Publications by authors named "Simon Farnebo"

52 Publications

Stretchable gold nanowire-based cuff electrodes for low-voltage peripheral nerve stimulation.

J Neural Eng 2021 05 25;18(4). Epub 2021 May 25.

Laboratory of Organic Electronics, Department of Science and Technology, Linköping University, 601 74 Norrköping, Sweden.

. Electrical stimulation of the peripheral nervous system (PNS) can treat various diseases and disorders, including the healing process after nerve injury. A major challenge when designing electrodes for PNS stimulation is the mechanical mismatch between the nerve and the device, which can lead to non-conformal contact, tissue damage and inefficient stimulation due to current leakage. Soft and stretchable cuff electrodes promise to tackle these challenges but often have limited performance and rely on unconventional materials. The aim of this study is to develop a high performance soft and stretchable cuff electrode based on inert materials for low-voltage nerve stimulation.. We developed 50m thick stretchable cuff electrodes based on silicone rubber, gold nanowire conductors and platinum coated nanowire electrodes. The electrode performance was characterized under strain cycling to assess the durability of the electrodes. The stimulation capability of the cuff electrodes was evaluated in ansciatic nerve rat model by measuring the electromyography response to various stimulation pulses.. The stretchable cuff electrodes showed excellent stability for 50% strain cycling and one million stimulation pulses. Saturated homogeneous stimulation of the sciatic nerve was achieved at only 200 mV due to the excellent conformability of the electrodes, the low conductor resistance (0.3 Ohm sq), and the low electrode impedance.. The developed stretchable cuff electrode combines favourable mechanical properties and good electrode performance with inert and stable materials, making it ideal for low power supply applications within bioelectronic medicine.
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http://dx.doi.org/10.1088/1741-2552/abfebbDOI Listing
May 2021

Validation of a smartphone application and wearable sensor for measurements of wrist motions.

J Hand Surg Eur Vol 2021 Apr 19:17531934211004454. Epub 2021 Apr 19.

Department of Hand Surgery, Plastic Surgery, and Burns, Linköping University, Linköping, Sweden.

We developed a smartphone application to measure wrist motion using the mobile device's built-in motion sensors or connecting it via Bluetooth to a wearable sensor. Measurement of wrist motion with this method was assessed in 33 participants on two occasions and compared with those obtained with a standard goniometer. The test-retest reproducibility in healthy individuals ranged from good to excellent (intraclass correlation (ICC) 0.76-0.95) for all motions, both with and without the wearable sensor. These results improved to excellent (ICC 0.90-0.96) on the second test day, suggesting a learning effect. The day-to-day reproducibility was overall better with the wearable sensor (mean ICC 0.87) compared with the application without using sensor or goniometer (mean ICC 0.82 and 0.60, respectively). This study suggests that smartphone-based measurements of wrist range of motion are feasible and highly accurate, making it a powerful tool for outcome studies after wrist surgery.
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http://dx.doi.org/10.1177/17531934211004454DOI Listing
April 2021

Sampling insulin in different tissue compartments using microdialysis: methodological aspects.

Sci Rep 2020 12 15;10(1):21948. Epub 2020 Dec 15.

Department of Hand Surgery, Plastic Surgery and Burns, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Sampling the concentration of insulin in human skin using microdialysis is challenging because of low intracutaneous concentrations and low recovery, presumably due to adsorption of insulin to the microdialysis system. In this study, we aimed to (1) measure how the concentration of insulin varies in three different tissue compartments (intracutaneous, subcutaneous and intravenous) and (2) to study how much insulin is adsorbed to the microdialysis catheter membranes and tubing during a typical microdialysis experiment, both in vivo and in vitro. We hypothesized that (1) the concentration of insulin decreases from the intravenous compartment to the intracutaneous and subcutaneous tissue, and that (2) adsorption of insulin to the microdialysis membrane and tubing impairs the recovery of insulin from the tissue. In this experimental study, microdialysis catheters were inserted intracutaneously, subcutaneously and intravenously in 11 healthy subjects. Systemic endogenous hyperinsulinemia was induced by intake of an oral glucose load. Insulin concentration was measured in the dialysate and in the extracted samples from the catheter membrane and tubings. In vitro microdialysis was performed to investigate the temporal resolution of the adsorption. After an oral glucose load insulin concentration increased intravenously, but not in the intracutaneous or subcutaneous compartments, while glucose, lactate and pyruvate concentrations increased in all compartments. The adsorption of insulin to the microdialysis membrane in vivo was highest in the intravenous compartment (p = 0.01), compared to the intracutaneous and subcutaneous compartments. In vitro, the adsorption to the microdialysis membrane was highest one hour after sampling, then the concentration gradually decreased after three and five hours of sampling. The concentration of insulin in peripheral tissues is low, probably due to decreasing tissue vascularity. Adsorption of insulin to the microdialysis membrane is modest but time-dependent. This finding highlights the importance of a stabilization time for the microdialysis system before sampling tissue analytes.
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http://dx.doi.org/10.1038/s41598-020-78728-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738523PMC
December 2020

Differentially Expressed Proteins in Intra Synovial Compared to Extra Synovial Flexor Tendon Grafts in a Rabbit Tendon Transplantation Model.

