Biomedical subjects

D A Wilson

Publications and source records attributed to D A Wilson.

At least 37 records · Page 2Linked to original sources

PubMed2000

Incidence of focal white matter lesions in a population of hemophiliac children and their normal siblings. Hemophilia Growth and Development Study.

OBJECTIVE: This analysis was undertaken to evaluate the etiology and sequelae of 2- to 5-mm focal white matter hyperintensities on T2-weighted MR images of some participants enrolled in the Hemophilia Growth and Development Study (HGDS). MATERIALS AND METHODS: The HGDS is a multicenter study of the growth and development, neurological, neuropsychological, and immune functioning of a cohort of children and adolescents, 62% of whom were infected with HIV through the use of clotting factor concentrates, and their non-hemophiliac, non-HIV infected male siblings. The current investigation was conducted with all three groups of HGDS participants: HIV-positive hemophiliacs (n = 207), HIV-negative hemophiliacs (n = 126), and their siblings (n = 47). Magnetic resonance imaging was performed at each center, with a variety of 0.3 to 1.5 T instruments. Standard examinations included 5-mm-thick T1-weighted sagittal and axial images, intermediate, and T2-weighted axial images. A study of abnormalities of the coagulation system known to be associated with thrombotic events was conducted among a subgroup of participants (n = 51) from eight centers. RESULTS: Lesions were not associated with hemophilia-related factors, immune function, hematologic, or neurologic factors. There were no associations between the presence of white matter lesions and defects of coagulation in any of the assays completed. CONCLUSION: The 2- to 5-mm focal white matter hyperintensities on T2-weighted MR images of the brain were incidental findings in our study population.

Adolescent↗

PubMed2000

Association of an odor with activation of olfactory bulb noradrenergic beta-receptors or locus coeruleus stimulation is sufficient to produce learned approach responses to that odor in neonatal rats.

These experiments examined the sufficiency of pairing an odor with either intrabulbar activation of noradrenergic beta-receptors or pharmacological stimulation of the locus coeruleus to support learned odor preferences in Postnatal Day 6-7 rat pups. The results showed that pups exposed to odor paired with beta-receptor activation limited to the olfactory bulb (isoproterenol, 50 microM) displayed a conditioned approach response on subsequent exposure to that odor. Furthermore, putative stimulation of the locus coeruleus (2 microM idazoxan or 2 mM acetylcholine) paired with odor produced a subsequent preference for that odor. The effects of locus coeruleus stimulation could be blocked by a pretraining injection of the beta-receptor antagonist propranolol (20 mg/kg). Together these results suggest that convergence of odor input with norepinephrine release from the locus coeruleus terminals within the olfactory bulb is sufficient to support olfactory learning.

Adrenergic beta-Agonists↗

PubMed2000

Exposure to behaviourally relevant odour reveals differential characteristics in rat central olfactory pathways as studied through oscillatory activities.

This study investigated how changes in nutritional motivation modulate odour-related oscillatory activities at several levels of the olfactory pathway in non-trained rats. Local field potential recordings were obtained in freely moving animals in the olfactory bulb (OB), anterior and posterior parts of the piriform cortex (APC and PPC respectively) and lateral entorhinal cortex (EC). Dynamic signal analysis detected changes in power during odour presentation for several frequency bands The results showed that in most cases odour presentation was associated with changes in a wide 15-90 Hz frequency band of activity in each olfactory structure. However, nutritional state modulated initial responses to food odour (FO) in the OB and EC selectively in the 15-30 Hz frequency band. Changes in nutritional state also modulated responses to repeated FO stimuli. Habituation was expressed differentially across structures with a clear dissociation between the two parts of the piriform cortex. Finally, systemic injections of scopolamine (0.125 mg/kg) selectively blocked expression of the nutritional modulation in the OB found in the beta band. These results suggest that internal state can differentially modulate odour processing among different olfactory areas and point to a cholinergic-sensitive beta band oscillation during presentation of a behaviourally meaningful odorant.

Animals↗

PubMed2000

Odor specificity of habituation in the rat anterior piriform cortex.

