| 1. |
- Abrahamsson, Pernilla, 1972-
(author)
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Methodological aspects on microdialysis sampling and measurements
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Background: The microdialysis (MD) technique is widely spread and used both experimentally and in clinical practice. The MD technique allows continuous collection of small molecules such as glucose, lactate, pyruvate and glycerol. Samples are often analysed using the CMA 600 analyser, an enzymatic and colorimetric analyser. Data evaluating the performance of the CMA 600 analysis system and associated sample handling are sparse. The aim of this work was to identify sources of variability related to handling of microdialysis samples and sources of error associated with use of the CMA 600 analyser. Further, to develop and compare different application techniques of the microdialysis probes both within an organ and on the surface of an organ. Material and Methods: Papers I and II are mainly in vitro studies with the exception of the No Net Flux calibration method in paper I where a pig model (n=7) was used to examine the true concentration of glucose and urea in subcutaneous tissue. Flow rate, sampling time, vial and caps material and performance of the analyser device (CMA 600) were examined. In papers III and IV normoventilated anaesthetised pigs (n=33) were used. In paper III, heart ischemia was used as intervention to compare microdialysis measurements in the myocardium with corresponding measurements on the heart surface. In paper IV, microdialysis measurements in the liver parenchyma were compared with measurements on the liver surface in association with induced liver ischemia. All animal studies were approved by the Animal Experimental Ethics Committee at Umeå University Sweden. Results: In paper I we succeeded to measure true concentrations of glucose (4.4 mmol/L) and Urea (4.1 mmol/L) in subcutaneous tissue. Paper II showed that for a batch analyse of 24 samples it is preferred to store microdialysis samples in glass vials with crimp caps. For reliable results, samples should be centrifuged before analysis. Paper III showed a new application area for microdialysis sampling from the heart, i.e. surface sampling. The surface probe and myocardial probe (in the myocardium) showed a similar pattern for glucose, lactate and glycerol during baseline, short ischemic and long ischemic interventions. In paper IV, a similar pattern was observed as in paper III, i.e. data obtained from the probe on the liver surface showed no differences compared with data from the probe in liver parenchyma for glucose, lactate and glycerol concentrations during baseline, ischemic and reperfusion interventions. Conclusion: The MD technique is adequate for local metabolic monitoring, but requires methodological considerations before starting a new experimental serie. It is important to consider factors such as flow rate, sampling time and handling of samples in association with the analysis device chosen. The main finding in this thesis is that analyses of glucose, lactate and glycerol in samples from the heart surface and liver surface reflect concentrations sampled from the myocardium and liver parenchyma, respectively.
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| 2. |
- Amer-Wåhlin, Isis, et al.
(author)
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Fetal cerebral energy metabolism and electrocardiogram during experimental umbilical cord occlusion and resuscitation.
- 2010
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In: Journal of Maternal-Fetal & Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 23:2, s. 158-166
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Journal article (peer-reviewed)abstract
- Objective. The purpose of this experimental study was to elucidate alterations in fetal energy metabolism in relation to ECG changes during extreme fetal asphyxia, postnatal resuscitation and the immediate post-resuscitatory phase. Study design. Five near-term fetal sheep were subjected to umbilical cord occlusion until cardiac arrest followed by delivery, resuscitation and postnatal pressure-controlled ventilation. Four sheep served as sham controls and were delivered immediately after ligation of the umbilical cord. Fetal ECG was analysed online for changes of the ST segment. Fetal metabolism was monitored by intracerebral and subcutaneous microdialysis catheters. Results. Fetal ECG reacted on cord occlusion with an increase in the T-wave height followed by changes in intracerebral levels of oxidative parameters. Cerebral lactate/pyruvate ratio and glutamate increased to median (range) of 240 (200-744) and 34.0 (22.6-60.5) mmol/l, respectively; both parameters returned to baseline after resuscitation. Cerebral glucose decreased to 0.1 (0.08-0.12) mmol/l after occlusion and increased above baseline upon resuscitation. In subcutaneous tissue as well as blood the increase in lactate occurred with a delay compared to cerebral levels. Conclusion. The fetal ECG changes related to asphyxia preceded the increase in excitotoxicity as determined by increase in cerebral glutamate during asphyxia. Cerebral lactate increase was superior to subcutaneous lactate increase.
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| 3. |
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| 4. |
- Bergström, Sara K., et al.
