A multicenter comparison of maintenance and recovery with sevoflurane or isoflurane for adult ambulatory anesthesia. The Sevoflurane Multicenter Ambulatory Group.

Sevoflurane was compared with isoflurane in 246 adult ASA class I-III patients undergoing ambulatory surgery. After administration of midazolam 1-2 mg and fentanyl 1 microgram/kg, anesthesia was induced with propofol 2 mg/kg and maintained with either sevoflurane or isoflurane in 60% nitrous oxide to maintain arterial blood pressure at +/- 20% of baseline. Fresh gas flows were 10 L/min during induction and 5 L/min during maintenance. Times to eye opening, command response, orientation, and ability to sit without nausea and/or dizziness were significantly faster after sevoflurane. Significantly more sevoflurane patients met Phase 1 of postanesthesia care unit (PACU) Aldrete recovery criteria (> or = 8) at arrival, 95% vs 81%. Also, significantly more sevoflurane patients were able to complete psychomotor recovery tests during the first 60 min postanesthesia. Discharge times were not different. Sevoflurane patients had significantly lower incidences of postoperative somnolence (15% vs 26%) and of nausea both in the PACU (36% vs 51%) and in the 24-h postdischarge period (9% vs 24%). Patient satisfaction was high overall (sevoflurane 97%, isoflurane 93%). We conclude that sevoflurane is a useful inhaled anesthetic for maintenance of ambulatory anesthesia.

Global cerebral ischemia: effects of pentastarch after reperfusion.

There has been considerable interest in the use of synthetic hydroxyethyl starch macromolecules (e.g., pentastarch, a colloid used for intravascular fluid replacement) to reduce microvascular permeability and reperfusion injury after cerebral ischemia. A recent report found that hemodilution with pentastarch reduced brain injury and cerebral edema after temporary focal ischemia. We compared the effects of pentastarch versus 0.9% saline on brain edema after reperfusion in a model of temporary global ischemia in halothane-anesthetized rabbits. To ensure the validity of our model, we studied an additional group of animals in which we deliberately raised plasma osmolality with hypertonic saline (1.5%) in the expectation of finding a decreased brain water content at the conclusion of the experiment. Animals were hemodiluted to a hematocrit of 20% with normal saline (control group) (n = 9), pentastarch (n = 7), or hypertonic saline (n = 5). After hemodilution, the animals underwent a 25-min period of global cerebral ischemia, followed by 180 min of reperfusion. The animals were then killed and brain water content was assessed by microgravimetry and by the wet-dry weight method. As anticipated, colloid osmotic pressure was maintained in the pentastarch group, and plasma osmolality became significantly increased in the hypertonic saline group. There were no intergroup differences at any time for central venous pressure, mean arterial pressure, intracranial pressure, or PaCO2. Brain water content was significantly decreased in the hypertonic saline group. No difference in brain water content was detected between the control group and the pentastarch group.(ABSTRACT TRUNCATED AT 250 WORDS)

Sevoflurane versus halothane anesthesia after acute cryogenic brain injury in rabbits: relationship between arterial and intracranial pressure.

The relationship between intracranial pressure and arterial blood pressure during sevoflurane or halothane anesthesia was evaluated in New Zealand white rabbits after cryogenic brain injury. Fourteen rabbits were randomized to be anesthetized with 1.5 MAC of sevoflurane or halothane in oxygen. All animals were paralyzed with pancuronium, and mechanically ventilated. A cryogenic lesion was created over the left hemisphere. Thirty minutes later, the intracranial pressure had risen to a mean value of 15 mm Hg. The inhaled concentration of anesthetic drugs was then increased to achieve a blood pressure of 35 mm Hg. Baseline measurements were made of monitored variables including mean arterial pressure, intracranial pressure, esophageal temperature, end-tidal CO2, and arterial blood gases. Neosynephrine was then infused to raise the blood pressure from 35 to 100 mm Hg during 20 min. The PaCO2 was maintained between 38 and 42 mm Hg. At baseline, there were no significant differences in mean arterial pressure, intracranial pressure, and blood gas values between the two groups. The intracranial pressure in the sevoflurane anesthesia group increased from 11 +/- 1 to 44 +/- 4 mm Hg as mean arterial pressure increased from 35 to 100 mm Hg. Intracranial pressure in the halothane anesthesia group increased from 9 +/- 1 to 32 +/- 3 mm Hg during the same range of blood pressure. Linear regressions of intracranial pressure on mean arterial pressure were performed for each of the two anesthetic groups. The slope of the regression line for the sevoflurane animals (0.491) was significantly greater than that for the halothane animals (0.323, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of THAM and sodium bicarbonate on intracranial pressure and mean arterial pressure in an animal model of focal cerebral injury.

