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At least 19 recordsLinked to original sources
PubMed1996

Clinical microdialysis: the role of on-line measurement and quantitative microdialysis.

The use of microdialysis in the clinic is examined in the light of lessons learnt from microdialysis in freely moving rats. Changes in concentrations of metabolites are an important index of the state of health of tissues. For effective therapeutic intervention rapid assays are essential Enzyme-based on-line assays for glucose and lactate are described. By combining two of these assays simultaneous measurements of glucose and lactate, sampled at 2 min intervals can be obtained. The relation between dialysate concentrations and the true extracellular concentration of an analyte is dependent on conditions in the tissue sampled and cannot be calculated from in vitro probe recoveries. Furthermore, with acute implantation of the probe and possibly rapidly changing tissue conditions, there will be changes in probe recovery in vivo. Quantitative microdialysis allows the measurement of the true extracellular concentration and the probe recovery in vivo. The clinical applicability of a number of quantitative microdialysis methods is discussed, and three approaches highlighted. By increasing membrane length and reducing flow rate recovery in vivo can be increased to 100%. In this case dialysate concentrations equal extracellular ones. By perfusing an inert exogenous compound an index of changes to extracellular volume and hence tissue oedema can be obtained. In the zero net flux method the infusion of a few concentrations of the analyte under study allows the direct determination of both the ECF concentration and the in vivo recovery. The latter can provide valuable information about changes in the physical as well as chemical state of the tissue. This can guide rapid effective therapeutic intervention.

Animals↗
PubMed1996

In vivo microdialysis in the rat: low cost and low labor construction of a small diameter, removable, concentric-style microdialysis probe system.

A method for construction of a serviceable and low cost intracerebral microdialysis system is presented. The system includes a probe and its supporting components. The probe is of the concentric design. The supporting components are an implantable guide cannula, a tether, and a swivel. After minimal training, workers can make many probes of consistent performance characteristics in a short time. Because all of the parts are commercially produced, users may obtain custom-made components which are finished with factory precision and accuracy. The user may readily vary probe characteristics such as depth of implant and size of active portion, so that different types of dialysis may be performed in different brain regions. The available choices in tether and swivel configurations make this microdialysis system readily adaptable to diverse testing environments. Excluding labor and startup costs, the costs, the cost per probe is approximately $11.00 (US). Taken together, the system provides a flexible, low cost means for performing in vivo microdialysis in freely moving rats.

Animals↗
PubMed1993

Generation and detection of hydroxyl radical in vivo in rat spinal cord by microdialysis administration of Fenton's reagents and microdialysis sampling.

We developed a double microdialysis fiber technique to generate hydroxyl radicals (OH.) in rat spinal cord. H2O2 and FeCl2/EDTA were pumped through two parallel microdialysis fibers inserted into the spinal cord such that the reactants mix in the tissue to generate OH. by the Fenton reaction. Generated OH. was detected by administering phenylalanine through one fiber and measuring o-, m- and p-hydroxyphenylalanine in collected dialysates by high pressure liquid chromatography and fluorescence detection. The hydroxyphenylalanines are produced by OH. attacking the phenylalanine. OH. generation was also accomplished in in vitro experiments and the results were consistent with in vivo experiments. This novel method to generate and measure OH. radical in vivo overcomes difficulties in studying damage to tissue by short-lived OH.. Although developed to study the role of OH. in spinal cord injury, this method could be used to study other diseases involving OH. damage.

Animals↗
PubMed1995

Microdialysis sampling for hepatic metabolism studies. Impact of microdialysis probe design and implantation technique on liver tissue.

Microdialysis sampling of liver tissue was performed using several probe geometries. The extent of tissue damage and response in vivo caused by implantation and indwelling of the probe was evaluated by histological examination of the tissue. A linear probe, implanted using fused silica tubing, was less damaging than other probe designs and implantation procedures tested. A series of time points up to 48 hr after implantation ere histologically examined. Infiltration of inflammatory cells, predominantly polymorphonuclear leukocytes (PMNs), was evident adjacent to the probe membrane after approximately 8 hr. Mixed inflammatory infiltration, mainly PMNs but including some macrophages, was observed in tissue slices 18 hr after implantation. At 48 hr, the mixed inflammatory infiltration was still present, with some degeneration of PMNs. In implantations of longer than 12 hr, some necrosis appeared at eh implantation site. The rate of delivery of phenol via the probe was stable for at least 30 hr, despite changes in the surrounding tissue.

