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  • 1.
    Bergkvist, Max
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Iredahl, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Assessment of microcirculation of the skin using Tissue Viability Imaging: A promising technique for detecting venous stasis in the skin2015In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 101, p. 20-25Article in journal (Refereed)
    Abstract [en]

    Background: : Venous occlusion in the skin is difficult to detect by existing measurement techniques. Our aim was to find out whether Tissue Viability Imaging (TiVi) was better at detecting venous occlusion by comparing it with results of laser Doppler flowmetry (LDF) during graded arterial and venous stasis in human forearm skin. Methods: : Arterial and venous occlusions were simulated in 10 healthy volunteers by inflating a blood pressure cuff around the upper right arm. Changes in the concentration of red blood cells (RBC) were measured using TiVi, while skin perfusion and concentration of moving red blood cells (CMBC) were measured using static indices of LDF during exsanguination and subsequent arterial occlusion, postocclusive reactive hyperaemia, and graded increasing and decreasing venous stasis. Results: : During arterial occlusion there was a significant reduction in the mean concentration of RBC from baseline, as well as in perfusion and CMBC (p less than 0.008). Venous occlusion resulted in a significant 28% increase in the concentration of RBC (p = 0.002), but no significant change in perfusion (mean change -14%) while CMBC decreased significantly by 24% (p = 0.02). With stepwise increasing occlusion pressures there was a significant rise in the TiVi index and reduction in perfusion (p = 0.008), while the reverse was seen when venous flow was gradually restored. Conclusion: : The concentration of RBC measured with TiVi changes rapidly and consistently during both total and partial arterial and venous occlusions, while the changes in perfusion, measured by LDF, were less consistent This suggests that TiVi could be a more useful, non-invasive clinical monitoring tool for detecting venous stasis in the skin than LDF.

  • 2.
    Bergkvist, Max
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Zötterman, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Iredahl, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Vascular Occlusion in a Porcine Flap Model: Effects on Blood Cell Concentration and Oxygenation.2017In: Plastic and reconstructive surgery. Global open, ISSN 2169-7574, Vol. 5, no 11, article id e1531Article in journal (Refereed)
    Abstract [en]

    Background: Venous congestion in skin flaps is difficult to detect. This study evaluated the ability of tissue viability imaging (TiVi) to measure changes in the concentration of red blood cells (CRBC), oxygenation, and heterogeneity during vascular provocations in a porcine fasciocutaneous flap model.

    Methods: In 5 pigs, cranial gluteal artery perforator flaps were raised (8 flaps in 5 pigs). The arterial and venous blood flow was monitored with ultrasonic flow probes. CRBC, tissue oxygenation, and heterogeneity in the skin were monitored with TiVi during baseline, 50% and 100% venous occlusion, recovery, 100% arterial occlusion and final recovery, thereby simulating venous and arterial occlusion of a free fasciocutaneous flap. A laser Doppler probe was used as a reference for microvascular perfusion in the flap.

    Results: During partial and complete venous occlusion, increases in CRBC were seen in different regions of the flap. They were more pronounced in the distal part. During complete arterial occlusion, CRBC decreased in all but the most distal parts of the flap. There were also increases in tissue oxygenation and heterogeneity during venous occlusion.

    Conclusions: TiVi measures regional changes in CRBC in the skin of the flap during arterial and venous occlusion, as well as an increase in oxygenated hemoglobin during venous occlusion that may be the result of reduced metabolism and impaired delivery of oxygen to the tissue. TiVi may provide a promising method for measuring flap viability because it is hand-held, easy to-use, and provides spatial information on venous congestion.

  • 3.
    Droog Tesselaar, Erik
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Flejmer, Anna M.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Dasu, Alexandru
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. The Skandion Clinic, Uppsala, Sweden.
    Changes in skin microcirculation during radiation therapy for breast cancer2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 8, p. 1072-1080Article in journal (Refereed)
    Abstract [en]

    Abstract:

    Background: The majority of breast cancer patients who receive radiation treatment are affected by acute radiation-induced skin changes. The assessment of these changes is usually done by subjective methods, which complicates the comparison between different treatments or patient groups. This study investigates the feasibility of new robust methods for monitoring skin microcirculation to objectively assess and quantify acute skin reactions during radiation treatment.

    Material and methods: Laser Doppler flowmetry, laser speckle contrast imaging, and polarized light spectroscopy imaging were used to measure radiation-induced changes in microvascular perfusion and red blood cell concentration (RBC) in the skin of 15 patients undergoing adjuvant radiation therapy for breast cancer. Measurements were made before treatment, once a week during treatment, and directly after the last fraction.

    Results: In the treated breast, perfusion and RBC concentration were increased after 1–5 fractions (2.66–13.3 Gy) compared to baseline. The largest effects were seen in the areola and the medial area. No changes in perfusion and RBC concentration were seen in the untreated breast. In contrast, Radiation Therapy Oncology Group (RTOG) scores were increased only after 2 weeks of treatment, which demonstrates the potential of the proposed methods for early assessment of skin changes. Also, there was a moderate to good correlation between the perfusion (r = 0.52) and RBC concentration (r = 0.59) and the RTOG score given a week later.

