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At least 127 records · Page 7Linked to original sources
PubMed2006

Pharmacologic modulation of skeletal muscle metabolism: a microdialysis study.

Microdialysis is a valuable tool to measure tissue responses. We hypothesized that skeletal muscle metabolism can be modulated by microdialysis applied drugs which alter cytosolic calcium concentration. With approval of the local animal care committee, the hind limbs of sacrificed male Sprague Dawley rats were perfused either with Ringer's solution or with dantrolene 1 microM at 30 ml hr(-1) and 21 degrees. Microdialysis probes in both hind limbs were perfused at 1 microl min(-1) either with sorbitol 80 mM, calcium 20 mM, 40 mM, 80 mM, caffeine 40 mM, 80 mM, and halothane 10 vol% respectively, and at the contralateral adductor muscle with Ringer as control. Lactate was measured spectrophotometrically in the dialysate at 15 min. intervals. Lactate levels as measured by intramuscular microdialysis were not influenced by intramuscular application of sorbitol 80 mM compared to control measurements with Ringer's solution. Local application of calcium 20 mM, 40 mM, 80 mM, caffeine 40 mM, 80 mM, and halothane 10 vol% via microdialysis increased lactate concentrations, while organ perfusion by dantrolene 1 microM reduced the caffeine-induced lactate increase. Modulation of intramuscular lactate metabolism by exogenous compounds via microdialysis probes generates new insights in skeletal muscle metabolism.

Animals↗
PubMedDate not supplied

Cutaneous microdialysis in the rat: insertion trauma and effect of anaesthesia studied by laser Doppler perfusion imaging and histamine release.

Microdialysis makes it feasible to study compounds in the extracellular space of cutaneous tissue in vivo. The insertion of the microdialysis probe causes a trauma, which may be anticipated to influence the microdialysis process. The effect of anaesthesia on basal skin blood flow and the trauma in the skin after insertion of a microdialysis probe were investigated. Hairless rats were anaesthetized either with halothane or pentobarbital sodium. Basal skin blood flow and the effect of insertion of a microdialysis probe were measured by laser Doppler perfusion imaging. Trauma-induced histamine release was investigated. Rats anaesthetized with pentobarbital sodium showed a stable skin perfusion in contrast to rats anaesthetized with halothane. A significant increase in blood flow was seen after insertion of the microdialysis probe in the dermis of rats anaesthetized with pentobarbital sodium, while a change in skin blood flow was not observed in rats anaesthetized with halothane. Probe insertion caused histamine release in rats. A minimum equilibration period of 30 min between probe insertion and the start of the experiment is recommended in future studies, allowing immediate events of the trauma to subside and stabilize.

Adjuvants, Anesthesia↗
PubMed2005

A microdialysis technique for routine measurement of macromolecules in the injured human brain.

OBJECTIVE: To evaluate a new intracerebral microdialysis catheter with a high-cutoff membrane and its potential for the study of macromolecules in the human brain. METHODS: Paired intracerebral microdialysis catheters were inserted in 10 patients who became comatose after subarachnoid hemorrhage or traumatic brain injury and were then treated in our neurosurgical unit. The only differences from the routine use of microdialysis in our clinic were the length (20 mm) and cutoff properties of the catheter membranes (100 kD) and the perfusion fluids used (standard perfusion fluid, 3.5% albumin, or Ringer-dextran 60). Samples were weighed (for net fluid fluxes) and analyzed at bedside (for routine metabolites) and later in the laboratory (for total protein and interleukin-6). The in vitro recovery of glucose, glutamate, and glycerol were also investigated under different conditions. RESULTS: Even brief perfusion with standard perfusion fluid resulted in a significant loss of volume from the microdialysis system. For albumin and Ringer-dextran 60 fluid, recovery was comparable to standard settings. Interleukin-6 (highest value close to 25,000 pg/ml) was sampled from all catheters, and total protein was analyzed from catheters perfused with Ringer-dextran 60 (average concentration, 234 mug protein/ml). There were detectable patterns of variations in the concentration of interleukin-6, seemingly related to concomitant variations in intracerebral conditions. In the present study, no direct comparison was made with the standard CMA 70 catheter (CMA Microdialysis, Stockholm, Sweden), but in vivo, the measured mean concentrations of glucose, glycerol, lactate, and pyruvate were comparable to those previously reported from standard catheters. In vitro, the recovery of metabolites was better when using Ringer-dextran 60 compared with albumin. CONCLUSION: Microdialysis catheters with high-cutoff membranes can be used in routine clinical practice, allowing for sampling and analysis of cytokines and other macromolecules.

