechanism for cerebral protection during sevoflurane and propofol. A role of brain tissue catecholamines in mediating ischemic injury is consistent with our results.

IMPLICATIONS: During incomplete cerebral ischemia, the neuroprotective anesthetics sevoflurane and propofol suppressed cerebral increases in norepinephrine and glutamate concentrations. In contrast, propofol, but not sevoflurane, suppressed the ischemia-induced increase in circulating catecholamines to baseline levels. The results question a role for plasma catecholamines in cerebral ischemic injury.


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Studies indicate that sevoflurane and propofol anesthesia protect the brain from incomplete or focal cerebral ischemia (1–4). The protective effect of these anesthetics may be related to their ability to suppress sympathetic activity and the stress response related to hypotension and ischemia. Circulating catecholamines have been implicated in neuronal injury during incomplete ischemia (5,6), and the mechanism of injury may be due to increased cerebral metabolic activity (7). Increased brain tissue catecholamines and excitatory neurotransmitters have also been suggested to worsen brain ischemic injury (8–10). Although some studies suggest that anesthetics and sympatholytic treatments may decrease brain excitatory extracellular neurotransmitter concentrations and ischemic injury simultaneously (11–13), others have questioned the role of brain neurotransmitters in ischemic neuronal damage (14,15). The purpose of the present study was to investigate the effect of the neuroprotective anesthetics sevoflurane and propofol on circulating catecholamine and brain tissue neurotransmitter concentrations during and after cerebral ischemia.


   Methods
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 Abstract
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 Methods
Results
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After approval of the animal care committee, 40 male Sprague-Dawley rats (weighing 300–420 g) were anesthetized in a bell jar saturated with isoflurane. The trachea was intubated and the lungs mechanically ventilated with 1.5% isoflurane in nitrous oxide and oxygen (fraction of inspired oxygen [FIO2] = 0.33). Catheters were inserted into the right femoral artery and vein and into the right jugular vein for blood withdrawal, administration of drugs, and blood sampling. A loose ligature was placed around the right common carotid artery for later clamping. The rats were then placed in a stereotactic "U"-frame with nonpenetrating ear bars (Model 962, David Kopf Instruments, Tujunga, CA). The scalp was incised and penetrating burr holes, 1 mm in diameter, were drilled into the cranium 4.2 mm posterior and 2.5 mm lateral to bregma over both hemispheres according to the stereotactic coordinates of the rat brain (16). The tip of the drill was continuously flushed with saline to avoid thermal injury. The dura was incised and microdialysis probes (CMA12, 4.0 mm in length, 0.5 mm in diameter, CMA/Microdialysis AB, Solna, Sweden) were inserted into the cortex and dorsal hippocampus. The probes were then fixed using a zinc polycarboxylate cement (Poly-F Plus; Dentsply, York, PA) and perfused with Ringer’s lactate solution (Boehringer Ingelheim Delta Pharm GmbH, Pfullingen, Germany; Na+ 147 mmol/L, Ca2+ 2.25 mmol/L, K+ 4 mmol/L, and Cl- 155.5 mmol/L) at a rate of 1.0 µL/min. Small collector vials were filled with 10 µL of 0.5 M perchloric acid to stabilize catecholamines and placed in a refrigerated fraction collector (CMA 170, CMA/Microdialysis AB). Ninety minutes after implantation of the microdialysis probes, sample fractions of 30 min were collected and subsequently stored at -70°C.

