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.

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.

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.

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.

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.

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.

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.

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.

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.

Isoflurane, halothane, and regional cerebral blood flow at various levels of PaCO2 in rabbits.

The effects of halothane and isoflurane on regional cerebral blood flow (CBF) were studied in 18 New Zealand White rabbits anesthetized with nitrous oxide (N2O) and morphine sulfate (MS) at three different levels of PaCO2. CBF was measured using the hydrogen clearance technique. Monitored variables were intracranial pressure (ICP), central venous pressure, heart rate, mean arterial pressure, electroencephalogram, arterial blood gases, end-tidal (ET) volatile anesthetic, and ET CO2. Addition of 1 MAC halothane to the N2O/MS background anesthetic caused flow to increase significantly in all three regions studied (cortex, dorsal hippocampus, white matter) at all three levels of PaCO2 (low: 20-25 mmHg; normal: 35-40 mmHg; high: 50-55 mmHg). Addition of 1 MAC isoflurane to the background anesthetic caused CBF to decrease significantly in all regions during hypocapnia. During normocapnia, CBF was unchanged with the addition of 1 MAC isoflurane in all regions and during hypercapnia, CBF increased significantly only in the dorsal hippocampus following addition of 1 MAC isoflurane to the MS/N2O background anesthetic. Volatile anesthetic administration was associated with significant, although small, increases in ICP at all PaCO2 levels. We conclude that 1 MAC concentrations of halothane and isoflurane have opposite effects on CBF when added to a N2O/MS anesthetic during hypocapnia and that the effects of isoflurane on regional CBF are dependent on PaCO2 in rabbits under the anesthetic conditions of this experiment.

A comparison of the sensitivity of pulmonary artery pressure, end-tidal carbon dioxide, and end-tidal nitrogen in the detection of venous air embolism in the dog.

The authors sought to define the relative sensitivities of endtidal carbon dioxide analysis (ETCO2), end-tidal nitrogen analysis (ETN2), and pulmonary artery pressure (PAP) monitoring in the detection of venous air embolism (VAE). Serial injections of air (0.25, 0.5, 0.75, 1.0, and 1.5 ml/kg) were performed in six mongrel dogs. The frequency with which positive responses (PAP increase greater than 2 mm Hg; ETCO2 decrease greater than 0.2%; ETN2 increase greater than 0.04%) were observed following VAE was not different for the three methods. The response time (time to maximum change following VAE) was significantly more rapid for PAP and ETN2 than for ETCO2; although the range for the three methods was narrow, e.g., for 1.5 ml/kg--PAP, 0.92 +/- 0.7 (SD) min; ETN2, 1.20 +/- 0.5 min; ETCO2, 1.85 +/- 0.7 min. The time from injection of air to return to baseline levels was significantly more rapid for ETN2 than for ETCO2 which was in turn significantly faster than PAP, e.g., for 1.5 ml/kg--ETN2, 8.0 +/- 4.3 min; ETCO2, 19.4 +/- 6.0 min; PAP, 23.8 +/- 6.1 min. The results indicate that, where the capacity to identify increases in expired nitrogen on the order of 0.04% can be achieved, ETN2 monitoring will identify VAE events with a sensitivity similar to that of PAP and ETCO2. However, the difficulties inherent in achieving this level of nitrogen detection sensitivity probably represent a current major limitation in the application of this method. Furthermore, the data indicate that, after VAE, ETN2 will return to preinjection levels although PAP and ETCO2 remain abnormal. This observation suggests that ETN2 may not be a reliable indicator of recovery from the physiologic impact of VAE, and may therefore not be the optimum method to base decisions regarding resumption of the head-up posture and continuation of surgery during procedures in which VAE has occurred.

The relationship of beta-endorphin and ACTH in the cerebrospinal fluid and plasma of adult surgical patients.