Exposure to odorants results in a rapid (<10 s) reduction in odor-evoked activity in the rat piriform cortex despite relatively maintained afferent input from olfactory bulb mitral cells. To further understand this form of cortical plasticity, a detailed analysis of its odor specificity was performed. Habituation of odor responses in anterior piriform cortex single units was examined in anesthetized, freely breathing rats. The magnitude of single-unit responses of layer II/III neurons to 2-s odor pulses were examined before and after a 50-s habituating stimulus of either the same or different odor. The results demonstrated that odor habituation was odor specific, with no significant cross-habituation between either markedly different single odors or between odors within a series of straight chain alkanes. Furthermore, habituation to binary 1:1 mixtures produced minimal cross-habituation to the components of that mixture. These latter results may suggest synthetic odor processing in the olfactory system, with novel odor mixtures processed as unique stimuli. Potential mechanisms of odor habituation in the piriform cortex must be able to account for the high degree of specificity of this effect.

Analysis of Variance↗

PubMed2000

Comparison of odor receptive field plasticity in the rat olfactory bulb and anterior piriform cortex.

Recent work in the anterior piriform cortex (aPCX) has demonstrated that cortical odor receptive fields are highly dynamic, showing rapid changes of both firing rate and temporal patterning within relatively few inhalations of an odor, despite relatively maintained, patterned input from olfactory bulb mitral/tufted cells. The present experiment examined the precision (odor-specificity) of this receptive field plasticity and compared it with the primary cortical afferent, olfactory bulb mitral/tufted cells. Adult Long-Evans hooded rats, urethan anesthetized and freely breathing, were used for single-unit recording from mitral/tufted and aPCX layer II/III neurons. Partial mapping of receptive fields to alkane odors (pentane, heptane, and nonane) was performed before and immediately after habituation (50-s exposure) to one of the alkanes. The results demonstrated that odor habituation of aPCX responses was odor specific, with minimal cross-habituation between alkanes differing by as few as two carbons. Mitral/tufted cells, however, showed strong cross-habituation within the odor set with the most profound cross effects to carbon chains shorter than the habituating stimulus. The results suggest that although mitral/tufted cells and aPCX neurons have roughly similar odor receptive fields, aPCX neurons have significantly better odor discrimination within their receptive field. The results have important implications for understanding the underlying bases of receptive fields in olfactory system neurons and the mechanisms of odor discrimination and memory.

Action Potentials↗

PubMed2000

Kinematics of the hind limb in trotting horses after induced lameness of the distal intertarsal and tarsometatarsal joints and intra-articular administration of anesthetic.

OBJECTIVE: To identify hind limb and pelvic kinematic variables that change in trotting horses after induced lameness of the distal intertarsal and tarsometatarsal joints and after subsequent intra-articular administration of anesthetic. ANIMALS: 8 clinically normal adult horses. PROCEDURE: Kinematic measurements were made before and after transient endotoxin-induced lameness of the distal intertarsal and tarsometatarsal joints and after intra-articular administration of anesthetic. Fourteen displacement and joint angle (metatarsophalangeal [fetlock] and tarsal joints) measurements were made on the right hind limb, sacrum, and the right and left tubera coxae. Kinematic measurements were compared by general linear models, using a repeated measures ANOVA. Post hoc multiple comparisons between treatments were evaluated with a Fisher least squared difference test at alpha = 0.05. RESULTS: After lameness induction, fetlock and tarsal joint extension during stance decreased, fetlock joint flexion and hoof height during swing increased, limb protraction decreased, and vertical excursion of the tubera coxae became more asymmetric. After intra-articular administration of anesthetic, limb protraction returned to the degree seen before lameness, and vertical excursion of the tubera coxae became more symmetric. CONCLUSIONS AND CLINICAL RELEVANCE: Increased length of hind limb protraction and symmetry of tubera coxae vertical excursion are sensitive indicators of improvement in tarsal joint lameness. When evaluating changes in tarsal joint lameness, evaluating the horse from the side (to assess limb protraction) is as important as evaluating from the rear (to assess pelvic symmetry).

Anesthetics↗

PubMed2000

Changes in kinematic variables observed during pressure-induced forelimb lameness in adult horses trotting on a treadmill.

