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PubMed2001

Glucose monitoring with long-term subcutaneous microdialysis in neonates.

BACKGROUND: Microdialysis is a new approach for continuous monitoring of small molecules in the extracellular space, and hypoglycemia is a common problem in neonatal intensive care. The objective of this study was to evaluate subcutaneous microdialysis for long-term glucose monitoring in neonatal intensive care. We determined the relative recovery of the microdialysis system in vitro and in vivo, the stability of the relative recovery in vivo during long-term microdialysis, and the correlation between blood and dialysate concentrations of glucose and urea. Furthermore, we evaluated the sensitivity and specificy of subcutaneous microdialysis for the diagnosis of hypoglycemia. PATIENT AND METHODS: Thirteen infants (10 neonates) with gestational ages of 30.2 to 45.6 weeks were investigated by microdialysis of subcutaneous adipose tissue and blood sampling. Subcutaneous microdialysis was performed for a median (range) duration of 9 (4-16) days. RESULTS: The application was safe, even in extremely low birth weight infants (<1000 g) with scanty subcutaneous adipose tissue. The mean +/- standard deviation of the relative recovery in vitro was 101 +/- 3% for glucose and 100 +/- 2% for urea. Using urea as the internal standard, the mean relative recovery in vivo was 96.4 +/- 12.7% at the beginning and remained constant up to 16 days. The correlation between microdialysate and blood was significant for glucose (r = 0.88) and urea (r = 0.98). Subcutaneous microdialysis allowed the detection of asymptomatic hypoglycemias. The diagnostic sensitivity of a dialysate glucose </=2.9 mM to predict a blood glucose level </=2.8 mM was 92.3%, with 88.1% specificy. The positive predictive value with a 13.4% prevalence of a blood glucose </=2.8 mM was 54.5%, with a negative predictive value of 98.7% and an accuracy of 88.7%. CONCLUSIONS: Subcutaneous microdialysis is a safe method, well suited for long-term glucose monitoring in neonates during intensive care. Subcutaneous microdialysis can be used to reduce blood loss and painful stress resulting from diagnostic blood sampling in high-risk neonates.

Blood Glucose↗
PubMed2001

Role of bedside microdialysis in the diagnosis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

OBJECT: Ischemia due to vasospasm is a feared complication in patients following aneurysmal subarachnoid hemorrhage (SAH). Cerebral online microdialysis monitoring may detect the metabolic changes in the extracellular fluid associated with ischemia. The aims of the present study were to correlate clinical course, microdialysis-recorded data, transcranial Doppler (TCD) ultrasonography findings, and angiographic findings in patients with SAH. METHODS: In 60 patients a microdialysis catheter was inserted into the brain parenchyma that is most likely to be affected by vasospasm directly after aneurysm clipping. Hourly analyses of glucose, pyruvate, lactate, and glutamate levels were performed using a bedside device. Blood-flow velocities were obtained using serial TCD measurements. Cerebral angiography was routinely performed on Day 7 after aneurysm clipping or earlier in cases of clinical deterioration (30 patients). In all patients the results of microdialysis monitoring, TCD ultrasonography, and angiography were correlated. The mean duration of monitoring was 7.3+/-2.5 days. In patients with acute ischemic neurological deficits (18 patients) immediate microdialysis-recorded alterations were observed if the probe was placed close to the malperfused region. In 13 of 15 patients with symptomatic vasospasm (delayed ischemic neurological deficit [DIND]), the microdialysis-recorded values revealed secondary deterioration. In terms of confirming DIND, microdialysis had the highest specificity (0.89, 95% confidence interval [CI] 0.78-1) compared with TCD ultrasonography (0.63, 95% CI 0.46-0.8) and angiography (0.53, 95% CI 0.35-0.7). For microdialysis, the positive likelihood ratio was 7.8, whereas this was significantly lower for TCD ultrasonography (1.7) and angiography (2.1). CONCLUSIONS: Although angiography also demonstrates vessel narrowing in asymptomatic patients, online microdialysis reveals characteristic metabolic changes that occur during vasospasm. Thus, online microdialysis may be used to confirm the diagnosis of vasospasm.