Episodes of arterial hypotension are associated with an increased mortality in head injury patients. Rapid infusion of sodium bicarbonate in such patients may cause hypotension and elevate intracranial pressure. Therefore, we examined the effects of tromethamine (THAM) versus bicarbonate on intracranial pressure and blood pressure in a model of focal cerebral injury. THAM is a buffer that in previous studies has been shown to lower intracranial pressure. After creation of a cryogenic lesion in 13 New Zealand white rabbits, equivalent infusions (15 s duration) of sodium bicarbonate and THAM (2 mEq/kg) were administered sequentially to each animal in random order. Rapid infusion was chosen to simulate the administration of these drugs during a resuscitation. THAM infusion was associated with a significantly lower intracranial pressure and blood pressure than bicarbonate. The fall in blood pressure was great enough that cerebral perfusion pressure after THAM infusion was significantly lower than after bicarbonate infusion. In this model of cerebral injury, rapid infusion of THAM offered no therapeutic advantage over bicarbonate.

Effects of hypothermic metabolic suppression on hippocampal glutamate concentrations after transient global cerebral ischemia.

The cerebroprotective effects of mild and moderate hypothermia cannot be explained solely by a temperature-induced decrease in cerebral metabolic rate. This study examined the effects of graded hypothermia (32 degrees C, 28 degrees C, and 22 degrees C, vs 38 degrees C) on periischemic extracellular hippocampal glutamate concentrations in the New Zealand White rabbit. Global cerebral ischemia (15 min) was produced by a combination of neck tourniquet inflation and induction of systemic hypotension. Glutamate, an important mediator of ischemic neuronal injury, was measured using in vivo microdialysis and high-performance liquid chromatography. Mean extracellular glutamate concentrations increased by 11 microM in the 38 degrees C group during the ischemic period. Glutamate increased by < 1 microM in the 32 degrees C and 28 degrees C groups and by 3 microM in the 22 degrees C group. Thus, mild degrees of hypothermia profoundly reduced glutamate release during ischemia. This reduction greatly exceeded the estimated temperature-induced decrease in cerebral metabolic rate. We conclude that hypothermic inhibition of glutamate release during episodes of transient ischemia may significantly contribute to neuronal protection.

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.

Effects of hypothermia or anesthetics on hippocampal glutamate and glycine concentrations after repeated transient global cerebral ischemia.

BACKGROUND: The search for cerebroprotective pharmacologic interventions has been based on the assumption that reducing the cerebral metabolic rate may enhance the cerebral tolerance for ischemic episodes. Recently, evidence has accumulated implicating excitatory amino acids (e.g., glutamate) as mediators of ischemic brain injury. We investigated the effects of mild hypothermia (32 degrees C), pentobarbital, isoflurane, and propofol on hippocampal extracellular concentrations of glutamate and glycine after repeated global ischemia. METHODS: New Zealand white rabbits were initially anesthetized with halothane in oxygen. Brain epidural temperature was reduced by external cooling in the hypothermia group to 32 degrees C (n = 5). A burst-suppressed electroencephalogram pattern was achieved in the other groups with isoflurane (n = 7), pentobarbital (n = 6), or propofol (n = 6). Halothane-anesthetized rabbits (1% inspired) served as the control group (n = 5). In all groups, two global cerebral ischemic episodes (each 7.5 min) were produced by a combination of neck tour niquet inflation and induction of systemic hypotension. Periischemic hippocampal glutamate and glycine concentrations were estimated using in vivo microdialysis and high-performance liquid chromatography (two-way analysis of variance, P < 0.05). RESULTS: Glutamate concentrations were similar in the five groups during the baseline period. Hypothermia (32 degrees C) was associated with significantly lower concentrations of glutamate during both the first and second ischemic periods when compared with all other groups. Although there were no differences in glycine concentrations among groups during the first ischemic episode, glycine concentrations were significantly lower in the hypothermic group compared with the control, isoflurane, and pentobarbital groups during the second episode of cerebral ischemia. Glycine concentrations also were lower in the propofol group when compared to the isoflurane and pentobarbital groups. CONCLUSION: Hypothermia (32 degrees C) attenuates ischemia-induced increases in both glutamate and glycine concentrations after repeated global cerebral ischemia. Propofol attenuated glycine increases in a manner similar to that of hypothermia but did not attenuate ischemia-induced glutamate increases. There were no differences in hippocampal glutamate or glycine concentrations for animals receiving isoflurane, halothane, or pentobarbital.