Animals↗
PubMed1992

Brain microdialysis study of the effects of hazardous chemicals on the central nervous system. 1. Changes in monoamine metabolites induced by cerebral methyl bromide administration measured by two-probe microdialysis (TPMD) method.

The two-probe microdialysis (TPMD) method, in which two probes were applied simultaneously to the rat head, was developed to directly investigate the effects of chemicals on the brain. The first and the second probes were implanted into the right striatum and the left ventricle, respectively. Chemicals were dissolved in the perfusion fluid and given into the brain by diffusion through the ventricle probe. Monoamine metabolites were recovered through the striatum probe to investigate changes in neurotransmitter substances. Both intraperitoneal and intraventricular administration of haloperidol (a dopamine receptor blocker) increased 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA, dopamine metabolites) concentrations in the striatum. On the other hand, apomorphine (a dopamine receptor stimulant), which was given both intraperitoneally and intraventricularly, decreased striatal DOPAC and HVA concentrations. 5-Hydroxyindoleacetic acid (5HIAA, a serotonin metabolite) concentration was not affected by these drugs. Regarding changes in monoamine neurotransmitters, systemic and intraventricular administration produced similar effects. These findings indicate that the drugs were effectively incorporated into the brain by the TPMD method and the drug effect was observed in the opposite brain hemisphere. In the same procedure as used in the administration of haloperidol and apomorphine, methyl bromide was given into the rat brain. DOPAC and HVA in the striatum were increased by methyl bromide given by the TPMD method. These changes were the same as observed in the homogenate of rat brain exposed to methyl bromide. 5HIAA was reduced by intraventricular administration by the TPMD method, and this change in 5HIAA was not observed in the exposure experiments. We could detect the direct effects of methyl bromide on the brain by the TPMD method.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

[Microdialysis: a method to construct a microdialysis probe and its applications].

This paper describes a removable microdialysis probe constructed inexpensively and easily from a commercially available iv catheter placement unit and flexible fused silica tubing. The probe is characterized in in vitro recovery tests. As an example of its applications, experimental results measuring extracellular dopamine concentrations in the nucleus accumbens of rats during intracranial self-stimulation behavior are reported.

Animals↗
PubMed1992

Microdialysis sampling for the investigation of dermal drug transport.

Microdialysis perfusion in vivo has the potential to be a powerful sampling technique in dermal and transdermal drug delivery studies. Characterization of a commercially available microdialysis probe in vitro considering relevant physiological parameters is a vital first step in the evaluation of microdialysis as a dermal sampling technique. In previous microdialysis studies, analyte concentration and neutrality have been implicated in altering microdialysis recovery. The recovery of a model compound 5-fluorouracil (5-FU) was investigated at several pH values and donor concentrations. The relative recovery of 5-FU by the microdialysis probe was affected by pH but not by donor concentration. To confirm further that the changing concentration and pH profile presented by the flux of 5-FU was not significantly altering microdialysis recovery, an experiment comparing direct and microdialysis sampling of a Franz diffusion cell receptor compartment was performed. Although the 5-FU concentration (0-686 ng/ml) and pH (7.40-7.24) changed substantially, the recovery of 5-FU was not adversely affected. To demonstrate the feasibility of dermal microdialysis, the flux of a commercial preparation of 5-fluorouracil was monitored utilizing a microdialysis probe implanted in excised rat skin in vitro. The results from the dermally implanted probe demonstrate the potential of the technique while establishing the limitations of the current microdialysis system.

Animals↗
PubMed1994

Combination of microdialysis and glucose sensor for continuous on line measurement of the subcutaneous glucose concentration: theory and practical application.