Adult↗
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↗
PubMed2006

Applicability of reverse microdialysis in pharmacological and toxicological studies.

A recent application of microdialysis is the introduction of a substance into the extracellular space via the microdialysis probe. The inclusion of a higher amount of a drug in the perfusate allows the drug to diffuse through the microdialysis membrane to the tissue. This technique, actually called as reverse microdialysis, not only allows the local administration of a substance but also permits the simultaneous sampling of the extracellular levels of endogenous compounds. Local effects of exogenous compounds have been studied in the central nervous system, hepatic tissue, dermis, heart and corpora luteae of experimental animals by means of reverse microdialysis. In central nervous studies, reverse microdialysis has been extensively used for the study of the effects on neurotransmission at different central nuclei of diverse pharmacological and toxicological agents, such as antidepressants, antipsychotics, antiparkinsonians, hallucinogens, drugs of abuse and experimental drugs. In the clinical setting, reverse microdialysis has been used for the study of local effects of drugs in the adipose tissue, skeletal muscle and dermis. The aim of this review is to describe the principles of the reverse microdialysis, to compare the technique with other available methods and finally to describe the applicability of reverse microdialysis in the study of drugs properties both in basic and clinical research.

Anesthesia↗
PubMed2003

[Interstitial microdialysis study of changes in metabolism and blood flow in skeletal muscles during cardiac surgery with normothermic and hypothermic extracorporeal circulation].

AIM: Hypoperfusion of peripheral tissues and splanchnic organs during cardiac surgery in extracorporeal circulation may lead to the origin of serious complications. The aim of the study was to monitor metabolism and blood pressure in interstital peripheral tissue, skeletal muscle, during the operation on the patient with extracorporeal circulation (ECC) in an early post-operation period by means of microdialysis. METHODS: The interstitial microdialysis is a minimally invasive method for the biochemical monitoring of metabolic changes and blood pressure in extracellular space of tissue. The substances in interstitium pass across a semipermeable membrane of the inserted microdialysis probe and may be analyzed. Microdialysis in this study was performed by means of two microdialysis probes CMA (CMA Microdialysis AB, Sweden) inserted into the deltoid muscle of the surgically treated patient. The probes were perfused by the Ringer solution at the rate of 0.3 ml/hour. The dialysates were sampled in the following intervals: beginning of the operation, beginning of ECC, end of ECC, end of the operation, two hours during the post-operation period. Standard biochemical methods were to evaluate, in the dialysates, glucose, urea, glycerol and lactate. The blood flow in the interstitium was monitored by means of dynamic microdialysis of gentamycine as a marker. Microdialysis was performed in 40 patients with ischemic heart disease, operated on in the extracorporeal circulation. In 20 patients the ECC was performed in normothermia (NT), while in the other 20 patients it was made in hypothermia (HT). RESULTS: In both groups, NT versus HT, a similar dynamism of interstitial concentration of the observed substances in relation to the operation phase and in early post-operation period. Low initial concentrations were gradually increasing during the extracorporeal circulation and increased further after the end of extracorporeal circulation and also in the subsequent phase of the operation. The concentration values of the analytes under observation were higher in the groups operated on under normothermia, apparently due to normal cellular activity during normothermia (versus values in hypothermia). Immediately after the operation the observed values decreased in the both groups and subsequently gradually increased in the post-operation period in the both groups. The trend of dynamic changes of the observed analytes, selected as compounds indicating metabolic activity of skeletal muscles during hypothermia documents a lower metabolic activity of the cells during hypothermia and its marked increase (against NT) in the phase of subsequent normalization of the tissue temperature. Analysis of the concentrations of lactate, as a compounds mapping anaerobic metabolism of skeletal muscle, revealed similar dynamic changes in the both groups (NT vs. HT). There were no significant differences, related to the phase of the operation or the phase of immediate post-operation course when the both groups were compared. The analysis of gentamycine concentrations as a flow marker revealed lower gentamycine concentrations in dialysate during the operation, ECC and the early post-operation course in the group operated on in normotheramia (vs. HT), indicating a higher tissue flow in skeletal muscle against the group of patients operated on under hypothermia. CONCLUSION: The results of the microdialysis study demonstrated dynamic changes in interstitial concentrations of the observed compounds (glucose, urea, glycerol and lactate) related to the phase of operation on the heart in extracorporeal circulation and in early post-operation period. A higher perfusion of skeletal muscle was documented in patients operated on under normothermia. It became obvious that the dynamism in the changes of the compounds observed in the interstitium of skeletal muscle was determined by metabolic activity of the tissue as well as by blood flow in the muscle interstitium.