Brain Chemistry↗
PubMed2005

Comparison of a needle-type and a microdialysis continuous glucose monitor in type 1 diabetic patients.

OBJECTIVE: We examined the reliability of two continuous glucose sensors in type 1 diabetic patients at night and during rapid glucose excursions and verified the hypothesized nocturnal hypoglycemic drift of the needle-type sensor (CGMSgold) and delay of the microdialysis sensor (GlucoDay). RESEARCH DESIGN AND METHODS: Blood was sampled overnight twice per hour in 13 patients. Rapid-acting insulin was given subcutaneously 30 min after breakfast. Sampling once per minute started 45 min after breakfast and 75 min after insulin injection for 30 min, with the aim of determining peak and nadir glucose values. Mean absolute differences (MADs) between sensor and blood glucose values were calculated. Sensor curves were modeled for all patients using linear regression. Horizontal and vertical shifts of sensor curves from the blood glucose curves were assessed. A vertical shift indicates sensor drift and a horizontal shift sensor delay. RESULTS: Drift was minimal in the needle-type and microdialysis sensors (-0.02 and -0.04 mmol/l). Mean +/- SD delay was 7.1 +/- 5.5 min for the microdialysis sensor (P < 0.001). MAD was 15.0% for the needle-type sensor and 13.6% for the microdialysis sensor (P = 0.013). After correction for the 7-min delay, the microdialysis MAD improved to 11.7% (P < 0.0001). CONCLUSIONS: The microdialysis sensor was more accurate than the needle-type sensor, with or without correction for a 7-min delay. In contrast to the previous version, the current needle-type sensor did not exhibit nocturnal hypoglycemic drift. Continuous subcutaneous glucose sensors are valuable adjunctive tools for glucose trend analyses. However, considering the large MADs, individual sensor values should be interpreted with caution.

Blood Glucose↗
PubMed2004

Formalin-induced spinal glutamate release in freely moving rats: comparison of two spinal microdialysis approaches.

Two different spinal microdialysis approaches using either a linear tissue probe (LM-3) or a loop probe were explored on freely-moving rats to investigate the basal and formalin-evoked release of glutamate (Glu) in the spinal dorsal horn or in the cerebrospinal fluid (CSF). Adult male Wistar rats were implanted either with a LM-3 probe transversely through the spinal dorsal horn or with a loop probe in the CSF. After 24 hours recovery, microdialysis was initiated with perfusion of modified Ringer's solution at a flow rate of 5 microliters/min and the basal Glu concentrations were sampled for 1 hour. The effects of altering the microdialysis flow rate and perfusion solution on basal Glu release were next investigated. Following the injection of 50 microliters of formalin 5% into the hind paw, 10-min samples were collected for 90 min. The baseline levels of Glu were 0.82 +/- 0.09 microM with LM-3 probes and 5.96 +/- 0.22 microM with the loop probes. Decreasing the flow rate from 5 to 2 microliters/min increased extracellular Glu concentrations by 222.7 +/- 7.3%, whereas perfusion with artificial CSF reduced baseline Glu by 61.5 +/- 9.5% with LM-3 probes. Injection of formalin induced a short-lasting but significant increase of Glu with a similar profile and time course when using either of the microdialysis approaches. In conclusion, microdialysis in the dorsal horn or in the CSF are both effective techniques to assess the alterations in Glu release following peripheral nociceptive input. The loop probe technique in CSF is more reproducible for routine investigation of drug effects, whereas the microdialysis of the dorsal horn provides a useful tool to precisely locate where the release of the neurotransmitters occurs.

Analysis of Variance↗
PubMed1996

Microdialysis methodology for the measurement of dermal interstitial fluid in humans.

In this study we aimed to validate the microdialysis technique for metabolic measurements in the dermal interstitial fluid. The abdominal and forearm skin was used for microdialysis in 15 healthy normal weight volunteers. The depth of the microdialysis catheter was assessed by ultrasound measurement. Structural impairment and blood flow were judged from biopsies and from laser Doppler measurements taken adjacent to the catheters. Dermal interstitial lactate and pyruvate concentrations were measured, under steady state fasting conditions, after equilibrium calibration of each catheter in situ. The dermal interstitial glucose concentration was estimated by means of the retrodialysis calibration method, which has previously not been evaluated for skin microdialysis. The mean catheter depth (+/- standard deviation) was 0.8 +/- 0.3 mm. Small areas of localized bleeding, but no inflammatory reaction, was found surrounding the catheters. The perfusion in the microdialysis region was slightly increased (15-25%). The lactate/pyruvate ratio (12 +/- 0.7) showed non-ischaemic values. The dermal interstitial lactate concentration was significantly higher (1171 +/- 228 mumol/l) than the plasma lactate (781 +/- 180 mumol/l), indicating an ongoing nonoxidative glucose metabolism. Retrodialysis calibration correctly estimated the dermal glucose level to be similar to that in plasma, which may indicate the usefulness of this calibration method for microdialysis studies of endogenous substrates in the dermal interstitial fluid.

