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At least 19 recordsLinked to original sources
PubMed1990

Morphological estimation of brain extracellular fluid dynamics in cold-induced edema from the aspect of cerebrospinal fluid-extracellular fluid communication.

Following the induction of cold injury in the parietal cortex of rats, the brain extracellular fluid dynamics under conditions of cryogenic edema were investigated morphologically from the aspect of extracellular fluid (ECF)-cerebrospinal fluid (CSF) communication using horseradish peroxidase (HRP) injected into the cisterna magna as a marker. About 24 h after the induction of cold injury, HRP was distributed in the subjacent white matter of the lesion and around the ventricle. Forty-eight hours after injury, the distribution of HRP around the lesion became distinctive. This distribution of HRP became more concentrated at the same location on day 3-4 after injury. At this time, HRP was observed to be distributed along the walls of small vessels, in the cytoplasm of a few neurons and in the neuropil around the lesion by light microscopy. At small vessels around the lesion, a dense deposit of HRP at the basement membrane and many abluminal vesicles were evident by electron microscopy. These findings indicate that ECF-CSF communication changes drastically under the influence of edema fluid dynamics. In particular, the dense distribution of HRP around the lesion on day 3-4 after injury can be attributed to active retrograde transport by vessels in this area, a phenomenon considered important for edema resolution.

Animals↗
PubMed1985

Cerebrospinal fluid and extracellular fluid: their relationship to pressure and duration of canine hydrocephalus.

Fifteen greyhound dogs were made hydrocephalic by the transsphenoidal injection of silicone into the basal cisterns at the level of the tentorial incisura. Six of these animals had ventriculocisternal perfusions 4 weeks later and six at 8 weeks, half at 150 and half at 100 mm H2O. Three 12-week dogs were perfused at 150 mm H2O. Serial sections of brain from the ependyma of the left frontal horn to the overlying pia were counted for 14C inulin and 3H methotrexate uptake. Tissue concentrations of both markers varied indirectly with distance from ependyma and from pia, and varied directly with perfusion pressure. The data indicate that the diffusional pathway between cerebrospinal fluid (CSF) and extracellular fluid (ECF) can be modified by CSF pressure changes, i.e., CSF flows from the ventricles and subarachnoid space into the extracellular space when CSF pressures are raised. Brain uptake of inulin and methotrexate was significantly increased in the dogs made hydrocephalic 4 weeks prior to perfusion, but was less so in the 8-week hydrocephalics. Uptake of the tracers in three 12-week animals was similar to that found previously in normal dogs at elevated pressures. These findings correspond in location and time to the periventricular lucencies that are seen by computed tomography in human subacute hydrocephalus. They are apparently due to pressure-related changes in the volume of the ECF.

Animals↗
PubMed1999

Estimation of topiramate in subdural cerebrospinal fluid, subcutaneous extracellular fluid, and plasma: a single case microdialysis study.

PURPOSE: To estimate topiramate (TPM) concentrations in subdural cerebrospinal fluid (CSF), subcutaneous extracellular fluid (ECF), and plasma and to study the correlation of TPM concentrations in these three different compartments. METHODS: In this single case study of a patient with drug-resistant partial epilepsy undergoing presurgical evaluation with subdural EEG monitoring, we used microdialysis to estimate concentrations of unbound TPM in CSF of the subdural space and ECF of abdominal subcutaneous tissue. Blood samples were drawn for estimation of TPM concentrations in plasma. RESULTS: The correlation between unbound TPM concentrations in subdural CSF and abdominal subcutaneous ECF was good. The mean ratio of ECF/CSF TPM concentration was 0.93 (SD+/-0.03) and the correlation coefficient was 0.98. The mean ratio of ECF/total plasma TPM was 0.75 (SD+/-0.06), and the correlation coefficient was 0.99. The mean ratio of CSF/total plasma TPM was 0.81 (SD+/-0.06), and the correlation coefficient was 0.97. CONCLUSIONS: Assuming a protein binding of TPM of approximately 13%. it is concluded that, based on nine microdialysis samples from a single subject, TPM levels in the CSF at the cortical surface are approximately the same as the unbound plasma levels. Additional patients should be studied to confirm the results.