(author)
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Screening of microdialysates taken before and after induced liver damage; on-line solid phase extraction-electrospray ionization-mass spectrometry
- 2006
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In: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1120:1-2, s. 21-26
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Journal article (peer-reviewed)abstract
- A novel method is described to follow known and unknown compounds in biological processes using microdialysis sampling and mass spectrometric detection. By implementation of internal standard, desalting/enrichment for the sample work-up, and multivariate data analysis, this methodology is a basis for future applications in early diagnosis of diseases and organ damage, as a complement to the routinely used clinical methods for biological samples. The present study includes screening without specific target analytes, of samples collected by microdialysis from liver of anaesthetized rats before and after local damage to this organ. Sample series were classified by principal component analysis, and the stimulation was identified in the chemical patterns produced by the presented analytical tool.
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| 5. |
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| 6. |
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| 7. |
- Chaurasia, Chandra S., et al.
(author)
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AAPS-FDA workshop white paper : microdialysis principles, application and regulatory perspectives
- 2007
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In: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 24:5, s. 1014-1025
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Journal article (peer-reviewed)abstract
- Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (microD) is the only tool available that explicitly provides data on the extracellular space. Although microD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of microD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of microD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on microD as a tool in drug research and development.
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| 8. |
- Chaurasia, Chandra S., et al.
(author)
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AAPS-FDA Workshop White Paper : microdialysis principles, application, and regulatory perspectives
- 2007
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In: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 47:5, s. 589-603
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Journal article (peer-reviewed)abstract
- Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (μD) is the only tool available that explicitly provides data on the extracellular space. Although μD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of μD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of μD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on μD as a tool in drug research and development.
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| 9. |
- Ederoth, Per, et al.
(author)
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Blood-brain barrier transport of morphine in patients with severe brain trauma
- 2004
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In: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 57:4, s. 427-435
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Journal article (peer-reviewed)abstract
- AIMS: In experimental studies, morphine pharmacokinetics is different in the brain compared with other tissues due to the properties of the blood-brain barrier, including action of efflux pumps. It was hypothesized in this clinical study that active efflux of morphine occurs also in human brain, and that brain injury would alter cerebral morphine pharmacokinetics. METHODS: Patients with traumatic brain injury, equipped with one to three microdialysis catheters in the brain and one in abdominal subcutaneous fat for metabolic monitoring, were studied. The cerebral catheter locations were classified as 'better' and 'worse' brain tissue, referring to the degree of injury. Morphine (10 mg) was infused intravenously over a 10-min period in seven patients in the intensive care setting. Tissue and plasma morphine concentrations were obtained during the subsequent 3-h period with microdialysis and regular blood sampling. RESULTS: The area under the concentration-time curve (AUC) ratio of unbound morphine in brain tissue to plasma was 0.64 (95% confidence interval 0.40, 0.87) in 'better' brain tissue (P < 0.05 vs. the subcutaneous fat/plasma ratio), 0.78 (0.49, 1.07) in 'worse' brain tissue and 1.00 (0.86, 1.13) in subcutaneous fat. The terminal half-life and T(max) were longer in the brain vs. plasma and fat, respectively. The relative recovery for morphine was higher in 'better' than in 'worse' brain tissue. The T(max) value tended to be shorter in 'worse' brain tissue. CONCLUSIONS: The unbound AUC ratio below unity in the 'better' human brain tissue demonstrates an active efflux of morphine across the blood-brain barrier. The 'worse' brain tissue shows a decrease in relative recovery for morphine and in some cases also an increase in permeability for morphine over the blood-brain barrier.
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| 10. |
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| 11. |
- Fuchi, Tokio, et al.
(author)
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Microdialysis of rat skeletal muscle and adipose tissue : dynamics of the interstitial glucose pool.