    Conclusion: We conclude that radiation-induced microvascular changes in the skin can be objectively measured using novel camera-based techniques before visual changes in the skin are apparent. Objective measurement of microvascular changes in the skin may be valuable in the comparison of skin reactions between different radiation treatments and possibly in predicting acute skin effects at an earlier stage.

  • 4.
    Elmasry, Moustafa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Egypt.
    Mirdell, Robin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Laser speckle contrast imaging in children with scalds: Its influence on timing of intervention, duration of healing and care, and costs2019In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 45, no 4, p. 798-804Article in journal (Refereed)
    Abstract [sv]

    Background

    Scalds are the most common type of burn injury in children, and the initial evaluation of burn depth is a problem. Early identification of deep dermal areas that need excision and grafting would save unnecessary visits and stays in hospital. Laser speckle contrast imaging (LSCI) shows promise for the evaluation of this type of burn. The aim of this study was to find out whether perfusion measured with LSCI has an influence on the decision for operation, duration of healing and care period, and costs, in children with scalds.

    Methods

    We studied a group of children with scalds whose wounds were evaluated with LSCI on day 3–4 after injury during the period 2012–2015. Regression (adjustment for percentage total body surface area burned (TBSA%), age, and sex) was used to analyse the significance of associations between degree of perfusion and clinical outcome.

    Results

    We studied 33 children with a mean TBSA% of 6.0 (95% CI 4.4–7.7)%. Lower perfusion values were associated with operation (area under the receiver-operating characteristic curve 0.86, 95% CI 0.73–1.00). The perfusion cut-off with 100% specificity for not undergoing an operation was ≥191 PU units (66.7% sensitivity and 72.7% accurately classified). Multivariable analyses showed that perfusion was independently associated with duration of healing and care period.

    Conclusion

    Lower perfusion values, as measured with LSCI, are associated with longer healing time and longer care period. By earlier identification of burns that will be operated, perfusion measurements may further decrease the duration of care of burns in children with scalds.

  • 5.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
    On microvascular blood flow assessment with the new microdialysis urea clearance technique2010Doctoral 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.

    List of papers
    1. Continuous assessment of concentrations of cytokines in experimental injuries of the extremity
    Open this publication in new window or tab >>Continuous assessment of concentrations of cytokines in experimental injuries of the extremity
    Show others...
    2009 (English)In: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, Vol. 2, no 4, p. 354-362Article in journal (Refereed) Published
    Abstract [en]

    Background. Inflammation plays an important part in the healing process. Little is known about the extent local inflammatory trauma response interacts with the central circulation and inflammation produced by central organs. The aim of the present study was to examine whether high cut-off microdialysis catheters offer potential to in real time assess interstitial cytokines variations in conjunction to markers of metabolism distal to a blunt vascular contusion. Methods. In a standardised contusion trauma model, microdialysis catheters (high MW (100kDa)) were inserted in the gracilis muscle distal to the trauma for the local assessment of IL-6, IL-8, TNF-a, total protein and the metabolic mediators (glycerol, puruvate and lactate). The contra lateral uninjured leg served as control of the centrally mediated inflammation propagated to the extremities. Results. The trauma led to a significant and quantitatively large (8-10 fold) increase in inflammatory cytokines (IL6 and 8) as measured both in the injured and control legs. There was only a minor, and not significant increase in concentrations of cytokines in the injured leg compared to the control leg.. There were no signs of ischemia in either leg. Conclusion. The new finding in this study is that both central, and local, inflammatory responses as well as metabolic mediators may be assessed continuously in skeletal muscle tissue distal to a major injury in an animal model. The findings suggest that the large trauma elicits a generalised inflammatory response to trauma rather than propagating a local one distal to the trauma.

    Place, publisher, year, edition, pages
    e-Century Publishing Corporation, 2009
    Keywords
    Blunt trauma; Inflammation; Microcirculation; Microdialysis; Rat
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-57062 (URN)20057979 (PubMedID)
    Available from: 2010-06-11 Created: 2010-06-09 Last updated: 2010-12-28
    2. Urea clearance: a new method to register local changes in blood flow in rat skeletal muscle based on microdialysis
    Open this publication in new window or tab >>Urea clearance: a new method to register local changes in blood flow in rat skeletal muscle based on microdialysis
    Show others...
    2010 (English)In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 30, no 1, p. 57-63Article 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%).