Aged↗
PubMed2005

Online microdialysis-dynamic nanoelectrospray ionization-mass spectrometry for monitoring neuropeptide secretion.

Although mass spectrometric approaches offer a sensitive method for identifying cell-cell signaling peptides, the high salt-containing environment of extracellular solutions often complicates characterization of these microscale samples. Accordingly, we have developed a miniature hollow-fiber microdialysis device optimized for desalting small-volume neuronal samples online, with the device directly connected to a modified dynamic nanoelectrospray ionization assembly interfaced with an ion trap mass spectrometer. Improvements over existing designs include placement of a capillary insert within the microdialysis fiber to minimize volume, as well as the use of a microinjector that enables 1 microl sample injections. We present detailed evaluation of peptide recoveries within the microdialysis fiber by liquid chromatography-electrospray ionization-ion trap-mass spectrometry analysis of tissue homogenate in artificial seawater with and without microdialysis. Analyte recoveries after microdialysis ranged from 6 to 78% with higher recoveries of more hydrophilic peptides, while little correlation between mass and percentage recovery was observed in the range studied (2000 to 6000 Da). Recoveries of peptides were the lowest for the analytes with the highest initial mass spectrometry signal intensity. Finally, we illustrate the utility of this microdialysis device for desalting neuropeptides secreted from preparations of the peptidergic bag cell neurons of the marine mollusk, Aplysia californica. Without microdialysis, the high concentration of salts ( approximately 0.5 M) prevented detection of peptides, whereas following online microdialysis-dynamic nanoelectrospray mass spectrometry of stimulated releasate, three peptides (acidic peptide, acidic peptide 1-24 and delta-bag cell peptide) were detected.

Animals↗
PubMed1999

Microdialysis of skeletal muscle at rest.

Techniques in human skeletal muscle research are by necessity predominantly 'descriptive'. Microdialysis has raised high expectations that it could meet the demand for a method that allows 'mechanistic' investigations to be performed in human skeletal muscle. In the present review, some views are given on how well the initial expectations on the use of the microdialysis technique in skeletal muscle have been fulfilled, and the areas in which additional work is needed in order to validate microdialysis as an important metabolic technique in this tissue. The microdialysis catheter has been equated to an artificial blood vessel, which is introduced into the tissue. By means of this 'vessel' the concentrations of compounds in the interstitial space can be monitored. The concentration of substances in the collected samples is dependent on the rate of perfusate flow. When perfusate flow is slow enough to allow complete equilibration between interstitial and perfusate fluids, the concentration in the perfusate is maximal and identical to the interstitial concentration. Microdialysis data may be influenced by changes in blood flow, especially in instances where the tissue diffusivity limits the recovery in vivo, i.e. when recovery in vitro is 100%, whereas the recovery in vivo is less than 100%. Microdialysis data indicate that a significant arterial-interstitial glucose concentration gradient exists in skeletal muscle but not in adipose tissue at rest. While the concentrations of glucose and lactate in the dialysate from skeletal muscle are close to the expected values, the glycerol values obtained for muscle are still puzzling. Ethanol added to the perfusate will be cleared by the tissue at a rate that is determined by the nutritive blood flow (the microdialysis ethanol technique). It is concluded that microdialysis of skeletal muscle has become an important technique for mechanistic studies in human metabolism and nutrition.

