Dexmedetomidine decreases cerebral blood flow velocity in humans.

This study was designed to determine the effects of dexmedetomidine on CBF velocity as measured by transcranial Doppler sonography in human volunteers. Dexmedetomidine, a potent alpha-2 adrenergic agonist, was administered by computer-driven infusion pump to six male volunteers. Serial measurements of middle cerebral artery blood flow velocity at four steady-state plasma concentrations of dexmedetomidine were made with a 2-MHz transcranial Doppler transducer via the temporal window. The targeted plasma concentrations were 0.49, 0.65, 0.81, and 0.97 ng/ml. These represent 60, 80, 100, and 120%, respectively, of the mean peak concentration following the intramuscular administration of 2 micrograms/kg of dexmedetomidine. Subjects experienced a significant degree of sedation at the highest infusion rates. Mean CBF velocity decreased with each increase in plasma concentration of dexmedetomidine and then began to return to basal levels after termination of the infusion. A trend toward an increase in the pulsatility index at the higher levels of dexmedetomidine suggests that the observed decrement in CBF velocity was due to an increase in cerebral vascular resistance. Upon initiation of the drug infusion, mean arterial pressure decreased from approximately 95 mm Hg to 78 mm Hg. There were no further decreases in arterial pressure with subsequent increases in plasma concentrations of dexmedetomidine. Arterial carbon dioxide tension increased to a maximum of 45 mm Hg during the drug infusion, but this increase from baseline was not statistically significant. These studies are in agreement with previous animal studies which demonstrate a decrease in CBF after administration of dexmedetomidine.

MK-801, an excitatory amino acid antagonist, does not improve neurologic outcome following cardiac arrest in cats.

The excitatory amino antagonist MK-801 was administered to cats following resuscitation from cardiac arrest to evaluate its effect on neurologic and neuropathologic outcome in a clinically relevant model of complete cerebral ischemia. In 29 cats studied, cardiac arrest (ventricular fibrillation) was maintained for 18 min and resuscitation was successfully performed in 21 cats. Four animals underwent a sham arrest. MK-801 or placebo was administered in a blinded, randomized manner. Beginning at 5 min post resuscitation (PR), MK-801 330 micrograms/kg over 2 min followed by 73 micrograms/kg/h for 10 h or the same volume of placebo was administered. Resuscitated animals remained paralyzed and sedated in an intensive care setting for 24-30 h PR. Neurologic examinations were performed at 2, 4, and 7 days PR by observers blinded to the treatment groups. Seventeen cats were entered into data analysis (nine MK-801-treated and eight placebo-treated). MK-801-treated animals had a significantly greater neurologic deficit score (NDS) rank (0 = normal, 100 = brain death) 2 days PR (mean rank 12.1 vs. 5.6; p = 0.008). This difference is most likely due to ongoing sedative actions of MK-801. There were no significant differences in NDS rank at 4 (10.3, MK-801 vs. 7.5, placebo) and 7 (9.6, MK-801 vs. 8.3, placebo) days PR. There were no significant differences in frontal cortex, hippocampus, occipital cortex, or cerebellar neuropathology between groups. Sham-arrested cats had normal neurologic and neuropathologic evaluations. In the circumstance of complete cerebral ischemia as employed in the current study, MK-801 had no beneficial effect upon neurologic or neuropathologic outcome.

Ventilatory, hemodynamic and sedative effects of the alpha 2 adrenergic agonist, dexmedetomidine.