    Keywords
    extracellular fluid; glucose; lactate; metabolism; recovery
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-52899 (URN)10.1111/j.1475-097X.2009.00904.x (DOI)
    Available from: 2010-01-13 Created: 2010-01-12 Last updated: 2017-12-12
    3. Urea Clearance: A New Technique Based on Microdialysis to Assess Liver Blood Flow Studied in a Pig Model of Ischemia/Reperfusion
    Open this publication in new window or tab >>Urea Clearance: A New Technique Based on Microdialysis to Assess Liver Blood Flow Studied in a Pig Model of Ischemia/Reperfusion
    Show others...
    2010 (English)In: EUROPEAN SURGICAL RESEARCH, ISSN 0014-312X, Vol. 45, no 2, p. 105-112Article in journal (Refereed) Published
    Abstract [en]

    Delayed detection of ischemia is one of the most feared postoperative complications. Early detection of impaired blood flow and close monitoring of the organ-specific metabolic status may therefore be critical for the surgical outcome. Urea clearance is a new technique for continuous monitoring of alterations in blood flow and metabolic markers with acceptable temporal characteristics. We compare this new microdialysis technique with the established microdialysis ethanol technique to assess hepatic blood flow. Six pigs were used in a liver ischemia/reperfusion injury model. Microdialysis catheters were placed in liver segment IV and all circulation was stopped for 80 min, followed by reperfusion for 220 min. Urea and ethanol clearance was calculated from the dialysate and correlated with metabolic changes. A laser Doppler probe was used as reference of restoration of blood flow. Both urea and ethanol clearance reproducibly depicted changes in liver blood flow in relation to metabolic changes and laser Doppler measurements. The two techniques highly correlated both overall and during the reperfusion phase (r = 0.8) and the changes were paralleled by altered perfusion as recorded by laser Doppler.

    Place, publisher, year, edition, pages
    S. Karger AG, 2010
    Keywords
    Liver perfusion, Lactate, Ethanol, Metabolism, Recovery
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-62299 (URN)10.1159/000319868 (DOI)000283851400006 ()
    Available from: 2010-11-26 Created: 2010-11-26 Last updated: 2012-03-20
    4. Assessment of blood flow changes in human skin by microdialysis urea clearance
    Open this publication in new window or tab >>Assessment of blood flow changes in human skin by microdialysis urea clearance
    2011 (English)In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 18, no 3, p. 198-204Article, review/survey (Refereed) Published
    Abstract [en]

    Objective: The aim of this study was to evaluate the urea clearance technique for the measurement of drug-induced blood flow changes in human skin, and compare it with two non-invasive techniques: polarization light spectroscopy and laser Doppler perfusion imaging.

    Methods: Fifteen microdialysis catheters were placed intracutaneously on the volar aspect of the forearms of healthy human subjects, and were perfused with nitroglycerine, noradrenaline, and again nitroglycerine, to induce local tissue hyperaemia, hypoperfusion, and hyperaemia, respectively.

    Results: Urea clearance, but not the other techniques, detected the changes in blood flow during all three periods of altered flow.  The last hyperaemic response was detected by all three methods.

    Conclusion: Urea clearance can be used as a relatively simple method to estimate blood flow changes during microdialysis of vasoactive substances, in particular when the tissue is preconditioned in order to enhance the contrast between baseline and the responses to the provocations. Our results support that, in the model described, urea clearance was superior to the optical methods as it detected both the increases and decrease in blood flow, and the returns to baseline between these periods.

    Place, publisher, year, edition, pages
    Wiley, 2011
    Keywords
    microcirculation; laser Doppler perfusion imaging; polarisation light spectroscopy; ischaemia; reperfusion; hypoperfusion; hyperaemia
    National Category
    Physiology
    Identifiers
    urn:nbn:se:liu:diva-63115 (URN)10.1111/j.1549-8719.2010.00077.x (DOI)000288759900004 ()
    Note
    The original title of article IV was "Assessment of blood flow changes in a new pharmacological model of microdosing in human skin by microdialysis urea clearance".Available from: 2010-12-11 Created: 2010-12-11 Last updated: 2018-01-12Bibliographically approved
  • 6.
    Farnebo, Simon
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Gerber Ekblom, A.
    Karolinska Institute, Sweden.
    Hand surgery in Sweden2017In: Journal of Hand Surgery, European Volume, ISSN 1753-1934, E-ISSN 2043-6289, Vol. 42, no 5, p. 537-539Article in journal (Other academic)
    Abstract [en]

    n/a

  • 7.
    Farnebo, Simon
    et al.
    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.
    Karlander, Lars-Erik
    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.
    Steinwall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Sjögren, Florence
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Continuous assessment of concentrations of cytokines in experimental injuries of the extremity2009In: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, Vol. 2, no 4, p. 354-362Article in journal (Refereed)
    Abstract [en]

    Background. Inflammation plays an important part in the healing process. Little is known about the extent local inflammatory trauma response interacts with the central circulation and inflammation produced by central organs. The aim of the present study was to examine whether high cut-off microdialysis catheters offer potential to in real time assess interstitial cytokines variations in conjunction to markers of metabolism distal to a blunt vascular contusion. Methods. In a standardised contusion trauma model, microdialysis catheters (high MW (100kDa)) were inserted in the gracilis muscle distal to the trauma for the local assessment of IL-6, IL-8, TNF-a, total protein and the metabolic mediators (glycerol, puruvate and lactate). The contra lateral uninjured leg served as control of the centrally mediated inflammation propagated to the extremities. Results. The trauma led to a significant and quantitatively large (8-10 fold) increase in inflammatory cytokines (IL6 and 8) as measured both in the injured and control legs. There was only a minor, and not significant increase in concentrations of cytokines in the injured leg compared to the control leg.. There were no signs of ischemia in either leg. Conclusion. The new finding in this study is that both central, and local, inflammatory responses as well as metabolic mediators may be assessed continuously in skeletal muscle tissue distal to a major injury in an animal model. The findings suggest that the large trauma elicits a generalised inflammatory response to trauma rather than propagating a local one distal to the trauma.

