The effects of cerebral pressure autoregulation status and CPP levels on cerebral metabolism in pediatric traumatic brain injury.

BACKGROUND: Cerebral perfusion pressure (CPP) management in the developing child with traumatic brain injury (TBI) is challenging. The pressure reactivity index (PRx) may serve as marker of cerebral pressure autoregulation (CPA) and optimal CPP (CPPopt) may be assessed by identifying the CPP level with best (lowest) PRx. To evaluate the potential of CPPopt guided management in children with severe TBI, cerebral microdialysis (CMD) monitoring levels of lactate and the lactate/pyruvate ratio (LPR) (indicators of ischemia) were related to actual CPP levels, autoregulatory state (PRx) and deviations from CPPopt (ΔCPPopt). METHODS: Retrospective study of 21 children ≤ 17 years with severe TBI who had both ICP and CMD monitoring were included. CPP, PRx, CPPopt and ΔCPPopt where calculated, dichotomized and compared with CMD lactate and lactate-pyruvate ratio. RESULTS: Median age was 16 years (range 8-17) and median Glasgow coma scale motor score 5 (range 2-5). Both lactate (p = 0.010) and LPR (p = < 0.001) were higher when CPP ≥ 70 mmHg than when CPP < 70. When PRx ≥ 0.1 both lactate and LPR were higher than when PRx < 0.1 (p = < 0.001). LPR was lower (p = 0.012) when CPPopt ≥ 70 mmHg than when CPPopt < 70, but there were no differences in lactate levels. When ΔCPPopt > 10 both lactate (p = 0.026) and LPR (p = 0.002) were higher than when ΔCPPopt < -10. CONCLUSIONS: Increased levels of CMD lactate and LPR in children with severe TBI appears to be related to disturbed CPA (PRx). Increased lactate and LPR also seems to be associated with actual CPP levels ≥ 70 mmHg. However, higher lactate and LPR values were also seen when actual CPP was above CPPopt. Higher CPP appears harmful when CPP is above the upper limit of pressure autoregulation. The findings indicate that CPPopt guided CPP management may have potential in pediatric TBI.

Brain metabolism response to intrahospital transfers in neurocritical ill patients and the impact of microdialysis probe location.

Intrahospital transfer (IHT), a routine in the management of neurocritical patients requiring imaging or interventions, might affect brain metabolism. Studies about IHT effects using microdialysis (MD) have produced conflicting results. In these studies, only the most damaged hemisphere was monitored, and those may not reflect the impact of IHT on overall brain metabolism, nor do they address differences between the hemispheres. Herein we aimed to quantify the effect of IHT on brain metabolism by monitoring both hemispheres with bilateral MD. In this study, 27 patients with severe brain injury (10 traumatic brain injury and 17 subarachnoid hemorrhage patients) were included, with a total of 67 IHT. Glucose, glycerol, pyruvate and lactate were measured by MD in both hemispheres for 10 h pre- and post-IHT. Alterations in metabolite levels after IHT were observed on both hemispheres; although these changes were more marked in hemisphere A (most damaged) than B (less damaged). Our results suggest that brain metabolism is altered after an IHT of neurocritical ill patients particularly but not limited to the damaged hemisphere. Bilateral monitorization may be more sensitive than unilateral monitorization for detecting metabolic disturbances not directly related to the course of the disease.

Negligible In Vitro Recovery of Macromolecules from Microdialysis Using 100 kDa Probes and Dextran in Perfusion Fluid.

Microdialysis is applied in neurointensive care to monitor cerebral glucose metabolism. If recoverable, macromolecules may also serve as biomarkers in brain disease and provide clues to their passage across the blood-brain barrier. Our study aimed to investigate the in vitro recovery of human micro- and macromolecules using microdialysis catheters and perfusion fluids approved for clinical use. In vitro microdialysis of a bulk solution containing physiological or supraphysiological concentrations of glucose, lactate, pyruvate, human IgG, serum albumin, and hemoglobin was performed using two different catheters and perfusion fluids. One had a membrane cut-off of 20 kDa and was used with a standard CNS perfusion fluid, and the other had a membrane cut-off of 100 kDa and was perfused with the same solution supplemented with dextran. The flow rate was 0.3 µl/min. We used both push and push-pull methods. Dialysate samples were collected at 2-h intervals for 6 h and analyzed for relative recovery of each substance. The mean relative recovery of glucose, pyruvate, and lactate was > 90% in all but two sets of experiments. In contrast, the relative recovery of human IgG, serum albumin, and hemoglobin from both bulk solutions was below the lower limit of quantification (LLOQ). Using a push-pull method, recovery of human IgG, serum albumin, and hemoglobin from a bulk solution with supraphysiological concentrations were above LLOQ but with low relative recovery (range 0.9%-1.6%). In summary, exchanging the microdialysis setup from a 20 kDa catheter with a standard perfusion fluid for a 100 kDa catheter with a perfusion solution containing dextran did not affect the relative recovery of glucose and its metabolites. However, it did not result in any useful recovery of the investigated macromolecules at physiological levels, either with or without a push-pull pump system.