Adult↗
PubMed2001

Distribution of valproate to subdural cerebrospinal fluid, subcutaneous extracellular fluid, and plasma in humans: a microdialysis study.

We sought to study the time course of the distribution of valproate (VPA) to subdural cerebrospinal fluid (CSF) in relation to subcutaneous extracellular fluid (ECF) and plasma after a single oral dose and to study the distribution to these three compartments under steady-state conditions. Microdialysis was used to estimate unbound VPA concentrations in subdural CSF and subcutaneous ECF, and blood samples were drawn for estimation of total and unbound VPA plasma concentrations in four patients with drug-resistant partial epilepsy undergoing presurgical evaluation with subdural EEG monitoring. Three patients were given a single oral dose of VPA, and one patient was receiving regular VPA treatment. VPA was analyzed by gas chromatography with flame ionization detection. The distribution of VPA to subdural CSF was rapid (Tmax, 3.5 h in two patients and 5.5 h in one patient) and subject to a minor delay in all three patients compared with that in the subcutaneous tissue ECF (Tmax, 2.5 h in all three patients), which in turn exhibited no evidence of a distribution delay compared with plasma. Subdural CSF levels of VPA were slightly lower than subcutaneous ECF levels (mean ratio, 0.78) and unbound plasma levels (mean ratio, 0.91). VPA rapidly enters the subdural CSF in unbound concentrations marginally lower than those obtained in subcutaneous ECF and plasma. These findings provide a pharmacokinetic rationale for acute administration of VPA. The good correlation between VPA concentrations in subcutaneous ECF and subdural CSF indicates that estimation of unbound VPA concentrations in subcutaneous tissue using microdialysis sampling has the potential to be useful for monitoring purposes.

Administration, Oral↗
PubMed2000

Influence of ovariectomy on extracellular fluid volume in rats: assessment of extracellular fluid volume by means of bromide.

There is considerable evidence that the extracellular fluid volume (ECV) may change in disease states or during longitudinal Intervention studies. Therefore, the measurement of ECV is Important for studying body composition in patients and laboratory animals. We present a modified plasma bromide (Br-, non-radioactive) assay using anion-exchange chromatography, in which a small blood sample of 200 microL (100 microL of plasma) appeared to be enough to reproducibly measure ECV. The inter- and intra-assay accuracy of the Br- analysis ranged from -1.6% to 0.9% and from -0.5% to 0%, respectively. The inter- and intra-assay precision ranged from 1.3% to 1.7% and from 0.6% to 1.2%, respectively. This modified precise and accurate Br- analysis in a small blood sample was applied to investigate whether the ECV changed in rats after ovariectomy. Ovariectomy significantly (P < .05) reduced the ECV as compared with results in SHAM rats. This observation indicates that a change in clinical condition may change ECV, which has consequences for the determination of, for example, the fractional absorption and the relative bioavailability of compounds principally distributed through the ECV.

Animals↗
PubMed2000

Comparison of serum, cerebrospinal fluid and brain extracellular fluid pharmacokinetics of lamotrigine.

We investigated the rate of penetration into and the intra-relationship between the serum, cerebrospinal fluid (CSF) and regional brain extracellular fluid (bECF) compartments following systemic administration of lamotrigine in rat. The serum pharmacokinetics were biphasic with an initial distribution phase, (half-life approximately 3 h), and then a prolonged elimination phase of over 30 h. The serum pharmacokinetics were linear over the range 10 - 40 mg kg(-1). Using direct sampling of CSF with concomitant serum sampling, the calculated penetration half-time into CSF was 0.42+/-0.15 h. At equilibrium, the CSF to total serum concentration ratio (0.61+/-0.02) was greater than the free to total serum concentration (0.39+/-0.01). Using in vivo recovery corrected microdialysis sampling in frontal cortex and hippocampus with concomitant serum sampling, the calculated penetration half-time of lamotrigine into bECF, 0.51+/-0.11 h, was similar to that for CSF and was not area or dose dependent. At equilibrium, the bECF to total serum concentration ratio (0.40+/-0.04) was similar to the free to total serum concentration (0.39+/-0.01), and did not differ between hippocampus and frontal cortex. The species specific serum kinetics can explain the prolonged action of lamotrigine in rat seizure models. Lamotrigine has a relatively slow penetration into both CSF and bECF compartments compared with antiepileptic drugs used in acute seizures. Furthermore, the free serum drug concentration is not the sole contributor to the CSF compartment, and the CSF concentration is an overestimate of the bECF concentration of lamotrigine.