Biomedicines 2020 Oct 12;8(10). Epub 2020 Oct 12.

Pain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linköping University, SE 581 83 Linköping, Sweden.

 Uncomplicated healing of grafts for tendon reconstruction remains an unsolved problem in hand surgery. Results are limited by adhesion formation and decreased strength properties, especially within the tight fibro-osseous sheath of the digits. This is especially problematic when an extra synovial tendon graft is used to replace an intra synovial flexor tendon. Compositional differences are likely to play an important role in these processes. The aim of this study was, therefore, to compare protein expression in pair-matched intra synovial tendon grafts with extra synovial tendon grafts, using a rabbit tendon injury model. We hypothesized that there would be significant differences in proteins critical for response to tensile loading and adhesion formation between the two groups. Using mass spectrometry and multivariate statistical data analysis, we found tissue-specific differences in 22 proteins, where 7 explained 93% (R2) of the variation, with a prediction of 81% (Q2). Among the highest discriminating proteins were Galectin, Histone H2A, and Periostin, which were found in a substantially larger amount in the extra synovial tendons compared to the intra synovial tendons. These findings may contribute to improved understanding of the differences in outcome seen after tendon reconstruction using tendon grafts with intra synovial and extra synovial grafts.
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http://dx.doi.org/10.3390/biomedicines8100408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650534PMC
October 2020

Objective assessment of skin microcirculation using a smartphone camera.

Skin Res Technol 2021 Mar 15;27(2):138-144. Epub 2020 Jul 15.

Department of Hand and Plastic Surgery and Burns and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Background: Existing techniques for assessment of microcirculation are limited by their large size and high costs and are often not so easy to use. Advances in mobile technology have enabled great improvements in smartphone sensor technology. In this study, we used SkinSight, an app for iPhone and iPad, to measure changes in skin microcirculation during physiological provocations. The system estimates changes in the concentration of hemoglobin in the skin by analyzing the reflected light emitted from the built-in light-emitting diode and detected by the camera of the smartphone.

Methods: A relative hemoglobin (Hb) index was measured during a 5-min arterial occlusion, post-occlusive reactive hyperemia, and a 5-min venous occlusion in 10 healthy subjects, on two separate days. The index was calculated in an area of the skin from the color information in the images acquired by the phone camera. Polarized light spectroscopy imaging was used to measure changes in red blood cell concentration for comparison.

Results: During arterial occlusion, relative Hb index was unchanged compared to baseline (P = .40). After release of the cuff, a sudden 60%-75% increase in Hb index was observed (P < .001) followed by a gradual return to baseline. During venous occlusion, Hb index increased by 80% (P < .001) followed by a gradual decrease to baseline after reperfusion. Day-to-day reproducibility of the relative Hb index was excellent (ICC: 0.92, r = 0.94), although relative Hb index was consistently higher during the second day, possibly as a result of changed lighting conditions or calibration issues.

Conclusion: Microvascular responses to physiological provocations in the skin can be accurately and reproducibly measured using a smartphone application. Although the system offers a handheld, easy to use and flexible technique for skin microvascular assessment, the effects of lighting on the measured values and need for calibration need to be further investigated.
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http://dx.doi.org/10.1111/srt.12919DOI Listing
March 2021

Striving for scientific excellence in hand surgery.

J Hand Surg Eur Vol 2020 Oct 29;45(8):890-891. Epub 2020 May 29.

Department of Plastic Surgery, Hand Surgery, and Burns, Linköping University, Linköping, Sweden.

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http://dx.doi.org/10.1177/1753193420927581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542995PMC
October 2020

Artelon spacer for post-traumatic distal radioulnar joint post-traumatic osteoarthritis: 10 years follow-up in five patients.

J Hand Surg Eur Vol 2020 Oct 12;45(8):879. Epub 2020 May 12.

Department of Plastic Surgery, Hand Surgery, and Burns, Linköping University, Linköping, Sweden.

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http://dx.doi.org/10.1177/1753193420924261DOI Listing
October 2020

Using blood flow pulsatility to improve the accuracy of laser speckle contrast imaging in the assessment of burns.

Burns 2020 09 13;46(6):1398-1406. Epub 2020 Apr 13.

Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Radiation Physics, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.

Objectives: Measurement of perfusion is an established method to evaluate the depth of burns. However, high accuracy is only achievable >48 h after injury. The aim of the study was to investigate if measurement of blood flow pulsatility, combined with perfusion measurement, can improve early assessment of burn depth using laser speckle contrast imaging (LSCI).