Blood Flow Velocity↗
PubMed2004

A feasibility study of solid supported enhanced microdialysis.

For the first time, a solid supported enhanced microdialysis methodology for analysis of neuropeptides is described. The microdialysis samples were, in this study, subsequently collected in fractions, dissolved from the solid particles, dried, and resolved in a formic acid buffer in order to make them suitable for capillary liquid chromatography-mass spectrometry. Different microdialysis flow profiles were evaluated where air-gapped continuous flow was considered most suitable for the solid supported microdialysis mode. Six endogenous neuropeptides were initially used to investigate the feasibility of this enhanced microdialysis methodology. The improved relative recovery obtained from the solid supported enhanced microdialysis was varying from no effect to 10 times higher as compared to ordinary microdialysis. The most efficient enrichment was obtained for luteinizing hormone releasing hormone, which was the largest but also the most hydrophilic of the peptides. In contrast, no significant difference in recovery was observed for Leu-enkephalin being the smallest and the most hydrophobic peptide tested. These results indicate an increased flux and selective uptake of hydrophilic peptides across the membrane and enrichment on the particles in solid supported microdialysis.

Chromatography, High Pressure Liquid↗
PubMed2002

Subcutaneous microdialysis for metabolic monitoring in abdominal aortic surgery.

UNLABELLED: Microdialysis, that is the sampling of interstitial fluid via semi-permeable tubes, has been shown to be suitable for detecting ischemic changes e.g. in brain and heart tissue. The purpose of the present study was to investigate the possibility of monitoring with subcutaneous microdialysis peri-operative metabolic sequelac of elective abdominal aortic surgery. In 22 patients microdialysis catheters were inserted subcutaneously in the lower leg as well as the shoulder serving as a reference topographic region. Lactate, pyruvate and glycerol, which indicate ischemia or reperfusion, were measured. We observed severe metabolic changes within the interstitial fluid of the lower extremity during ischemia followed by normalization during reperfusion. Despite high interstitial concentrations of lactate and glycerol indicating severe ischemia during clamping of the abdominal aorta these parameters returned to pre-operative values within 2 hrs after declamping and all patients recovered completely. OBJECTIVE: Information about the metabolic state of the lower extremity during and after infrarenal aortic aneurysm repair should modify peri-operative treatment. The aim of the study was to evaluate whether microdialysis of the subcutaneous tissue reflects metabolic changes during ischemia and reperfusion. Lactate, pyruvate and glycerol concentrations were measured in the subcutaneous tissue of the lower extremity and compared to the microdialysis measurements from shoulder subcutaneous tissue. METHOD: In 22 patients microdialysis catheters were inserted preoperatively in the subcutaneous space of the left shoulder and the left calf. Samples were taken at timed intervals before, during and after clamping of the abdominal aorta. RESULTS: The subcutaneous glycerol concentration of the calf was increased during the clamping period from initially 68 +/- 11 microM up to 182 +/- 27 microM (p < 0.05); the lactate/pyruvate (L/P) ratio was increased eightfold. After declamping these values normalized to baseline. Microdialysis measurements of the shoulder showed no prominent changes during the entire course of observation. CONCLUSIONS: Subcutaneous microdialysis was able to detect metabolic changes due to ischemia during clamping of the abdominal aorta as well as reperfusion there after. It is a suitable technique to monitor the peri-operative course of the dependent tissue after abdominal aortic vascular surgery.