Animals↗
PubMed1985

Increased digitalis-like activity in human cerebrospinal fluid after expansion of the extracellular fluid volume.

The present study was designed to determine whether acute expansion of the extracellular fluid volume influenced the digitalis-like activity of human cerebrospinal fluid (CSF), previously described by our laboratory. Human CSF samples, drawn before and 30 minutes after the intravenous infusion of 1 liter of either saline or glucose solutions, were assayed for digitalis-like activity by inhibition of either the 86Rb+ uptake into human erythrocytes or by the activity of a purified Na+ - K+ ATPase. The CSF inhibitory activity on both systems significantly increased after the infusion of sodium solutions but did not change after the infusion of glucose. These results indicate that the digitalis-like factor of human CSF might be involved in the regulation of the extracellular fluid volume and electrolyte content and thereby in some of the physiological responses to sodium loading.

Calcium↗
PubMed1983

Effects of isotonic fluid load on plasma water and extracellular fluid volumes in the rat.

An isotonic fluid load was given to rats by infusing 12 ml saline i.v. in 60 min. The plasma water and extracellular fluid volumes of the whole animal and selected tissues were subsequently studied with 125I human serum albumin and 51Cr EDTA. The fluid infused was equivalent to 130% of the plasma water volume. The total extracellular fluid volume increased by 17%, while the total plasma water measured with RIHSA remained unchanged. The regional extracellular fluid volumes increased in the lung (14%), the gastric fundus (15%), large intestine (21%) and skin (28%). The results illustrate the selective distribution of an isotonic fluid overload, those tissues being effected having high compliances.

Animals↗
PubMed1984

Compliance of the interstitial space in rats. III. Contribution of skin and skeletal muscle interstitial fluid volume to changes in total extracellular fluid volume.

The contribution to the extracellular fluid volume (ECV) from plasma volume (PV) and the total interstitial volumes contained in skin ( IFVS ) and skeletal muscle ( IFVM ) has been studied in rats over a wide range of overhydration and dehydration. ECV was measured as the two-hour distribution space for 51Cr-EDTA after nephrectomy while PV was measured with radiolabelled albumin or erythrocytes. Total interstitial volumes in skin and skeletal muscle were calculated from measurement of local interstitial volumes and the amount of skin and skeletal muscle in the rat. In control conditions ECV was on average 24.12 ml/100 g body weight. PV was 11.0% of ECV in control while IFVS and IFVM was 28.1% and 19.0% respectively. In dehydration the change in PV was 13.3% of the change in ECV, while the change in IFVS and IFVM was 30.0% and 21.0% of the change in ECV respectively. In overhydration (ECV on average 33.76 ml/100 g rat) the changes in PV, IFVS and IFVM were 7.5%, 22.1% and 17.2% of the change in ECV respectively. The regression coefficients describing the change between ECV and IFVS and IFVM were not significantly different in overhydration and dehydration while the regression coefficient between ECV and PV in overhydration was significantly less than the regression coefficient in dehydration. Thus, the fraction of ECV contained in skin and skeletal muscle is similar over the range of hydration studied. The fraction of ECV located in plasma is similar in control and dehydration, while in overhydration less of ECV is localized in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Isotopically labelled compounds in the study of extracellular fluid space in dog bone.