Dexmedetomedine is a potent alpha 2 adrenergic agonist which can reduce anesthetic requirements by over 90% in rats and dogs. This study examined the effects of various doses of dexmedetomidine on the following monitored variables in New Zealand white rabbits: arterial blood gases, mean arterial pressure, respiratory rate, heart rate, and level of sedation. Following the percutaneous insertion of arterial and venous catheters, 21 rabbits received an infusion of saline or dexmedetomidine (20, 80 or 320 micrograms/kg). Monitored variables were recorded at 5, 15, 30 and 60 min following the infusion. Dexmedetomidine produced significant dose-dependent increases in PaCO2 and level of sedation. There were significant decreases in heart rate, PaO2 and respiratory rate. There was no significant change in mean arterial pressure even at the highest (320 micrograms/kg) dose. To examine the ability of an alpha 2 adrenergic antagonist to reverse the effects of dexmedetomidine, 5 rabbits initially received 320 micrograms/kg of dexmedetomidine as described above. Seven minutes after completion of the infusion, 900 micrograms/kg of the alpha 2 adrenergic antagonist, idazoxan, was administered. This resulted in a prompt and sustained reversal of the hypercarbia and sedation produced by the dexmedetomidine.

The noncompetitive N-methyl-D-aspartate receptor antagonist, MK-801 profoundly reduces volatile anesthetic requirements in rabbits.

Rabbits anesthetized with volatile anesthetics were given bolus doses of the n-methyl-D-aspartate (NMDA) receptor antagonist MK-801. Following observation and recording of the hemodynamic and electroencephalographic effects of MK-801, the animals were tested for requirements of volatile anesthetic to prevent movement to a noxious stimulus. It was demonstrated that MK-801 significantly reduced anesthetic requirements in a dose-dependent manner, while also affecting hemodynamics and the electroencephalogram in a manner consistent with the production of a deeper plane of anesthesia.

Spurious identification of critical intercostal arteries by evoked responses during aortic resection.

A patient with an acute dissection of the thoracic aorta is described. Intraoperative evoked-response evaluation suggested the presence of a critical intercostal vessel in the excluded segment, but no major vessel could be identified. Expedient grafting and reestablishment of flow led to prompt recovery of the evoked response, suggesting that mechanical distortion of the aorta by the distal cross-clamp led to a compromised flow through a subadjacent intercostal artery that was an important source of cord perfusion. Recognition of this possibility is important because it may prevent time-consuming attempts to implant small vessels in the excluded segment, which are not major contributors to spinal cord blood flow.

Effects of adenosine agonists and an antagonist on excitatory transmitter release from the ischemic rabbit hippocampus.

The purpose of this study was to determine the effects of adenosine agonists and an antagonist on ischemia-induced extracellular glutamate concentrations in an animal model of transient cerebral ischemia using in vivo cerebral microdialysis. Fifty New Zealand white rabbits were randomly assigned to one of five groups (normothermia, hypothermia, cyclopentyladenosine (CPA), theophylline, or propentofylline). Microdialysis probes were stereotactically placed in the dorsal hippocampus. Twenty minutes before the onset of ischemia, either 1 mg/kg CPA, 5 mg/kg propentofylline, or 20 mg/kg theophylline were administered intravenously. Esophageal temperature was maintained at 38 degrees C, except in the hypothermic animals, which were cooled to 30 degrees C throughout the entire experiment. Two 12-min periods of cerebral ischemia, separated by a 105-min interval of reperfusion, were produced by inflating a neck tourniquet. High-performance liquid chromatography was used to determine the glutamate concentration in the microdialysate. There were no significant increases in glutamate concentrations during the first ischemic period in any of the five groups. During the second ischemic episode, glutamate concentrations in the normothermic group peaked at levels approximately three times higher than the initial values. A similar pattern of changes in glutamate concentrations was observed in the CPA, propentofylline, and theophylline groups. In the hypothermic group, the concentrations of glutamate remained at baseline levels during the entire experiment. Contrary to expectations, neither the adenosine agonists (CPA, propentofylline) nor the antagonist (theophylline) had any effect on extracellular glutamate concentrations in the peri-ischemic period. Although adenosine and its analogs may be cerebroprotective agents, their mechanism of action is not fully understood. The data derived from this study indicates that the acute administration of such agents had no effect on ischemia-induced glutamate release within the hippocampus under these experimental conditions. Based on these results, further work is needed to compare in vivo versus in vitro experimental results in acute and long-term treatment studies with adenosine receptor agonists and antagonists.