Microdialysis coupled with droplet microfluidics and mass spectrometry for determination of neurotransmitters in vivo with high temporal resolution.

Monitoring the concentration fluctuations of neurotransmitters in vivo is valuable for elucidating the chemical signals that underlie brain functions. Microdialysis sampling is a widely used tool for monitoring neurochemicals in vivo. The volume requirements of most techniques that have been coupled to microdialysis, such as HPLC, result in fraction collection times of minutes, thus limiting the temporal resolution possible. Further the time of analysis can become long for cases where many fractions are collected. Previously we have used direct analysis of dialysate by low-flow electrospray ionization-tandem mass spectrometry (ESI-MS/MS) on a triple quadrupole mass spectrometer to monitor acetylcholine, glutamate, and γ-amino-butyric acid to achieve multiplexed in vivo monitoring with temporal resolution of seconds. Here, we have expanded this approach to adenosine, dopamine, and serotonin. The method achieved limits of detection down to 2 nM, enabling basal concentrations of all these compounds, except serotonin, to be measured in vivo. Comparative analysis with LC-MS/MS showed accurate results for all compounds except for glutamate, possibly due to interference for this compound in vivo. Pairing this analysis with droplet microfluidics yields 11 s temporal resolution and can generate dialysate fractions down to 3 nL at rates up to 3 fractions per s from a microdialysis probe. The system is applied to multiplexed monitoring of neurotransmitter dynamics in response to stimulation by 100 mM K+ and amphetamine. These applications demonstrate the suitability of the droplet ESI-MS/MS method for monitoring short-term dynamics of up to six neurotransmitters simultaneously.

Cutaneous Pharmacokinetics of Topically Applied Novel Dermatological Formulations.

Novel formulations are developed for dermatological applications to address a wide range of patient needs and therapeutic challenges. By pushing the limits of pharmaceutical technology, these formulations strive to provide safer, more effective, and patient-friendly solutions for dermatological concerns, ultimately improving the overall quality of dermatological care. The article explores the different types of novel dermatological formulations, including nanocarriers, transdermal patches, microsponges, and microneedles, and the techniques involved in the cutaneous pharmacokinetics of these innovative formulations. Furthermore, the significance of knowing cutaneous pharmacokinetics and the difficulties faced during pharmacokinetic assessment have been emphasized. The article examines all the methods employed for the pharmacokinetic evaluation of novel dermatological formulations. In addition to a concise overview of earlier techniques, discussions on novel methodologies, including tape stripping, in vitro permeation testing, cutaneous microdialysis, confocal Raman microscopy, and matrix-assisted laser desorption/ionization mass spectrometry have been conducted. Emerging technologies like the use of microfluidic devices for skin absorption studies and computational models for predicting drug pharmacokinetics have also been discussed. This article serves as a valuable resource for researchers, scientists, and pharmaceutical professionals determined to enhance the development and understanding of novel dermatological drug products and the complex dynamics of cutaneous pharmacokinetics.

Bioequivalence Evaluation of Topical Metronidazole Products Using Dermal Microdialysis in New Zealand Rabbits.

Comparative assessment of cutaneous pharmacokinetics (cPK) by dermal microdialysis (dMD) appears to be suitable to evaluate the bioequivalence (BE) of topical dermatological drug products applied to the skin (TDDPs). Although dMD studies in the literature have reported inconclusive BE assessments, we have addressed several methodological deficiencies to improve dMD's capability to assess BE between reference (R) and approved generic (referred to as test (T)) gel and cream products of metronidazole (MTZ). The 90% confidence interval (CI) of the geometric mean ratios for the Ln(AUC0-24) and Ln(Cmax) endpoints was centered within the BE limits of 80-125%. The CIs extended outside this range as the proof-of-principle study was not statistically powered to demonstrate BE (N = 7 rabbits). A power analysis suggests that, with the variability observed in this study, 21 rabbits for the cream and 11 rabbits for the gel would be sufficient to support an evaluation of BE with the 2 probe replicates we used, and only 10 and 5 rabbits would be sufficient to power the study for the cream and gel, respectively, if 4 probe replicates are used for each treatment per rabbit. These results indicate that dMD when properly controlling variables can be used to support BE assessments for TDDPs.