- 1994
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In: Acta Physiologica Scandinavica. - 0001-6772 .- 1365-201X. ; 151:2, s. 249-60
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Journal article (peer-reviewed)abstract
- Microdialysis was evaluated as a method for studying glucose metabolism in skeletal muscle. Dialysis probes (0.5 x 10 mm) were perfused at 0.5 or 1.0 microliter min-1. Based upon perfusion with glucose, the muscle interstitial glucose concentration was estimated to be 6.9 +/- 0.3 mM (n = 14), which was not significantly different from the blood glucose level. With insulin infusion (1200 mU kg-1 body wt i.v.), the insulin-induced change in the glucose concentration of the interstitial space of muscle was of equal magnitude to that of blood and adipose tissue. In spite of this, when the perfusion medium was not supplemented with glucose, the glucose concentration decreased more in skeletal muscle dialysates (to 36.7 +/- 4.9% of the initial level) than in blood (to 29.7 +/- 5.0%) but less than in adipose tissue (to 17.7 +/- 4.9% of the initial level) (P < 0.05). The results indicate that these differences are due to tissue-specific differences in the dynamic balance between the supply to, and removal from, the interstitial glucose pool. This balance is revealed as a result of the constant glucose drainage by the microdialysis probe. The present results show that, in skeletal muscle, increases in glucose uptake occur with a concomitant increase in tissue blood flow as revealed by the microdialysis ethanol technique, whereas in adipose tissue the glucose uptake increases in the absence of a corresponding increase in blood flow.
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| 12. |
- Hamrin, Kerstin, et al.
(author)
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Microdialysis in human skeletal muscle : effects of adding a colloid to the perfusate.
- 2002
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In: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 92:1, s. 385-93
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Journal article (peer-reviewed)abstract
- Microdialysis catheters (CMA-60 with a polyamide dialysis membrane; 20,000-molecular wt cutoff) were either immersed in an external medium or were inserted in the quadriceps femoris muscle of healthy subjects, using perfusate with or without dextran 70. Varying the position of the outflow tubing induced changes in hydrostatic pressure. The sample volumes were significantly smaller in catheters perfused without a colloid compared with those perfused with a colloid [11-50% (in vitro) and 8-59% (in vivo) lower than in colloid-perfused catheters with the same position of the outflow tubing]. The sample volumes were also significantly smaller when the dialysis membrane was influenced by maximal hydrostatic pressure (above position) compared with minimal hydrostatic pressure (below position) [7-38% (in vitro) and 3-46% (in vivo) lower than in catheters in the below position with the same perfusion fluid]. In vivo, glucose concentration at a perfusion flow rate of 0.33 microl/min was higher when the catheters were perfused without a colloid [18-28% higher than in colloid-perfused catheters with the same position of the outflow tubing (P < 0.001)] than with a colloid. A corresponding difference also tended to occur with lactate, glycerol, and urea. At 0.16 microl/min, the glucose concentration was the same irrespective of whether fluid loss had been counteracted by colloid inclusion or by lowering of outlet tubing. The mechanism behind the observed concentration difference is thought to be a higher effective perfusion flow rate when fluid loss is prevented at low-perfusion flows. This study shows that fluid imbalances can have important implications for microdialysis results at low-perfusion flow rates.
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| 13. |
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| 14. |
- Hickner, R C, et al.
(author)
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The ethanol technique of monitoring local blood flow changes in rat skeletal muscle : implications for microdialysis.
- 1992
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In: Acta Physiologica Scandinavica. - 0001-6772 .- 1365-201X. ; 146:1, s. 87-97
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Journal article (peer-reviewed)abstract
- We have investigated the feasibility of monitoring local skeletal muscle blood flow in the rat by including ethanol in the perfusion medium passing through a microdialysis probe placed in muscle tissue. Ethanol at 5, 55, or 1100 mM did not directly influence local muscle metabolism, as measured by dialysate glucose, lactate, and glycerol concentrations. The clearance of ethanol from the perfusion medium can be described by the outflow/inflow ratio ([ethanol]collected dialysate/[ethanol]infused perfusion medium), which was found to be similar (between 0.36 and 0.38) at all ethanol perfusion concentrations studied. With probes inserted in a flow-chamber, this ratio changed in a flow-dependent way in the external flow range of 5-20 microliters min-1. The ethanol outflow/inflow ratio in vivo was significantly (P less than 0.001) increased (to a maximum of 127 +/- 2.8% and 144 +/- 7.4% of the baseline, mean +/- SEM) when blood flow was reduced by either leg constriction or local vasopressin administration, and significantly (P less than 0.001) reduced (to 62 +/- 6.4% and 43 +/- 4.4% of baseline) with increases in blood flow during external heating or local 2-chloroadenosine administration, respectively. Dialysate glucose concentrations correlated negatively with the ethanol outflow/inflow ratio (P less than 0.01) and consequently decreased (to 46 +/- 7.6% and 56 +/- 5.6% of baseline) with constriction and vasopressin administration and increased (to 169 +/- 32.5% and 262 +/- 16.7% of baseline) following heating and 2-chloroadenosine administration. Dialysate lactate concentrations were significantly increased (approximately 2-fold, P less than 0.001) during all perturbations of blood flow. In conclusion, this technique makes it possible to monitor changes in skeletal muscle blood flow; however, methods of quantification remain to be established. The fact that blood flow changes were found to significantly affect interstitial glucose and lactate concentrations as revealed by microdialysis indicates that this information is critical in microdialysis experiments.