Adult↗
PubMed1992

The combined EEG-intracerebral microdialysis technique: a new tool for neuropharmacological studies on freely behaving animals.

In this study we combined EEG and intracerebral microdialysis techniques in freely behaving rats. Various drugs were delivered into the hippocampus and cerebral cortex by means of microdialysis and, simultaneously, the EEG activity of the dialyzed area was monitored. The microdialysis procedure itself, when artificial cerebrospinal fluid was perfused, did not change the normal hippocampal or cortical EEG pattern. Drug inclusions into the microdialysis fluid, however, caused marked changes in the electrical activity of the dialyzed sites. In this report we present the following examples: (1) the dose-dependent spike-provoking effect of NMDA in hippocampus, (2) the potentiation of this NMDA effect in hippocampus by dibutyryl cyclic AMP, and (3) the EEG depressant effect of high concentration of K+ in the cerebral cortex. The artificial cerebrospinal fluid and drug solutions were alternated in the microdialysis system with a 2-way valve placed outside the test chamber. As a consequence, the drugs were delivered into the brain without interrupting the ongoing behavior, including sleep, of the examined animals. This study shows that the combined EEG-intracerebral microdialysis technique is a useful tool, with many unique advantages, for in vivo neuropharmacological studies.

Animals↗
PubMed1992

Coupling of microdialysis with capillary electrophoresis: a new approach to the study of drug transfer between two compartments of the body in freely moving rats.

The feasibility of in vivo microdialysis and capillary electrophoresis for pharmacokinetic studies was tested. Microdialysis probes were inserted in the jugular vein and brain of rats. After an intraperitoneal injection of phenobarbital, microdialysis was performed in the brain and the blood simultaneously in each rat under freely moving conditions. Capillary electrophoresis with ultraviolet absorption was used to measure phenobarbital in blood and brain dialysates. The time course of phenobarbital in the blood and in the extracellular space of the brain was followed. The results demonstrated that microdialysis can be used for pharmacokinetic studies in freely moving animals. Capillary electrophoresis has the potential to improve the time resolution of microdialysis. Other advantages of microdialysis and capillary electrophoresis for pharmacokinetic studies are discussed.

Animals↗
PubMed1991

In vivo microdialysis sampling for pharmacokinetic investigations.

In vivo microdialysis sampling coupled to liquid chromatography was used to study acetaminophen disposition in anesthetized rats. The pharmacokinetics of acetaminophen and its sulfate and glucuronide metabolites were determined using both microdialysis sampling and collection of whole blood. For microdialysis, samples were continuously collected for over 5 hr without fluid loss using a single experimental animal. Microdialysis sampling directly assesses the free drug concentration in blood. The pharmacokinetic results obtained with microdialysis sampling were the same as those obtained from blood collection. The administration of heparin, necessary when collecting blood samples, was found to double the elimination half-life of acetaminophen. Microdialysis sampling is a powerful tool for pharmacokinetic studies, providing accurate and precise pharmacokinetic data.

Acetaminophen↗
PubMed1990

Effects of different semipermeable membranes on in vitro and in vivo performance of microdialysis probes.

The in vitro and in vivo performance of three different semipermeable microdialysis membranes was compared: a proprietary polycarbonate-ether membrane made by Carnegie Medecin; cuprophan, a regenerated cellulose membrane; and polyacrylonitrile. When microdialysis probes were tested in a stirred in vitro solution, large and statistically significant differences among the three membranes in extraction of acid metabolites (3,4-dihydroxyphenylacetic acid, 5-hydroxyindoleacetic acid, and homovanillic acid) and acetaminophen were found. Polyacrylonitrile had the highest extractions in vitro. In contrast, when microdialysis probes were implanted in vivo (in rat striatum), extraction of acid metabolites and acetaminophen did not differ significantly among the different membranes. These results are consistent with predictions made by a mathematical model of microdialysis and can be explained by the fact that in vitro the main factor limiting extraction is membrane resistance to diffusion, whereas tissue resistance to diffusion plays a more dominant role in vivo. These findings suggest that (aside from differences in surface area), the choice of semipermeable membrane will generally have little effect on in vivo microdialysis results. Furthermore, in vitro measurements of microdialysis probe extractions are not a reliable way of calibrating in vivo performance.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2003

Microdialysis--a model for studying chronic wounds.