  • 8.
    Farnebo, Simon
    et al.
    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.
    Samuelsson, A.
    Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Henriksson, J.
    Karolinska Inst, Dept Physiol and Pharmacol, Stockholm, Sweden.
    Karlander, Lars-Erik
    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.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Urea clearance: a new method to register local changes in blood flow in rat skeletal muscle based on microdialysis2010In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 30, no 1, p. 57-63Article in journal (Refereed)
    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%).

  • 9.
    Farnebo, Simon
    et al.
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Thorfinn, Johan
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Hyperaemic changes in forearm skin perfusion and RBC concentration after increasing occlusion times2010In: MICROVASCULAR RESEARCH, ISSN 0026-2862, Vol. 80, no 3, p. 412-416Article in journal (Refereed)
    Abstract [en]

    Tissue occlusion and the hyperaemic response upon reperfusion can be used as a tool to assess microvascular function in various vascular diseases. Currently, laser Doppler flowmetry (LDF) is applied most often to measure hyperaemic responses. In this study, we have applied tissue viability imaging (TiVi) and LDF to measure the change in red blood cell concentration and perfusion in the skin after occlusions of the forearm with increasing duration. We have found that there is a strong correlation between the changes in perfusion and red blood cell (RBC) concentration during post-occlusive hyperaemia (perfusion: r = 0.80; RBC concentration: r = 0.94). This correlation increases with longer occlusion durations (1, 5 and 10 min). Furthermore, for both perfusion and RBC concentration, the maximum responses (perfusion: r(2) = 0.59; RBC concentration: r(2) = 0.78) and the recovery times (perfusion: r(2) = 0.62; RBC concentration: r(2) = 0.91) increase linearly with the duration of the occlusion. Maximum responses and recovery times were more reproducible for RBC concentration (as measured with TiVi) than for perfusion (as measured with LDF). These results show that perfusion and RBC concentration are related during post-occlusive hyperaemia and that TiVi can be used as a tool in the assessment of hyperaemic responses that has advantages in terms of reproducibility, sensitivity and ease of use.

  • 10.
    Farnebo, Simon
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Winbladh, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Zettersten, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Gullstrand, P
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Urea Clearance: A New Technique Based on Microdialysis to Assess Liver Blood Flow Studied in a Pig Model of Ischemia/Reperfusion2010In: EUROPEAN SURGICAL RESEARCH, ISSN 0014-312X, Vol. 45, no 2, p. 105-112Article in journal (Refereed)
    Abstract [en]

    Delayed detection of ischemia is one of the most feared postoperative complications. Early detection of impaired blood flow and close monitoring of the organ-specific metabolic status may therefore be critical for the surgical outcome. Urea clearance is a new technique for continuous monitoring of alterations in blood flow and metabolic markers with acceptable temporal characteristics. We compare this new microdialysis technique with the established microdialysis ethanol technique to assess hepatic blood flow. Six pigs were used in a liver ischemia/reperfusion injury model. Microdialysis catheters were placed in liver segment IV and all circulation was stopped for 80 min, followed by reperfusion for 220 min. Urea and ethanol clearance was calculated from the dialysate and correlated with metabolic changes. A laser Doppler probe was used as reference of restoration of blood flow. Both urea and ethanol clearance reproducibly depicted changes in liver blood flow in relation to metabolic changes and laser Doppler measurements. The two techniques highly correlated both overall and during the reperfusion phase (r = 0.8) and the changes were paralleled by altered perfusion as recorded by laser Doppler.

  • 11.
    Farnebo, Simon
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
    Zettersten, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Assessment of blood flow changes in human skin by microdialysis urea clearance2011In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 18, no 3, p. 198-204Article, review/survey (Refereed)
    Abstract [en]

    Objective: The aim of this study was to evaluate the urea clearance technique for the measurement of drug-induced blood flow changes in human skin, and compare it with two non-invasive techniques: polarization light spectroscopy and laser Doppler perfusion imaging.

    Methods: Fifteen microdialysis catheters were placed intracutaneously on the volar aspect of the forearms of healthy human subjects, and were perfused with nitroglycerine, noradrenaline, and again nitroglycerine, to induce local tissue hyperaemia, hypoperfusion, and hyperaemia, respectively.

    Results: Urea clearance, but not the other techniques, detected the changes in blood flow during all three periods of altered flow.  The last hyperaemic response was detected by all three methods.

    Conclusion: Urea clearance can be used as a relatively simple method to estimate blood flow changes during microdialysis of vasoactive substances, in particular when the tissue is preconditioned in order to enhance the contrast between baseline and the responses to the provocations. Our results support that, in the model described, urea clearance was superior to the optical methods as it detected both the increases and decrease in blood flow, and the returns to baseline between these periods.