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| 15. |
- Hutchinson, Peter J, et al.
(author)
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Consensus statement from the 2014 International Microdialysis Forum
- 2015
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In: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 41:9, s. 1517-1528
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Journal article (peer-reviewed)abstract
- Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.
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| 16. |
- Mantovani, Vittorio, 1965, et al.
(author)
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Microdialysis for myocardial metabolic surveillance: developing a clinical technique.
- 2006
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In: Clinical physiology and functional imaging. - 1475-0961. ; 26:4, s. 224-31
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Journal article (peer-reviewed)abstract
- Metabolic surveillance of the myocardium is of great interest in cardiac surgery. Microdialysis allows sampling of chemical substances from the interstitial fluid for immediate analysis. The two objectives of this study were to develop a technique for simple and safe implantation of a commercially available microdialysis probe (CMA-70) into the myocardium and to obtain reference data for further use and metabolic control. Eighteen pigs were used in an experimental ischaemic heart model where the left anterior descending coronary artery was occluded for 20 min. Microdialysis was performed proximally as well as distally to the arterial occlusion site corresponding to a control and an ischaemic area in the heart. Two techniques were tried for probe implantation, using either a pacemaker wire attached to the probe tip or a needle introducer. Metabolic substrates (glucose, lactate, glycerol and pyruvate) were collected before, during and after ischaemia, for up to 6 h. Both techniques were highly effective in registering metabolic changes due to ischaemia with sharp time resolution, but the needle introducer was superior regarding probe durability. It is concluded that the CMA-70 microdialysis probe implanted with the needle introducer allows for an accurate monitoring of myocardial metabolism during a prolonged period of time. Future studies in the human heart are warranted to further validate the technique.
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| 17. |
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| 18. |
- Nordström, Carl Henrik, et al.
(author)
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Biochemical indications of cerebral ischaemia and mitochondrial dysfunction in severe brain trauma analysed with regard to type of lesion
- 2016
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In: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 158:7, s. 1231-1240
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Journal article (peer-reviewed)abstract
- Background: The study focuses on three questions related to the clinical usefulness of microdialysis in severe brain trauma: (1) How frequently is disturbed cerebral energy metabolism observed in various types of lesions? (2) How often does the biochemical pattern indicate cerebral ischaemia and mitochondrial dysfunction? (3) How do these patterns relate to mortality? Method: The study includes 213 consecutive patients with severe brain trauma (342 intracerebral microdialysis catheters). The patients were classified into four groups according to the type of lesion: extradural haematoma (EDH), acute subdural haematoma (SDH), cerebral haemorrhagic contusion (CHC) and no mass lesion (NML). Altogether about 150,000 biochemical analyses were performed during the initial 96 h after trauma. Results: Compromised aerobic metabolism occurred during 38 % of the study period. The biochemical pattern indicating mitochondrial dysfunction was more common than that of ischaemia. In EDH and NML aerobic metabolism was generally close to normal. In SDH or CHC it was often severely compromised. Mortality was increased in SDH with impaired aerobic metabolism, while CHC did not exhibit a similar relation. Conclusions: Compromised energy metabolism is most frequent in patients with SDH and CHC (32 % and 49 % of the study period, respectively). The biochemical pattern of mitochondrial dysfunction is more common than that of ischaemia (32 % and 6 % of the study period, respectively). A correlation between mortality and biochemical data is obtained provided the microdialysis catheter is placed in an area where energy metabolism reflects tissue outcome in a large part of the brain.
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| 19. |
- Reinstrup, Peter, et al.