Aged↗
PubMed2003

Human subcutaneous tissue distribution of fluconazole: comparison of microdialysis and suction blister techniques.

AIMS: To investigate uptake of fluconazole into the interstitial fluid of human subcutaneous tissue using the microdialysis and suction blister techniques. METHODS: A sterile microdialysis probe (CMA/60) was inserted subcutaneously into the upper arm of five healthy volunteers following an overnight fast. Blisters were induced on the lower arm using gentle suction prior to ingestion of a single oral dose of fluconazole (200 mg). Microdialysate, blister fluid and blood were sampled over 8 h. Fluconazole concentrations were determined in each sample using a validated HPLC assay. In vivo recovery of fluconazole from the microdialysis probe was determined in each subject by perfusing the probe with fluconazole solution at the end of the 8 h sampling period. Individual in vivo recovery was used to calculate fluconazole concentrations in subcutaneous interstitial fluid. A physiologically based pharmacokinetic (PBPK) model was used to predict fluconazole concentrations in human subcutaneous interstitial fluid. RESULTS: There was a lag-time (approximately 0.5 h) between detection of fluconazole in microdialysate compared with plasma in each subject. The in vivo recovery of fluconazole from the microdialysis probe ranged from 57.0 to 67.2%. The subcutaneous interstitial fluid concentrations obtained by microdialysis were very similar to the unbound concentrations of fluconazole in plasma with maximum concentration of 4.29 +/- 1.19 microg ml(-1) in subcutaneous interstitial fluid and 3.58 +/- 0.14 microg ml(-1) in plasma. Subcutaneous interstitial fluid-to-plasma partition coefficient (Kp) of fluconazole was 1.16 +/- 0.22 (95% CI 0.96, 1.35). By contrast, fluconazole concentrations in blister fluid were significantly lower (P < 0.05, paired t-test) than unbound plasma concentrations over the first 3 h and maximum concentrations in blister fluid had not been achieved at the end of the sampling period. There was good agreement between fluconazole concentrations derived from microdialysis sampling and those estimated using a blood flow-limited PBPK model. CONCLUSIONS: Microdialysis and suction blister techniques did not yield comparable results. It appears that microdialysis is a more appropriate technique for studying the rate of uptake of fluconazole into subcutaneous tissue. PBPK model simulation suggested that the distribution of fluconazole into subcutaneous interstitial fluid is dependent on tissue blood flow.

Adult↗
PubMed2002

Theory relating in vitro and in vivo microdialysis with one or two probes.

In this paper, we further develop the general theory of microdialysis by extending the linear model of Bungay et al. to provide a theoretical basis for in vitro and in vivo microdialysis. Specifically, we considered the effect of active clearance processes on in vivo microdialysis, and thereby elaborated the theory of Benveniste et al. to endogenous compounds. We examined the use of steady state tissue diffusion resistance with negligible clearance processes to interpret microdialysis data. The influence of the tissue properties on the in vitro and in vivo recoveries in dual-probe microdialysis was analyzed and we simulated the effect of the operating parameters on dual probe microdialysis performance. We estimated that the minimum clearance rate constant detectable by microdialysis in a quasi-steady state is about 5.5 x 10(-5) s(-1). This minimum rate constant establishes a criterion, below which inhibition of the active clearance processes does not show detectable influences on the microdialysis extraction efficiency.

Agar↗
PubMed2002

Correlation between cerebral blood flow, substrate delivery, and metabolism in head injury: a combined microdialysis and triple oxygen positron emission tomography study.

