| 1. |
- Ekberg, NR, et al.
(author)
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Analyte flux at a biomaterial-tissue interface over time: implications for sensors for type 1 and 2 diabetes mellitus
- 2010
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In: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 4:5, s. 1063-72
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Journal article (peer-reviewed)abstract
- The very presence of an implanted sensor (a foreign body) causes changes in the adjacent tissue that may alter the analytes being sensed. The objective of this study was to investigate changes in glucose availability and local tissue metabolism at the sensor-tissue interface in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Method: Microdialysis was used to model implanted sensors. Capillary glucose and subcutaneous (sc) microdialysate analytes were monitored in five T1DM and five T2DM patients. Analytes included glucose, glycolysis metabolites (lactate, pyruvate), a lipolysis metabolite (glycerol), and a protein degradation byproduct (urea). On eight consecutive days, four measurements were taken during a period of steady state blood glucose. Results: Microdialysate glucose and microdialysate-to-blood-glucose ratio increased over the first several days in all patients. Although glucose recovery eventually stabilized, the lactate levels continued to rise. These trends were explained by local inflammatory and microvascular changes observed in histological analysis of biopsy samples. Urea concentrations mirrored glucose trends. Urea is neither produced nor consumed in sc tissue, and so the initially increasing urea trend is explained by increased local capillary presence during the inflammatory process. Pyruvate in T2DM microdialysate was significantly higher than in T1DM, an observation that is possibly explained by mitochondrial dysfunction in T2DM. Glycerol in T2DM microdialysate (but not in T1DM) was higher than in healthy volunteers, which is likely explained by sc insulin resistance (insulin is a potent antilipolytic hormone). Urea was also higher in microdialysate of patients with diabetes mellitus compared to healthy volunteers. Urea is a byproduct of protein degradation, which is known to be inhibited by insulin. Therefore, insulin deficiency or resistance may explain the higher urea levels. To our knowledge, this is the first histological evaluation of a human tissue biopsy containing an implanted glucose monitoring device. Conclusions: Monitoring metabolic changes at a material-tissue interface combined with biopsy histology helped to formulate an understanding of physiological changes adjacent to implanted glucose sensors. Microdialysate glucose trends were similar over 1-week in T1DM and T2DM; however, differences in other analytes indicated wound healing and metabolic activities in the two patient groups differ. We propose explanations for the specific observed differences based on differential insulin insufficiency/resistance and mitochondrial dysfunction in T1DM versus T2DM.
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| 4. |
- Jansson, Kjell, et al.
(author)
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Human intraperitoneal microdialysis : increased lactate/pyruvate ratio suggests early visceral ischaemia
- 2003
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 38:9, s. 1007-1011
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Journal article (peer-reviewed)abstract
- Background: Previous studies suggest that visceral ischaemia precedes shock and multiple organ failure, though methods for studying humans are lacking. We aimed to evaluate intraperitoneal microdialysis, a new technique for detecting splanchnic ischaemia in clinical practice. Methods: Right-sided hemicolectomy was performed in eight patients who were studied by microdialysis postoperatively for glucose, lactate, pyruvate and glycerol levels. Results: Six of the eight patients showed a normal postoperative course and had lactate/pyruvate ratios between 7.1 and 21.7, glucose between 4.5 and 14.3 r mmol/L and glycerol between 10.4 and 296 r 7 mol/L. In one patient, intraperitoneal lactate/pyruvate ratio and glycerol increased and glucose decreased 5 r h before low oxygenation appeared. Another patient exhibited a period of increased lactate/pyruvate ratio before a period of atrial fibrillation. Conclusion: Intraperitoneal microdialysis was performed safely. Two out of the eight patients exhibited changes of metabolic markers followed by clinical symptoms that were probably related to transient visceral ischaemia. Our findings suggest that intraperitoneal microdialysis may become a useful tool for monitoring splanchnic ischaemia in clinical practice.
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| 9. |
- Rasmussen, I, et al.
(author)
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Detection of liver ischemia using microdialysis during experimental peritonitis in pigs.