Within-Mice Comparison of Microdialysis and Fiber Photometry-Recorded Dopamine Biosensor during Amphetamine Response.

A fundamental concept in neuroscience is the transmission of information between neurons via neurotransmitters, -modulators, and -peptides. For the past decades, the gold standard for measuring neurochemicals in awake animals has been microdialysis (MD). The emergence of genetically encoded fluorescence-based biosensors, as well as in vivo optical techniques such as fiber photometry (FP), has introduced technologically distinct means of measuring neurotransmission. To directly compare MD and FP, we performed concurrent within-animal recordings of extracellular dopamine (DA) in the dorsal striatum (DS) before and after administration of amphetamine in awake, freely behaving mice expressing the dopamine sensor dLight1.3b. We show that despite temporal differences, MD- and FP-based readouts of DA correlate well within mice. Down-sampling of FP data showed temporal correlation to MD data, with less variance observed using FP. We also present evidence that DA fluctuations periodically reach low levels, and naïve animals have rapid, predrug DA dynamics measured with FP that correlate to the subsequent pharmacodynamics of amphetamine as measured with MD and FP.

Quantitative monitoring and modelling of retrodialysis drug delivery in a brain phantom.

A vast number of drug molecules are unable to cross the blood-brain barrier, which results in a loss of therapeutic opportunities when these molecules are administered by intravenous infusion. To circumvent the blood-brain barrier, local drug delivery devices have been developed over the past few decades such as reverse microdialysis. Reverse microdialysis (or retrodialysis) offers many advantages, such as a lack of net volume influx to the intracranial cavity and the ability to sample the tumour's micro-environment. However, the translation of this technique to efficient drug delivery has not been systematically studied. In this work, we present an experimental platform to evaluate the performance of microdialysis devices in reverse mode in a brain tissue phantom. The mass of model drug delivered is measured by computing absorbance fields from optical images. Concentration maps are reconstructed using a modern and open-source implementation of the inverse Abel transform. To illustrate our method, we assess the capability of a commercial probe in delivering methylene blue to a gel phantom. We find that the delivery rate can be described by classical microdialysis theory, except at low dialysate flow rates where it is impacted by gravity, and high flow rates where significant convection to the gel occurs. We also show that the flow rate has an important impact not only on the overall size of the drug plume, but also on its shape. The numerical tools developed for this study have been made freely available to ensure that the method presented can be used to rapidly and inexpensively optimise probe design and protocol parameters before proceeding to more in-depth studies.

Microdialysis-Based Classifications of Abnormal Metabolic States after Traumatic Brain Injury: A Systematic Review of the Literature.

After traumatic brain injury (TBI), cerebral metabolism can become deranged, contributing to secondary injury. Cerebral microdialysis (CMD) allows cerebral metabolism assessment and is often used with other neuro-monitoring modalities. CMD-derived parameters such as the lactate/pyruvate ratio (LPR) show a failure of oxidative energy generation. CMD-based abnormal metabolic states can be described following TBI, informing the etiology of physiological derangements. This systematic review summarizes the published literature on microdialysis-based abnormal metabolic classifications following TBI. Original research studies in which the populations were patients with TBI were included. Studies that described CMD-based classifications of metabolic abnormalities were included in the synthesis of the narrative results. A total of 825 studies underwent two-step screening after duplicates were removed. Fifty-three articles that used CMD in TBI patients were included. Of these, 14 described abnormal metabolic states based on CMD parameters. Classifications were heterogeneous between studies. LPR was the most frequently used parameter in the classifications; high LPR values were described as metabolic crisis. Ischemia was consistently defined as high LPR with low CMD substrate levels (glucose or pyruvate). Mitochondrial dysfunction, describing inability to use energy substrate despite availability, was identified based on raised LPR with near-normal levels of pyruvate. This is the first systematic review summarizing the published literature on microdialysis-based abnormal metabolic states following TBI. Although variability exists among individual classifications, there is broad agreement about broad definitions of metabolic crisis, ischemia, and mitochondrial dysfunction. Identifying the etiology of deranged cerebral metabolism after TBI is important for targeting therapeutic interventions.