The extracellular fluid space in dog bone has been examined using a series of isotopically labelled compounds. Sodium-77 bromide and indium-113m ethylenediaminetetracetic acid were used as extracellular fluid space markers, radioactive water as a total fluid space marker, and potassium-43 chloride to examine the existence of a bone membrane. The clearance of each tracer from bone was monitored for a period of 2h post-injection. Graphical analysis of the clearance curves shows that the number of exponential functions vary depending on the type of tracer used. The fact that a sum of three exponential terms can completely describe each curve indicates that a simple model consisting of three compartments is sufficient to approximate the clearance of these tracers from bone and its associated fluid space. It is concluded that bone consists of an extracellular fluid space, and that this space may well play an important part in the transference of solutes and the mechanisms involved in their localization on the hydroxyapatite crystals of bone.

Animals↗
PubMed1974

The effects of pentobarbitone anaesthesia on the volume and composition of the extracellular fluid of dogs.

1. The effects of pentobarbitone sodium (Nembutal) anaesthesia in dogs on extracellular fluid and plasma volumes, plasma protein concentration, haematocrit and extracellular fluid electrolyte composition were measured.2. Induction of pentobarbitone anaesthesia caused a rapid rise in extracellular fluid volume, accompanied by decreases in the haematocrit, in extracellular fluid potassium concentration, and in plasma calcium, magnesium, and protein concentrations. There were no significant changes in plasma osmolality and extracellular fluid concentrations of sodium and chloride.3. Extracellular fluid volume did not alter significantly during six hours of anaesthesia, but the haematocrit and extracellular fluid potassium concentration showed an increase towards control values.4. The relevance of these findings to the interpretation of experiments carried out under pentobarbitone anaesthesia is noted.

Anesthesia, Intravenous↗
PubMed1996

[Distribution of irrigating fluid to intracellular and extracellular fluid space during transurethral prostatectomy I--Estimation of irrigating fluid absorbed by measuring serum osmolality].

Twenty-three patients undergoing transurethral resection of the prostate (TURP) under spinal anesthesia were studied. The irrigating fluid widely used in Japan is a hypo-osmolar solution with 3% sorbitol (Uromatic S, 170 mOsm.kgH2O-1, Baxter). The blood loss and the distribution of the irrigating fluid absorbed were computed from serum osmolality, blood urea nitrogen, and hematocrit using the equation we had formulated. The blood loss, the total fluid absorbed (ABS), and the volumes distributed to intracellular space (delta ICF) and extracellular space (delta ECF) were 419 +/- 677 ml, 1,582 +/- 1,446 ml, 384 +/- 348 ml and 778 +/- 1,279 ml (mean+/-SD), respectively. The correlation coefficient of delta OSM (difference between pre- and post-surgical serum osmolality) vs ABS and that of delta OSM vs delta ICF were high (0.98, 0.98) but that of delta Na (difference between pre- and postsurgical serum sodium) vs ABS was low (0.56). The linear regression equations of ABS vs delta OSM and delta ICF vs delta OSM were ABS (L) = 0.362 x delta OSM and delta ICF (L) = 0.088 x delta OSM, respectively. These equations means that one mOsm.kgH2O-1 reduction of the serum osmolality is the result of 362 ml of irrigating fluid absorbed, 88 ml of which shifting into the intracellular space.

Aged↗
PubMed1989

Neuroactive metabolites of L-tryptophan, serotonin and quinolinic acid, in striatal extracellular fluid. Effect of tryptophan loading.

Extracellular fluid levels of the neurotoxin quinolinic acid in the corpus striatum of rats, measured by in vivo microdialysis, were increased in a dose-dependent manner following the intraperitoneal administration of tryptophan. The lowest dose of tryptophan (12.5 mg/kg), equivalent to about 5% of the normal daily intake, increased peak quinolinic acid levels nearly 3-fold. At higher doses of tryptophan (up to 250 mg/kg), concentrations of quinolinic acid increased over 200-fold and exceeded potentially neurotoxic levels (10 microM). In contrast, the increase in extracellular serotonin following even the highest tryptophan dose was small (less than 2-fold). These data indicate that quinolinic acid is present in the extracellular fluid where it may function as a neuromodulator and that it is very responsive to physiological changes in precursor availability.

Animals↗