(author)
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Intracerebral microdialysis in clinical practice: baseline values for chemical markers during wakefulness, anesthesia, and neurosurgery
- 2000
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In: Neurosurgery. - : Ovid Technologies (Wolters Kluwer Health). - 0148-396X .- 1524-4040. ; 47:3, s. 701-710
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The study was undertaken to measure baseline values for chemical markers in human subjects during wakefulness, anesthesia, and neurosurgery, using intracerebral microdialysis. METHODS: Microdialysis catheters were inserted into normal posterior frontal cerebral cortex in nine patients who were undergoing surgery to treat benign lesions of the posterior fossa. The perfusion rate was 1.0 microl/min during anesthesia/neurosurgery and the early postoperative course and 0.3 microl/min during the later course. Bedside biochemical analyses of glucose, pyruvate, lactate, glycerol, glutamate, and urea were performed before, during, and after neurosurgery. After the bedside analyses, all samples were frozen for subsequent high-performance liquid chromatographic analyses of amino acids. RESULTS: The following baseline values were obtained during wakefulness (perfusion rate, 0.3 microl/min): glucose, 1.7+/-0.9 mmol/L; lactate, 2.9+/-0.9 mmol/L; pyruvate, 166+/-47 micromol/L; lactate/pyruvate ratio, 23+/-4; glycerol, 82+/-44 micromol/L; glutamate, 16+/-16 mmol/L; urea, 4.4+/-1.7 mmol/L. Marked increases in the levels of all chemical markers were observed at the beginning and end of anesthesia/surgery. CONCLUSION: The study provides human baseline levels for biochemical markers that can presently be measured at the bedside during neurointensive care. In addition, some changes that occurred under varying physiological conditions are described.
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| 20. |
- Rosdahl, Hans, et al.
(author)
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A microdialysis method for the in situ investigation of the action of large peptide molecules in human skeletal muscle : detection of local metabolic effects of insulin.
- 2000
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In: International Journal of Biological Macromolecules. - : Elsevier BV. - 0141-8130 .- 1879-0003. ; 28:1, s. 69-73
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Journal article (peer-reviewed)abstract
- The possibility of using microdialysis catheters with a large pore size dialysis membrane (100 kDa) to investigate the action of macromolecules perfused into the interstitial space of peripheral tissues was explored. This was made possible by increasing the colloid osmotic pressure of the perfusate with 40 g/l of dextran-70 to prevent perfusate loss across the dialysis membranes. Microdialysis catheters were inserted into the quadriceps femoris muscle of 13 human subjects. With different perfusion flow rates (1. 33, 0.66, 0.33 and 0.16 microl/min) the recorded concentrations of glucose, lactate, and urea were in agreement with values previously obtained using a conventional membrane with a smaller pore size (20 kDa) [Rosdahl H, Hamrin K, Ungerstedt U, Henriksson. J Am J Physiol 1998;274:E936-45.]. When insulin was added to the perfusate, the concentration of glucose was significantly reduced, indicating that insulin diffuses across the dialysis membrane and has cellular effects that can be simultaneously recorded. The present findings are the first documentation on the use of microdialysis to study the local metabolic action of large peptide molecules in human tissues and may open new avenues for in-vivo metabolic research.
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| 21. |
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| 22. |
- Rosdahl, Hans, et al.
(author)
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Effect of physiological hyperinsulinemia on blood flow and interstitial glucose concentration in human skeletal muscle and adipose tissue studied by microdialysis
- 1998
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 47:8, s. 1296-1301
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Journal article (peer-reviewed)abstract
- The effect of an euglycemic-hyperinsulinemic glucose clamp (94 +/- 5 microU/ml) on blood flow and glucose extraction fraction in human skeletal muscle and adipose tissue was investigated. Limb blood flow was measured by venous occlusion pletysmography and tissue blood flow by the microdialysis ethanol technique. Insulin infusion resulted in an increased blood flow in the calf and forearm (64 and 36%, respectively; P < 0.01) but not in the studied muscles of these limbs (ethanol outflow-to-inflow ratio: m. gastrocnemius 0.144 +/- 0.009 to 0.140 +/- 0.011, NS; m. brachioradialis 0.159 +/- 0.025 to 0.168 +/- 0.027, NS). This was accompanied by an increased extraction fraction of glucose, as measured by an increased arteriovenous difference over the forearm (0.16 +/- 0.04 to 0.70 +/- 0.10 mmol/l; P < 0.001) and by an increase in the estimated arterial-interstitial glucose difference in the gastrocnemius (0.82-1.42 mmol/l) and brachioradialis muscle (0.82-1.97 mmol/l). The blood flow in adipose tissue was significantly increased during insulin infusion, as evidenced by a decreased ethanol outflow-to-inflow ratio (0.369 +/- 0.048 to 0.325 +/- 0.046; P < 0.01). This was accompanied by an unchanged concentration of glucose in the dialysate (-2.6%, NS). In summary, during physiological hyperinsulinemia 1) a blood flow increase was detected in the calf and forearm, but not in the studied muscles of these limbs; 2) the blood flow increased in the subcutaneous adipose tissue; and 3) the estimated arterial-interstitial glucose difference increased in both muscles studied and was larger in the forearm muscle than the arteriovenous glucose difference over the forearm. The present study shows that microdialysis is a useful tool to obtain tissue-specific information about the effect of insulin on blood flow and glucose extraction in human skeletal muscle and adipose tissue.