Pilot Pharmacokinetic Study in Healthy Adults Using Intravascular Microdialysis Catheters Modified for Use in Paediatric Patients to Assess Vancomycin Blood Levels.

BACKGROUND AND OBJECTIVE: Exhaustive pharmacokinetic (PK) studies in paediatric patients are unavailable for most antibiotics and feasibility of PK studies is limited by challenges, such as low blood volume and venipuncture-related pain. Microdialysis (MD) represents a promising method to overcome these obstacles. The aim of this proof-of-concept study was to develop and validate modified MD catheters that can be used to obtain concentration-time profiles of antibiotics in paediatric patients. METHODS: Following extensive in vitro MD experiments, a prospective open-labelled study in ten healthy adult volunteers (HVs) was conducted. Subjects received a single intravenous dose of 1000 mg vancomycin, then plasma and intravascular microdialysate were sampled over 24 h. In vivo MD probe calibration was conducted using the retrodialysis technique. Plasma protein binding was measured using ultrafiltration. Confirmation of the measurements was performed using a Bland-Altman plot, relevant PK parameters were calculated, and a pharmacometric model was established. RESULTS: No safety issues were encountered. The concentration-time curves of microdialysate and plasma measurements showed good alignment. The Bland-Altman plot yielded a mean bias of 0.19 mg/L and 95% limits of agreement of - 9.34 to 9.71 mg/L. A two-compartment model best described plasma PK, model-based estimates for recovery of the MD probes being in high agreement with the observed values. Quantified estimates of fraction unbound were comparable between plasma and microdialysate (p = 0.56). CONCLUSIONS: An innovative MD catheter that can be inserted into small intravenous lines was successfully developed and applied in HV. This proof-of-concept study is encouraging and opens the way to further experiments leading towards future use of MD in paediatric patients.

Real-Time Dynamic Collection of Hippocampal Extracellular Fluid from Conscious Rats Using a Microdialysis System.

A variety of central nervous system (CNS) diseases are associated with changes in the composition of hippocampal extracellular fluid (HECF). However, difficulty in obtaining HECF in real time from conscious rats has long restricted the evaluation of CNS disease progression and the effectiveness of ethnomedicine therapy. Encouragingly, a brain microdialysis technique can be used for continuous sampling with the advantages of dynamic observation, quantitative analysis, and a small sampling size. This allows the monitoring of changes in the extracellular fluid content for compounds from traditional herbs and their metabolites in the brain of living animals. The aim of this study was thus to accurately implant a cerebrospinal fluid microdialysis probe into the hippocampal region of Sprague Dawley (SD) rats with a three-dimensional brain stereotaxic apparatus, cutting off molecular weights greater than 20 kDa. The high-quality HECF was then obtained from conscious rats using a microdialysis sampling control system with an adjustable sampling rate from 2.87 nL/min - 2.98 mL/min. In conclusion, our protocol provides an efficient, rapid, and dynamic method to obtain HECF in awake rats with the help of microdialysis technology, which provides us with unlimited possibilities to further explore the pathogenesis of CNS-related diseases and evaluate drug efficacy.

Reversible Immunosensor for the Continuous Monitoring of Cortisol in Blood Plasma Sampled with Microdialysis.

Cortisol is a steroid hormone involved in a wide range of medical conditions. The level of the hormone fluctuates over time, but with traditional laboratory-based assays, such dynamics cannot be monitored in real time. Here, a reversible cortisol sensor is reported that allows continuous monitoring of cortisol in blood plasma using sampling by microdialysis. The sensor is based on measuring single-molecule binding and unbinding events of tethered particles. The particles are functionalized with antibodies and the substrate with cortisol-analogues, causing binding and unbinding events to occur between particles and substrate. The frequency of binding events is reduced when cortisol is present in the solution as it blocks the binding sites of the antibodies. The sensor responds to cortisol in the high nanomolar to low micromolar range and can monitor cortisol concentrations over multiple hours. Results are shown for cortisol monitoring in filtered and in microdialysis-sampled human blood plasma.

Dynamic Continuous Blood Extraction from Rat Heart via Noninvasive Microdialysis Technique.