Nonpenetrating burr holes were drilled 0.5 mm anterior and 1 mm lateral to bregma into the cranium over both hemispheres for continuous measurement of red blood cell flow velocity using a laser Doppler flowmeter (PeriFlux System 4001, Perimed, Järfälla, Sweden). Local cerebral blood flow was continuously measured and expressed in arbitrary perfusion units, which were sampled over 0.3 s. The laser Doppler flow probes (Probe 403, Perimed) were placed over both hemispheres and fixed using the stereotactic frame. Care was taken to place the probes over a tissue area devoid of large blood vessels visible through the thinned bone, and responsivity of the probes was confirmed by transient hypoventilation. Pericranial temperature was measured with a 22-gauge stainless steel needle thermistor (model 73A, YSI temperature controller, Yellow Springs, OH) placed beneath the right temporal muscle and was maintained constant at 37.5°C throughout the experiment by a servomechanism using an overhead heating lamp and a heating pad. An electroencephalogram (EEG) was recorded continuously using subdermal platinum needle electrodes placed over both hemispheres at the parietotemporal versus frontal cortex recording sites (AC/AD Strain Gage Amplifier, Model P122, Grass Instruments Division, Berkshire, UK).

At the end of the preparation, all surgical incisions were infiltrated with bupivacaine 0.5%. Mechanical ventilation was adjusted to maintain PaCO2 at 38–42 mm Hg. The nonpenetrating ear bars of the stereotactic frame were released. During cerebral ischemia, arterial pH values were maintained at physiologic levels by IV infusion of sodium bicarbonate. Vecuronium was given as a continuous IV infusion (0.1 mg · kg-1 · min-1) to maintain neuromuscular blockade. Animals were randomly assigned to one of the following treatment groups, and the background anesthetics were discontinued. Group 1 (n = 10) (control) received fentanyl IV (bolus, 10 µg/kg; infusion, 25 µg · kg-1 · h-1) and nitrous oxide in oxygen (FIO2 = 0.33). Rats in Group 2 (n = 10) received 2.0% sevoflurane (1.0 minimum anesthetic alveolar concentration) in oxygen and air (FIO2 = 0.33). Rats in Group 3 (n = 10) received 0.8–1.2 mg · kg-1 · min-1 of propofol IV (to induce EEG burst suppression) and oxygen in air (FIO2 = 0.33). Rats in Group 4 (n = 10) were sham-operated (i.e., complete instrumentation and no ischemia), and anesthesia was the same as in the control animals with fentanyl IV, with nitrous oxide in oxygen (FIO2 = 0.33). After an equilibration period of 2 h, cerebral ischemia was induced by hemorrhagic hypotension and clip occlusion of the right common carotid artery. Mean arterial blood pressure was maintained at 32 ± 2 mm Hg during ischemia. After 30 min, the clip was released, and the shed blood was reinfused over 15 min. Arterial blood gases and plasma glucose concentrations were analyzed at baseline, at the end of ischemia, during reperfusion, and 90 min after ischemia (recovery). Blood samples for measurement of plasma catecholamine concentrations were collected at baseline, at the end of ischemia, and 90 min after ischemia during recovery. The blood samples were centrifuged at 4°C for 10 min, and the plasma was stored at -70°C. Brains were removed 4 h after ischemia and placed in tissue freezing medium (Jung Tissue Freezing Medium, Leica Instruments GmbH, Nussloch, Germany), frozen in methyl butane on dry ice, and stored at -70°C. The correct position of the microdialysis probes was verified, and histologic damage caused by the probes was evaluated in 7-µm brain slices stained with hematoxylin and eosin, and animals were excluded from the study in case of major bleeding.

Samples for plasma norepinephrine- and epine-phrine-analyses were processed using the ClinRep test kit for high-performance liquid chromatography (HPLC) analysis of catecholamines (Recipe Chemicals and Instruments GmbH, Munich, Germany). Plasma samples (0.25 mL) were mixed with 50 µL of dihydroxybenzylamine (internal standard). The mixture was passed through the sample preparation column filled with aluminum oxide. The remaining particles of plasma proteins were washed out. Norepinephrine and epinephrine were eluted by adding 120 µL of elution buffer. No pretreatment was required to analyze cerebral dialysate for cerebral extracellular norepinephrine concentration. Samples were placed into a cooled autosampler (AS2000A, Merck Hitachi, Darmstadt, Germany). Sixty microliters of the plasma elute or 10 µL of the cerebral dialysate was injected into the HPLC circulation system (mobile phase ClinRep, Recipe Chemicals and Instruments) for electrochemical detection (0.5 V potential). The elute and the cerebral dialysate were passed over the analytical column (ClinRep) with a flow of 1.0 mL/min to the electrochemical detector (Waters 460, Waters, Milford, MA). The entire system was controlled, and data were stored by the HPLC-systems manager software (Merck Hitachi). The system was calibrated with a catecholamine standard (ClinRep).