  • 12.
    Iredahl, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Löfberg, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Linköping University, Faculty of Medicine and Health Sciences.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Non-Invasive Measurement of Skin Microvascular Response during Pharmacological and Physiological Provocations2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 8, p. 1-15, article id e0133760Article in journal (Refereed)
    Abstract [en]

    Introduction Microvascular changes in the skin due to pharmacological and physiological provocations can be used as a marker for vascular function. While laser Doppler flowmetry (LDF) has been used extensively for measurement of skin microvascular responses, Laser Speckle Contrast Imaging (LSCI) and Tissue Viability Imaging (TiVi) are novel imaging techniques. TiVi measures red blood cell concentration, while LDF and LSCI measure perfusion. Therefore, the aim of this study was to compare responses to provocations in the skin using these different techniques. Method Changes in skin microcirculation were measured in healthy subjects during (1) iontophoresis of sodium nitroprusside (SNP) and noradrenaline (NA), (2) local heating and (3) post-occlusive reactive hyperemia (PORH) using LDF, LSCI and TiVi. Results Iontophoresis of SNP increased perfusion (LSCI: baseline 40.9 +/- 6.2 PU; 10-min 100 +/- 25 PU; pless than0.001) and RBC concentration (TiVi: baseline 119 +/- 18; 10-min 150 +/- 41 AU; p = 0.011). No change in perfusion (LSCI) was observed after iontophoresis of NA (baseline 38.0 +/- 4.4 PU; 10-min 38.9 +/- 5.0 PU; p = 0.64), while RBC concentration decreased (TiVi: baseline 59.6 +/- 11.8 AU; 10-min 54.4 +/- 13.3 AU; p = 0.021). Local heating increased perfusion (LDF: baseline 8.8 +/- 3.6 PU; max 112 +/- 55 PU; pless than0.001, LSCI: baseline 50.8 +/- 8.0 PU; max 151 +/- 22 PU; pless than0.001) and RBC concentration (TiVi: baseline 49.2 +/- 32.9 AU; max 99.3 +/- 28.3 AU; pless than0.001). After 5 minutes of forearm occlusion with prior exsanguination, a decrease was seen in perfusion (LDF: p = 0.027; LSCI: pless than0.001) and in RBC concentration (p = 0.045). Only LSCI showed a significant decrease in perfusion after 5 minutes of occlusion without prior exsanguination (pless than0.001). Coefficients of variation were lower for LSCI and TiVi compared to LDF for most responses. Conclusion LSCI is more sensitive than TiVi for measuring microvascular changes during SNP-induced vasodilatation and forearm occlusion. TiVi is more sensitive to noradrenaline-induced vasoconstriction. LSCI and TiVi show lower inter-subject variability than LDF. These findings are important to consider when choosing measurement techniques for studying skin microvascular responses.

  • 13.
    Iredahl, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sadda, Veeranjaneyulu
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Ward, Liam
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Hackethal, Johannes
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. University of Appl Science, Austria.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Modeling Perfusion Dynamics in the Skin During Iontophoresis of Vasoactive Drugs Using Single-Pulse and Multiple-Pulse Protocols2015In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 22, no 6, p. 446-453Article in journal (Refereed)
    Abstract [en]

    Objective: After iontophoresis of vasoactive drugs into the skin, a decrease in perfusion is commonly observed. We delivered vasoactive drugs by iontophoresis using different delivery protocols to study how these affect this decrease in perfusion as measured using LDF. Methods: We measured skin perfusion during iontophoresis of (ACh), MCh, andNAusing a single pulse or separate pulses at different skin sites, and during repeated delivery of ACh at the same site. Results: Perfusion half-life was 6.1 (5.6-6.6) minutes for ACh and 41 (29-69) minutes for MCh (p less than 0.001). The maximum response with multiple pulses of ACh iontophoresis was lower than with a single pulse, 30 (22-37) PU vs. 43 (36-50) PU, p less than 0.001. Vasoconstriction to NA was more rapid with a single pulse than with multiple pulses. The perfusion half-life of ACh decreased with repeated delivery of ACh at the same site-first 16 (14-18), second 5.9 (5.1-6-9) and third 3.2 (2.9-3.5) minutes, p less than 0.001. Conclusions: The drug delivery protocol affects microvascular responses to iontophoresis, possibly as a result of differences in the dynamics of local drug concentrations. Perfusion half-life may be used as a measure to quantify the rate of perfusion recovery after iontophoresis of vasoactive drugs.