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| 23. |
- Rosdahl, Hans, et al.
(author)
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Influence of adrenergic agonists on the release of amino acids from rat skeletal muscle studied by microdialysis.
- 1998
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In: Acta Physiologica Scandinavica. - 0001-6772 .- 1365-201X. ; 163:4, s. 349-60
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Journal article (peer-reviewed)abstract
- The microdialysis technique was used to study the effects of adrenergic agonists on the release of amino acids from rat skeletal muscle. The release was monitored indirectly by measurements of interstitial concentrations. To distinguish metabolic from vasoactive effects, the adrenaline and isoprenaline results were compared with those of vasopressin, alpha-agonists and adenosine. As determined by the microdialysis ethanol technique, adrenaline, alpha-agonists and vasopressin induced vasoconstriction, whereas isoprenaline and adenosine induced vasodilatation. The lactate-to-pyruvate ratio increased fourfold with adrenaline (P < 0.001) and by 54% with isoprenaline (P < 0.05), whereas no change was observed with alpha-agonists and adenosine. Vasopressin induced a fivefold increase in the lactate-to-pyruvate ratio (P < 0.001), but with an unchanged pyruvate concentration, indicating that the effect may have been secondary to ischaemia. Adrenaline induced a twofold and vasopressin a 34% increase in the concentration of alanine (P < 0.001), whereas isoprenaline, adenosine and alpha-agonists had no significant effect. Adrenaline-perfusion induced an initial anabolic effect as evidenced by a reduced concentration of tyrosine. A significant decrease in the glutamate-to-glutamine ratio was observed with adrenaline and isoprenaline (22 and 27%, P < 0.01) whereas alpha-agonists, vasopressin and adenosine were without effect. In conclusion, the present study showed that adrenaline, via a beta-adrenergically mediated activation of glycogenolysis, possibly further stimulated by ischaemia, induced an increased release of alanine from skeletal muscle. The study indicates a beta-adrenergic stimulation on the glutamine synthetase step and a short lasting anabolic effect of adrenaline. Differences in the magnitude of the effects of adrenaline and isoprenaline could be related to their different vasoactive properties.
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| 24. |
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| 25. |
- Rosdahl, Hans, et al.
(author)
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Interstitial glucose and lactate balance in human skeletal muscle and adipose tissue studied by microdialysis.
- 1993
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In: Journal of Physiology. - 0022-3751 .- 1469-7793. ; 471, s. 637-57
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Journal article (peer-reviewed)abstract
- 1. Microdialysis was used to gain insight into the substrate exchanges in the interstitial space of skeletal muscle and adipose tissue. Probes were inserted in the quadriceps femoris muscle and para-umbilical subcutaneous adipose tissue of thirteen subjects and microdialysis was performed at different flow rates (1-4 microliters min-1) and during changes in tissue blood flow. 2. When ethanol (5 mM) is included in the perfusion solution, the ethanol clearance from the probe is a measure of tissue blood flow. Blood flow changes induced by adenosine or vasopressin perfusion, by exercise or by circulatory occlusion resulted in ethanol clearance values of 69-139% of the basal level. The ethanol clearance was higher in skeletal muscle than in adipose tissue (32-62%, P < 0.001), a difference compatible with a higher blood flow in muscle tissue. 3. The fraction of the interstitial glucose concentration that was recovered with the microdialysis was similar in skeletal muscle (the absolute values being 1.70 +/- 0.14 mM at 1 microliter min-1 and 0.59 +/- 0.05 mM at 4 microliters min-1) and adipose tissue (1.89 +/- 0.20 mM at 1 microliter min-1; 0.54 +/- 0.05 mM at 4 microliters min-1) and correlated inversely with the tissue ethanol clearance, both in the basal state and during changes in tissue blood flow (muscle: r = -0.56 to -0.67; adipose tissue r = -0.72 to -0.95). Coefficients of variation were 6-8% (glucose) and 11-16% (lactate) and were similar during isometric exercise. The reproducibility of the technique (comparison of two contralateral probes; perfusion flow rate 4 microliters min-1) was 5.3-8.3% (ethanol) and 23.9-20.8% (glucose) in muscle (n = 6) and adipose tissue (n = 4) respectively. 