Microdialysis continuously monitors the chemistry of a small focal volume of the cerebral extracellular space. Conversely, positron emission tomography (PET) establishes metabolism of the whole brain, but only for the duration of the scan. The objective of this study was to apply both techniques to head-injured patients simultaneously to assess the relation between microdialysis (glucose, lactate, lactate/pyruvate [L/P] ratio, and glutamate) and PET (cerebral blood flow [CBF], cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen) parameters. Microdialysis catheters were inserted into the frontal cerebral cortex and adipose tissue of the anterior abdominal wall of 17 severely head-injured patients. Microdialysis was performed during PET scans, with regions of interest defined by the location of the microdialysis catheter membrane. An intervention (hyperventilation) was performed in 13 patients. The results showed that combining PET and microdialysis to monitor metabolism in ventilated patients is feasible and safe, although logistically complex. There was a significant relation between the L/P ratio and the OEF (Spearman r = 0.69, P = 0.002). There was no significant relation between CBF and the microdialysis parameters. Moderate short-term hyperventilation appeared to be tolerated in terms of brain chemistry, although no areas were sampled by microdialysis where the OEF exceeded 70%. Hyperventilation causing a reduction of the arterial carbon dioxide tension by 0.9 kPa resulted in a significant elevation of the OEF, in association with a reduction in glucose, but no significant elevation in the L/P ratio or glutamate.

Adolescent↗
PubMed2005

Evidence on extracellular dopamine level in rat striatum: implications for the validity of quantitative microdialysis.

Microdialysis zero-net-flux (ZNF) method is commonly used to monitor drug-induced changes in neurotransmitter baseline and release/uptake processes. Recent studies in this field suggest that microdialysis ZNF method seriously underestimates the resting concentration of extracellular dopamine in the rat neostriatum because probe implantation preferentially damages nearby dopamine release sites and that dopamine uptake inhibition increases the relative recovery of dopamine by microdialysis. This study assessed the validity of these claims by examining current data on extracellular dopamine levels at rest and after drug application obtained by voltammetry, a technique thought to induce less tissue disruption than microdialysis. To obtain the extracellular baseline value for dopamine from the evoked overflow data, we modified the existing dopamine kinetic model to suit both the resting and stimulated circumstances. It was found that dopamine uptake inhibition did in fact decrease the microdialysis relative recovery of dopamine, implying that the average basal extracellular dopamine level is within the range of 7-20 nm in rat striatum. This study concludes that the microdialysis ZNF method indeed underestimates the extracellular dopamine concentration, although not by as much as had been thought. Chronic microdialysis damages both neurotransmitter release and uptake, but it does so in a somewhat relative and proportional way for both processes. Thus the validity of the microdialysis ZNF method is not seriously undermined.

Corpus Striatum↗
PubMed2004

Use of an intraluminal guide wire in linear microdialysis probes: effect on recovery?

BACKGROUND/PURPOSE: For microdialysis studies in the skin, laboratory-made linear probes are often used. Probes can be assembled with or without a stainless-steel guide wire in the lumen of the dialysis fibre. From a theoretical viewpoint, this will alter the performance of the probe. The aim of this study was to compare the in vitro microdialysis recovery using probes with and without an internal guide wire, employing two different model drugs and a range of perfusate flow rates. METHODS: In vitro microdialysis recovery experiments were performed with and without internal guide wires at perfusion flow rates from 1 to 15 microL/min, using either salicylic acid or metronidazole as test compounds at 5 mg/L. Phosphate buffer (pH 7.4) was used as perfusate. Dialysates were analysed by a validated HPLC assay with spectrophotometric detection. RESULTS: For both test compounds, the mean microdialysis recovery did not differ significantly between microdialysis probes with and without an internal guide wire at lower flow rates. At very high flow rates (10-15 microL/min), a significant difference in recovery could be seen for probes with internal guide wires when compared with probes without. CONCLUSIONS: The use of a stabilizing internal guide wire in linear microdialysis probes did not influence the in vitro recovery of microdialysis at volumetric flow rates below 10 microL/min. These are the flow rates most frequently used for in vivo microdialysis studies in the skin.

Equipment Design↗
PubMed2002

Cation dysfunction associated with cerebral ischemia followed by reperfusion: a comparison of microdialysis and ion-selective electrode methods.