For analysis of the cerebral glutamate and aspartate concentration, the microdialysis-samples were placed into an autoinjector (Gina 50 Probengeber, Dionex, Germering, Germany). Twenty microliters of Ortho-Phthaldialdehyd, diluted with boracic buffer (1:10), was mixed with 10 µL of cerebral dialysate for derivatisation. This mixture was injected into the HPLC circulation system (Pumpensystem M480, Dionex) for fluorometrical detection and was passed over the analytical column (Grom-Sil OAA-2, 250 x 4 mm, Grom, Herrenberg, Germany) with a flow of 0.8 mL/min to the fluorescence-detector (Fluoreszenzdetektor RF-2000, Dionex; wavelength, extinction 280 nm–emission 475 nm). The mobile phase A consisted of 23 mmol/L of sodium acetate adjusted with human cultured lymphoblasts to a pH of 6.0. The mobile phase B consisted of 600 mL of methanol and 50 mL of acetonitrile. The gradient was changed as follows: after beginning, 100% phase A:0% phase B; after 29.8 min, 79% phase A:21% phase B; after 32.5 min, 47% phase A:53% phase B; and after 34 min, 0% phase A:100% phase B. The analysis refers to a 4-point standard curve of a custom made standard.

Animals treated with sevoflurane or propofol were separately compared with control and sham-operated animals, resulting in two sets of experiments. The sevoflurane experiment compared sevoflurane versus control versus sham-operated rats. The propofol experiment compared propofol versus control versus sham-operated rats. Because the control and the sham-operated rats were used for two experimental sets, the level of significance was corrected (P < 0.05/2 = 0.025).

Physiological values were measured at four times: before hemorrhagic hypotension (baseline); at 30 min of ischemia onset (ischemia); 15 min after ischemia on reinfusion of the withdrawn blood (reperfusion); and 90 min after ischemia (recovery). To address the multiple comparisons, a hierarchical statistical model based on consecutively calculated repeated-measurement analyses of variance and t-tests was chosen using the within-groups factor, time2, the between-groups factor, group, and their interaction term (time2 x group). Post hoc analyses were restricted on two hypotheses: (a) differences among groups at each treatment and (b) differences between baseline and ischemia within each group. The same statistical analysis was performed for the plasma catecholamine concentrations, which were measured at only three time points (baseline, ischemia, and recovery). All variables are presented as mean ± SD. Statistical analyses were performed using SPSS 10.0 for Windows (SPSS Inc., Chicago, IL).


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Table 1 shows the physiologic values. According to the study protocol, mean arterial blood pressure was decreased in control animals (Group 1) and in animals anesthetized with sevoflurane and propofol (Groups 2 and 3) during ischemia compared with sham-operated animals (Group 4). There were no differences for PaO2 and PaCO2 within (baseline versus ischemia) or among groups. Laser Doppler flow decreased to statistically similar levels in all groups during ischemia, with the exception of the sham-operated animals. In control animals and in sevoflurane-anesthetized animals, plasma glucose concentration decreased during ischemia compared with baseline. During ischemia, plasma glucose concentration was smaller in control animals and propofol-anesthetized animals compared with sham-treated animals.


