Microdialysis—theoretical background and recent implementation in applied life-sciences

Plock, Nele; Kloft, Charlotte

doi:10.1016/j.ejps.2005.01.017

Cited by 262 publications

(229 citation statements)

References 207 publications

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“…Microdialysis has been applied to a variety of tissues including the measurement of drugs in the perilymphatic space of the cochlea (Hibi et al, 2001;Hunter et al, 2003;Plock and Kloft, 2005). A microdialysis probe consists of an inner tube and an outer tube that has a semipermeable membrane on its distal tip.…”

Section: Microdialysismentioning

confidence: 99%

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Cochlear microdialysis for quantification of dexamethasone and fluorescein entry into scala tympani during round window administration

et al. 2006

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Before new drugs for the treatment of inner ear disorders can be studied in controlled clinical trials, it is important that their pharmacokinetics be established in inner ear fluids. Microdialysis allows drug levels to be measured in perilymph without the volume disturbances and potential cerebrospinal fluid contamination associated with fluid sampling. The aims of this study were to show: (i) that despite low recovery rates from miniature dialysis probes, significant amounts of drug are removed from small fluid compartments, (ii) that dialysis sampling artifacts can be accounted for using computer simulations and (iii) that microdialysis allows quantification of the entry rates through the round window membrane (RWM) into scala tympani (ST). Initial experiments used microdialysis probes in small compartments in vitro containing sodium fluorescein. Stable concentrations were observed in large compartments (1000 μl) but significant concentration declines were observed in smaller compartments (100, 10 and 5.6 μl) comparable to the size of the inner ear. Computer simulations of these experiments closely approximated the experimental data. In in vivo experiments, sodium fluorescein 10 mg/ml and dexamethasone-dihydrogen-phosphate disodium salt 8 mg/ml were simultaneously applied to the RWM of guinea pigs. Perilymph concentration in the basal turn of ST was monitored using microdialysis. The fluorescein concentration reached after 200 min application (585 ± 527 μg/ml) was approximately twice that of dexamethasone phosphate (291 ± 369 μg/ml). Substantial variation in concentrations was found between animals by approximately a factor of 34 for fluorescein and at least 41 for dexamethasone phosphate. This is, to a large extent, thought to be the result of the RWM permeability varying in different animals. It was not caused by substance analysis variations, because two different analytic methods were used and the concentration ratio between the two substances remained nearly constant across the experiments and because differences were apparent for the repeated samples obtained in each animal. Interpretation of the results using computer simulations allowed RWM permeability to be quantified. It also demonstrated, however, that cochlear clearance values could not be reliably obtained with microdialysis because of the significant contribution of dialysis to clearance. The observed interanimal variation, e.g., in RWM permeability, is likely to be clinically relevant to the local application of drugs in patients.

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Section: Microdialysismentioning

confidence: 99%

“…It is also possible however to use this method to deliver substances to the extracellular environment. For that purpose a substance is added to the perfusate and then diffuses through the semipermeable membrane into the surrounding fluids (Plock and Kloft, 2005;Ungerstedt, 1991).…”

Section: Microdialysismentioning

confidence: 99%

Cochlear microdialysis for quantification of dexamethasone and fluorescein entry into scala tympani during round window administration

et al. 2006

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“…where R is metabolite recovery, K is exchange membrane surface area times mass transport coefficient and f is flow rate 19 .…”

Section: Methodsmentioning

confidence: 99%

Microdialysis to Optimize Cord Perfusion and Drug Delivery in Spinal Cord Injury

Phang

Zoumprouli

Papadopoulos

et al. 2016

Annals of Neurology

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OBJECTIVE:There is lack of monitoring from the injury site to guide management of patients with acute traumatic spinal cord injury. Here we describe a bedside microdialysis monitoring technique for optimizing spinal cord perfusion and drug delivery at the injury site.METHODS: 14 patients were recruited within 72 hours of severe spinal cord injury. We inserted intradurally at the injury site a pressure probe, to monitor continuously spinal cord perfusion pressure, and a microdialysis catheter, to monitor hourly glycerol, glutamate, glucose, lactate and pyruvate. The pressure probe and microdialysis catheter were placed on the surface of the injured cord. RESULTS:Microdialysis monitoring did not cause serious complications. Spinal cord perfusion pressure 90 -100 mmHg and tissue glucose >4.5 mM minimized metabolic derangement at the injury site. Increasing spinal cord perfusion pressure by ~10 mmHg, increased the entry of intravenously administered dexamethasone at the injury site three-fold. INTERPRETATION:This study determined the optimum spinal cord perfusion pressure and optimum tissue glucose concentration at the injury site. We also identified spinal cord perfusion pressure as a key determinant of drug entry into the injured spinal cord. Our findings challenge current guidelines, which recommend maintaining mean arterial pressure at 85 -90 mmHg for a week after spinal cord injury. We propose that future drug trials for spinal cord injury include pressure and microdialysis monitoring to optimize spinal cord perfusion and maximize drug delivery at the injury site.

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“…Microdialysis (MD) is a sampling technique that uses a hollow fiber dialysis or ultrafiltration membrane to collect time resolved samples from the area of interest (Ungerstedt 1991;Chaurasia 1999;Plock and Kloft 2005). MD is well established as a clinical sampling tool for monitoring small hydrophilic molecules such as lactate, puruvate and glucose in neurointensive care settings (Hillered et al 2005;Helmy et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Influence of surface modification and static pressure on microdialysis protein extraction efficiency

Chu

Undin

Lind

et al. 2015

Biomed Microdevices

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Influence of surface modification and static pressure on microdialysis protein extractionefficiency. Biomedical microdevices (Print)http://dx.doi.org/10.1007/s10544-015-0005-3Access to the published version may require subscription. N.B. When citing this work, cite the original published paper. ABSTRACTThere is growing interest in using microdialysis (MD) for monitoring larger and more complex molecules such as neuropeptides and proteins. This promotes the use of MD membranes with molecular weight cut off (MWCO) of 100 kDa or above. The hydrodynamic property of the membrane goes to ultrafiltration or beyond, making the MD catheters more sensitive to pressure.In the meantime, despite the large pore size, studies have shown that membrane biofouling still lead to unstable catheter performance. The objective is to study in vitro how 500 kDa dextran and Poloxamer 407 surface modification affect the fluid recovery (FR) and extraction efficiency (EE) of 100 kDa MWCO MD catheters. A pressure chamber was designed to facilitate the tests, using as MD sample a protein standard with similar concentrations as in human cerebral spinal fluid, comparing native and Poloxamer 407 modified MD catheters. The collected dialysate fractions were examined for FR and protein EE, employing Dot-it Spot-it Protein Assay for total protein EE and targeted mass spectrometry (MS) for EE of individual proteins and peptides. The FR results suggested that the surface modified catheters were less sensitive to the pressure and provide higher precision, and provided a FR closer to 100%. The surface modification did not show a significant effect on the protein EE. The average total protein EE of surface modified catheters was slightly higher than that of the native ones. The MS EE data of individual proteins showed a clear trend of complex response in EE with pressure.

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Microdialysis—theoretical background and recent implementation in applied life-sciences

Cited by 262 publications

References 207 publications

Cochlear microdialysis for quantification of dexamethasone and fluorescein entry into scala tympani during round window administration

Cochlear microdialysis for quantification of dexamethasone and fluorescein entry into scala tympani during round window administration

Microdialysis to Optimize Cord Perfusion and Drug Delivery in Spinal Cord Injury

Influence of surface modification and static pressure on microdialysis protein extraction efficiency

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