Methods: Perfusion and pulsatility were measured with LSCI in 187 regions of interest in 32 patients, between 0 and 5 days after injury. The reproducibility of pulsatility was tested for recording durations between 1 and 12 s. The most reproducible duration was chosen, and receiver operator characteristics were created to find suitable pulsatility cut-offs to predict surgical need.

Results: A measurement duration of 8 s resulted in a good reproducibility of the pulsatility (%CV: 15.9%). Longer measurement durations resulted in a small improvement of the accuracy of the assessment. A pulsatility of <1.45 (Perfusion Units) on day 0-2 after injury predicted surgical need with a sensitivity of 100% (95% CI: 83.2-100%), specificity of 100% (95% CI: 95.2-100%), a positive predictive value of 100%, and a negative predictive value of 100%. Pulsatility was not significantly different when comparing measurements done day 0-2 to day 3-5. Perfusion was however significantly higher day 3-5 compared to day 0-2 for wounds healing within 3 weeks.

Conclusion: Measurement of pulsatility improves the accuracy of the assessment of burns with LSCI and makes it possible to predict the need for surgery during day 0-2 after injury with a high accuracy.
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http://dx.doi.org/10.1016/j.burns.2020.03.008DOI Listing
September 2020

Assessment of oxygenation with polarized light spectroscopy enables new means for detecting vascular events in the skin.

Microvasc Res 2020 07 16;130:104000. Epub 2020 Mar 16.

Department of Hand Surgery, Plastic Surgery and Burns, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Introduction: Impaired oxygenation in the skin may occur in disease states and after reconstructive surgery. We used tissue viability imaging (TiVi) to measure changes in oxygenation and deoxygenation of haemoglobin in an in vitro model and in the dermal microcirculation of healthy individuals.

Materials And Methods: Oxygenation was measured in human whole blood with different levels of oxygenation. In healthy subjects, changes in red blood cell concentration (C), oxygenation (ΔC) and deoxygenation (ΔC) of haemoglobin were measured during and after arterial and venous occlusion using TiVi and were compared with measurements from the enhanced perfusion and oxygen saturation system (EPOS).

Results: During arterial occlusion, C remained unchanged while ΔC decreased to -44.2 (10.4) AU (p = 0.04), as compared to baseline. After release, C increased to 39.2 (18.8) AU (p < 0.001), ΔC increased to 38.5. During venous occlusion, C increased to 28.9 (11.2) AU (p < 0.001), ΔC decreased to -52.2 (46.1) AU (p < 0.001) compared to baseline after 5 min of venous occlusion. There was a significant correlation between the TiVi Oxygen Mapper and EPOS, for arterial (r = 0.92, p < 0.001) and venous occlusion (r = 0.87, p < 0.001), respectively.

Conclusion: This study shows that TiVi can measure trends in oxygenation and deoxygenation of haemoglobin during arterial and venous stasis in healthy individuals.
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http://dx.doi.org/10.1016/j.mvr.2020.104000DOI Listing
July 2020

Intraoperative Laser Speckle Contrast Imaging in DIEP Breast Reconstruction: A Prospective Case Series Study.

Plast Reconstr Surg Glob Open 2020 Jan 20;8(1):e2529. Epub 2020 Jan 20.

Department of Medical Radiation Physics, Linköping University, Linköping, Sweden.

Laser speckle contrast imaging (LSCI) is a laser-based perfusion imaging technique that recently has been shown to predict ischemic necrosis in an experimental flap model and predicting healing time of scald burns. The aims were to investigate perfusion in relation to the selected perforator during deep inferior epigastric artery perforator (DIEP) flap surgery, and to evaluate LSCI in assisting of prediction of postoperative complications.

Methods: Twenty-three patients who underwent DIEP-procedures for breast reconstruction at 2 centers were included. Perfusion was measured in 4 zones at baseline, after raising, after anastomosis, and after shaping the flap. The perfusion in relation to the selected perforator and the accuracy of LSCI in predicting complications were analyzed.

Results: After raising the flap, zone I showed the highest perfusion (65 ± 10 perfusion units, PU), followed by zone II (58 ± 12 PU), zone III (53 ± 10 PU), and zone IV (45 ± 10 PU). The perfusion in zone I was higher than zone III ( = 0.002) and zone IV ( < 0.001). After anastomosis, zone IV had lower perfusion than zone I ( < 0.001), zone II ( = 0.01), and zone III ( = 0.02). Flaps with areas <30 PU after surgery had partial necrosis postoperatively (n = 4).

Conclusions: Perfusion is highest in zone I. No perfusion difference was found between zones II and III. Perfusion <30 PU after surgery was correlated with partial necrosis. LSCI is a promising tool for measurement of flap perfusion and assessment of risk of postoperative ischemic complications.
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http://dx.doi.org/10.1097/GOX.0000000000002529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015619PMC
January 2020

Skin blood flow response to topically applied methyl nicotinate: Possible mechanisms.

Skin Res Technol 2020 May 27;26(3):343-348. Epub 2019 Nov 27.