Effect of S-emopamil, nimodipine, and mild hypothermia on hippocampal glutamate concentrations after repeated cerebral ischemia in rabbits.

BACKGROUND AND PURPOSE: We sought to determine the effects of two different calcium channel antagonists, S-emopamil and nimodipine, on hippocampal glutamate and glycine release and to compare their effects to those of mild hypothermia. METHODS: New Zealand White rabbits were subjected to two 7.5-minute episodes of global cerebral ischemia at a 1-hour interval produced by neck tourniquet inflation (20 psi) combined with hypotension during halothane anesthesia. Hippocampal extracellular concentrations of glutamate and glycine were monitored using in vivo microdialysis. Animals were randomized to receive either S-emopamil (1 mg.kg-1 bolus, 0.1 mg.kg-1.min-1 infusion), nimodipine (10 micrograms.kg-1 bolus, 1 microgram.kg-1.min-1 infusion), hypothermia (32 degrees C), or saline (control) before ischemia. Drug infusion and hypothermia were continued throughout the study periods. RESULTS: In all four groups, both ischemic episodes resulted in significant elevations of hippocampal extracellular concentrations of glutamate and glycine (baseline vs peak, P < .01 in all groups). However, glutamate levels were significantly lower in the S-emopamil (P = .0001) and hypothermia (P = .0003) groups when compared with the control group after the onset of the first ischemic episode through 1 hour after the second ischemic episode. There was no significant difference between the four groups in the concentrations of glycine. There was no significant difference between the peak concentrations of glutamate or glycine after each ischemic period. CONCLUSIONS: These results suggest that preischemic administration of S-emopamil, but not nimodipine, attenuates the increase in hippocampal extracellular concentrations of glutamate in the peri-ischemic period in this model, and that this effect is also observed when mild hypothermia is instituted before ischemia. Decreased concentrations of glutamate after ischemic episodes may be a possible mechanism for the observed neuroprotective properties of S-emopamil and mild hypothermia (32 degrees C).

Tracheal intubation without the use of muscle relaxants: a technique using propofol and varying doses of alfentanil.

We have noted that tracheal intubation can be accomplished in many patients after induction of anesthesia with propofol and alfentanil without the simultaneous use of muscle relaxants. This study was designed to evaluate airway and intubating conditions after administration of propofol and alfentanil in 75 ASA physical status I or II outpatients with Mallampati class I airways undergoing various surgical procedures. The patients were randomly assigned to one of five groups for induction of anesthesia. All patients received midazolam 1 mg IV before induction of anesthesia. Group I patients (n = 15) received d-tubocurarine 3 mg, thiamylal 4 mg/kg, and succinylcholine 1 mg/kg IV. Groups II-V patients (n = 15 each) received alfentanil 30, 40, 50, or 60 micrograms/kg followed by propofol 2 mg/kg IV. No muscle relaxants were given to patients in groups II-V. Airway management was performed by one of the authors who was blinded as to the dose of alfentanil administered. After loss of consciousness, patients' lungs were ventilated via face mask, and the ease of ventilation was recorded. Jaw mobility was also assessed. Ninety seconds after administration of the propofol or thiamylal, laryngoscopy was performed and exposure of the glottis and position of the vocal cords were noted. Intubation of the trachea was performed and patient response was noted. Heart rate and arterial blood pressure were also recorded before induction of anesthesia, after induction, and then again after intubation of the trachea. The lungs of all patients were easily ventilated via mask, and the jaw was judged to be relaxed in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of the effects on neuronal Golgi morphology, assessed with electron microscopy, of cardiopulmonary bypass, low-flow bypass, and circulatory arrest during profound hypothermia.