Transient brain ischemia in rabbits: the effect of omega-conopeptide MVIIC on hippocampal excitatory amino acids.

Neurologic injury that occurs after ischemia results from a cascade of events involving the release of various endogenous neurotoxins. A portion of the release of excitatory neurotransmitters is calcium dependent and may be attenuated by administration of calcium channel blockers. Using an in vivo model of ischemia, we studied the effects of omega-conopeptide MVIIC, a voltage-sensitive calcium channel blocker, and hypothermia (32 degrees C) on hippocampal glutamate and aspartate release in the peri-ischemic period. Thirty-four New Zealand white rabbits of either sex were anesthetized with halothane, intubated, and mechanically ventilated. Monitored variables included blood gases, mean arterial blood pressure, and the electroencephalogram. Microdialysis catheters were transversely inserted through the anterior portion of the dorsal hippocampus and perfused with artificial cerebrospinal fluid at a rate of 2 microliters/min. After stabilization period, animals were randomly assigned to one of the following groups: Control group (n = 8), 10 microM omega-conopeptide MVIIC group (n = 7), 100 microM omega-conopeptide MVIIC group (n = 7), Hypothermia group (n = 6; cranial temperature = 32 degrees C), and omega-conopeptide MVIIC + hypothermia group (n = 6; 100 microM omega-conopeptide MVIIC and cranial temperature 32 degrees C). All the rabbits were subjected to 10 minutes of global cerebral ischemia produced by neck tourniquet inflation combined with hypotension during halothane anesthesia. Conopeptide MVIIC was administered in the artificial cerebrospinal fluid used to perfuse the microdialysis catheter. In control animals, ischemia caused a significant increase in glutamate (9.7 fold) and aspartate (11.3 fold) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

The alpha 2 adrenergic agonist, dexmedetomidine, selectively attenuates ischemia-induced increases in striatal norepinephrine concentrations.

This study was designed to evaluate the ability of a selective alpha 2 adrenergic agonist (dexmedetomidine) to attenuate ischemia-induced increases in striatal norepinephrine, 3 methoxy-4-hydroxyphenethyleneglycol (MHPG), dopamine, and 5-hydroxyindoleacetic acid (5-HIAA). Following the induction of anesthesia with halothane and oxygen, microdialysis catheters were stereotactically inserted into the striatum of 9 New Zealand white rabbits. Monitored variables included epidural temperature, arterial blood gases and pH, mean arterial pressure, blood glucose concentrations and the electroencephalogram. Following collection of baseline samples of dialysate, animals were randomized to receive a continuous infusion of saline (n = 4) or dexmedetomidine (n = 5). Cerebral ischemia was produced by the inflation of a neck tourniquet and induction of deliberate hypotension. Dialysate collection continued during the ischemic period and for the ensuing 140 min of reperfusion. All dialysate was frozen at -80 degrees C prior to its analysis by liquid chromatography for catecholamine content. There were no significant differences between the two groups for temperature, arterial blood gases, or mean arterial pressure. Blood glucose concentrations increased in the dexmedetomidine group. The electroencephalogram became isoelectric within 30 s of tourniquet inflation in all animals. Analysis of the norepinephrine and MHPG levels revealed significantly lower values for the dexmedetomidine-treated group during and following the ischemic period. There were no differences between groups for extracellular dopamine or 5-HIAA concentrations. These results suggest that the alpha 2 agonist dexmedetomidine can selectively attenuate ischemia-induced increases in striatal norepinephrine concentrations.

Effect of a neuronal sodium channel blocker on magnetic resonance derived indices of brain water content during global cerebral ischemia.