OBJECTIVE: To determine whether kinematic changes induced by heel pressure in horses differ from those induced by toe pressure. ANIMALS: 10 adult Quarter Horses. PROCEDURE: A shoe that applied pressure on the cuneus ungulae (frog) or on the toe was used. Kinematic analyses were performed before and after 2 levels of frog pressure and after 1 level of toe pressure. Values for stride displacement and time and joint angles were determined from horses trotting on a treadmill. RESULTS: The first level of frog pressure caused decreases in metacarpophalangeal (fetlock) joint extension during stance and increases in head vertical movement and asymmetry. The second level of frog pressure caused these changes but also caused decreases in stride duration and carpal joint extension during stance as well as increases in relative stance duration. Toe pressure caused changes in these same variables but also caused maximum extension of the fetlock joint to occur before midstance, maximum hoof height to be closer to midswing, and forelimb protraction to increase. CONCLUSION AND CLINICAL RELEVANCE: Decreased fetlock joint extension during stance and increased head vertical movement and asymmetry are sensitive indicators of forelimb lameness. Decreased stride duration, increased relative stance duration, and decreased carpal joint extension during stance are general but insensitive indicators of forelimb lameness. Increased forelimb protraction, hoof flight pattern with maximum hoof height near midswing, and maximum fetlock joint extension in cranial stance may be specific indicators of lameness in the toe region. Observation of forelimb movement may enable clinicians to differentiate lameness of the heel from lameness of the toe.

Animals↗

PubMed2000

A curve-fitting technique for evaluating head movement to measure forelimb lameness in horses.

Evaluation of the asymmetry of vertical head movement is used during kinematic evaluation of forelimb lameness in horses. For mild lameness, absolute translational measurements are not sensitive enough to detect small differences in the asymmetry of vertical head movement. Also, conscious movement of the head by the horse, not associated with lameness, interferes with accurate measurement. We describe an improved method of evaluating vertical head movement as a measure of lameness, using an model of induced lameness in 9 horses and a time-domain processing technique of curve-fitting. The technique assumes that vertical head movement can be broken down into 3 components; the natural inertially-driven vertical head movement, the alteration of vertical head movement caused by forelimb lameness, and extraneous head movement. The technique uses data from several contiguous strides, eliminates the natural inertially-driven and extraneous head movements, and quantifies lameness as a single value. The technique is shown to more sensitive to change in lameness than absolute measurement of head height translation and to be more accurate than a previously reported frequency-domain technique.

Animals↗

PubMed1999

Functional coupling in rat central olfactory pathways: a coherence analysis.

This experiment determined the importance of functional coupling between structures of central olfactory pathways: the olfactory bulb (OB), anterior (APC), posterior (PPC) parts of the piriform cortex and lateral entorhinal cortex (EC). From local field potential signals obtained in awake rats, coupling during spontaneous activity was estimated with variables reflecting level of coherence computed with a dynamical method. Results revealed a clear hierarchy in the strength of coupling between structures with dissociation within the piriform cortex: PPC was more tightly coupled with the EC than with APC. Systemic injection of a cholinergic antagonist, scopolamine, suggested that tonic coupling is strongly mediated by cortico-cortical connections and not by an external synchronizer, except between OB and APC.

Action Potentials↗

PubMed1999

Frequency-dependent modulation of inhibition in the rat olfactory bulb.

Active sniffing in rodents at theta frequency during exploratory behavior has been hypothesized to enhance odorant access to the receptor sheet and to evoke activity patterns in olfactory and limbic structures which facilitate induction of synaptic plasticity. The present results demonstrate a third potential consequence of theta frequency sniffing -- reversible enhancement of lateral/feedback inhibition in the rat olfactory bulb. Suppression of mitral/tufted cell single-unit spontaneous activity evoked by single lateral olfactory tract (LOT) shocks was examined during LOT stimulation at either 1 or 5 Hz (theta frequency). Theta frequency stimulation rapidly and reversibly enhanced LOT-evoked suppression compared with 1 Hz stimulation. This enhancement was not stimulus intensity dependent. Sniffing-induced modification of lateral/feedback inhibition may enhance odor processing during exploration.

Animals↗

PubMed1999

Sudden death of two horses associated with pulmonary aspergillosis.

The sudden death of two horses was attributed to the rapid and acute development of pulmonary aspergillosis. One horse was making excellent postoperative progress after a jejunal resection and anastomosis for intestinal adhesions. The other horse was being treated routinely for equine protozoal myeloencephalitis (EPM). Signs of fever and an increased respiratory rate were detected shortly before death in the first horse, but no premonitory clinical signs characteristic of pulmonary infection were detected in the horse being treated for EPM. Both horses developed rapidly debilitating, acute pulmonary mycosis and died unexpectedly.

Acute Disease↗

PubMed1999

No evidence for an ischemic penumbra in massive experimental intracerebral hemorrhage.