Adult swine (n = 18) were studied to compare the effects on neuronal morphology of hypothermic circulatory arrest with hypothermic very-low-flow cardiopulmonary bypass. Animals were anesthetized with halothane and prepared in a standard manner for nonpulsatile cardiopulmonary bypass. Monitored variables included mean arterial pressure, arterial blood gases, the processed electroencephalogram, and subdural brain temperature. Bypass was initiated with pump flows of 100 ml.kg-1.min-1, and mean arterial pressure was kept above 50 mm Hg at all times. Animals were cooled to 18 degrees C, using a heat exchanger, and were randomly assigned to one of three groups. Group 1 animals were control animals who underwent 1 hour of hypothermic cardiopulmonary bypass. Group 2 animals underwent 1 hour of circulatory arrest. Group 3 animals underwent 1 hour of very-low-flow cardiopulmonary bypass (10% of normal). At the end of the 1 hour of hypothermic bypass, very-low-flow bypass, or arrest period, animals were rewarmed to 37 degrees C with normal bypass flows, and normothermic perfusion continued for 1 additional hour. Animals were then perfusion fixed with formalin and the brains were removed for electron microscopic analysis. Electron microscopic analysis was used to determine the effects of treatment and was limited to 20 neurons of the CA1 sector of the hippocampus in each animal. Golgi bodies were identified and classified as normal, mildly affected, or severely affected. Animals subjected to either very-low-flow bypass or circulatory arrest had significantly more severely affected and significantly fewer normal Golgi bodies than control animals (p < 0.001). Animals maintained with very-low-flow bypass, however, had significantly more severely affected and fewer normal Golgi bodies than animals subjected to circulatory arrest (p < 0.001). We conclude that under the conditions of this experiment very-low-flow hypothermic cardiopulmonary bypass is associated with significantly greater neuronal Golgi abnormalities than total circulatory arrest.

AMPA and NMDA receptor antagonists do not decrease hippocampal glutamate concentrations during transient global ischemia.

Increased extracellular concentrations of glutamate during episodes of cerebral ischemia may be due in part to a positive glutaminergic feedback loop. We evaluated the effect of selective AMPA or NMDA receptor antagonists on hippocampal extracellular concentrations of excitatory amino acids during ischemia and reperfusion. Thirteen New Zealand white rabbits were subjected to 10 min of global cerebral ischemia produced by neck tourniquet inflation (20 psi) combined with systemic hypotension during halothane (1-1.5%) anesthesia. Hippocampal extracellular concentrations of glutamate, aspartate, and glycine were monitored using in vivo microdialysis. NBQX (a selective AMPA receptor antagonist), MK801 (a noncompetitive NMDA receptor antagonist), or 5% dextrose was administered starting 1 h before ischemia. The NBQX group (n = 4) received 5 mg.kg-1 of NBQX intravenously (dissolved in 5% dextrose) over 5 min followed by an infusion of 5 mg.kg-1.h-1. The 5% dextrose group (n = 4) received an equivalent volume of 5% dextrose. The peak concentrations of glutamate, aspartate, and glycine in the early reperfusion period were 5-8-fold, 9-10-fold, and 4-5-fold higher than preischemic values, respectively. There were no significant differences, however, among the three groups in the concentrations of glutamate, aspartate, or glycine at any time during the study. These results do not support the existence of a positive feedback loop for glutamate mediated via AMPA or NMDA autoreceptors in the hippocampus during transient global ischemia or reperfusion.

Effects of ischemia duration on neurological outcome, CA1 histopathology, and nonmatching to sample learning in monkeys.

BACKGROUND AND PURPOSE: Male cynomolgus monkeys (n = 10) were subjected to varying durations of global cerebral ischemia to determine the relation between dose (ischemic duration) and response (outcome). METHODS: Each monkey was anesthetized with halothane, and global cerebral ischemia was produced by a neck tourniquet and trimethaphan-induced hypotension. The animal was subjected to 3 (n = 3), 9 (n = 3), or 12 (n = 4) minutes of ischemia. Neurological examinations were performed daily for 30 days or until the monkey was neurologically normal. Approximately 1 month after ischemia, the animal was evaluated for evidence of neurobehavioral abnormalities with the nonmatching to sample test. When testing was complete, the monkey was killed with an overdose of pentobarbital and the brain perfused with formalin and removed for histopathologic analysis, with particular attention devoted to the hippocampal CA1 region. RESULTS: Monkeys subjected to 3 or 9 minutes of ischemia were neurologically normal (except for a very mild injury in one 9-minute animal) immediately after ischemia and had normal CA1 histology. Monkeys subjected to 12 minutes of ischemia were grossly abnormal neurologically after ischemia, but two of the four animals made a complete recovery (neurological deficit score of 0) by 30 days. Monkeys subjected to 12 minutes of ischemia had mild damage in the CA1 region, with all other brain regions appearing normal. None of the animals had demonstrable decrements in neurobehavioral function as measured by the nonmatching to sample test. CONCLUSIONS: We conclude that neurobehavioral testing after global cerebral ischemia in primates is feasible, but the ischemic time necessary to produce CA1 damage that could potentially be quantified antemortem with the nonmatching to sample test is greater than 12 minutes in cynomolgus monkeys and may produce temporary severe gross neurological abnormalities as well.