- 1994
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In: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322 .- 1540-0514. ; 1:1, s. 60-6
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Journal article (peer-reviewed)abstract
- The liver oxygen delivery (DO2) and consumption (VO2) were measured in a porcine model of septic shock induced by fecal peritonitis. Lactate and hypoxanthine were simultaneously monitored in hepatic extracellular fluid and in central venous blood using a microdialysis technique. Animals were divided into a control group (n = 6) and a peritonitis group (n = 6). Peritonitis was induced by installation of a standardized amount of autologous feces into the abdominal cavity. The animals were followed for 5 h. The changes in the liver during peritonitis were, a decreased DO2, a increased, maintained, or decreased VO2, an increased oxygen extraction, and a loss of net hepatic lactate uptake. Parallel to these changes, systemic lactic acidosis developed. Intrahepatic lactate and hypoxanthine increased during peritonitis reflecting liver ischemia. The increase of these metabolites was seen concomitantly in the liver and in central venous blood. There was a wide variability of the individual response to the septic challenge among the animals. The limited hepatic oxygen delivery, and the increased needs for oxygen led to flow-dependent oxygen consumption, and signs of liver ischemia in severe sepsis. Intrahepatic and intravenous microdialysis may be useful for monitoring of the individual time course of hepatic and systemic ischemia in sepsis.
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| 13. |
- Wisniewski, N, et al.
(author)
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Analyte flux through chronically implanted subcutaneous polyamide membranes differs in humans and rats
- 2002
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In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 282:6, s. E1316-E1323
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Journal article (peer-reviewed)abstract
- The rat is commonly used to evaluate physiological responses of subcutaneous tissue to implanted devices. In vivo longevity of various devices and the biocompatibility of biomaterials depend on how adjacent tissue interacts. How closely the rat model predicts the human response has not been well characterized. The objective of this study was to compare rat and human subcutaneous foreign body responses by monitoring the biochemical environment at a polymer-tissue interface over 8 days using microdialysis. Polyamide microdialysis probes were implanted subcutaneously in humans and rats ( n = 12). Daily microdialysis samples were analyzed for glucose, lactate, pyruvate, glycerol, and urea. Blood glucose was also monitored. Analyte concentrations differed significantly between rats and humans at the implant-tissue interface. There were also qualitative differences in the 8-day trends. For example, over 8 days, microdialysate glucose increased two- to fourfold in humans but decreased in rats ( P < 0.001). This study reveals profound physiological differences at material-tissue interfaces in rats and humans and highlights the need for caution when extrapolating subcutaneous rat biocompatibility data to humans.
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| 14. |
- Alquist, M, et al.
(author)
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Development of a urea concentration gradient between muscle interstitium and plasma during hemodialysis
- 1999
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In: The International journal of artificial organs. - : SAGE Publications. - 0391-3988 .- 1724-6040. ; 22:12, s. 811-815
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Journal article (peer-reviewed)abstract
- In this pilot study, muscle interstitial urea concentrations during hemodialysis (HD) were determined with a microdialysis technique and the results were compared with plasma water urea concentrations. Three patients were investigated during a total of five treatments. Under predialysis steady-state conditions, no difference was observed. During treatment, the muscle interstitial urea concentration was on average 19% higher (range 13–28%, n=4) than the plasma urea concentration after 17±3 min, 29% higher (25–31%, n=3) after 53±10 min, 40% higher (26–50%, n=3) after 117±6 min, 31% higher (26–34%, n= 3) after 179±5 min, and 31% higher (27–36%, n=4) after 231±5 min. The gradient declined after the conclusion of HD, muscle interstitial concentrations being on average 16% (9–26%, n=4) higher than plasma urea concentrations 9±2 min after treatment, and 8% (6–10%, n=3) 25±3 min after treatment. Thus, a urea concentration gradient with a higher concentration in muscle interstitium than in plasma, developed during HD, and dissipated gradually after treatment. This is consistent with blood flow-dependent urea sequestration in muscle tissue, causing intercompartment disequilibrium of urea during HD, and its consequent redistribution after treatment contributing to postdialysis urea rebound.
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| 18. |
- Bellander, B M, et al.
(author)
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Consensus meeting on microdialysis in neurointensive care
- 2004
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In: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 30, s. 2166-2169
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Journal article (peer-reviewed)abstract
- Background: Microdialysis is used in many European neurointensive care units to monitor brain chemistry in patients suffering subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI). Discussion: We present a consensus agreement achieved at a meeting in Stockholm by a group of experienced users of microdialysis in neurointensive care, defining the use of microdialysis, placement of catheters, unreliable values, chemical markers, and clinical use in SAH and in TBI. Conclusions: As microdialysis is maturing into a clinically useful technique for early detection of cerebral ischemia and secondary brain damage, there is a need to following such definition regarding when and how to use microdialysis after SAH and TBI.