  • 14.
    Iredahl, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Sarker, Saikat
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    The Microvascular Response to Transdermal Iontophoresis of Insulin is Mediated by Nitric Oxide2013In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 20, no 8, p. 717-723Article in journal (Refereed)
    Abstract [en]

    ObjectiveInsulin has direct effects on blood flow in various tissues, most likely due to endothelial NO production. We investigated whether insulin delivered to the skin by iontophoresis increases microvascular perfusion and whether this effect is partly or completely mediated by the release of NO. MethodsIn healthy subjects, regular insulin and monomeric insulin were delivered to the skin by cathodal iontophoresis. The skin was pretreated either with L-NAME or control solution (PBS) using anodal iontophoresis. Microvascular responses were measured using laser Doppler flowmetry. ResultsA dose-dependent increase in perfusion was observed during iontophoresis of regular and monomeric insulin. The maximum perfusion was significantly elevated compared with control after PBS (regular insulin 53.6 (12.7-95.6) PU vs. 4.2 (3.4-4.8) PU, p = 0.002; monomeric insulin 32.6 (8.9-92.6) PU vs. 5.9 (3.4-56.0) PU, p = 0.03). The microvascular response to insulin was abolished after L-NAME (regular insulin: 25.6 (11.6-54.4) PU vs. control: 4.7 (2.9-11.5) PU, p = 0.15; monomeric insulin 10.9 (5.4-56.8) PU vs. control: 4.7 (2.9-11.5) PU, p = 0.22). ConclusionsThe main finding is that iontophoresis of insulin induces a dose-dependent vasodilation in the skin, which could be suppressed after pretreatment with a NO synthase inhibitor. This suggests that vasodilation in the skin after iontophoresis of insulin is mediated by the NO pathway.

  • 15.
    Mirdell, Robin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Iredahl, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Linköping University, Faculty of Medicine and Health Sciences.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Microvascular blood flow in scalds in children and its relation to duration of wound healing: A study using laser speckle contrast imaging2016In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 42, no 3, p. 648-654Article in journal (Refereed)
    Abstract [en]

    Background: Microvascular perfusion changes in scalds in children during the first weeks after injury is related to the outcome of healing, and measurements of perfusion, based on laser Doppler imaging, have been used successfully to predict the need for excision and grafting. However, the day-to-day changes in perfusion during the first weeks after injury have not to our knowledge been studied in detail. The aim of this study, based on a conservative treatment model where excision and grafting decisions were delayed to day 14 after injury, was to measure changes in perfusion in scalds using laser speckle contrast imaging (LSCI) during the first three weeks after injury. Methods: We measured perfusion with LSCI in 34 patients at regular intervals between 6 h after injury until complete reepithelialization or surgery. Duration of healing was defined as the time to complete reepithelialization. Results: Less perfusion, between 6 and 96 h after injury, was associated with longer duration of healing with the strongest association occurring between 72 and 96 h. Burns that healed within 14 days had relatively high initial perfusion, followed by a peak and subsequent slow decrease. Both the maximum perfusion and the time-to-peak were dependent on the severity of the burn. Burns that needed excision and grafting had less initial perfusion and a gradual reduction over time. Conclusion: The perfusion in scalds in children shows characteristic patterns during the first weeks after injury depending on the duration of wound healing, the greatest difference between wounds of different severity being on the 4th day. Perfusion should therefore preferably be measured on the fourth day if it is to be used in the assessment of burn depth. (c) 2015 Elsevier Ltd and ISBI. All rights reserved.

  • 16.
    Samuelsson, Anders
    et al.
    Linköping University, Department of Medicine and Health Sciences, Anesthesiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Magnusson, Beatrice
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Implications for critical care of a new in vivo human vascular microdosing technique for giving noradrenaline and nitroglycerine by microdialysisManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: Skin has a large dynamic capacity for alterations in blood flow, and is therefore often used for recruitment of blood during states of hypoperfusion. Little is known, however, about the metabolic consequences seen in skin secondary to hyporperfusion, particularly when the effects of vasoactive drugs are involved. The aims of this study were: to develop an in vivo, human microdosing model based on microdialysis in skin; and to investigate the effects on blood flow and metabolism of administering noradrenaline and nitroglycerine locally.

    Method: Nine healthy volunteers each had two or three microdialysis catheters placed intradermally in the volar surface of the lower arm. After a stabilisation period, the catheters were perfused with buffers containing noradrenaline 0.5 or 5 μg/ml for 60 minutes, and after a second period of equilibrium of 60 minutes, all catheters were perfused with buffer containing nitroglycerine (0.5mg/ml). Changes in the blood flow in the skin were measured by laser Doppler imaging urea and ethanol clearance. Simultaneous changes in tissue glucose, lactate, and pyruvate concentrations were recorded.

    Results: Perfusing skin with noradrenaline and nitroglycerine induced appreciable changes in all variables studied, depending on time and dose. The changes in glucose and lactate concentrations correlated with the change in blood flow assessed by either laser Doppler imaging or urea clearance. The changes in glucose and lactate that were induced by vasoconstriction (noradrenaline) continued until vasodilatation was induced by nitroglycerine.