Microdialysis has been used for more than 20 years as a method of sampling the interstitial fluid space. It has been used in both animals and human tissues, in vivo. The principle of microdialysis is based on the passive diffusion of a compound along its concentration gradient. One major advantage of this sampling technique is that it is simple, relatively cheap, and minimally invasive. Consequently, microdialysis has been employed in a variety of research and clinical settings to recover endogenous molecules and metabolites from the tissue space. It has also been used to measure the tissue penetration of xenobiotics and to follow their temporal and spatial distribution. Most recently, microdialysis has begun to be used as a diagnostic tool and its application to clinical investigation at the bedside explored. This review describes the principles of the technique of microdialysis and its current uses in both an experimental and clinical setting. It goes on to consider current methods of wound fluid sampling and the range of bioactive molecules that have been detected in wound fluid recovered using these techniques. Finally, the use of microdialysis as a novel method for sampling wound fluid in vivo and its ability to provide a fluid that is unaffected by the sampling method and that is representative of the wound environment is discussed.

Journal Article↗
PubMed1993

Use of the microdialysis technique in the monitoring of subcutaneous tissue glucose concentration.

For some time the subcutaneous (s.c.) tissue has been the target for continuous glucose measurement. The microdialysis technique permits an extracellular region approach, which has been used for about two decades for measuring various metabolites in dialysates obtained from different body regions. By connecting a s.c. implanted microdialysis probe to a flow chamber of an amperometric glucose sensor, the procedure of glucose sensing was transferred to ex vivo. Using this device it was possible to obtain, for up to 24 hours, s.c. tissue glucose profiles of healthy and diabetic people. The microdialysis theory, the calibration process and other microdialysis technique applications are discussed in this paper. Although the combination of the microdialysis technique and amperometric glucose sensing requires certain technical equipment, the combination of microdialysis and glucose sensor seems to be a promising approach to a continuously functioning glucose sensing system.

Blood Glucose↗
PubMed1996

Manipulation of pyramidal cell firing in the hippocampus of freely behaving rats by local application of K+ via microdialysis.

In this study, microdialysis was performed in the hippocampus of freely behaving rats, and the firing of pyramidal cells, including place cells, was recorded at the site of the microdialysis probe. For 10-min periods, the artificial cerebrospinal fluid (ACSF) in the microdialysis system was replaced with ACSF containing 50 mM K+ (high K+ solution). Complementary in vitro tests determined that microdialysis with such high K+ solution produced an outflow of 5% of the perfused K+ from the microdialysis probe. Application of K+ with this method into the CA1 region significantly increased the firing of the local pyramidal cells, including place cells, during both movement and sleep. On average, K+ exposures increased the firing rate of the neurons to 306% and 448% of the control firing rate during movement and sleep, respectively. After the termination of the K+ outflow, the cells continued to discharge for 5-30 min with a significantly higher frequency than before the K+ challenge. This phenomenon also occurred in both behavioral states. During the period of enhanced firing, the out-of-field firing rate of the recorded place cells was dramatically increased. It was also found that during the K+ applications, otherwise silent pyramidal cells often became electrically active. The K(+)-induced firing modifications were usually not accompanied by behavioral or EEG changes. The data raise the possibility that transient elevations in the extracellular K+ concentration contribute to the ionic/molecular processes which are responsible for plastic firing pattern modifications in hippocampus. Pharmacological manipulation of place cells with the described method offers a new strategy to understand the molecular bases of spatial memory.

Animals↗
PubMed2002

Muscle distribution of the neuromuscular blocker gallamine using microdialysis.

Measurement of drug concentrations in target tissue has the potential to provide insight into the pharmacokinetics and pharmacodynamics of a drug. In this study, the distribution of the neuromuscular blocker, gallamine, into muscle tissue was investigated in urethane-anesthetized rats after an intravenous bolus dose (6 mg/kg). Microdialysis sampling was used to continuously determine gallamine concentrations in muscle interstitial fluid (MIF). In vivo microdialysis recovery of gallamine was determined as the relative loss of gallamine from the perfusate into muscle tissue after perfusion with gallamine (2 microg/mL). Recovery was determined in each rat before the pharmacokinetic studies. Terminal muscle sampling followed by homogenization was also performed to examine gallamine distribution within muscle tissue. All samples were assayed for gallamine using a validated high-performance liquid chromatography assay. Gallamine was rapidly distributed into MIF with a MIF-plasma partition coefficient of 0.9 +/- 0.1 (n = 6). By contrast, the estimated gallamine concentration in muscle tissue homogenate was only 23 +/- 5% (n = 5) of the concentration in MIF as estimated by microdialysis sampling at the terminal sampling time. These findings suggest that gallamine is not distributed uniformly within muscle but selectively distributes into MIF. Simulations using a hybrid physiologically based pharmacokinetic model which describes uptake of drug only into the interstitial space showed good agreement between predicted and observed concentration data obtained from microdialysis sampling, supporting the findings that gallamine selectively distributes into MIF. These studies demonstrate microdialysis combined with conventional terminal tissue sampling provides valuable information on intra-tissue drug distribution.

