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Urea clearance: a new method to register local changes in blood flow in rat skeletal muscle based on microdialysis
Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL. (Landstinget i Östergötland)
Karolinska Inst, Dept Physiol and Pharmacol, Stockholm, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
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2010 (English)In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 30, no 1, 57-63 p.Article in journal (Refereed) Published
Abstract [en]

Pgreater thanIncreasing evidence suggests that local blood flow should be monitored during microdialysis (MD) as the recovery of analytes is affected by local blood flow. At present ethanol clearance is the standard technique for this purpose, but it is not functional at very low perfusion velocities. Here, we introduce a technique for MD whereby local tissue blood flow is recorded by the use of urea clearance (changes inflow/outflow concentration), in conjunction with measurements of tissue metabolism (glucose, lactate and puruvate). MD probes were inserted into the gracilis muscle of 15 rats and perfused with a medium containing urea (20 mmol l-1). Changes in muscle blood flow were made by addition of noradrenaline (5 mu g ml-1) to the perfusion medium at two perfusion velocities (0 center dot 6 and 0 center dot 4 mu l min-1). The clearance of urea from the perfusion medium was then calculated and examined in relation to the dose of noradrenaline and to the coexisting changes in extracellular metabolites. The results showed reproducible and dose-dependent changes in blood flow that were induced by noradrenaline. These were characterized by dose-dependent changes in the urea clearance as well as blood-flow-specific changes in the MD metabolic markers (reduction in glucose and increase in lactate). The sensitivity for blood flow changes as assessed by urea clearance (MD) was increased at 0 center dot 4 compared with the 0 center dot 6 mu l min-1 perfusion speed. The results indicate that inclusion of urea to the perfusion medium may be used to monitor changes in skeletal muscle blood flow at low perfusion velocities and in parallel assess metabolic variables with a high recovery (greater than 90%).

Place, publisher, year, edition, pages
2010. Vol. 30, no 1, 57-63 p.
Keyword [en]
extracellular fluid; glucose; lactate; metabolism; recovery
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-52899DOI: 10.1111/j.1475-097X.2009.00904.xOAI: diva2:285758
Available from: 2010-01-13 Created: 2010-01-12 Last updated: 2012-03-13
In thesis
1. On microvascular blood flow assessment with the new microdialysis urea clearance technique
Open this publication in new window or tab >>On microvascular blood flow assessment with the new microdialysis urea clearance technique
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to develop and evaluate a new way of monitoring blood flow with microdialysis. A thin catheter consisting of a semipermeable membrane is implanted in the tissue being studied. The catheter is perfused by a solution that closely resembles interstitial fluid, and small water-soluble substances are allowed to diffuse passively through the pores of the membrane with the aim at reaching equilibrium with the surrounding tissue.  The minimally invasive character of microdialysis, and its ability to sample from the organ being studied, make microdialysis attractive in most research settings as well as for clinical surveillance. It has, however, become increasingly evident that microdialysis under conditions of non-equilibrium - for example, fluctuating regional blood flow, will alter the results gained. We have therefore aimed to explore the possibilities of developing a new marker of blood flow that will yield information about changes in blood flow that occur in the area of the microdialysis catheter itself.

We hypothesised that the changes in the diffusion of exogenous urea could be used as markers of changes in tissue blood flow. The theoretical basis for this approach is that the mass transfer of urea will increase across the dialysis membrane secondary to increased blood flow. As removal of urea from the vicinity of the dialysis membrane increases with increased blood flow, the concentration gradient of urea between the perfusate and tissue will also increase. This in turn will result in a greater loss of urea from the perfusate. The changes noted in retrieval of urea from dialysate by the system are therefore thought to be inversely related to changes in blood flow. We tested our hypothesis in two species of animal (rat and pig) and in man, and in three organ systems (muscle, liver, and skin), and present four papers that indicate that the urea clearance technique provides reliable and reproducible results. The technique was evaluated against conventional metabolic markers (lactate and glucose), the ethanol clearance technique (microdialysis), laser Doppler perfusion imaging (LDPI), and polarisation light spectroscopy (TiVi).

We present evidence that the urea clearance technique can be used to assess blood flow in the organs studied reliably and reproducibly with microdialysis. The microdialysis technique is minimally invasive and safe for the recipient, and catheters can easily be implanted during operation to monitor organs at risk. Urea is easily analysed as a standard assay among other “basic” metabolic markers (in a standard microdialysis kit) and has favourable characteristics with a standardised measurement system that is routinely used for monitoring metabolites in the clinic. The technique is also effective when used at lower perfusate flow rates (<1 μl/minute), which is advantageous as the recovery of metabolic markers increases at low perfusate flow rates.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. 69 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1204
microdialysis, microcirculation
National Category
urn:nbn:se:liu:diva-63116 (URN)978-91-7393-320-9 (ISBN)
Public defence
2010-12-03, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Available from: 2010-12-28 Created: 2010-12-11 Last updated: 2012-03-13Bibliographically approved

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Farnebo, SimonKarlander, Lars-ErikSjöberg, Folke
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SurgeryFaculty of Health SciencesDepartment of Plastic Surgery, Hand surgery UHLDepartment of Intensive Care UHLBurn CenterDepartment of Plastic Surgery, Hand surgery UHLDepartment of Anaesthesiology and Surgery UHL
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