The effects of fentanyl and sufentanil on intracranial pressure and cerebral blood flow in rabbits with an acute cryogenic brain injury.

The cerebrovascular response to the administration of equipotent doses of fentanyl and sufentanil was evaluated in New Zealand white rabbits following cryogenic brain injury. In a preliminary study consisting of 10 animals, it was documented that the cerebral blood flow response to alterations in the PaCO2 remained intact in this model of brain injury. Subsequently, 28 rabbits were anesthetized with 1.5% halothane in oxygen, paralyzed with pancuronium, and mechanically ventilated. A cryogenic lesion was created over the left hemisphere. One hour later, the intracranial pressure had risen to a mean value of 15 mm Hg. Baseline measurements were then made of monitored variables, which included heart rate, mean arterial pressure, central venous pressure, intracranial pressure, temperature, and arterial blood gases. Global cerebral blood flow was measured utilizing a hydrogen clearance technique. The animals were then randomized to receive an infusion of fentanyl (N = 9, 200 microg/kg), sufentanil (N = 10, 20 microg/kg), or an equal volume of normal saline (N = 9) by i.v. infusion over 5 min. At the conclusion of the opioid infusions, repeated measurements of hemodynamic variables and intracranial pressure were recorded for 15 min and a second cerebral blood flow measurement was made. There were no significant differences in mean arterial pressure, heart rate, central venous pressure, intracranial pressure, cerebral blood flow, or blood gas values between the three groups prior to the administration of fentanyl, sufentanil, or normal saline. At the conclusion of the 5 min infusion, the intracranial pressure had increased by approximately 5 mm Hg in all three groups. The mean arterial pressure decreased to a similar degree in the fentanyl and sufentanil groups and was significantly lower than the mean arterial pressure in the saline group. Although the cerebral perfusion pressure decreased in all three groups, cerebral blood flow was not significantly affected. These results suggest that there is no significant difference in the effects of fentanyl vs. sufentanil on mean arterial pressure, intracranial pressure, or cerebral blood flow in this model of acute brain injury and elevated intracranial pressure.

Intracranial pressure effects of dexmedetomidine in rabbits.

The alpha 2-adrenergic receptor agonist dexmedetomidine produces an anesthetic state in a variety of species. Although its effects on cerebral blood flow and the electroencephalogram have been investigated, the effect of this drug on intracranial pressure (ICP) has not been reported previously. Dexmedetomidine therefore was intravenously administered to 24 New Zealand white rabbits that had been anesthetized with halothane and mechanically ventilated to maintain a constant arterial CO2 tension (PaCO2) between 34 and 39 mm Hg. After placement of an arterial catheter and ventricular cannula, baseline measurements of monitored variables, including heart rate, mean arterial blood pressure, ICP, end-tidal CO2, body temperature, and arterial blood gases, were recorded. Dexmedetomidine (20, 80, or 320 micrograms/kg IV) or saline solution was then infused over a 10-min period. The ICP transiently decreased by 31% in the 20-micrograms/kg group (from a mean value of 9.4 +/- 1.3 [SEM] to 6.5 +/- 1.0 mm Hg, P less than 0.05). In the 320-micrograms/kg group, ICP remained unchanged over the course of the study despite a significant increase in arterial blood pressure (32 mm Hg). The effects of dexmedetomidine on ICP were next investigated in the presence of intracranial hypertension produced by a cryogenic lesion (mean baseline ICP 16.8 mm Hg). In addition to the previously monitored variables, sagittal sinus blood flow was measured by the hydrogen clearance technique before and after the administration of dexmedetomidine (320 micrograms/kg IV). In these experiments, dexmedetomidine was associated with a 14% decrease in sagittal sinus blood flow that was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Flow increases with an enlarging intravenous catheter.