Diffusion-weighted magnetic resonance imaging (DWI) with calculation of the apparent diffusion coefficient (ADC) of water is a widely used noninvasive method to measure movement of water from the extracellular to the intracellular compartment during cerebral ischemia. Lamotrigine, a neuronal Na(+) channel blocker, has been shown to attenuate the increase in extracellular concentrations of excitatory amino acids (EAA) during ischemia and to improve neurological and histological outcome. Because of its proven ability to reduce EAA levels during ischemia, lamotrigine should also minimize excitotoxic-induced increases in intracellular water content and therefore attenuate changes in the ADC. In this study, we sought to determine the effect of lamotrigine on intra- and extracellular water shifts during transient global cerebral ischemia. Fifteen New Zealand white rabbits were anesthetized and randomized to one of three groups: a control group, a lamotrigine-treated group, or a sham group. After being positioned in the bore of the magnet, a 12-min 50-s period of global cerebral ischemia was induced by inflating a neck tourniquet. During ischemia and early reperfusion there was a similar and significant decrease of the ADC in both the lamotrigine and control group. The ADC in the sham ischemia group remained at baseline throughout the experiment. Lamotrigine-mediated blockade of voltage-gated sodium channels did not prevent the intracellular movement of water during 12 min 50 s of global ischemia, as measured by the ADC, suggesting that the ADC decline may not be mediated by voltage-gated sodium influx and glutamate release.

Lubeluzole inhibits accumulation of extracellular glutamate in the hippocampus during transient global cerebral ischemia.

Increases in extracellular glutamate during cerebral ischemia may play an important role in neuronal injury. Lubeluzole is a novel neuroprotective drug, which in previous in vitro and focal ischemia studies has been shown to inhibit nitric oxide synthesis, to block voltage-gated Na+-ion channels, and to inhibit glutamate release. In this study, we investigated the ability of lubeluzole to inhibit glutamate accumulation during episodes of transient global cerebral ischemia. Twenty-five New Zealand white rabbits were randomized to one of four groups: a normothermic control group; a hypothermic group; a 1.25 mg/kg lubeluzole group; or a 2.5 mg/kg lubeluzole group. The animals were anesthetized, intubated, and ventilated before microdialysis probes were placed in the hippocampus. Lubeluzole was given intravenously 90 min before the onset of ischemia. Esophageal temperature was maintained at 38 degrees C in the control, and lubeluzole treated groups, while the animals in the hypothermia group were cooled to 30 degrees C. A 15-min period of global cerebral ischemia was produced by inflating a neck tourniquet. Glutamate concentrations in the microdialysate were determined using high-performance liquid chromatography (HPLC). During ischemia and early reperfusion, glutamate concentrations increased significantly in the control group and returned to baseline after 15 min of reperfusion. In the lubleuzole 2.5 mg/kg and hypothermia groups, glutamate levels were significantly lower (P<0.05) than in the control group and there was no significant change from baseline levels during the entire experiment. This study suggests that lubeluzole is effective in inhibiting extracellular glutamate accumulation during global cerebral ischemia, and has the potential to produce potent neuroprotection when instituted prior to an ischemic event.

Effect of hyperglycemia on peri-ischemic neurotransmitter levels in the rabbit hippocampus.

This study examined the effect of preexisting hyperglycemia on the extracellular concentrations of glutamate and glycine in the rabbit hippocampus using in vivo microdialysis during brief episodes of transient global ischemia. Hyperglycemia has repeatedly been shown to exacerbate the neurologic injury produced by episodes of global cerebral ischemia. Under hypoxic conditions, glucose may be metabolized to glutamate, a known neurotoxin which has been implicated as a mediator of ischemic neuronal cell death. In this study, microdialysis probes were stereotactically inserted into the dorsal hippocampus of anesthetized rabbits. Animals were randomized to receive an i.v. infusion of either saline or dextrose. Global cerebral ischemia was then produced by the combination of neck tourniquet inflation and the induction of systemic hypotension. Administration of dextrose had no effect on these basal levels of glutamate or glycine. During ischemia, glutamate and glycine concentrations increased several-fold when compared with baseline. However, hippocampal glutamate concentrations were lower in the dextrose-treated groups during the peri-ischemic period (P = 0.02). Glycine concentrations were higher during the reperfusion period in the dextrose-treated animals when compared with saline controls (P = 0.03). The increased concentration of extracellular glycine which was observed in the dextrose-treated animals may contribute to the neurologic injury which occurs during episodes of global ischemia. The results of this study suggest that hyperglycemia does not exert its detrimental effects by increasing the extracellular concentration of glutamate.