Dynamic analysis of blood components is of great importance in understanding cardiovascular diseases and their related diseases, such as myocardial infarction, arrhythmia, atherosclerosis, cardiogenic pulmonary edema, pulmonary embolism, and cerebral embolism. At the same time, it is urgent to break through the continuous heart blood sampling technique in live rats to evaluate the effectiveness of distinctive ethnic medicine therapy. In this study, a blood microdialysis probe was implanted in the right jugular vein of rats in a precise and noninvasive surgical procedure. Cardiac blood samples were then collected at a rate of 2.87 nL/min to 2.98 mL/min by connecting to an online microdialysis sample collection system. Even more momentously, the acquired blood samples can temporarily be stored in microdialysis containers at 4 °C. The microdialysis-based online continuous blood collection program from rat heart has greatly guaranteed the quality of blood samples, advancing and invigorating the scientific rationality of the research on systemic cardiovascular diseases and evaluating ethnomedicine therapy from the perspective of hematology.

Microdialysis of Drug and Drug Metabolite: a Comprehensive In Vitro Analysis for Voriconazole and Voriconazole N-oxide.

PURPOSE: Voriconazole is a therapeutically challenging antifungal drug associated with high interindividual pharmacokinetic variability. As a prerequisite to performing clinical trials using the minimally-invasive sampling technique microdialysis, a comprehensive in vitro microdialysis characterization of voriconazole (VRC) and its potentially toxic N-oxide metabolite (NO) was performed. METHODS: The feasibility of simultaneous microdialysis of VRC and NO was explored in vitro by investigating the relative recovery (RR) of both compounds in the absence and presence of the other. The dependency of RR on compound combination, concentration, microdialysis catheter and study day was evaluated and quantified by linear mixed-effects modeling. RESULTS: Median RR of VRC and NO during individual microdialysis were high (87.6% and 91.1%). During simultaneous microdialysis of VRC and NO, median RR did not change (87.9% and 91.1%). The linear mixed-effects model confirmed the absence of significant differences between RR of VRC and NO during individual and simultaneous microdialysis as well as between the two compounds (p > 0.05). No concentration dependency of RR was found (p = 0.284). The study day was the main source of variability (46.3%) while the microdialysis catheter only had a minor effect (4.33%). VRC retrodialysis proved feasible as catheter calibration for both compounds. CONCLUSION: These in vitro microdialysis results encourage the application of microdialysis in clinical trials to assess target-site concentrations of VRC and NO. This can support the generation of a coherent understanding of VRC pharmacokinetics and its sources of variability. Ultimately, a better understanding of human VRC pharmacokinetics might contribute to the development of personalized dosing strategies.

Pineal Microdialysis.

Pineal microdialysis is characterized by the real-time monitoring of melatonin, neurotransmitters, metabolites, and other compounds released by the pineal gland throughout 24 h. It is a technique with great advantages that allows in vivo study of the ongoing pineal gland metabolism. In this chapter, we describe the entire process of pineal microdialysis that includes probe manufacturing, surgical procedure for its implantation, and the sample collection process.

On-Demand Nanoliter Sampling Probe for the Collection of Brain Fluid.

Continuous fluidic sampling systems allow collection of brain biomarkers in vivo. Here, we propose a new sequential and intermittent sampling paradigm using droplets, called Droplet on Demand (DoD). It is implemented in a microfabricated neural probe and alternates phases of analyte removal from the tissue and phases of equilibration of the concentration in the tissue. It allows sampling droplets loaded with molecules from the brain extracellular fluid punctually, without the long transient equilibration periods typical of continuous methods. It uses an accurately defined fluidic sequence with controlled timings, volumes, and flow rates, and correct operation is verified by the embedded electrodes and a flow sensor. As a proof of concept, we demonstrated the application of this novel approach in vitro and in vivo, to collect glucose in the brain of mice, with a temporal resolution of 1-2 min and without transient regime. Absolute quantification of the glucose level in the samples was performed by direct infusion nanoelectrospray ionization Fourier transform mass spectrometry (nanoESI-FTMS). By adjusting the diffusion time and the perfusion volume of DoD, the fraction of molecules recovered in the samples can be tuned to mirror the tissue concentration at accurate points in time. Moreover, this makes quantification of biomarkers in the brain possible within acute experiments of only 20-120 min. DoD provides a complementary tool to continuous microdialysis and push-pull sampling probes. Thus, the advances allowed by DoD will benefit quantitative molecular studies in the brain, i.e., for molecules involved in volume transmission or for protein aggregates that form in neurodegenerative diseases over long periods.

Steady-state concentrations of flucloxacillin in porcine vertebral cancellous bone and intervertebral disc following oral and intravenous administration assessed by microdialysis.