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| 23. |
- Bouw, R., et al.
(author)
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Increased blood-brain barrier permeability of morphine in a patient with severe brain lesions as determined by microdialysis
- 2001
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 45, s. 390-
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Journal article (peer-reviewed)abstract
- Intracerebral microdialysis was utilised to obtain information regarding how morphine is transported across the blood-brain barrier (BBB). In a patient with a severe brain injury, we measured simultaneously unbound extracellular fluid (ECF) concentrations of morphine in human brain and in subcutaneous fat tissue, which were compared to morphine levels in arterial blood. This report shows an increase in morphine levels near the trauma site in the brain compared to uninjured brain tissue. The half-life of morphine in uninjured and injured brain tissue of 178 min and 169 min, respectively, were comparable but were longer than in blood (64 min) and adipose tissue (63 min). This indicates that morphine is retained in brain tissue for a longer time than what could be expected from the blood concentration-time profile. These results show the potential of the microdialysis technique in providing new information regarding the pharmacokinetics of drug in the human brain close to the trauma site and in macroscopically intact tissue.
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| 28. |
- Diaz-Parejo, P, et al.
(author)
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Cerebral energy metabolism during transient hyperglycemia in patients with severe brain trauma
- 2003
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In: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 29:4, s. 544-550
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Journal article (peer-reviewed)abstract
- Objective: To study whether transient hyperglycemia adversely affects cerebral energy metabolism in patients with severe traumatic brain lesions. Design and setting: Prospective, nonrandomized study in the neurosurgical intensive care unit of a university hospital. Patients: 108 patients treated for severe traumatic brain lesions. Interventions: All patients were treated according to neurosurgical intensive care routine including monitoring of, intracranial pressure. One microdialysis catheter was inserted via a burr hole frontally to that used for the intraventricular catheter ("better" position). In patients with focal lesions one or more catheters were inserted into cerebral cortex surrounding an evacuated focal contusion or underlying an evacuated hematoma ("worse" position). Perfusion rate was 0.3 mul/min and samples were taken every. 30 or 60 min. The levels of glucose, pyruvate, lactate, glutamate, and glycerol were analyzed and displayed bedside. Measurements and results: There were 18 episodes of moderate (12-15 mmol/1) and 6 episodes of pronounced (>15 mmol/1) hyperglycemia. Moderate hyperglycemia did not change intracerebral levels of lactate, pyruvate, glutamate, glycerol, or lactate/pyruvate ratio. Lactate concentrations increased during pronounced hyperglycemia. Pronounced cerebral lactic acidosis and a moderate increase in interstitial glycerol concentration indicating cell membrane degradation was observed in a single patient with pronounced, long-lasting hyperglycemia. Conclusions: Cerebral energy metabolism was affected by transient hyperglycemia only at blood glucose concentration above 15 mmol/l as shown by a moderate increase in interstitial lactate level.
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| 31. |
- Ederoth, Per, et al.
(author)
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Local metabolic changes in subcutaneous adipose tissue during intravenous and epidural analgesia.
- 2002
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 46:5, s. 585-591
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Journal article (peer-reviewed)abstract
- BACKGROUND: This clinical study aimed at investigating the impact of postoperative thoracic epidural analgesia on extracellular glycerol concentration and glucose metabolism in subcutaneous adipose tissue, using the microdialysis technique. The sympathetic nervous activity, which can be attenuated by epidural anesthesia, influences lipolysis and the release of glycerol. METHODS: Fourteen patients who underwent major abdominal or thoraco-abdominal surgery were studied postoperatively over 3 days. For postoperative analgesia the patients were prospectively randomized to receive either thoracic epidural analgesia with a bupivacaine/morphine infusion (EPI-group, n=6) or a continuous i.v. infusion of morphine (MO-group, n=8). The concentration of glycerol, glucose and lactate in the abdominal and deltoid subcutaneous adipose tissue were measured using a microdialysis technique. RESULTS: The abdominal glycerol levels were equal in both groups. In the deltoid region of the EPI-group, glycerol concentrations started to increase on Day 2, and reached significantly higher levels on Day 3 compared with the MO-group. The glucose and lactate levels showed no differences between groups in the two regions. CONCLUSION: The uniform glycerol levels in abdominal subcutaneous adipose tissue in conjunction with the difference in glycerol levels in the deltoid area indicate that the local lipolysis is different in the two study groups. This might be explained by a regional metabolic influence of thoracic epidural analgesia, possibly via the sympathetic nervous system.