Antinociceptive properties of intrathecal dexmedetomidine in rats.

Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist. In this study, the intrathecal administration of dexmedetomidine into the rat lumbar subarachnoid space produced dose-dependent, prolonged antinociception as measured by hot plate and tail flick testing. Intrathecal administration of 3 or 10 micrograms of dexmedetomidine increased hot plate and tail flick latencies to cutoff values within 15 min of injection. Animals receiving 1 microgram of intrathecal dexmedetomidine did not show any significant antinociception when compared to saline controls. The intrathecal administration of the alpha 2-adrenoceptor antagonist, idazoxan, ablated all measurable antinociception produced by the prior injection of 10 micrograms of dexmedetomidine.

Continuous monitoring of intracranial pressure with a miniaturized fiberoptic device.

A No. 4 French fiberoptic catheter initially developed as an intravascular pressure sensor was incorporated into a system to be used as an intracranial pressure (ICP) monitor. Initially, a series of acute and chronic animal experiments carried out in the rabbit and pig, respectively, demonstrated the reliability and safety of the device. Subsequently, this new monitor was compared to a concurrently functioning ICP monitor in 15 adult and five pediatric patients. This clinical experience also confirmed the safety, accuracy, and reliability of the device. Since these initial studies, this monitor has been used to routinely measure ICP in a large number of adult and pediatric patients. The monitor has functioned well, and there have been no complications related to its use except for an occasional problem with breakage of the optic fiber as a result of patient movement or nursing maneuvers, which has been easily corrected by replacement of the probe. As nursing personnel and ancillary services have become familiar with this new monitor, breakage has not been a problem. This new device can be placed into the ventricular system, the brain parenchyma, or the subdural space, and appears to offer substantial advantages over other monitors presently in use.

Failure of nimodipine to improve neurologic outcome after eighteen minutes of cardiac arrest in the cat.

The calcium entry blocker nimodipine was administered to cats following resuscitation from 18 min of cardiac arrest to evaluate its effect on neurologic and neuropathologic outcome in a clinically relevant model of complete cerebral ischemia. Cardiac arrest (ventricular fibrillation) was maintained for 18 min and resuscitation was performed by a standardized protocol in 40 cats. Beginning at 5 min post-resuscitation, nimodipine, 10 micrograms/kg over 2 min followed by 1 microgram/kg per min for 10 h, or the same volume of placebo was administered in a randomized, blinded fashion. Neurologic deficits were scored at 2, 4, and 7 days post-resuscitation by observers blinded to the treatment group. Thirty cats were evaluated neurologically at 7 days post-resuscitation and were entered into data analysis (n = 15 per group). Neither neurologic deficit scores nor neuropathologic scores were significantly different between groups. The authors conclude that nimodipine administration in the manner and doses stated does not improve neurologic outcome in cats following resuscitation from cardiac arrest.

Inhibition of glutamate release: a possible mechanism of hypothermic neuroprotection.