The microdialysis technique can be used to get dialysates of the subcutaneous tissue, which can be continuously measured by an amperometric glucose sensor. In order to get further insight into the microdialysis procedure, we used a steady-state theory for microdialysis to predict the recovery of glucose in the dialysate and compared the results to experimental data obtained by a combination of the microdialysis technique with continuous amperometric glucose sensing. The recovery of glucose obtained in vitro for two different microdialysis probes was close to the theoretical predictions. When quantifying the predictions of the model with regard to the spatial concentration profile in the subcutaneous tissue, it appeared, that the presence of the microdialysis probe depressed the concentration of glucose for 0.2 mm from the probe surface. In a 24 hour in vivo experiment, there were less fluctuations in the sensor signal when the patient was lying in bed compared to the time, when the patient could move freely. In conclusion, the combination of microdialysis and glucose sensor seems to be a promising approach to a continuously functioning glucose sensing system. However, the microdialysis procedure itself disturbs the surrounding of the probe leading to a concentration gradient of glucose. This might explain some differences between the course of blood glucose and the course of subcutaneous glucose, measured by the combination of microdialysis and an amperometric glucose sensor. Further developments of such systems should aim at implanting microdialysis devices which have a minimal influence upon the tissue metabolism.

Biosensing Techniques↗
PubMed1992

Intravenous microdialysis sampling in awake, freely-moving rats.

Intravenous microdialysis sampling in the awake, freely-moving rat for the determination of free drug concentrations in blood is described. Intravenous microdialysis was performed with a nonmetallic, flexible dialysis probe. The pharmacokinetics of theophylline were determined using both microdialysis sampling and collection of whole blood following an iv dose. There was no difference in the half-life of elimination of theophylline determined by microdialysis, 4.4 +/- 0.4 h, and whole blood sampling, 4.5 +/- 0.7 h. The kinetics of elimination were affected by removing blood samples and by using anesthesia. The half-life of elimination was 4.4 +/- 0.4 h when using simultaneous microdialysis and whole-blood sampling and only 3.0 +/- 0.4 h using microdialysis alone. The half-life of elimination was 17.0 +/- 7.1 h in chloral hydrate anesthesized rats. Microdialysis samples were continuously collected for over 7 h without fluid loss using a single experimental animal. Microdialysis sampling directly assesses the free drug concentration in blood. The extent of theophylline binding to blood proteins was determined in vitro in rat plasma and rat whole blood using both ultrafiltration and microdialysis. Theophylline was (47.3 +/- 1.3)% bound in rat plasma and (52.2 +/- 1.6)% bound in rat whole blood. Microdialysis sampling is a powerful tool for pharmacokinetic studies, providing accurate and precise pharmacokinetic data.

Anesthesia↗
PubMed1994

Evaluation of methotrexate tissue exposure by in situ microdialysis in a rat model.

The feasibility of using a microdialysis technique to obtain pharmacokinetic data on tissue exposure to methotrexate (MTX) was investigated. Microdialysis probes were implanted in the jugular vein, femoral muscle, and liver of anesthetized male Wistar rats. MTX (100 mg/kg) was given as a bolus injection through an indwelling venous catheter, and blood samples were obtained through a second venous access and by microdialysis for a total of 6 h. Heparinized plasma, ultrafiltered plasma, and microdialysis effluent from tissue and venous probes were analyzed by high-performance liquid chromatography. Centrifugal ultrafiltration of rat plasma spiked in vitro with MTX (1-100 microM) revealed a mean binding to plasma proteins of 21%. In vitro microdialysis of this spiked plasma resulted in 23% relative recovery of the unbound fraction. In rats receiving MTX, plasma protein binding was 23% and the relative drug recovery as assessed with venous microdialysis probes was 18%. Plotting of unbound (i.e., ultrafiltrate) MTX concentrations in the blood against venous microdialysis perfusate values in the blood gave a good linear correlation with a coefficient of correlation (r2) of 0.98. There was also a linear correlation between the total MTX concentrations in venous blood and the drug levels in microdialysis samples from muscle and liver (r2 = 0.93 and 0.74, respectively). Area under the curve estimations were consistent with an MTX exposure of 30% and 46% for the muscle and liver as compared with the circulation. The present study demonstrates that the microdialysis technique can provide reproducible data on tissue exposure to MTX in an animal model and indicates that the methodology is adaptable to clinical settings.

Animals↗
PubMed1996

Quantitative assessment of blood-brain barrier damage during microdialysis.