AIMS: Flucloxacillin is a frequently used antibiotic in the treatment of spondylodiscitis. We assessed steady-state concentrations and time above minimal inhibitory concentration (fT > MIC) of flucloxacillin in the intervertebral disc, vertebral cancellous bone, subcutaneous tissue and plasma, after intravenous and oral administration. METHODS: Sixteen pigs were randomized into two groups; Group Peroral (Group PO) and Group Intravenous (Group IV) received 1 g flucloxacillin every 6 h for 24 h orally or intravenously. Microdialysis was used for sampling in the compartments of interest. A flucloxacillin target of 50% fT > MIC was applied for three MIC targets: 0.125, 0.5 and 2.0 µg/mL. RESULTS: Intravenous administration resulted in significantly longer fT > MIC for all targets. Target attainment was only reached for the low target of 0.125 µg/mL in Group IV in vertebral cancellous bone, subcutaneous tissue, and plasma (intervertebral disc 47%). In Group IV, mean fT > MIC values in the investigated compartments were in the range of 47-67% of the dosing interval for 0.125 µg/mL, 20-35% for 0.5 µg/mL, and 0-15% for 2.0 µg/mL. In Group PO, mean fT > MIC values for 0.125 µg/mL were in the range of 1-33%. No pigs reached a concentration of 0.5 µg/mL in any of the investigated compartments in Group PO. CONCLUSION: Administration of 1 g flucloxacillin every 6 h resulted in surprisingly low steady-state fT > MIC after intravenous and oral administration. However, intravenous administration resulted in significantly higher concentrations across compartments compared to oral administration. Sufficient target tissue concentrations for treatment of spondylodiscitis may require a dose increase or alternative dosing regimens.

Real-time analysis of metabolites in vivo by online extraction electrospray ionization mass spectrometry coupled to microdialysis.

In vivo and real-time analysis could reflect a more real biological state, which was of great significance to the study of complex life processes. In this work, we constructed an online extraction electrospray ionization (OE-ESI) ion source as the interface of microdialysis and mass spectrometry, which realized real-time analysis of metabolites in vivo without sample pretreatment process. The ion source was consisted of three coaxial capillaries, and the parameters of the ion source were optimized. The OE-ESI ion source could simultaneously extract, desalt and ionize the analyte, successfully perform MS analysis of analyte in high salt system, and overcome the ion suppression caused by salt ion. Compared with commercial ESI MS, the OE-ESI ion source had excellent salt tolerance and stability. MD-OE-ESI MS realized the real-time MS detection of metabolites in the living body, avoiding the complex desalting process. In the rat liver ischemia-reperfusion model, a total of 24 metabolites, including glucose, glutamate, glutamine, etc., were monitored in real time mode, and their concentrations had varying degrees of change during the experimental process compared with the control group. This platform, we believed, would be helpful for real-time monitoring of biological metabolites in vivo, and had great application prospects to study physiological processes.

Modeling the measurement bias in interstitial glucose concentrations derived from microdialysis in skeletal muscle.

Muscle tissue utilizes glucose as a fuel during exercise and stores glucose in form of glycogen during rest. The associated glucose transport includes delivery of glucose from blood plasma into the interstitial space and subsequent, GLUT-4 facilitated diffusion into muscle cells. The extent to which the vascular endothelium acts as a barrier to glucose transport, however, remains debated. While accurate measurements of interstitial glucose concentration (IGC) are key to resolve this debate, these are also challenging as removal of interstitial fluid may perturb glucose transport and therefore bias IGC measurements. We developed a three-compartment model to infer IGC in skeletal muscle from its local metabolism and blood flow. The model predicts that IGC remains within 5% of that of blood plasma during resting conditions but decreases more as metabolism increases. Next, we determined how microdialysis protocols affect IGC. Our model analysis suggests that microdialysis-based IGC measurements underestimate true values. Notably, reported increases in muscle capillary permeability surface area product (PS) to glucose under the condition of elevated metabolism may owe in part to such measurements bias. Our study demonstrates that microdialysis may be associated with significant measurement bias in the context of muscle IGC assessment. Reappraising literature data with this bias in mind, we find that muscle capillary endothelium may represent less of a barrier to glucose transport in muscle than previously believed. We discuss the impact of glucose removal on the microdialysis relative recovery and means of correcting microdialysis IGC values.

Microdialysis techniques and microdialysis-based patient-near diagnostics.

This article will debate the usefulness of POCT measurements and the contribution microdialysis can make to generating valuable information. A particular theme will be the rarely considered difference between ex vivo sampling, which typically generates only a static measure of concentration, and in vivo measurements that are subject to dynamic changes due to mass transfer. Those dynamic changes provide information about the patients' physiological state.