Cerebrospinal fluid and plasma beta-endorphin/beta-lipotropin immunoreactivity and adrenocorticotropin hormone were determined in simultaneously obtained samples from 25 healthy, adult surgical patients about to undergo spinal anesthesia using radioimmunoassay techniques. Cerebrospinal fluid adrenocorticotropin concentrations were significantly higher than those in plasma (25.76 +/- 2.11 fm/ml vs. 8.83 +/- 0.84 fm/ml), whereas beta-endorphin/beta-lipotropin concentrations in cerebrospinal fluid were significantly lower than those in plasma (6.60 +/- 0.43 fm/ml vs. 3.35 +/- 0.30 fm/ml). In cerebrospinal fluid, a significant positive correlation was found between beta-endorphin/beta-lipotropin and adrenocorticotropin (r = 0.64, p less than 0.01), whereas no such relationship could be demonstrated in plasma. This suggests that beta-endorphin/beta-lipotropin and adrenocorticotropin might enter the cerebrospinal fluid via a mechanism unrelated to their entry into plasma. This may have implications for the pharmacologic manipulation of these peptides within the central nervous system.

The effect of nitrous oxide on cortical cerebral blood flow during anesthesia with halothane and isoflurane, with and without morphine, in the rabbit.

The effect of nitrous oxide on cortical cerebral blood flow (CBF) was examined during a varying background anesthetic state in the New Zealand White rabbit. Seventy percent nitrous oxide resulted in significant and similar increases in CBF during anesthesia with both 0.5 MAC of halothane (44 +/- 14 to 63 +/- 17 ml.100 g-1.min-1) (mean +/- SD) and anesthesia with isoflurane (34 +/- 9 to 41 +/- 11 ml.100 g-1.min-1). During anesthesia with 1.0 MAC halothane or isoflurane, N2O also increased CBF, but the increments (halothane, 73 +/- 34 to 111 +/- 54 ml.100 g-1 min-1; isoflurane 34 +/- 13 to 69 +/- 34 ml.100 g-1.min-1) were significantly greater than those observed at 0.5 MAC. When 0.5 MAC halothane or isoflurane was supplemented with morphine (10 mg/kg followed by an infusion of 2 mg.kg-1.min-1), the CBF effect of N2O was not significantly different from that observed with 0.5 MAC alone. It was concluded that, in the rabbit, the effects of N2O on cortical CBF vary with the background anesthetic state and that the increase in CBF caused by N2O becomes greater as the end-tidal concentration of halothane or isoflurane increases from 0.5 to 1.0 MAC. Morphine, when added to 0.5 MAC of halothane or isoflurane, does not alter the effect of 70% N2O on cortical CBF.

The efficacy of three different methods of transtracheal ventilation.

The ability of three different techniques of transtracheal ventilation to reverse hypoxia and provide pulmonary ventilation were examined. Five swine were anaesthetized with isoflurane in oxygen, their tracheas were intubated, and their lungs mechanically ventilated to produce a PaCO2 of 35-40 mmHg. A 14-gauge catheter was inserted percutaneously into the trachea caudad to the tip of the tracheal tube. The animals were then left apnoeic until their oxygen saturation fell to 60 per cent. At this point, attempts were made to ventilate and oxygenate the animals through the tracheal catheter with one of three systems (Jet--50 psi [2585 mmHg] driving pressure controlled with a thumb operated valve, Flush-fresh gas outlet of an anaesthetic machine with flow controlled by the flush button, or Circle--standard anaesthesia circle system with pressures greater than 60 mmHg). Arterial blood gas determinations were made every minute for five minutes after beginning transtracheal ventilation. Both the Jet and Flush modes resulted in a mean PaO2 greater than 250 mmHg within one minute of their initiation whereas the PaO2 with the Circle system never exceeded 180 mmHg even at five minutes. The Flush and Jet modes produced a decrease in the PaCO2 (from 80 mmHg to 35-45 mmHg) over the five minutes. In contrast, it was not possible to provide adequate ventilation with the Circle system as evidence by an increasing PaCO2 (from 80 mmHg to less than 110 mmHg at five minutes).(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of fresh gas flow and inspiratory/expiratory ratio on tidal volume and arterial CO2 tension in mechanically ventilated surgical patients.