In view of the increasing use of microdialysis for monitoring drug uptake into the brain, the consequences of tissue/blood-brain barrier (BBB) damage that occurs on microdialysis probe insertion on the extent and rate of solute uptake need to be more carefully examined. In this study, both microdialysis and a classic method were used to compare the apparent brain uptake of two polar permeants, [3H]sucrose and [14C]urea. The blood-to-brain transfer constants of these compounds differ significantly, with the value of urea exceeding that of sucrose by a factor of approximately 20 when compared by the classic one-point-per-animal method. The BBB selectivity to these nonmetabolized permeants as assessed by microdialysis provides a sensitive measure of the integrity of the BBB to polar nonelectrolytes within the molecular size range of most drugs. The following evidence for blood-brain barrier damage during microdialysis sampling was obtained: (1) the loss of [3H]sucrose from the extracellular fluid in brain on termination of an intravenous infusion is biphasic, with the initial phase evident immediately on termination by the infusion, suggesting that a fraction of the microdialysis probe resides in a region in rapid equilibrium with plasma; (2) complete loss of selectivity in the rate constants for CNS entry of sucrose vs. urea and (3) there were substantially higher area under the concentration vs. time curve AUCECF/AUCplasma ratios for both sucrose and urea generated by microdialysis than the corresponding ratios (AUCCSF/AUCplasma or AUCbrain/AUCplasma) obtained by classic methods. These results suggest that the BBB to small molecule transport likely remains compromised for some time after microdialysis probe insertion.

Animals↗
PubMed1993

Distribution of spin-trapping compounds in rat blood and brain: in vivo microdialysis determination.

Microdialysis was utilized to determine blood and brain distribution of spin-trapping nitrone compounds in the rat following intraperitoneal administration. In vivo quantitation by high-pressure liquid chromatography (HPLC) analysis, in vitro calibration of microdialysis probes, optimum perfusion rate, and the relationship of microdialysis sample recovery to tissue levels were evaluated in detail. The microdialysis sampling and HPLC analysis provided on-line, within-animal pharmacokinetic time-course determinations. At equimolar concentrations, 150 mg/kg alpha-phenyl-N-tert-butyl nitrone (PBN) or 165 mg/kg alpha-4-pyridyl-N-oxide N-tert-butyl nitrone (POBN) reached a similar, steady-state venous blood concentration of 224 +/- 21 microM and 210 +/- 10 microM, respectively. The POBN steady-state brain concentration was 149 +/- 9 microM, a significantly (p < .05) lower concentration than in the blood. In contrast, the brain concentration of PBN was 331 +/- 25 microM, significantly (p < .05) higher than its concentration in the blood. The increased brain distribution/penetration of PBN was attributed to its greater lipophilicity as measured by its octanol/water partition coefficient. All microdialysis results were validated by direct measurement of blood and brain levels at steady-state using conventional extraction procedures and assays. Also, the amount of tissue/cell bound versus unbound nitrones was determined by comparing the microdialysis "dialyzable" fraction with the total amount from whole tissue extracts. These data demonstrate that on-line determinations of nitrone spin-trap brain penetration/levels can be carried out accurately using in vivo microdialysis. The implication of these results for potential use of the microdialysis technique for detection of free radical products in in vivo animal models is discussed.

Animals↗
PubMed1995

Brain microdialysis and its application for the study of animal behaviour.

Microdialysis is a sampling method that is used to determine the extracellular concentration of neurotransmitters in the brain. The method can be applied to conscious and unrestrained animals and is very suitable for the study of the chemistry of endogenous behaviour. This article reviews the contribution that microdialysis made to our understanding of the chemistry of behaviour. Methodological and practical considerations such as the implantation time and the use of guide cannulas are reviewed. The question whether neurotransmitters and related metabolites in dialysates reflect true synaptic release is critically discussed. There is much evidence that dopamine, noradrenaline, acetylcholine and serotonin in dialysates are related to neurotransmission, but there is serious doubt whether this is the case with amino acid transmitters such as GABA, glutamate and aspartate. Until now far over 100 papers appeared that used microdialysis in behavioural studies. Behavioural activation, the sleep-awake cycle and diurnal rhythms were subject of several of these studies. Various workers have described neurochemical changes in the brain that are related to feeding. Other studies were concerned with sexual behaviour and the sexual cycle in females. Parturition, maternal behaviour and offspring recognition have been studied in a series of microdialysis studies carried out in sheep. An overview is given of the microdialysis studies that were carried out to understand the biochemistry of stress. In this respect dopamine and noradrenaline have received much attention. A great number of microdialysis studies dealt with the role of dopamine in self-stimulation, reward and aversive emotions. It is concluded that microdialysis is at presently the most versatile and practical method to study the chemistry of behaviour and it is to be expected that it will soon be a routine methodology in behavioural research. Finally, perspectives and possible future developments of the methods are discussed.