    Conclusion: Noradrenaline given by microdialysis in healthy volunteers induced reproducible and dose-dependent hypoperfusion and ischaemia with simultaneous metabolic consequences. Among these, we particularly note that: tissue glucose concentrations responded rapidly to hypoperfusion but remained considerably higher than zero, which suggests an energy-dependent deficiency in cellular uptake; and vasoconstriction remained after cessation of the noradrenaline perfusion, implicating vasospasm and a lack of autoregulatory (recovery) capacity in skin. These findings are particularly interesting from the critical care perspective, where noradrenaline is used extensively for circulatory support. The metabolic consequences may be underestimated and our results suggest that further investigations are warranted.

  • 17.
    Samuelsson, Anders
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Magnusson, Beatrice
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Zettersten, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Implications for burn shock resuscitation of a new in vivo human vascular microdosing technique (microdialysis) for dermal administration of noradrenaline2012In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 38, no 7, p. 975-983Article in journal (Refereed)
    Abstract [en]

    Introduction: Skin has a large dynamic capacity for alterations in blood flow, and is therefore often used for recruitment of blood during states of hypoperfusion such as during burn shock resuscitation. However, little is known about the blood flow and metabolic consequences seen in the dermis secondary to the use vasoactive drugs (i.e. noradrenaline) for circulatory support. The aims of this study were therefore: to develop an in vivo, human microdosing model based on dermal microdialysis; and in this model to investigate effects on blood flow and metabolism by local application of noradrenaline and nitroglycerin by the microdialysis system simulating drug induced circulatory support. less thanbrgreater than less thanbrgreater thanMethod: Nine healthy volunteers had microdialysis catheters placed intradermally in the volar surface of the lower arm. The catheters were perfused with noradrenaline 3 or 30 mmol/L and after an equilibrium period all catheters were perfused with nitroglycerine (2.2 mmol/L). Dermal blood flow was measured by the urea clearance technique and by laser Doppler imaging. Simultaneously changes in dermal glucose, lactate, and pyruvate concentrations were recorded. less thanbrgreater than less thanbrgreater thanResults: Noradrenaline and nitroglycerine delivered to the dermis by the microdialysis probes induced large time- and dose-dependent changes in all variables. We particularly noted that tissue glucose concentrations responded rapidly to hypoperfusion but remained higher than zero. Furthermore, vasoconstriction remained after the noradrenaline administration implicating vasospasm and an attenuated dermal autoregulatory capacity. The changes in glucose and lactate by vasoconstriction (noradrenaline) remained until vasodilatation was actively induced by nitroglycerine. less thanbrgreater than less thanbrgreater thanConclusion: These findings, i.e., compromised dermal blood flow and metabolism are particularly interesting from the burn shock resuscitation perspective where noradrenaline is commonly used for circulatory support. The importance and clinical value of the results obtained in this in vivo dermal model in healthy volunteers needs to be further explored in burn-injured patients.

  • 18.
    Tesselaar, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences.
    Bergkvist, Max
    Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Polarized Light Spectroscopy for Measurement of the Microvascular Response to Local Heating at Multiple Skin Sites2012In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 19, no 8, p. 705-713Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate whether TiVi, a technique based on polarized light, could measure the change in RBC concentration during local heating in healthy volunteers. Methods: Using a custom-made transparent heater, forearm skin was heated to 42 degrees C for 40 minutes while the change in RBC concentration was measured with TiVi. The perfusion response during local heating was measured at the same time with Laser Doppler flowmetry. Results: Mean RBC concentration increased (91 +/- 34 vs. 51 +/- 34 A.U. at baseline, p less than 0.001). The spatial heterogeneity of the RBC concentration in the measured skin areas was 26 +/- 6.4% at baseline, and 23 +/- 4.6% after 40 minutes of heating. The mean RBC concentrations in two skin sites were highly correlated (0.98 at baseline and 0.96 after 40 minutes of heating). The change in RBC concentration was less than the change in perfusion, measured with LDF. Unlike with LDF, a neurally mediated peak was not observed with TiVi in most of the test subjects. Conclusions: TiVi is a valuable technique for measuring the microvascular response to local heating in the skin, and offers a high reproducibility for simultaneous measurements at different skin sites, provided carefully controlled experiments are ensured.

  • 19.
    Tesselaar, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Measurement of red blood cell concentration in skin during vascular provocations using polarization light spectroscopy imaging in JOURNAL OF VASCULAR RESEARCH, vol 48, issue , pp 164-1642011In: JOURNAL OF VASCULAR RESEARCH, Karger , 2011, Vol. 48, p. 164-164Conference paper (Refereed)
    Abstract [en]

    n/a

  • 20.
    Tesselaar, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Nezirevic Dernroth, Dzeneta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Acute effects of coffee on skin blood flow and microvascular function2017In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 114, p. 58-64Article in journal (Refereed)
    Abstract [en]

    Objective

    Studies on the acute effects of coffee on the microcirculation have shown contradicting results. This study aimed to investigate if intake of caffeine-containing coffee changes blood flow and microvascular reactivity in the skin.

    Methods

    We measured acute changes in cutaneous vascular conductance (CVC) in the forearm and the tip of the finger, the microvascular response to transdermaliontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) and post-occlusive reactive hyperemia (PORH) in the skin, after intake of caffeinated or decaffeinated coffee.