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  		Table 1. Mean arterial blood pressure (MAP), arterial blood gas tensions, laser Doppler flow (LDF; PU = perfusion units), and plasma glucose concentration during baseline, ischemia, reperfusion, and recovery (90 min after cerebral ischemia)
 
Figure 1 shows the plasma norepinephrine and epinephrine concentrations before, during, and after ischemia. In control animals, plasma norepinephrine concentration was increased during ischemia compared with baseline. Anesthesia with sevoflurane and propofol decreased plasma norepinephrine concentration compared with control animals during ischemia. Plasma epinephrine increased in sevoflurane and control treated rats during ischemia.



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  		Figure 1. Plasma norepinephrine and epinephrine concentration before, during, and after cerebral ischemia. Sevoflurane and propofol suppressed the plasma norepinephrine concentration during cerebral ischemia, whereas the increase in plasma epinephrine concentration was suppressed only by propofol. *P < 0.05 compared with control group during ischemia; §P < 0.05 compared with sham-operated animals during ischemia; #P < 0.05 baseline versus ischemia within control group; $P < 0.05 baseline versus ischemia within sevoflurane-anesthetized animals.

 
Figure 2 shows norepinephrine (A) and glutamate (B) concentrations in the cerebral cortex and hippocampus before, during, and after ischemia in the ischemic hemisphere. Ischemia increased norepinephrine and glutamate concentrations in control rats, and this increase was suppressed by sevoflurane and propofol. Norepinephrine and glutamate concentrations were not increased in the contralateral hemisphere during ischemia in any treatment group.



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  		Figure 2. Cerebral norepinephrine concentration (A) and glutamate concentration (B) in the ischemic and nonischemic hemisphere before, during, and after cerebral ischemia. Both cerebral norepinephrine and glutamate concentration increased in the ischemic hemisphere during ischemia in control animals. Anesthesia with sevoflurane and propofol suppressed this increase. *P < 0.05 compared with control group during ischemia; §P < 0.05 compared with sham-operated animals during ischemia; #P < 0.05 baseline versus ischemia within control group; +P < 0.05 baseline versus ischemia within propofol-anesthetized animals.

 

   Discussion
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 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
In this study, we found that brain tissue norepinephrine and glutamate concentrations were increased in ischemic tissue of control rats compared with sevoflurane- or propofol-anesthetized rats. Hypotension was associated with an increase in circulating norepinephrine and epinephrine that was significantly larger in ischemic control rats than propofol or sham-treated rats. During ischemia, plasma epinephrine increased in sevoflurane-anesthetized rats to a level not different from control ischemic animals. The results show that propofol, but not sevoflurane, anesthesia completely suppressed the increase in plasma catecholamines during ischemia and hypotension. Because both sevoflurane and propofol protect the brain from incomplete cerebral ischemia (1,17), the role of circulating catecholamines in mediating ischemic injury is questioned.

Reports indicate that anesthetic treatments and ganglionic blockade decreased plasma catecholamines dur-ing ischemia, and this was related to improved outcome from incomplete brain ischemia compared with fentanyl/N2O (5,6). Other studies found that isoflurane decreased circulating catecholamines during near-complete ischemia and improved ischemic outcome compared with a control treatment of fentanyl/N2O (18,19). In contrast, studies in the rat showed that propofol at a concentration producing EEG burst suppression improved neurological outcome from incomplete ischemia, but this improvement could not be completely explained by the attenuating effect on circulating catecholamines (20). In addition, during near-complete ischemia, isoflurane decreased circulating catecholamines and ischemic injury on one hand, but this effect was reversed, and the injury was worsened when rats also were treated with ganglionic blockade (19,21). This suggests a positive relationship between plasma catecholamines and ischemic injury when anesthetics are compared with control treatments, but this relationship cannot explain how brain protection can be reversed when ganglionic blockade is included. Our data question the role of plasma catecholamines in ischemic injury because propofol, but not sevoflurane, decreased plasma epinephrine, whereas both anesthetics have protected the brain from incomplete ischemia in former studies (1,2).