Animals↗
PubMed1994

Microdialysis: an alternative for in vitro and in vivo protein binding studies.

The aim of the present study was to compare the performance of conventional equilibrium dialysis method with a microdialysis method in studying drug protein binding. The two methods were assessed by comparing the measured mean unbound drug fraction in different plasma species in vitro in plasma of four different species and at two concentrations of the non-indolic melatonin analog S 20098. For the microdialysis study, the unbound drug fraction was calculated after correction for membrane recovery. Plasma protein binding of S 20098 ranged from 75 to 95%. In humans, rabbits and rats (10 ng/ml), equal unbound percentages were found between equilibrium dialysis and microdialysis. Microdialysis gave slightly but significantly higher values in rat (2000 ng/ml), and in monkey plasma independent of the drug concentration. Microdialysis was also performed in vivo in freely moving rats under steady-state conditions, yielding similar unbound fraction values (26.0 +/- 0.9%) to those obtained using microdialysis probes in rat plasma in vitro (24.4 +/- 1.6%). These results support the use of in vivo microdialysis in pharmacokinetic studies in freely moving animals.

Acetamides↗
PubMed1994

Intracerebral microdialysis combined with recording of extracellular field potential: a novel method for investigation of depolarizing drugs in vivo.

1. The purpose of this study was to examine whether depolarizations evoked by excitatory amino acids can be recorded quantitatively, in vivo, with a microelectrode incorporated within a microdialysis probe. 2. Microdialysis probes incorporating a chlorided silver wire were implanted in the striatum of anaesthetized rats and perfused with artificial cerebrospinal fluid (ACSF). Increasing concentrations of excitatory amino acids were applied for 2 min via the microdialysis probe, and the extracellular direct current (d.c.) potential was recorded between the microdialysis electrode and a reference electrode placed under the scalp. 3. N-methyl-D-aspartate (NMDA, 25-500 microM), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA, 5-1000 microM), kainate (5-500 microM), and glutamate (0.25-100 mM) evoked concentration-dependent depolarizations with maxima ranging from 7 to 10 mV, i.e. 3 to 10 times larger than those recorded from brain slices in vitro. Depolarizations evoked by glutamate receptor agonists applied by microdialysis shared several features with those recorded from brain slices. The most characteristic were: steep onset and recovery of NMDA and glutamate responses; marked post-depolarization hyperpolarization with NMDA; and very slow recovery after kainate application. At high concentrations (500 microM), NMDA occasionally initiated spreading depression. The relative potency of glutamate and NMDA was of the same order of magnitude to that obtained with the cortical wedge and hippocampal slices, glutamate being 100 to 400 times less potent than NMDA. 4. Two consecutive series of NMDA-stimuli within the same procedure evoked comparable depolarizations, indicating that reliable quantitative analysis of drug action can be performed, with each animal serving as its own control. This is relevant to the study of drugs acting on glutamate receptors especially antagonists. The remarkable inter-animal reproducibility is also a valuable feature.5. Pretreatment with dizocilpine maleate (MK-801, 2mgkg'1, i.p.) reduced by 65% the responses evoked by NMDA (500 fM). The non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX,100 1M) applied via the microdialysis probe reduced by around 78% the responses to AMPA and kainate (250 micro M). The fact that drugs, especially antagonists, can be administered either systemically, or directly through the dialysis probe to by-pass the blood-brain barrier or avoid peripheral effects, is especially relevant for neuropharmacological studies.6. Intracerebral microdialysis combined with in vivo recording of extracellular field potential is a novel and valuable method for the quantitative analysis of the action of drugs acting on glutamate receptors.This method should prove especially useful for comparing the sensitivity of specific brain structures to selective glutamate receptor agonists under normal conditions and when the neuronal micro environment is altered. It should also be useful for investigating the action of other depolarizing agents, such as veratridine, and their antagonists.