Department of Medical Radiation Physics, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.

Background: Methyl nicotinate (MN) induces a local cutaneous erythema in the skin and may be valuable as a local provocation in the assessment of microcirculation and skin viability. The mechanisms through which MN mediates its vascular effect are not fully known. The aim of this study was to characterize the vasodilatory effects of topically applied MN and to study the involvement of nitric oxide (NO), local sensory nerves, and prostaglandin-mediated pathways.

Methods: MN was applied on the skin of healthy subjects in which NO-mediated (L-NMMA), nerve-mediated (lidocaine/prilocaine), and cyclooxygenase-mediated (NSAID) pathways were selectively inhibited. Microvascular responses in the skin were measured using laser speckle contrast imaging (LSCI).

Results: NSAID reduced the MN-induced perfusion increase with 82% (P < .01), whereas lidocaine/prilocaine reduced it with 32% (P < .01). L-NMMA did not affect the microvascular response to MN.

Conclusion: The prostaglandin pathway and local sensory nerves are involved in the vasodilatory actions of MN in the skin.
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http://dx.doi.org/10.1111/srt.12807DOI Listing
May 2020

Incidence of distal ulna fractures in a Swedish county: 74/100,000 person-years, most of them treated non-operatively.

Acta Orthop 2020 02 4;91(1):104-108. Epub 2019 Nov 4.

Department of Orthopaedics, Linköping University.

Background and purpose - Fractures of the distal ulna can occur in isolation or in conjunction with a distal radius fracture. They may result in incongruence and instability of the distal radioulnar joint. We investigated the incidence of distal ulna fractures, whether any fracture types were more common, and the methods of treatment used.Patients and methods - Data were collected from patients 18 years or older, treated for a fracture of the distal ulna in Östergötland, Sweden, during 2010-2012. Patients were identified in the patient registry. The fractures were classified according to the AO comprehensive classification of fractures.Results - The incidence of distal ulna fractures was 74/100,000 person-years. The most common fracture type was that of the ulnar styloid Q1 (79%), followed by the ulnar neck Q2 (11%). Rarest was ulna head fracture, type Q4 (1%). Incidental findings were a mean age of 63 years (SD 18), a concomitant distal radius fracture in 92% of the patients and that 79% were caused by falling from standing height. Internal fixation was performed in 30% of the Q2-Q6 fractures. This indicates that most were considered stable without internal fixation or stable after fixation of a concomitant radius fracture.Interpretation - Our results show that fractures of the distal ulna are not very common, and some fracture types are even rare. There seem to be no consensus on treatment.
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http://dx.doi.org/10.1080/17453674.2019.1686570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006799PMC
February 2020

Effect of N -monomethyl l-arginine on microvascular blood flow and glucose metabolism after an oral glucose load.

Microcirculation 2020 04 7;27(3):e12597. Epub 2019 Nov 7.

Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Objective: The aim of this study was to investigate whether the effects on local blood flow and metabolic changes observed in the skin after an endogenous systemic increase in insulin are mediated by the endothelial nitric oxide pathway, by administering the nitric oxide synthase inhibitor N -monomethyl l-arginine using microdialysis.

Methods: Microdialysis catheters, perfused with N -monomethyl l-arginine and with a control solution, were inserted intracutaneously in 12 human subjects, who received an oral glucose load to induce a systemic hyperinsulinemia. During microdialysis, the local blood flow was measured by urea clearance and by laser speckle contrast imaging, and glucose metabolites were measured.

Results: After oral glucose intake, microvascular blood flow and glucose metabolism were both significantly suppressed in the N -monomethyl l-arginine catheter compared to the control catheter (urea clearance: P < .006, glucose dialysate concentration: P < .035). No significant effect of N -monomethyl l-arginine on microvascular blood flow was observed with laser speckle contrast imaging (P = .81).

Conclusion: Local delivery of N -monomethyl l-arginine to the skin by microdialysis reduces microvascular blood flow and glucose delivery in the skin after oral glucose intake, presumably by decreasing local insulin-mediated vasodilation.
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http://dx.doi.org/10.1111/micc.12597DOI Listing
April 2020

Research activity among European hand surgery residents.

J Hand Surg Eur Vol 2019 Sep;44(7):764-765

4 Department of Plastic Surgery, Hand Surgery, and Burns, Linköping University, Linköping, Sweden.

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http://dx.doi.org/10.1177/1753193419841875DOI Listing
September 2019

A Novel Technique to Assess Distal Radioulnar Joint Stability Using Increasing Torque.

J Wrist Surg 2019 Aug 16;8(4):327-334. Epub 2018 Nov 16.

Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

 Previous studies on computed tomography (CT) in patients with a suspected triangular fibrocartilage complex (TFCC) injury have not been successful in assessing distal radioulnar joint (DRUJ) laxity. The aim of this study was to develop a novel servomotor-driven device for the assessment of DRUJ by applying increasing torque to the DRUJ in pronation and supination.  A custom-built device was designed to function during four-dimensional (4D) CT of the wrist. A torque meter, positioned between the incoming hand holder, and a direct current (DC) servomotor were used for angular positioning and for applying rotational force to the patient's arm. A total of 110 healthy participants were recruited to gather reference values for the range of motion (ROM), maximum torque in neutral and supinated/pronated position, and the ability to withstand an increasing, device-generated torque in these positions. The device was also used during 4D DRUJ CT in five patients with suspected TFCC injuries.  A gender- and age-relevant reference chart for ROM and torque was created. Men showed a tendency (ns) toward having a larger ROM and increasing strength with increasing age, whereas women showed the opposite. Also, the dominant hand showed a tendency toward having a larger ROM and being stronger than the nondominant hand (ns). A smaller cohort of patients (  = 5) with suspected TFCC injuries showed a significantly decreased ability to withstand increasing torque in both supination (2.1 ± 0.3 vs. 3.1 ± 0.2 s;  < 0.005) and pronation (2.3 ± 0.5 vs. 3.1 ± 0.4 s;  < 0.0005) and also showed a clear laxity on real-time 4D CT image sequences. Decreased strength at all positions was also found (average 74% decrease compared to noninjured side).  Reference values for torque strength and ability to withstand increasing torque can be used clinically in the assessment of patients with symptoms that could represent ligamentous injuries to the TFCC. The ability to use the device during CT enables radiographic evaluation of instability during increasing torque. This is a Level II study.
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http://dx.doi.org/10.1055/s-0038-1675561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685783PMC
August 2019

Interobserver reliability of laser speckle contrast imaging in the assessment of burns.

Burns 2019 09 21;45(6):1325-1335. Epub 2019 Jun 21.

Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Radiation Physics, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.

Objectives: Laser speckle contrast imaging (LSCI) is an emerging technique for the assessment of burns in humans and interobserver differences have not been studied. The aim of this study was to compare assessments of perfusion images by different professional groups regarding (i) perfusion values and (ii) burn depth assessment.

Methods: Twelve observers without LSCI experience were included. The observers were evenly recruited from three professional groups: plastic surgeons with experience in assessing burns, nurses with experience in treating burns, and junior doctors with limited experience of burns. Ten cases were included. Each case consisted of one digital photo of the burn with a pre-marked region of interest (ROI) and two unmarked perfusion images of the same area. The first and the second perfusion image was from 24h and 72-96h after injury, respectively. The perfusion values from both perfusion images were used to generate a LSCI recommendation based on the perfusion trend (the derivative between the two perfusion values). As a last step, each observer was asked to estimate the burn depth using their clinical experience and all available information. Intraclass correlation (ICC) was calculated between the different professional groups and among all observers.

Results: Perfusion values and perfusion trends between all observers had an ICC of 0.96 (95% CI 0.91-0.99). Burn depth assessment by all observers yielded an ICC of 0.53 (95% CI: 0.31-0.80) and an accuracy of 0.53 (weighted kappa). LSCI recommendations generated by all observers had an ICC of 0.95 (95% CI: 0.90-0.99).

Conclusion: Observers can reliably identify the same ROI, which results in observer-independent perfusion measurements, irrespective of burn experience. Extensive burn experience did not further improve burn depth assessment. The LSCI recommendation was more accurate in all professional groups. Introducing LSCI measurements would be likely improve early assessment of burns.
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http://dx.doi.org/10.1016/j.burns.2019.01.011DOI Listing
September 2019

The microvascular response in the skin to topical application of methyl nicotinate: Effect of concentration and variation between skin sites.

Microvasc Res 2019 07 12;124:54-60. Epub 2019 Mar 12.

Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Plastic Surgery, Hand Surgery, and Burns, Linköping University, Linköping, Sweden.

Background: Methyl nicotinate (MN) induces a local cutaneous erythema in the skin and may be used as a local provocation in the assessment of microcirculation and skin viability. The aims were to measure the effects of increasing doses of MN, to find the concentration that yields the most reproducible effect from day to day and between sites, and to study the variation between skin sites.

Methods: Microvascular responses to topically applied MN at different concentrations were measured in 12 subjects on separate days and on contralateral sides, using laser speckle contrast imaging (LSCI). MN effects were measured in four different body sites.

Results: At 20 mmol/L, the response to MN was most reproducible day-to-day and site-to-site, and resulted in a plateau response between 5 and 20 min after application. The skin region of the lower back had a lower perfusion value compared to the epigastric region (p = 0.007). When responses were compared to nearby, unprovoked areas, a significantly larger increase in perfusion was seen in the forearm, compared to all other anatomical sites (p < 0.03).

Conclusion: A concentration of 20 mmol/L MN generated the most reproducible microvascular response in the skin. The response varies between different body sites.
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http://dx.doi.org/10.1016/j.mvr.2019.03.002DOI Listing
July 2019

Laser speckle contrast imaging in children with scalds: Its influence on timing of intervention, duration of healing and care, and costs.