4. The skeletal muscle dialysate lactate concentration (1 microliter min-1: 1.16 +/- 0.2 mM) was higher than in adipose tissue (0.76 +/- 0.08 mM, P < 0.05), where the absolute amount of lactate that could be removed from the tissue (at 4 microliters min-1) was only half of that in skeletal muscle (0.8 +/- 0.11 vs. 1.76 +/- 0.23 nmol min-1, P < 0.05). The dialysate lactate level was not affected in either tissue by large changes in the interstitial glucose concentration indicating that in neither tissue is blood glucose a significant source of lactate formation. 5. The blood flow effects on the dialysate glucose concentration are the likely consequence of probe glucose drainage artificially shifting the balance between the supply and consumption of interstitial glucose.(ABSTRACT TRUNCATED AT 400 WORDS)
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| 26. |
- Rosdahl, Hans, et al.
(author)
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Metabolite levels in human skeletal muscle and adipose tissue studied with microdialysis at low perfusion flow.
- 1998
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In: The American journal of physiology. - 0002-9513. ; 274:5 Pt 1, s. E936-45
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Journal article (peer-reviewed)abstract
- To identify a perfusion flow at which the interstitial fluid completely equilibrates with the microdialysis perfusion fluid, a protocol with successively lower perfusion flows was used. A colloid was included in the perfusion fluid to make sampling possible at the lowest perfusion flows. At 0.16 microliter/min, the measured metabolites had reached a complete equilibration in both tissues, and the measured concentrations of glucose, glycerol, and urea were in good agreement with expected tissue-specific levels. The glucose concentration in adipose tissue (4.98 +/- 0.14 mM) was equal to that of plasma (5.07 +/- 0.07 mM), whereas the concentration in muscle (4.41 +/- 0.11 mM) was lower than in plasma and adipose tissue (P < 0.001). The concentration of lactate was higher (P < 0.001) in muscle (2.39 +/- 0.22 mM) than in adipose tissue (1.30 +/- 0.12 mM), whereas the glycerol concentration in adipose tissue (233 +/- 19.7 microM) was higher (P < 0.001) than in muscle (40.8 +/- 3.0 microM) and in plasma (68.7 +/- 3.97 microM). The concentration of urea was equal in the two tissues. Overall, the study indicates that microdialysis at a low perfusion flow may be a tool to continuously monitor tissue interstitial concentrations.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Rostami, Elham, et al.
(author)
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Brain metabolism and oxygenation in healthy pigs receiving hypoventilation and hyperoxia
- 2013
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In: Respiratory Physiology & Neurobiology. - : Elsevier BV. - 1569-9048 .- 1878-1519. ; 189:3, s. 537-542
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Journal article (peer-reviewed)abstract
- Modulation in ventilatory settings is one of the approaches and interventions used to treat and prevent secondary brain damage after traumatic brain injury (TBI). Here we investigate the effect of hyperoxia in combination with hypoventilation on brain oxygenation, metabolism and intracranial pressure. Twelve pigs were divided into three groups; groupl-100% hyperoxia (n=4), group 2-100% hyperoxia and 20% decrease in minute volume (MV) (n=4) and group 3-100% hyperoxia and 50% decrease in MV (n=4). Neither of the ventilator settings affected the lactate/pyruvate ratio significantly. However, there was a significant decrease of brain lactate (2.6+/-1.7 to 1.8+/-1.6 mM) and a rapid and marked increase in brain oxygenation (7.9+/-0.7 to 61.3+/-17.6 mmHg) in group 3. Intracranial pressure (ICP) was not significantly affected in this group, however, the ICP increased significantly in group 2 with 100% hyperoxia plus 20% reduction in minute volume. We conclude that hyperoxia in combination with 50% decrease in MV showed pronounced increase in partial brain oxygen tension (pbrO(2)) and decrease in brain lactate. The ventilatory modification, used in this study should be considered for further investigation as a possible therapeutic intervention for TBI patients.