OBJECTIVES: To determine the effect of massive intracerebral hemorrhage (ICH) on regional cerebral blood flow (rCBF) and metabolism, and to test the hypothesis that there is persistent ischemia in the perihematoma region after ICH. BACKGROUND: Cerebral ischemia is postulated to be one of the mechanisms of neural injury after ICH. Presumably the hematoma induces ischemia by mechanical compression of the surrounding microvasculature. METHODS: The authors induced ICH in eight anesthetized mongrel dogs by autologous blood injection (7.5 mL) under arterial pressure in the deep white matter adjacent to the left basal ganglia. They measured serial rCBF using radiolabeled microspheres in regions around and distant to the hematoma, as well as cerebral oxygen extraction, oxygen consumption (CMRO2), glucose utilization, and lactate production by serial sampling of cerebral venous blood from the sagittal sinus. Mean arterial pressure (MAP) and intracranial pressure (ICP) were monitored continuously. All measurements were recorded at 0.5, 1.0, 2.0, 3.5, and 5.0 hours after induction of ICH and compared with prehematoma values. Evans Blue dye was injected at the end of the experiment, and intensity of staining was compared with three control animals. RESULTS: Compared with prehematoma ICP (12.5+/-2.0 mm Hg, mean+/-standard error), significant elevation in ICP was observed after ICH peaking at 5 hours (34.4+/-5.2 mm Hg). Compared with prehematoma MAP (125.8+/-7.0 mm Hg), significant elevation in MAP was observed at 120 minutes after onset of hematoma (139.1+/-4.6 mm Hg), with return to the prehematoma value by 5 hours. There were no significant changes observed in cerebral oxygen extraction (51.4+/-4.3% versus 44.8+/-4.9%) and CMRO2 (1.8+/-0.3 versus 1.64+/-0.2 mL O2/100 g/min) at 5 hours posthematoma (or any other posthematoma measurement) compared with prehematoma values. There were no significant differences observed in rCBF in the perihematoma gray (18.2+/-0.9 mL/100 g/min versus 20.1+/-1.5 mL/100 g/min) or white matter (15.6+/-1.4 mL/100 g/min versus 15.3+/-1.1 mL/100 g/min) at 5 hours posthematoma (or any other posthematoma measurement) compared with prehematoma values. No changes were observed in cerebral glucose utilization, lactate production, and rCBF in other regions after introduction of ICH. Permeability of the blood-brain barrier was more prominent in the ipsilateral hemisphere in animals with ICH compared with control animals. CONCLUSIONS: Despite a prominent increase in ICP and MAP after ICH, the authors found no evidence to support the presence of an ischemic penumbra in the first 5 hours after ICH. Thus, other mechanisms for acute neural injury and late rCBF changes after ICH must be investigated.

Animals↗

PubMed1999

Acidosis-induced coronary constriction in the rat heart: evidence for the activation of L-type calcium channels.

Perfused rat hearts were used to study the effects of acidosis on coronary tone. When pH was decreased, over the range pH 7.4 to pH 6.2, by reducing perfusate bicarbonate levels, under constant flow conditions, there was a transient decrease in coronary perfusion pressure (CPP), followed by a sustained acidosis-dependent increase in CPP, which reversed when pH was returned to pH 7.4. This increase in CPP was seen at perfusion rates of 5, 10, and 20 ml/min(-1). When using constant pressure perfusion acidosis reduced coronary flow. In a HEPES-buffered bicarbonate-free solution, acidosis did not cause a transient fall in CPP but it did produce a sustained increase in CPP. Addition of ammonium chloride (10 mM) reduced CPP, while washout of ammonium chloride increased CPP. The acidosis-induced increase in CPP was not affected by indomethacin, nitro-L-arginine, the nonselective adenosine receptor antagonist, 8-phenyl theophylline, or the thromboxane receptor antagonist, ZD 1542. The acidosis-induced increase in CPP was independent of the myocardial depressant effects of acidosis, but was attenuated by three different L-type calcium channel blockers. These results demonstrate that the coronary circulation of the rat constricts in response to acidosis. Experiments performed with L-type calcium channel blockers, and the calcium channel activator BAY K8644, suggest that constriction occurs via activation of L-type calcium channels. This would not be expected on the basis of electrophysiological studies, which have shown an inhibition of L-type calcium channels by acidosis.

Acidosis↗

PubMed1999

Respiratory airflow pattern at the rat's snout and an hypothesis regarding its role in olfaction.