Burns 2019 06 28;45(4):798-804. Epub 2019 Feb 28.

Department of Hand Surgery, Plastic Surgery and Burns, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. Electronic address:

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.
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http://dx.doi.org/10.1016/j.burns.2019.02.001DOI Listing
June 2019

The use of laser speckle contrast imaging to predict flap necrosis: An experimental study in a porcine flap model.

J Plast Reconstr Aesthet Surg 2019 May 3;72(5):771-777. Epub 2019 Jan 3.

Department of Hand and Plastic Surgery and Burns and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Background: We evaluated the use of laser speckle contrast imaging (LSCI) in the perioperative planning in reconstructive flap surgery. The aim of the study was to investigate whether LSCI can predict regions with a high risk of developing postoperative necrosis. Our hypothesis was that, perioperatively, such regions have perfusion values below a threshold value and show a negative perfusion trend.

Methods: A porcine flap model based on the cranial gluteal artery perforator was used. Images were acquired before surgery, immediately after surgery (t = 0), after 30 min (t = 30 min), and after 72 h (t = 72 h). Regions of interest (ROIs) were chosen along the central axis of the flap. Clinical evaluation of the flap was made during each time point.

Results: At t = 72 h, a demarcation line could be seen at a distance of 15.8 ± 0.4 cm away from the proximal border of the flaps. At t = 0, perfusion decreased gradually from the proximal to the distal ROI. At t = 30 min, perfusion was significantly lower in the ROI distal to the final demarcation line than that at t = 0, and in all flaps, these ROIs had a perfusion <25 PU. At t = 72 h, perfusion in the ROI proximal to this line returned to baseline levels, whereas perfusion in the distal ROI remained low.

Conclusions: In our model, a decrease in perfusion during the first 30 min after surgery and a perfusion <25 PU at t = 30 min was a predictor for tissue morbidity 72 h after surgery, which indicates that LSCI is a promising technique for perioperative monitoring in reconstructive flap surgery.
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http://dx.doi.org/10.1016/j.bjps.2018.11.021DOI Listing
May 2019

Data on microcirculatory perfusion dips in the resting nail bed.

Data Brief 2018 Dec 27;21:1232-1235. Epub 2018 Oct 27.

Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.

This article contains the raw data from the article entitled: "The presence of synchronized perfusion dips in the microcirculation of the resting nail bed" Mirdell et al. (in press). A laser speckle contrast imager (LSCI) was used to make a total of 21 recordings of the perfusion in the resting nail bed of 10 healthy test subjects. The first 10 recordings were acquired after 5 min of acclimatization. An additional 10 recordings were acquired in the same test subjects, after 20 min of acclimatization. In the last recording, a digital nerve block was applied to the left dig III. The data show the presence of highly irregular perfusion variations, a phenomenon we like to call perfusion dips. The data also show how the perfusion dips can be abolished through a digital nerve block. An algorithm for the quantification of the perfusion dips is included in the data.
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http://dx.doi.org/10.1016/j.dib.2018.10.077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231364PMC
December 2018

The presence of synchronized perfusion dips in the microcirculation of the resting nail bed.

Microvasc Res 2019 01 12;121:71-81. Epub 2018 Oct 12.

Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Radiation Physics, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.

Objectives: Laser speckle contrast imaging (LSCI) has seen limited use in the study of perfusion dynamics such as vasomotion. The aim of this study was to investigate the effects of a prolonged seated position on perfusion dynamics in the nail bed using LSCI.

Methods: Perfusion was recorded in digits II to IV bilaterally for 20 min during two separate sessions in ten healthy volunteers. The acclimatization period was 5 min for the 1st session and 20 min for the 2nd. Perfusion variability and the presence of recurring perfusion dips were analyzed. A digital nerve block was done to verify suspected nervous origin of phenomenon.

Results: Synchronized phases of vasoconstriction were observed in all subjects with perfusion dips in all digits bilaterally and simultaneously. Application of a digital nerve block abolished perfusion dips. The frequency of this phenomenon increased by 25.0% (95% CI: 1.6 to 49.2%) in the left-hand digits after a prolonged seated position. Perfusion variability increased by 11.6% (95% CI: 2.6 to 20.3%) in the digits of the left hand. Perfusion changes in right-hand digits did not significantly increase. During the 1st session, temperature increased by 2.7 °C (1.1 to 4.2) while it decreased by 1.3 °C (0.2 to 2.4) during the 2nd session.

Conclusion: The observed perfusion dips are of a centrally mediated nervous origin but are also affected by local factors. They are affected by seating duration and differ between left and right hands, likely because of local micro perfusion dips. This phenomenon seems related to digital thermoregulation.
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http://dx.doi.org/10.1016/j.mvr.2018.10.004DOI Listing
January 2019

Vascular Occlusion in a Porcine Flap Model: Effects on Blood Cell Concentration and Oxygenation.