    Results

    Vasodilatation during iontophoresis of ACh was significantly stronger after intake of caffeinated coffee compared to after intake of decaffeinated coffee (1.26 ± 0.20 PU/mm Hg vs. 1.13 ± 0.38 PU/mm Hg, P < 0.001). Forearm CVC before and after PORH were not affected by caffeinated and decaffeinated coffee. After intake of caffeinated coffee, a more pronounced decrease in CVC in the fingertip was observed compared to after intake of decaffeinated coffee (− 1.36 PU/mm Hg vs. − 0.52 PU/mm Hg, P = 0.002).

    Conclusions

    Caffeine, as ingested by drinking caffeinated coffee acutely improves endothelium-dependent microvascular responses in the forearm skin, while endothelium-independent responses to PORH and SNP iontophoresis are not affected. Blood flow in the fingertip decreases markedly during the first hour after drinking caffeinated coffee compared to decaffeinated coffee.

  • 21.
    Zötterman, Johan
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Bergkvist, Max
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Iredahl, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Linköping University, Faculty of Medicine and Health Sciences.
    Monitoring of partial and full venous outflow obstruction in a porcine flap model using laser speckle contrast imaging2016In: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1532-1959, Vol. 69, no 7, p. 936-943Article in journal (Refereed)
    Abstract [en]

    Background: In microsurgery, there is a demand for more reliable methods of postoperative monitoring of free flaps, especially with regard to tissue-threatening obstructions of the feeding arteries and draining veins. In this study, we evaluated laser speckle contrast imaging (LSCI) and laser Doppler flowmetry (LDF) to assess their possibilities to detect partial and full venous outflow obstruction, as well as full arterial occlusion, in a porcine flap model. Methods: Cranial gluteal artery perforator flaps (CGAPs) were raised, and arterial and venous blood flow to and from the flaps was monitored using ultrasonic flow probes. The venous flow was altered with an inflatable cuff to simulate partial and full (50% and 100%) venous obstruction, and arterial flow was completely obstructed using clamps. The flap microcirculation was monitored using LSCI and LDF. Results: Both LDF and the LSCI detected significant changes in flap perfusion. After partial (50%) venous occlusion, perfusion decreased from baseline, LSCI: 63.5 +/- 12.9 PU (p = 0.01), LDF 31.3 +/- 15.7 (p = 0.64). After 100% venous occlusion, a further decrease in perfusion was observed: LSCI 54.6 +/- 14.2 PU (p amp;lt; 0.001) and LDF 16.7 +/- 12.8 PU (p amp;lt; 0.001). After release of the venous cuff, LSCI detected a return of the perfusion to a level slightly, but not significantly, below the baseline level 70.1 +/- 11.5 PU (p=0.39), while the LDF signal returned to a level not significant from the baseline 36.1 +/- 17.9 PU (p amp;gt; 0.99). Perfusion during 100% arterial occlusion decreased significantly as measured with both methods, LSCI: 48.3 +/- 7.7 (PU, pamp;lt;0.001) and LDF: 8.5 +/- 4.0 PU (pamp;lt;0.001). During 50% and 100% venous occlusion, LSCI showed a 20% and 26% inter-subject variability (CV%), respectively, compared to 50% and 77% for LDF. Conclusions: LSCI offers sensitive and reproducible measurements of flap microcirculation and seems more reliable in detecting decreases in blood perfusion caused by venous obstruction. It also allows for perfusion measurements in a relatively large area of flap tissue. This may be useful in identifying areas of the flap with compromised microcirculation during and after surgery. (C) 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  • 22.
    Zötterman, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Mirdell, Robin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Horsten, Sandra
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Methodological concerns with laser speckle contrast imaging in clinical evaluation of microcirculation2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174703Article in journal (Refereed)
    Abstract [en]

    Background Laser Speckle Contrast Imaging (LSCI) is a non-invasive and fast technique for measuring microvascular blood flow that recently has found clinical use for burn assessment and evaluation of flaps. Tissue motion caused by for example breathing or patient movements may however affect the measurements in these clinical applications, as may distance between the camera and the skin and tissue curvature. Therefore, the aims of this study were to investigate the effect of frame rate, number of frames/image, movement of the tissue, measuring distance and tissue curvature on the measured perfusion. Methods Methyl nicotinate-induced vasodilation in the forearm skin was measured using LSCI during controlled motion at different speeds, using different combinations of frame rate and number of frames/image, and at varying camera angles and distances. Experiments were made on healthy volunteers and on a cloth soaked in a colloidal suspension of polystyrene microspheres. Results Measured perfusion increased with tissue motion speed. The relation was independent of the absolute perfusion in the skin and of frame rate and number of frames/image. The measured perfusion decreased with increasing angles (16% at 60, p = 0.01). Measured perfusion did not vary significantly between measurement distances from 15 to 40 cm (p = 0.77, %CV 0.9%). Conclusion Tissue motion increases and measurement angles beyond 45 decrease the measured perfusion in LSCI. These findings have to be taken into account when LSCI is used to assess moving or curved tissue surfaces, which is common in clinical applications.

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