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| 31. |
- Rostami, Elham, 1979-, et al.
(author)
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Microdialysis in neurointensive care.
- 2004
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In: Current pharmaceutical design. - : Bentham Science Publishers Ltd.. - 1381-6128 .- 1873-4286. ; 10:18, s. 2145-2152
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Journal article (peer-reviewed)abstract
- Microdialysis is a technique for sampling the chemistry of the interstitial fluid of tissues and organs in animal and man. It is minimally invasive and simple to perform in a clinical setting. Although microdialysis samples essentially all small molecular substances present in the interstitial fluid the use of microdialysis in neurointensive care has focused on markers of ischemia and cell damage. The lactate / pyruvate ratio is a well-known marker of changes in the redox state of cells caused by ischemia Glycerol is an integral component of cell membranes. Loss of energy due to ischemia eventually leads to an influx of calcium and a decomposition of cell membranes, which liberates glycerol into the interstitial fluid. Thus the lactate / pyruvate ratio and glycerol have become the most important markers of ischemia and cell membrane damage. While the primary insult at the site of the accident is beyond our control, secondary insults during intensive care should be avoided by all means. Therefore, the single most important finding from microdialysis studies is the dramatic difference in the vulnerability of the penumbra surrounding a lesion as compared to normal brain tissue allowing early detection of secondary insults after traumatic brain injury as well as the onset of vasospasm after subarachnoid hemorrhage.
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| 32. |
- Tossman, Ulf, et al.
(author)
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γ-aminobutyric acid and taurine release in the striatum of the rat during hypoglycemic coma, studied by microdialysis
- 1985
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In: Neuroscience Letters. - 0304-3940. ; 62:2, s. 231-235
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Journal article (peer-reviewed)abstract
- Extracellular levels of striatal γ-aminobutyric acid (GABA) and taurine were monitored during insulin-induced hypoglycemia using microdialysis. At the onset of isoelectricity in the electroencephalogram (EEG), a transient 5-fold increase in the levels of GABA occurred. Taurine levels increased 5 min following the onset of isoelectricity and continued to increase during the entire isoelectric period. The results demonstrate that events associated with the onset of isoelectricity during hypoglycemia trigger an increase in extracellular concentrations of GABA and taurine. The discrepancy in time-course of these changes may reflect differences in compartmentation, function and metabolism of the two amino acids.
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| 33. |
- You, Zhi-Bing, et al.
(author)
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Effect of morphine on dynorphin B and GABA release in the basal ganglia of rat
- 1996
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In: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 710:1-2, s. 241-248
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Journal article (peer-reviewed)abstract
- In vivo microdialysis was used to study the effects of systemic, as well as intracerebral administration of morphine and naloxone on dynorphin B release in neostriatum and substantia nigra of rats. The release of dopamine (DA), gamma-aminobutyric acid (GABA), glutamate (Glu) and aspartate (Asp) was also investigated. Systemic injection of morphine (1 mg/kg s.c.) induced long-lasting increases in extracellular dynorphin B and GABA levels in the substantia nigra, whereas DA, Glu and Asp levels, measured in the same region, were not significantly affected. No effect on striatal neurotransmitter levels was observed following systemic morphine administration. Local perfusion of the substantia nigra with morphine (100 microM) through the microdialysis probe also increased nigral dynorphin B and GABA levels. Perfusion of the neostriatum with morphine (100 microM) significantly increased GABA and dynorphin B levels in the ipsilateral substantia nigra, but no effect was observed locally. Naloxone blocked the effect of systemic morphine administration on nigral dynorphin B and GABA release, already at a dose of 0.2 mg/kg s.c. Naloxone alone, given either systemically (0.2-4 mg/kg s.c.) or intracerebrally (1-100 microM), did not affect dynorphin B or amino acid levels, either in neostriatum or in substantia nigra. However, naloxone produced a concentration-dependent increase in DA levels. The present results indicate that systemic morphine administration stimulates the release of dynorphin B in the substantia nigra, probably by activating the mu-subtype of opioid receptor, since the effect of morphine on nigral dynorphin B and GABA was antagonized by a low dose of naloxone. The increase in extracellular DA levels produced by high concentrations of naloxone, both in neostriatum and substantia nigra, indicates a disinhibitory effect of this drug on DA release, probably via a non-mu subtype of opioid receptors located on nigro-striatal DA neurones.
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