The relative importance of fresh gas flow and inspiratory/expiratory ratio in determining delivered tidal volume and PaCO2 was studied in anesthetized adult patients ventilated with a fixed ventilator bellows volume. The fresh gas flows studied were 2, 6, and 10 L/min, and inspiratory/expiratory ratio was either 1:2 or 1:4.5. Bellows volume and respiratory rate were held constant throughout the study. At the lowest fresh gas flow and smallest inspiratory/expiratory ratio, PaCO2 was 43 +/- 2 mm Hg. The PaCO2 decreased progressively and significantly with each increase in fresh gas flow during ventilation with either inspiratory/expiratory ratio setting. PaCO2 averaged 30 +/- 3 during ventilation with the highest fresh gas flow and largest inspiratory/expiratory ratio. As fresh gas flow increased, PaCO2 and tidal volume changed to a significantly greater degree in response to changes in inspiratory/expiratory ratio. These data demonstrate that altering either fresh gas flow or inspiratory/expiratory ratio can produce clinically significant perturbations in PaCO2 and tidal volume during anesthesia. These perturbations occur even if bellows volume is held constant. Furthermore, changes in inspiratory/expiratory ratio will affect these parameters to a greater degree as fresh gas flow is increased.

A comparison of the cerebral and haemodynamic effects of mannitol and hypertonic saline in an animal model of brain injury.

There has recently been an increased interest in the use of hypertonic saline solutions in the fluid resuscitation of trauma victims and to control intracranial hypertension. In this study, the cerebral and haemodynamic effects of a 3.2% hypertonic saline solution were compared with those of either a 0.9% saline or 20% solution were compared with those of either a 0.9% saline or 20% mannitol solution in a rabbit model of brain injury. Forty-five minutes following the creation of a left hemispheric cryogenic brain lesion, equal volumes of hypertonic saline, 0.9% saline, or mannitol were infused over a 5 minute period. Monitored variables over the ensuing 120 minutes included mean arterial pressure, central venous pressure, intracranial pressure, hematocrit, serum osmolality and oncotic pressure. Upon conclusion of the two hour study period, hemispheric water contents were determined by the wet/dry weight method. There were no significant differences in mean arterial pressure between the three groups at any point during the experiment. Plasma osmolality was significantly increased by 10-11 mOsm/kg in both the mannitol and hypertonic groups. The infusion of either mannitol or hypertonic saline produced a transient decrease in intracranial pressure lasting approximately 60 minutes whereas animals in the saline group demonstrated a continual increase in intracranial pressure. The lesioned hemisphere demonstrated a significantly greater water content than the non-lesioned hemisphere.

Effect of a hypertonic lactated Ringer's solution on intracranial pressure and cerebral water content in a model of traumatic brain injury.

There has recently been an increased interest in the use of hypertonic solutions for fluid resuscitation of trauma victims. In this study, we examined the acute cerebral effects of a hypertonic lactated Ringer's solution (measured osmolality = 469 mOsm/kg) in an animal model of traumatic brain injury. Following the production of a cerebral cryogenic lesion, eight New Zealand white rabbits were randomized to undergo hemodilution with either lactated Ringer's (measured osmolality = 254 mOsm/kg) or hypertonic lactated Ringer's. Over the course of the experiment the lactated Ringer's group required significantly more fluid than the hypertonic group to maintain stable central venous and mean arterial pressure (245 +/- 5 ml vs. 132 +/- 20 ml; p less than 0.0001). Osmolality increased in the hypertonic group by 13.5 +/- 3.3 mOsm/kg whereas it decreased in the lactated Ringer's group by 5.5 +/- 2.6 mOsm/kg. Intracranial pressure increased in both groups over the course of the experiment but the increase in pressure was greater in the lactated Ringer's group than the hypertonic group (9.5 +/- 2.4 mm Hg vs. 1.7 +/- 1.5 mm Hg; p less than 0.001). Brain water content was significantly increased in the region of the lesion as assayed by both the wet/dry weight method and cortical specific gravity determinations, but there was no difference between the two treatment groups. Water content of the nonlesioned hemisphere was significantly less in the hypertonic group. This study suggests that hypertonic saline solutions may be useful for the resuscitation of hypovolemic patients with localized brain injury.