Algorithms↗
PubMed2003

Use of osmotic agents in microdialysis studies to improve the recovery of macromolecules.

The availability of microdialysis probes with higher molecular weight cutoff membranes has made it possible to measure larger molecular weight compounds like bioactive peptides and proteins. However, the higher molecular weight membrane cutoff allows for increased fluid loss from the probe, influencing both the physiology of the tissue compartment and analyte recovery. This study examined the ability of osmotic agents like bovine serum albumin (BSA) to offset the water loss from the microdialysis probe. In the presence of BSA, water loss from the microdialysis probe was minimized. Furthermore, addition of BSA to the perfusate produced significant increases in analyte recovery. Application of this technique to the measurement of bioactive macromolecules was examined using in vitro microdialysis of tumor necrosis factor (TNF) and interleukin-1 beta (IL-1B). The results of the present study suggest osmotic agents like BSA can prevent fluid loss from the microdialysis probe and improve analyte recovery.

Macromolecular Substances↗
PubMed2001

Microdialysis: intraoperative and posttraumatic applications in neurosurgery.

Microdialysis offers a unique opportunity to study the extracellular human brain environment. Our aim was to improve the ability to detect neuronal injury in patients undergoing complicated neurovascular procedures and to detect secondary brain lesions after severe head injury with the use of in vivo microdialytic monitoring. We employed intraoperative microdialysis monitoring in patients with a variety of neurovascular procedures including high-flow and low-flow bypass surgery and aneurysm clipping. In the second group there were patients after severe brain injury where in vivo microdialysis was performed as a bedside monitoring in the intensive care unit. In this review we present our results for these various groups of patients, in which a variety of neurochemical parameters which are known to change in ischemia were studied. The advantages and disadvantages of the technique are discussed. Our results show that microdialysis is a useful tool for detecting ischemic changes intraoperatively and in severe head trauma. However, further studies are needed to get more data and to better refine the online microdialysis technique before we can recommend it for routine clinical use.

Brain Chemistry↗
PubMed2005

Microdialysis in traumatic brain injury--methodology and pathophysiology.

The application of clinical microdialysis to monitor changes in cerebral extracellular chemistry is now well established in several neurosurgical units worldwide. In neuro-intensive care the technique has been predominantly applied to patients with traumatic brain injury and subarachnoid haemorrhage. There is no doubt that microdialysis has increased and continues to increase our understanding of the pathophysiology of these conditions. Current studies are addressing the potential role of microdialysis as a clinical monitoring technique assisting in the management of patients on an intention to treat basis. This involves establishing the relationship between microdialysis and outcome, and the effect of therapeutic manoeuvres on the chemistry. This manuscript describes the place of microdialysis in traumatic brain injury in terms of the fundamental principles, methodology, pathophysiology and clinical application.

Biomarkers↗
PubMed1999

Monitoring by subcutaneous microdialysis in neurosurgical intensive care.

Microdialysis is an in vivo sampling technique which provides a powerful approach to monitoring metabolic events. We have performed a study to determine the feasibility and effectiveness of subcutaneous microdialysis in monitoring patients on the Neurosurgical Intensive Care Unit (NICU). A microdialysis probe was placed in the subcutaneous fat of the anterior abdominal wall and perfused with Ringer's solution. Collecting vials were changed every 30 minutes and monitoring continued for 2-6 days. Biochemical analysis of glucose, lactate, and glutamate was correlated with clinical events. The normal ranges of glucose, lactate and glutamate were 3-6 mM. 1-2.5 mM and 5-20 microM, respectively. Periods of low tissue glucose were detected by microdialysis which were not detected by routine plasma sampling. In one patient, following an apparently brief period of hypoxia, there was a prolonged disturbance of tissue chemistry. Another patient with obesity had significantly higher concentrations of dialysate glucose, lactate and glutamate. Monitoring by subcutaneous microdialysis on intensive care units is feasible, reveals unexpected changes in tissue metabolism and might be an important adjunct for the interpretation of intracerebral data.

Adolescent↗