STUDY OBJECTIVE: To determine the increase in flow of a hydratable enlarging intravenous (IV) catheter in anesthetized patients. DESIGN: A randomized, nonblinded study, with standard Teflon IV catheters used as controls. SETTING: Operating room at a university medical center. PATIENTS: Thiry adult patients receiving general anesthesia for lower extremity surgery. INTERVENTIONS: An IV catheter was placed in the upper extremity, and flow measurements were made by measuring the time for infusion of 250 ml of normal saline within 1 minute after placement and at 1 hour after placement. MEASUREMENTS AND MAIN RESULTS: The enlarging catheters had a statistically significant average flow increase of 26% after 1 hour indwelling time. The standard Teflon catheters had no statistically significant change in flow after 1 hour. The percentage increase in flow for the enlarging catheters was not as great as previously seen in vitro. CONCLUSIONS: Flow through enlarging IV catheters placed in anesthetized patients increases after 1 hour. The percentage increase in flow is not as great as previously seen in vitro and may be due to skin, vein, and subcutaneous tissues preventing complete expansion.

Effects of levemopamil on neurologic and histologic outcome after cardiac arrest in cats.

BACKGROUND AND METHODS: A study was performed to examine the effects of the calcium-channel blocker levemopamil on neurologic outcome and neuropathology in a clinically relevant model of complete global cerebral ischemia (ventricular fibrillation in cats). Levemopamil was administered to cats starting 5 mins after resuscitation from 14 mins of cardiac arrest. In a "blinded" manner, 46 animals received levemopamil 1 mg/kg over 15 mins followed by 10 micrograms/kg.min for 16 hrs or vehicle. In a nonblinded manner, eight additional animals were pretreated with levemopamil beginning 45 mins before cardiac arrest. After resuscitation, levemopamil was infused at 10 micrograms/kg.min for 16 hrs. Animals in all three groups remained sedated, paralyzed, and mechanically ventilated for 24 to 30 hrs after resuscitation. Neurologic examinations were performed at 2, 4, and 7 days after resuscitation. Thirty-five cats were entered into data analysis (16 levemopamil posttreated, 14 vehicle-treated, and 5 levemopamil pretreated). RESULTS: Neurologic deficit scores and over-all neuropathologic scores did not differ among groups at any interval after resuscitation. However, the occipital cortex and CA1 region of the pretreated animals showed less severe damage than was observed in the animals that received levemopamil or vehicle, starting after resuscitation (p less than .01). CONCLUSIONS: Postarrest administration of levemopamil was not associated with improved neurologic or neuropathologic outcome. However, the data suggest that prearrest administration may result in regionally selective improvement in neuropathology.

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.

Changes in extracellular concentrations of glutamate, aspartate, glycine, dopamine, serotonin, and dopamine metabolites after transient global ischemia in the rabbit brain.

Although considerable evidence supports a role for excitatory amino acids in the pathogenesis of ischemic neuronal injury, few in vivo studies have examined the effect of increasing durations of ischemia on the extracellular concentrations of these agents. Recently, other neurotransmitters (e.g., glycine and dopamine) have been implicated in the mechanism of ischemic neuronal injury. Accordingly, this study was undertaken to examine the patterns of changes of extracellular glutamate, aspartate, glycine concentrations in the hippocampus, and dopamine, serotonin, and dopamine metabolites in the caudate nucleus with varying durations (5, 10, or 15 minutes) of transient global cerebral ischemia as evidence to support their pathogenetic roles. Microdialysis was used to sample the brain's extracellular space before, during, and after the ischemic period. Glutamate and aspartate concentrations in the dialysate increased from baseline by 1-, 5-, and 13-fold and by 4-, 9-, and 31-fold, respectively, for the three ischemic durations. The concentrations returned to baseline rapidly after reperfusion. The peak concentrations of glutamate and aspartate were significantly higher with increasing ischemic duration. Dopamine concentrations increased by approximately 700-fold in response to all three ischemic durations and returned to baseline within 10 min of reperfusion. Glycine, in contrast, increased during ischemia by a mean of 4-fold, but remained elevated throughout the 80-min period of reperfusion. The final concentrations of glycine were significantly higher than baseline levels (p = 0.0002, Mann-Whitney test). That glutamate and aspartate concentrations in the hippocampus co-vary with the duration of global ischemia is taken as supportive evidence of their pathogenetic role in ischemic neuronal injury.(ABSTRACT TRUNCATED AT 250 WORDS)