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| 44. |
- Gardenfors, F, et al.
(author)
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Adverse biochemical and physiological effects of prostacyclin in experimental brain oedema
- 2004
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 48:10, s. 1316-1321
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Journal article (peer-reviewed)abstract
- Background: Prostacyclin (PGI(2)) and its stable analogues are known to reduce capillary hydraulic permeability. This study explores the biochemical and physiological effects of i.v. infusion of low-dose PGI(2) in an experimental model of vasogenic brain oedema. Methods: Twenty-seven anaesthetized and mechanically ventilated piglets with brain oedema induced by intrathecal injection of lipopolysaccharide (LPS) were used. Five of the animals received a continuous infusion of PGI(2) (1 ng kg(-1) min(-1)) i.v. Four microdialysis catheters were placed in the brain to measure interstitial concentrations of glucose, lactate, and glycerol. Mean arterial pressure (MAP), intracranial pressure (ICP) and temperature were monitored continuously. Low-dose infusion of PGI(2) started 1 h before the LPS injection and was constant during the study period. Results: Intracranial pressure increased significantly in animals treated with PGI(2). The increase in ICP was associated with significant cerebral biochemical changes: decrease in glucose, increase in lactate, increase in lactate/glucose ratio and increase in glycerol. Conclusion: In LPS-induced brain oedema i.v. infusion of low-dose PGI(2) caused a further increase in ICP and a perturbation of energy metabolism, indicating cerebral ischemia and degradation of cellular membranes.
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| 50. |
- Herrera-Marschitz, M, et al.
(author)
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On the origin of extracellular glutamate levels monitored in the basal ganglia of the rat by in vivo microdialysis
- 1996
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In: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 66:4, s. 1726-1735
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Journal article (peer-reviewed)abstract
- Several putative neurotransmitters and metabolites were monitored simultaneously in the extracellular space of neostriatum, substantia nigra, and cortex and in subcutaneous tissue of the rat by in vivo microdialysis. Glutamate (Glu) and aspartate (Asp) were at submicromolar and gamma-aminobutyric acid (GABA) was at nanomolar concentrations in all brain regions. The highest concentration of dopamine (DA) was in the neostriatum. Dynorphin B (Dyn B) was in the picomolar range in all brain regions. Although no GABA, DA, or Dyn B could be detected in subcutaneous tissue, Glu and Asp levels were 5 and approximately 5 and approximately 0.4 microM, respectively. Lactate and pyruvate concentrations were approximately 200 and approximately 10 microM in all regions. The following criteria were applied to ascertain the neuronal origin of substances quantified by microdialysis: sensitivity to (a) K+ depolarization, (b) Na+ channel blockade, (c) removal of extracellular Ca2+, and (d) depletion of presynaptic vesicles by local administration of alpha-latrotoxin. DA, Dyn B, and GABA largely satisfied all these criteria. In contrast, Glu and Asp levels were not greatly affected by K+ depolarization and were increased by perfusing with tetrodotoxin or with Ca2+-free medium, arguing against a neuronal origin. However, Glu and Asp, as well as DA and GABA, levels were decreased under both basal and K+-depolarizing conditions by alpha-latrotoxin. Because the effect of K+ depolarization on Glu and Asp could be masked by reuptake into nerve terminals and glial cells, the reuptake blocker dihydrokainic acid (DHKA) or L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) was included in the microdialysis perfusion medium. The effect of K+ depolarization on Glu and Asp levels was increased by DHKA, but GABA levels were also affected. In contrast, PDC increased only Glu levels. It is concluded that there is pool of releasable Glu and Asp in the rat brain. However, extracellular levels of amino acids monitored by in vivo microdialysis reflect the balance between neuronal release and reuptake into surrounding nerve terminals and glial elements.
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