OBJECT: Disruption of ionic homeostasis during ischemia is a well-characterized event and is identified by a rise in the concentration of extracellular potassium [K+]e, with a concomitant reduction in the concentration of extracellular sodium [Na+]e. Results of clinical studies in which microdialysis has been used, however, have shown only modest changes in the levels of extracellular ions. The object of this study was to measure [K+]e and [Na+]e by using ion-selective electrodes (ISEs) and to compare these measurements with those obtained using the well-established method of microdialysis. METHODS: Fifteen Sprague-Dawley rats were separated into three groups. Five animals were subjected to a 15-minute period of ischemia, and another five animals to a 60-minute period of ischemia; animals in both of these groups received K+-free microdialysis perfusate. The third group of five rats underwent a 60-minute period of ischemia and received a reduced-Na+ microdialysis perfusate. Transient forebrain ischemia was produced by bilateral carotid artery occlusion combined with hypotension. A custom-fabricated glass Na+ electrode and a flexible plastic K+ and reference electrodes were used to monitor extracellular ion transients. Microdialysis samples were obtained with the aid of a 2-mm microdialysis probe that was perfused with K+-free mock cerebrospinal fluid at a rate of 2 microl/minute. Baseline measurements of [K+]e and [Na+]e, obtained using ISEs, were 3.41 +/- 0.09 mM and 145 +/- 7.75 mM. respectively. Ischemia resulted in a rapid accumulation of [K+]e (in animals subjected to 15 minutes of ischemia, the concentration was 41.9 +/- 13.7 mM; and in animals subjected to 60 minutes of ischemia, the concentration was 66.9 +/- 11.5 mM), with a concomitant decrease in [Na+]e (in animals subjected to 15 minutes of ischemia, the concentration was 71.7 +/- 2.9 mM; and in animals subjected to 60 minutes of ischemia, the concentration was 74.7 +/- 1.9 mM). A comparison of microdialysis and ISE methods revealed that microdialysis underestimated the [K+]e changes and was insensitive to concomitant [Na+]e alterations that occur during ischemia. CONCLUSIONS: Our results indicate that the flexible ISE is a reliable and accurate tool for monitoring ionic dysfunction that accompanies brain injury.

Animals↗
PubMed1999

Dynamic measurement of metabolic function in the rat liver: an application of reverse microdialysis.

BACKGROUND: Traditional markers of liver function and microsomal activity tests require regular samplings and tissue removal. The microdialysis technique is a promising tool for pharmacokinetic study without the need for actually removing samples of those tissues and fluids. We verified the possibility of using reverse microdialysis for dynamic monitoring of hepatic metabolic function. METHODS: Adult male Sprague-Dawley rats were used and anesthetized using pentobarbital sodium. Reverse microdialysis was done by implanting a microdialysis probe into the middle lobe of the liver; the probe was then perfused with a lidocaine-containing solution. Concentrations of lidocaine and its major metabolite, monoethylglycinexylidide (MEGX), were measured in the dialysate. Metabolic ability was assessed by dividing the MEGX production by lidocaine administration. Hepatic ischemia-reperfusion and liver cirrhosis models were used to verify its application in dynamic measurement of liver metabolic function. RESULTS: The implantable microdialysis probe had stable contact with the liver tissue. In normal rats, 4.73 +/- 0.41% of the lidocaine was transformed to MEGX in 20 min. Only 16% of this value was preserved in cirrhotic animals. Hepatic ischemia for 20 min transiently depressed the MEGX formation and did not cause further injury after reperfusion. CONCLUSION: We confirmed the ability of an implantable microdialysis probe to be in constant contact with the liver tissue and thus deliver a stable transmission of chemicals across a microdialysis membrane for a certain period of time. We also verified the feasibility of reverse microdialysis as a tool for the dynamic measurement of hepatic metabolic function.

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↗