Respiratory airflow outside the external nares of the rat was mapped by monitoring temperature fluctuations with a thermistor and simultaneous piezoelectric monitoring of respiration-associated chestwall movement. The results demonstrated that both exhalation and inhalation airflow were directed laterally. Relatively little air exchange occurred anterior to the nares. These results suggest that the two nares of the rat take independent, bilateral samples of the odor environment. Combined with recent descriptions of laterally specific, spatial receptive fields in piriform cortical neurons, an hypothesis is outlined describing a mechanism of odor orientation in the rat involving comparisons of timing or intensity of bilateral odor stimulation.

Animals↗

PubMed1999

Paroxetine in human milk.

AIMS: The primary aims of the study were to estimate the exposure of infants to paroxetine via breast milk and to determine the maternal milk:plasma ratio (M/P) of paroxetine. Secondary aims were to compare single point and area under the curve (AUC) estimates of M/P, to assess variability of M/P in fore and hind milk, and to compare the observed M/P with that predicted by a model. METHODS: Two studies were performed. In one study, six nursing mothers who were being treated with paroxetine were studied over a 24 h dose interval at steady-state. The total amount of paroxetine in the milk was measured, which represented the 'dose' to the infant. The M/PAUC was calculated and compared with a predicted value. In the second study, four nursing mothers who were being treated with paroxetine, were studied at steady-state, around a normal infant feeding time. A single plasma sample and a prefeed milk sample were taken approximately 3 h after the morning dose of paroxetine, and a postfeed milk sample taken around 1 h later. The dose received by the infant was estimated from the average milk concentrations of the pre and postfeed samples using standard assumptions, and M/P calculated directly. Plasma concentrations of paroxetine were measured in 8 of the 10 infants in the two studies. RESULTS: The mean dose of paroxetine received by the infants in the first study was 1.13% (range 0.5-1.7) of the weight adjusted maternal dose. The mean M/PAUC was 0.39 (range 0.32-0.51). The predicted M/P was 0.22. The mean dose of paroxetine received by the infants in the second study was 1.25% (range 0.38-2.24) of the weight adjusted maternal dose. The mean M/P was 0.96 (range 0.31-3.33) and did not differ between fore and hind milk. The drug was not detected in the plasma of seven of the infants studied and was detected but not quantifiable (<4 microg l-1 ) in one infant. No adverse effects were observed in any of the infants. CONCLUSIONS: Measured M/P and estimated infant dose were similar in the two studies, although the range was wider for the single point study. Paroxetine can be considered 'safe' during breast feeding because the dose transferred to the infant is well below the recommended safety limit of 10% of the weight adjusted maternal dose, concentrations in the infants were generally undetectable, and no adverse effects were reported.

Adult↗

PubMed1999

Prevalence and incidence of intracranial haemorrhage in a population of children with haemophilia. The Hemophilia Growth and Development Study.

The prevalence of intracranial haemorrhage (ICH) in our population of haemophiliacs was 12%. The incidence of ICH was approximately 2% per year. At entry, 7% (21/309) had clinical histories of ICH without MRI evidence of old haemorrhage, indicating that either the haemorrhages had completely resolved, that routine MRI sequences are not particularly sensitive for the detection of old blood products, or a combination of both of these factors. One half (4/8) of the ICHs documented by entry MRI were clinically silent, and three of the 11 incident cases documented by MRI were clinically silent. HIV infection did not increase the risk of ICH.

Adolescent↗

PubMed1999

Pharmacologic reduction of mean arterial pressure does not adversely affect regional cerebral blood flow and intracranial pressure in experimental intracerebral hemorrhage.