There is controversy about the role of brain catecholamines and excitatory neurotransmitters in ischemic neuronal injury. In rats, excitatory neurotransmitters were increased during ischemia, and it was hypothesized that increased extracellular concentrations of excitatory neurotransmitters worsened neuronal injury by increasing metabolic demand and ischemic acidosis (9,10). Our data are consistent with similar reports showing that both propofol and sevoflurane decreased central catecholamines and glutamate during ischemia compared with a control ischemic treatment (22–24). However, recent experiments evaluating incomplete and near-complete cerebral ischemia in rats have shown that anesthetic treatments that increased brain extracellular norepinephrine and glutamate concentrations during ischemia protected the brain from injury (14,18). In addition, drug-induced depletion of central catecholamines before ischemia abolished the increase in norepinephrine but did not improve or worsen ischemic injury compared with a control treatment (15,25). These results have led investigators to conclude that brain catecholamine concentrations during ischemia are not related to anesthetic-mediated brain protection.

Propofol anesthesia sufficient to produce EEG burst suppression may have suppressed neuronal function and brain oxygen consumption more than 1 minimum anesthetic alveolar concentration anesthesia with sevoflurane, and this difference in anesthetic depth may be related to catecholamine and neurotransmitter release or brain protection during ischemia. However, modest and moderate anesthetic doses of propofol suppress plasma catecholamines during incomplete ischemia (20) as opposed to the minimal effect we saw with sevoflurane. This suggests a difference in anesthetic action between propofol and sevoflurane that explains the disparity in plasma catecholamines during ischemia, rather than anesthetic dose. At the same time, increases in central norepinephrine and glutamate during ischemia were suppressed to a similar degree with propofol and sevoflurane in our study. Finally, we have seen similar improvement in ischemic outcome with the same doses of propofol and sevoflurane tested here (1,2). Other studies have evaluated the effect of anesthetic dose on brain protection and showed that increasing anesthesia from levels producing an active EEG to burst suppression provides no additional improvement in ischemic outcome (6,26). This suggests that anesthetic-mediated brain protection and neurotransmitter release from ischemia is not a dose-related phenomenon.

We assumed in this study that the magnitude of the ischemic challenge was similar in each group, based on the fact that each rat received unilateral carotid ligation combined with hemorrhagic hypotension to 32 mm Hg. This was supported by the fact that laser Doppler flow in the ischemic hemisphere was statistically similar in all of the anesthetic treatment groups during ischemia and are similar to values reported in this laboratory (14). Laser Doppler blood flow is determined by red blood cell volume and velocity in tissue and relates closely to capillary perfusion (24,27). Laser Doppler measurements do not indicate absolute tissue blood flow, but relative changes in flow from baseline values are valid. Our data support reports that propofol anesthesia produces cerebral vasoconstriction under baseline conditions in relation to its ability to decrease cerebral oxygen consumption (28). There was a trend for ischemic blood flow to be increased in sevoflurane-treated rats during ischemia, but this effect was not significant. Sevoflurane may enhance collateral perfusion during ischemia because of its cerebrovasodilatory effects (29,30).

In conclusion, our data indicate that plasma catecholamines and brain tissue norepinephrine and glutamate are increased in fentanyl/N2O-anesthetized rats during incomplete ischemia and that these changes are attenuated by propofol anesthesia. In contrast, sevoflurane produced a minimal attenuation in plasma catecholamines but suppressed central neurotransmitter release the same as propofol. These results raise doubts about the possible role of circulating catecholamines as a common mechanism for the neuroprotective effects of propofol and sevoflurane observed in previous studies (1,2). Whereas in the present study, the ischemia-induced increase in cerebral catecholamines were reduced by the neuroprotective anesthetics sevoflurane and propofol, other studies have indicated that central excitatory neurotransmitters are not important in the mediation of anesthetic-related ischemic protection (14,15). The inconsistency of studies showing that both low and high levels of circulating and central catecholamines are associated with improved ischemic outcome question the role of these neurotransmitters in anesthetic-related brain protection.