Plast Reconstr Surg Glob Open 2017 Nov 17;5(11):e1531. Epub 2017 Nov 17.

Department of Plastic Surgery, Hand Surgery and Burns, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; and Department of Radiation Physics, Linköping University, Linköping, Sweden.

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.
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http://dx.doi.org/10.1097/GOX.0000000000001531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732657PMC
November 2017

20-Year outcome of TFCC repairs.

J Plast Surg Hand Surg 2018 Jun 19;52(3):193-197. Epub 2017 Dec 19.

b Department of Clinical and Experimental Medicine , Linköping University , Sweden.

The aims of this study were to investigate the functional result and rate of osteoarthritis 15-25 years after a TFCC-repair. Forty-seven patients completed the questionnaire Patient Rated Wrist Evaluation (PRWE), and 43 had new X-rays. Fifty-seven percent had a simultaneous arthroscopy. Sixteen patients had later additional surgery to the wrist, of these eight had a reoperation of the TFCC-injury due to recurrent instability. Radiographs showed that 17.5% had developed radiocarpal osteoarthritis and 34% osteoarthritis in the distal radioulnar joint. The median PRWE result was 22.5. Patients with radiocarpal osteoarthritis and patients who had additional surgery had significantly worse scores. Patients who had undergone arthroscopy significantly less often had developed radiocarpal osteoarthritis. The result is acceptable but not impressive and efforts should be made to diagnose these injuries early and also diagnose associated injuries, advisably by arthroscopy.
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http://dx.doi.org/10.1080/2000656X.2017.1415914DOI Listing
June 2018

The Tissue-Engineered Tendon-Bone Interface: In Vitro and In Vivo Synergistic Effects of Adipose-Derived Stem Cells, Platelet-Rich Plasma, and Extracellular Matrix Hydrogel.

Plast Reconstr Surg 2017 Dec;140(6):1169-1184

Stanford and Palo Alto, Calif.

Background: Suboptimal healing of the tendon-bone interface remains an unsolved problem. The authors hypothesized that (1) platelet-rich plasma and prolonged in vitro incubation will produce interface scaffolds with greater reseeding of viable adipose-derived stem cells; and (2) when implanted with extracellular matrix hydrogel, constructs will display superior in vivo strength repair and biocompatibility.

Methods: Achilles-calcaneal composite tendon-bone interface scaffold grafts were harvested from 30 Wistar rats. After physicochemical decellularization and lyophilization, scaffolds were revitalized in rat plasma or 100% activated rat platelet-rich plasma and reseeded with viable adipose-derived stem cells. For part 2 of the study, 90 Sprague-Dawley rats underwent reconstruction with one of five decellularized, lyophilized scaffold revitalization/reseeding conditions: (1) phosphate-buffered saline; (2) lyophilized, 100% activated platelet-rich plasma; (3) platelet-rich plasma and extracellular matrix hydrogel; (4) platelet-rich plasma and 14-day reseeding with ASC-luc2-eGFP cells; and (5) plasma, reseeding, and hydrogel.

Results: In part 1, platelet-rich plasma-revitalized grafts demonstrated greater live viable adipose-derived stem cell loads at 3, 7, and 14 days and total adipose-derived stem cell loads at 7 and 14 days with visibly greater live surface cellularity, layering, migration, and penetration. In part 2, bioluminescence imaging confirmed cell viability to day 22 after implantation. Biomechanical strength testing demonstrated a significant increase in ultimate failure load for reseeded groups compared with all other groups at week 2, whereas only reseeded grafts with hydrogel remained significantly stronger at weeks 4 and 8. Histologic examination demonstrated most increased tendinous cellular invasion and fibrocartilage repopulation at 8 weeks in the reseeded group with hydrogel. Masson trichrome staining demonstrated persistence of the scaffold structure at week 8 and blinded ImageJ analysis demonstrated significantly more type III collagen in the reseeded/hydrogel group at 2, 4, and 8 weeks.

Conclusions: Decellularized lyophilized allogeneic tendon-bone interface scaffolds can be optimized by revitalization in platelet-rich plasma, reseeding with viable adipose-derived stem cells, and supplemented by an extracellular matrix tendon hydrogel at the time of implantation. When this is done, they display greater repair strength and biocompatibility.
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http://dx.doi.org/10.1097/PRS.0000000000003840DOI Listing
December 2017

Accuracy of laser speckle contrast imaging in the assessment of pediatric scald wounds.

Burns 2018 02 7;44(1):90-98. Epub 2017 Aug 7.

Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Radiation Physics, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.

Background: Changes in microvascular perfusion in scalds in children during the first four days, measured with laser speckle contrast imaging (LSCI), are related to the time to healing and need for surgical intervention. The aim of this study was to determine the accuracy (sensitivity and specificity) of LSCI on different days after injury in the prediction of healing outcome and if the accuracy can be improved by combining an early and a late measurement. Also, the accuracy of LSCI was compared with that of clinical assessment.