The neuroprotective properties of hypothermia are well recognized. For many years, the ability of hypothermia to decrease the neurologic morbidity associated with episodes of ischemia has been ascribed to the reduction in metabolic rate that accompanies decreases in temperature. More recently, evidence has accumulated that hypothermia may exert some of its neuroprotective effects by reducing the ischemia-induced release of excitatory amino acids. This attenuated release occurs even with the mild degrees of hypothermia that can easily be produced in operating rooms and intensive care units. Preliminary data suggest that mild hypothermia may be of benefit in surgical patients at risk for intraoperative cerebral ischemia and patients who have suffered traumatic brain injury. Because of the minimal risk associated with lowering body temperature to 34 degrees C, additional outcome studies are in progress to ascertain the potential benefits of this mode of therapy.

A comparison of the cerebral and hemodynamic effects of mannitol and hypertonic saline in a rabbit model of acute cryogenic brain injury.

There has recently been an increased interest in the use of hypertonic saline solutions in the fluid resuscitation of trauma victims and patients with uncontrollable intracranial hypertension. In this study, the cerebral and hemodynamic effects of 3.2% hypertonic saline solution were compared with those of an equiosmolar (20%) mannitol solution or 0.9% saline in a rabbit model of acute cryogenic brain injury. Forty-five minutes following the creation of a left hemispheric cryogenic brain lesion, equal volumes (10 ml/kg) of hypertonic saline, 0.9% saline, or mannitol were infused over a 5-min period. Monitored variables over the ensuing 120 min included mean arterial pressure, central venous pressure, intracranial pressure (ICP), hematocrit, and serum osmolality. At the conclusion of the 2-h study period, hemispheric water contents were determined by gravimetric analysis and the wet/dry weight method. There were no significant differences in mean arterial pressure between the three groups at any time during the experiment. Plasma osmolality was significantly increased by +/- 10 mOsm/kg following infusions in both the mannitol and hypertonic groups compared to the saline group. The infusion of either mannitol or hypertonic saline produced a transient and significant decrease in ICP during the first 60-90 min but not at 120 min after cryogenic brain lesion, whereas animals in the saline group demonstrated a continual increase in ICP. However, there appeared to be no significant differences in ICP between animals receiving mannitol or hypertonic saline at any time point following infusion of solutions. We conclude that following acute cryogenic brain injury, infusions of equal volumes of equiosmolar solutions of hypertonic saline or mannitol will transiently reduce ICP as compared to equal volumes of normal saline. However, hypertonic saline is not superior to mannitol in its ability to reduce ICP in this model of intracranial hypertension.

The combination of lamotrigine and mild hypothermia prevents ischemia-induced increase in hippocampal glutamate.

The excessive release of glutamate during cerebral ischemia may play an important role in subsequent neuronal injury. Both lamotrigine and hypothermia have independently been shown to attenuate the release of glutamate. In this study, the authors sought to determine whether these effects were additive. Thirty-five New Zealand White rabbits were randomized to one of six groups: a normothermic control group; a lamotrigine-treated group; two hypothermic groups at 33 degreesC or 34.5 degreesC; or two groups treated with both hypothermia at 33 degreesC or 34.5 degreesC plus lamotrigine. Animals were anesthetized before implanting microdialysis probes in the hippocampus. Esophageal temperature was maintained at 38 degreesC in the control and lamotrigine groups, while the temperatures of animals in the hypothermia and hypothermia-plus-lamotrigine groups were cooled to 33 degreesC or 34.5 degreesC. Two 10 minute periods of global cerebral ischemia were produced by inflating a neck tourniquet. Levels of glutamate in the microdialysate were then determined using high-performance liquid chromatography. Extracellular glutamate concentrations increased only slightly from baseline during the first ischemic period. Glutamate levels during the second ischemic episode in the hypothermia-plus-lamotrigine group (34.5 degreesC) were significantly lower than those in the hypothermia group alone (34.5 degreesC), lamotrigine, or control groups (P < .01). The fact that mild hypothermia (34.5 degreesC) plus lamotrigine (20 mg/kg) together were more effective in inhibiting extracellular glutamate accumulation than hypothermia (34.5 degreesC) or lamotrigine (20 mg/kg) alone, suggests the potential for increased neuroprotection by the addition of lamotrigine to mild hypothermia.