   Acknowledgments
 
Supported, in part, by a grant from Abbott GmbH, Wiesbaden, Germany, and by a grant from Else Kröner-Fresenius-Stiftung, Bad Homburg v.d. Höhe, Germany.


   References
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 Abstract
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 Methods
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 References
 

  1. Kochs E, Hoffman WE, Werner C, et al. The effect of propofol on brain electrical activity, neurologic outcome, and neuronal damage following incomplete ischemia in rats. Anesthesiology 1992; 76: 245–52.[Web of Science][Medline]
  2. Werner C, Möllenberg O, Kochs E, Schulte am Esch J. Sevoflurane improves neurological outcome after incomplete cerebral ischaemia in rats. Br J Anaesth 1995; 75: 756–60.[Abstract/Free Full Text]
  3. Pittman JE, Sheng H, Pearlstein R, et al. Comparison of the effects of propofol and pentobarbital on neurologic outcome and cerebral infarct size after temporary focal ischemia in the rat. Anesthesiology 1997; 87: 1139–44.[Web of Science][Medline]
  4. Gelb AW, Bayona NA, Wilson JX, Cechetto DF. Propofol anesthesia compared to awake reduces infarct size in rats. Anesthesiology 2002; 96: 1183–90.[Web of Science][Medline]
  5. Werner C, Hoffman WE, Thomas C, et al. Ganglionic blockade improves neurologic outcome from incomplete ischemia in rats: partial reversal by exogenous catecholamines. Anesthesiology 1990; 73: 923–9.[Web of Science][Medline]
  6. Engelhard K, Werner C, Reeker W, et al. Desflurane and isoflurane improve neurological outcome after incomplete cerebral ischaemia in rats. Br J Anaesth 1999; 83: 415–21.[Abstract/Free Full Text]
  7. Pulsinelli WA, Brierley JB, Plum F. Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol 1982; 11: 491–8.[Web of Science][Medline]
  8. Globus MYT, Busto R, Dietrich WD, et al. Direct evidence for acute and massive norepinephrine release in the hippocampus during transient ischemia. J Cereb Blood Flow Metab 1989; 9: 892–6.[Web of Science][Medline]
  9. Bhardwaj A, Brannan TS, Martinez-Tica J, Weinberger J. Ischemia in the dorsal hippocampus is associated with acute extracellular release of dopamine and norepinephrine. J Neural Transm 1990; 80: 195–201.[Web of Science][Medline]
  10. Stein SC, Cracco RQ. Cortical injury without ischemia produced by topical monoamines. Stroke 1982; 13: 74–83.[Abstract/Free Full Text]
  11. Moe MC, Berg-Johnsen J, Larsen GA, et al. Sevoflurane reduces synaptic glutamate release in human synaptosomes. J Neurosurg Anesthesiol 2002; 14: 180–6.[Web of Science][Medline]
  12. Graham SH, Chen J, Sharp FR, Simon RP. Limiting ischemic injury by inhibition of excitatory amino acid release. J Cereb Blood Flow Metab 1993; 13: 88–97.[Web of Science][Medline]
  13. Nellgård B, Mackensen GB, Sarraf-Yazdi S, et al. Pre-ischemic depletion of brain norepinephrine decreases infarct size in normothermic rats exposed to transient focal cerebral ischemia. Neurosci Lett 1999; 275: 167–70.[Web of Science][Medline]
  14. Engelhard K, Werner C, Kaspar S, et al. Effect of the a2-agonist dexmedetomidine on cerebral neurotransmitter concentrations during cerebral ischemia in rats. Anesthesiology 2002; 96: 450–7.[Web of Science][Medline]
  15. Nellgård BMG, Miura Y, Mackensen GB, et al. Effect of intracerebral norepinephrine depletion on outcome from severe forebrain ischemia in the rat. Brain Res 1999; 847: 262–9.[Web of Science][Medline]