OBJECTIVE: To determine the effect of mean arterial pressure (MAP) reduction on regional cerebral blood flow and intracranial pressure (ICP) in intracerebral hemorrhage. We tested the hypothesis that there is ischemia in the perihematoma region after intracerebral hemorrhage, which can be exacerbated by a pharmacologic reduction of MAP. DESIGN: Prospective, controlled, laboratory trial. SETTING: Animal research laboratory. SUBJECTS: Eighteen mongrel dogs, weighing 15 to 25 kg. INTERVENTIONS: We introduced intracerebral hemorrhage in 12 anesthetized dogs by autologous blood injection under arterial pressure in the deep white matter adjacent to the left caudate region. We measured serial regional cerebral blood flow using radiolabeled microspheres in animals with two different volumes of injected blood (2.8 mL [Group A, n = 6] and 4.4 mL [Group B, n = 6]) and compared them with control animals (n = 6). Intravenous labetalol was administered 90 mins after administration of hematoma, while maintaining cerebral perfusion pressure >65 mm Hg. Regional cerebral blood flow measurements were repeated 10 and 30 mins after labetalol administration. MAP and ICP were monitored continuously using intra-arterial and cisterna magna catheters, respectively. MEASUREMENTS AND MAIN RESULTS: Compared with control animals, significant elevation in ICP was observed in Groups A and B and elevation in MAP was observed in Group B at 45 mins after injection of blood. These hemodynamic alterations were not accompanied by any significant differences in regional cerebral blood flow in any group. Administration of labetalol resulted in a decrease in MAP (mm Hg+/-SEM) in Groups A (119.0+/-9.2 to 103.0+/-9.1) and B (124.5+/-7.4 to 100.5+/-4.8) and controls (103.5+/-4.3 to 85.0+/-8.0). No differences were observed in regional cerebral blood flow after MAP reduction in both Groups A and B compared with controls in regions around or distant to the hematoma. There were no changes in ICP in Groups A and B both at 10 and 30 mins after reduction in MAP compared with pretreatment values. CONCLUSIONS: In our model, pharmacologic reduction of MAP within the normal autoregulatory limits of cerebral perfusion pressure, 90 mins after onset, had no adverse effect on ICP and regional cerebral blood flow in regions around or distant to the hematoma. These results support the controlled use of antihypertensive treatment in intracerebral hemorrhage in the initial time period.

Animals↗

PubMed1999

Treatment of elevated intracranial pressure in experimental intracerebral hemorrhage: comparison between mannitol and hypertonic saline.

OBJECTIVE: Elevated intracranial pressure (ICP) is related to mortality after intracerebral hemorrhage (ICH). To develop effective strategies for the medical treatment of ICP in cases of ICH, we evaluated the therapeutic efficacy of mannitol and hypertonic saline in a canine model of ICH. METHODS: We introduced ICH in three groups of anesthetized mongrel dogs, consisting of seven animals each, by autologous blood injection (5.5-7.5 ml) under arterial pressure in the deep white matter adjacent to the left basal ganglia. We evaluated the effect of iso-osmolar doses (5.5 mOsm/kg) of intravenously administered mannitol (1 gm/kg), 3% NaCl (5.3 ml/kg), or 23.4% NaCl (0.7 ml/kg) administered 2 hours after the introduction of hematoma, on the following: ICP, cerebral perfusion pressure, cerebral oxygen extraction and oxygen consumption, and regional cerebral blood flow in regions around and distant to the hematoma. All measurements were recorded at baseline, before treatment, and 15, 30, 60, and 120 minutes after treatment. We also evaluated the water content (wet/dry weight) and blood-brain barrier permeability (Evans blue method) in pathologically demarcated regions of brain. RESULTS: There was an immediate reduction in ICP (mm Hg +/- standard error of the mean) in the 23.4% NaCl (27.6+/-4 to 11.0+/-2 mm Hg, P = 0.001), 3% NaCl (23.7+/-3 to 14.7+/-2 mm Hg, P = 0.009), and mannitol (25.6+/-3 to 15.9+/-4 mm Hg, P = 0.02) groups. Compared with pretreatment values, ICP was significantly lower in both the 23.4% NaCl (12.3+/-2 mm Hg, P = 0.002) and 3% NaCl (17.6+/-2 mm Hg, P = 0.008) groups but not in the mannitol group (18.7+/-4 mm Hg, P = 0.08) 15 minutes after the administration of treatment. There was a gradual rise in ICP observed in the 23.4% NaCl and mannitol groups with time. Only in the 3% NaCl group was the ICP significantly lower than the pretreatment value at 120 minutes (18.0+/-2 mm Hg, P = 0.02). A significantly higher cerebral perfusion pressure (108.4+/-4 versus 79.6+/-10 mm Hg, P = 0.048) and lower water content in the lesioned white matter (65.5+/-1% versus 67.9+/-1%, P = 0.07) was observed 2 hours after treatment in animals receiving 3% NaCl compared with animals receiving mannitol. There were no significant differences observed in regional cerebral blood flow, oxygen extraction, or oxygen consumption at any time point among the three groups. CONCLUSION: Hypertonic saline, in both 3 and 23.4% concentrations, is as effective as mannitol in the treatment of intracranial hypertension observed in association with ICH. Hypertonic saline may have a longer duration of action, particularly when used in 3% solution. None of three treatment regimens influence regional cerebral blood flow or cerebral metabolism.

Animals↗