Animals↗
PubMed1996

Microdialysis for metabolic monitoring in neonates after surgery.

Microdialysis is a new method for continuous metabolic monitoring. We studied the possibility of using microdialysis in neonates treated in a paediatric intensive care unit after surgery. A microdialysis catheter was inserted in the abdominal subcutaneous adipose tissue in 14 neonates for a median of 93 h (range 24-106 h). In four neonates, two microdialysis catheters were used simultaneously. Samples were taken hourly for analysis of glucose, lactate and glycerol. Dialysate and blood concentrations were compared. Serum/whole blood glucose values (n = 68) were in the range 2.1-15.4 mM. The serum glucose levels showed good agreement with the dialysate concentrations of glucose, although these infants were subjected to various forms of stress, drugs and glucose infusions. The whole blood glucose levels were significantly lower than the dialysate levels. The microdialysis concentrations of glucose varied considerably. As almost identical dialysate glucose levels were found when two microdialysis catheters were used simultaneously, the variability probably reflects true changes in blood glucose levels. Our results indicate that microdialysis can be used in neonates.

Anal Canal↗
PubMed1994

In vivo microdialysis for the transdermal absorption of valproate in rats.

The suitability of sampling via microdialysis for a lipophilic drug, valproate (VPA), was evaluated by the elimination rate constant of VPA solution in an in vitro experimental first-order elimination system. The elimination rate constant of VPA in dialysate was found to be 0.43 +/- 0.05h-1, which was in good agreement with the real elimination rate constant (0.46 +/- 0.02h-1). A change in VPA concentration in the solution surrounding a microdialysis probe was well maintained by the microdialysis method, suggesting no adsorption between the membrane of the microdialysis probe and VPA. On the basis of the in vitro experiment, the effect of a penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101), on the transdermal absorption of VPA was examined in rats by the use of microdialysis in vivo. An intradermal microdialysis was performed at a flow rate of 1.0 microliter/min for 7h after the dermal application of 50 mM VPA solution with or without 3% (w/v) HPE-101. HPE-101 increased the transdermal absorption rate of VPA by 80 times compared with the control. The microdialysis system was found to be quite useful for assessing the in vivo transdermal absorption of a lipophilic VPA.

Animals↗
PubMed1994

In vivo microdialysis for pharmacokinetic investigations: a plasma protein binding study of valproate in rabbits.

The use of microdialysis to study the binding of valproate (VPA) to plasma proteins was evaluated in rabbits. Prior to an in vivo microdialysis, in vitro relative recovery of VPA respectively from Ringer's solution, 5% (w/v) of albumin solution and plasma sample via a microdialysis probe was examined. The in vitro relative recovery was defined as a ratio of the VPA concentration determined in the dialysate to the free VPA concentration in the sample solution surrounding the membrane of the microdialysis probe. When the sample solution was well stirred at 700 rpm and maintained at 37 degrees C, the in vitro relative recovery of VPA was significantly different among them. It increased in the order of Ringer's solution (34.3 +/- 2.6%) > 5% (w/v) of albumin solution (25.7 +/- 4.6%) > rabbit plasma sample (15.8 +/- 1.2%). Thereafter, pharmacokinetics of VPA was determined using both microdialysis sampling via the rabbit femoral vein and collection of whole blood via the rabbit ear vein after intravenous administration of VPA at a dose of 43 mg/kg. Free concentrations of VPA in plasma were determined by ultrafiltration method as opposed to microdialysis method. There was no difference in the elimination half-life of VPA determined by microdialysis, 1.09 +/- 0.22 h, or ultrafiltration, 1.22 +/- 0.21 h. The AUC of VPA in dialysate was 15 +/- 4 micrograms.h/ml, which corresponded to 15% of that in ultrafiltrate (103 +/- 17 micrograms.h/ml). The value was in good agreement with the in vitro relative recovery of VPA from plasma sample (15.8 +/- 1.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