  16. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 4th ed. Academic Press Inc., 1998: 128–44.
  17. Todd MM, Weeks JB, Warner DS. Cerebral blood flow, blood volume, and brain tissue hematocrit during isovolemic hemodilution with hetastarch in rats. Am J Physiol 1992; 263: H75–82.
  18. Miura Y, Mackensen B, Nellgard B, et al. Effects of isoflurane, ketamine, and fentanyl/N2O on concentrations of brain and plasma catecholamines during near-complete cerebral ischemia in the rat. Anesth Analg 1999; 88: 787–92.[Abstract/Free Full Text]
  19. Mackensen GB, Nellgård B, Miura Y, et al. Sympathetic ganglionic blockade masks beneficial effect of isoflurane on histologic outcome from near-complete forebrain ischemia in the rat. Anesthesiology 1999; 90: 873–81.[Web of Science][Medline]
  20. Yamasaki T, Nakakimura K, Matsumoto M, et al. Effect of graded suppression of the EEG with propofol on the neurological outcome following incomplete cerebral ischemia in rats. Eur J Anaesthesiol 1999; 16: 320–9.[Web of Science][Medline]
  21. Koide T, Wieloch TW, Siesjö BK. Circulating catecholamines modulate ischemic brain damage. J Cereb Blood Flow Metab 1986; 6: 559–65.[Web of Science][Medline]
  22. Toner CC, Connelly K, Whelpton R, et al. Effects of sevoflurane on dopamine, glutamate and aspartate release in an in vitro model of cerebral ischaemia. Br J Anaesth 2001; 86: 550–4.[Abstract/Free Full Text]
  23. Yano T, Nakayama R, Ushijima K. Intracerebroventricular propofol is neuroprotective against transient global ischemia in rats: extracellular glutamate level is not a major determinant. Brain Res 2000; 883: 69–76.[Web of Science][Medline]
  24. Hans P, Bonhomme V, Collette J, et al. Propofol protects cultured rat hippocampal neurons against N-methyl-D-aspartate receptor-mediated glutamate toxicity. J Neurosurg Anesthesiol 1994; 6: 249–53.[Web of Science][Medline]
  25. Blomqvist P, Lindvall O, Wieloch T. Lesion of the locus coeruleus system aggravate ischemic damage in the rat brain. Neurosci Lett 1985; 58: 353–8.[Web of Science][Medline]
  26. Warner DS, Takaoka S, Wu B, et al. Electroencephalographic burst suppression is not required to elicit maximal neuroprotection from pentobarbital in a rat model of focal cerebral ischemia. Anesthesiology 1996; 84: 1475–84.[Web of Science][Medline]
  27. Uhl E, Stummer W, Lehmberg J, Baethmann A. Leukocyte-endothelium interactions in pial venules during the early and late reperfusion period after global cerebral ischemia in gerbils. J Cereb Blood Flow Metab 2000; 20: 979–87.[Web of Science][Medline]
  28. Werner C, Hoffman WE, Kochs E, et al. The effects of propofol on cerebral blood flow in correlation to cerebral blood flow velocity in dogs. J Neurosurg Anesthesiol 1992; 4: 41–6.
  29. Berkowitz RA, Hoffman WE, Cunningham F, McDonald T. Changes in cerebral blood flow velocity in children during sevoflurane and halothane anesthesia. J Neurosurg Anesthesiol 1996; 8: 194–8.[Web of Science][Medline]
  30. Iida H, Ohata H, Iida M, et al. Isoflurane and sevoflurane induce vasodilation of cerebral vessels via ATP-sensitive K+ channel activation. Anesthesiology 1998; 89: 954–60.[Web of Science][Medline]
Accepted for publication May 7, 2003.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2003 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press