Effects of profound anemia on brain tissue oxygen tension, carbon dioxide tension, and pH in rabbits.

This study sought to determine the maximum tolerable limit of anemia for the brain during halothane anesthesia. Using a multiparameter sensor, we continuously monitored brain tissue oxygen tension (PO2), carbon dioxide tension (PCO2), and pH during profound hemodilution and subsequent transfusion. Twelve New Zealand White rabbits were anesthetized, intubated, and mechanically ventilated at a fraction of inspired oxygen (FiO2) of 21% to produce an arterial carbon dioxide tension (PaCO2) of 35 to 40 mm Hg. The femoral artery was cannulated to continuously monitor arterial blood pressure and to intermittently measure arterial blood gases. The electroencephalogram (EEG) was recorded throughout the course of the study. A fiberoptic sensor was inserted into the brain for the continuous measurement of brain PO2, PCO2, pH, and temperature. Cerebral blood flow (CBF) was measured by the hydrogen clearance method. Severe anemia was induced by repeatedly withdrawing 50-mL aliquots of blood and infusing an equal volume of 6% hetastarch. This procedure was performed four times for each rabbit. After the forth blood draw and fluid infusion, a total of 60 mL of packed red blood cells were transfused. Upon completion of the hemodilution, the hemoglobin concentration was 2.4 +/- 0.3 g/dL (mean +/- SEM). Brain tissue PO2 decreased from 27 +/- 3 mm Hg to a minimum of 12 +/- 2 mm Hg. Brain tissue pH also decreased from 7.22 +/- 0.03 to 7.12 +/- 0.05 and returned to the baseline value with transfusion. Brain PCO2 did not change significantly during the experiment. Cerebral blood flow increased from 37 +/- 3 to 66 +/- 15 mL x 100 g(-1) x min(-1) during hemodilution and returned to baseline after infusion of red blood cells. There was some loss of EEG amplitude and the calculated cerebral metabolic rate (CMRO2) decreased from 4.3 +/- 0.6 to 1.9 +/- 0.3 mL x 100 g(-1) x min(-1) at the most profound level of anemia. This is the first report of which the authors are aware of continuous monitoring of brain tissue pH, PCO2, and PO2 during profound hemodilution and transfusion. Hemodilution results in a decrease in brain tissue PO2. Increases in CBF and oxygen extraction can only partially compensate for the decreased oxygen carrying capacity of the blood. Decreases in brain tissue PO2, pH, CMRO2, and a loss of EEG amplitude suggest that the maximum tolerable limit of hemodilution was achieved in this study.

Dexmedetomidine does not attenuate increases in excitatory amino acids after transient global ischemia in the rabbit.

This study was designed to evaluate the ability of dexmedetomidine, an alpha 2-adrenergic agonist, to attenuate increases in the hippocampal concentration of extracellular glutamate and glycine that result from episodes of transient global cerebral ischemia. After the induction of anesthesia with halothane and oxygen, microdialysis catheters were stereotactically inserted into the hippocampi of 16 New Zealand white rabbits. After the collection of baseline samples of dialysate, animals were randomly assigned to receive an intravenous infusion of either saline (n = 8) or dexmedetomidine (n = 8). Transient global cerebral ischemia was produced by the inflation of a neck tourniquet and induction of deliberate hypotension for 10 min. Dialysates were collected during the ischemic period and for the ensuing 60 min of reperfusion. During ischemia, the concentrations of glutamate and glycine increased from the preischemic baseline in both groups. Glutamate concentrations rapidly returned to baseline after reperfusion, whereas glycine concentrations remained elevated throughout the reperfusion period. There were no significant differences between the control and dexmedetomidine-treated groups. These results suggest that the mechanism of the putative neuroprotective effects of dexmedetomidine is not related to decreased concentrations of glutamate or glycine.