Methods: Perfusion was measured between 0-24h and between 72-96h using LSCI in 45 children with scalds. On the same occasions, burn surgeons assessed the burns as healing <14days or healing >14days/surgery. Receiver operating characteristic (ROC) curves were constructed for the early and late measurement and for the double measurement (DM) using two different methods.

Results: Sensitivity and specificity were 92.3% (95% CI: 64.0-99.8%) and 78.3% (95% CI: 69.9-85.3%) between 0-24h, 100% (95% CI: 84.6-100%) and 90.4% (95% CI: 83.8-94.9%) between 72-96h, and was 100% (95% CI: 59.0-100%) and 100% (95% CI: 95.1-100%) when combining the two measurements into a modified perfusion trend. Clinical assessment had an accuracy of 67%, Cohen's κ=0.23.

Conclusion: The perfusion in scalds between 72-96h after injury, as measured using LSCI, is highly predictive of healing outcome in scalds when measured. The predictive value can be further improved by incorporating an early perfusion measurement within 24h after injury.
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http://dx.doi.org/10.1016/j.burns.2017.06.010DOI Listing
February 2018

Acute effects of coffee on skin blood flow and microvascular function.

Microvasc Res 2017 11 15;114:58-64. Epub 2017 Jun 15.

Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Plastic Surgery, Hand Surgery, and Burns, Linköping University, Linköping, Sweden.

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 transdermal iontophoresis 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±0.20PU/mmHg vs. 1.13±0.38PU/mmHg, 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 (-1.36PU/mmHg vs. -0.52PU/mmHg, 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.
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http://dx.doi.org/10.1016/j.mvr.2017.06.006DOI Listing
November 2017

Methodological concerns with laser speckle contrast imaging in clinical evaluation of microcirculation.

PLoS One 2017 30;12(3):e0174703. Epub 2017 Mar 30.

Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

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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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174703PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373607PMC
August 2017

Changes in skin microcirculation during radiation therapy for breast cancer.

Acta Oncol 2017 Aug 10;56(8):1072-1080. Epub 2017 Mar 10.

a Department of Radiation Physics and Department of Medical and Health Sciences , Linköping University , Linköping , Sweden.

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.
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http://dx.doi.org/10.1080/0284186X.2017.1299220DOI Listing
August 2017

Optimized Repopulation of Tendon Hydrogel: Synergistic Effects of Growth Factor Combinations and Adipose-Derived Stem Cells.

Hand (N Y) 2017 01 15;12(1):68-77. Epub 2016 Mar 15.

VA Palo Alto Health Care System, Livermore, CA, USA; Stanford University, CA, USA.

Tendon-derived extracellular matrix (ECM) hydrogel has been shown to augment tendon healing in vivo. We hypothesized that reseeding of the gel with adipose-derived stem cells (ASCs) could further assist repopulation of the gel and that combinations of growth factors (GFs) would improve the survival of these cells after reseeding. A tendon-specific ECM solution was supplemented with varying concentrations of basic fibroblast growth factor (bFGF), insulin-like growth factor-1 (IGF-1), and platelet-derived growth factor-BB (PDGF-BB). Gels were then seeded with ASCs transfected with a green fluorescent protein/luciferin construct. Cell proliferation was determined using the MTT assay and histology, and GF and ASC augmented gels were injected into the back of Sprague Dawley rats. Bioluminescence of seeded gels was continuously followed after reseeding, and cell counts were performed after the gels were explanted at 14 days. Synergistic effects of the GFs were seen, and an optimal combination was determined to be 10 ng/mL bFGF, 100 ng/mL IGF-1, and 100 ng/mL PDGF-BB (2.8-fold increase; < .05). In vivo bioluminescence showed an improved initial survival of cells in gels supplemented with the optimal concentration of GF compared with the control group (10.6-fold increase at 8 days; < .05). Cell counts of explants showed a dramatic endogenous repopulation of gels supplemented by GF + ASCs compared with both gels with GF but no ASCs (7.6-fold increase) and gels with ASCs but no GF (1.6-fold increase). Synergistic effects of GFs can be used to improve cellular proliferation of ASCs seeded to a tendon ECM gel. Reseeding with ASCs stimulates endogenous repopulation of the gel in vivo and may be used to further augment tendon healing.
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http://dx.doi.org/10.1177/1558944715628005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207276PMC
January 2017

Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load.

Microcirculation 2016 10;23(7):597-605

Department of Hand Surgery, Plastic Surgery, and Burns, Linköping University, Linköping, Sweden.

Objective: Insulin causes capillary recruitment in muscle and adipose tissue, but the metabolic and microvascular effects of insulin in the skin have not been studied in detail. The aim of this study was to measure glucose metabolism and microvascular blood flow in the skin during local insulin delivery and after an oral glucose load.

Methods: Microdialysis catheters were inserted intracutanously in human subjects. In eight subjects two microdialysis catheters were inserted, one perfused with insulin and one with control solution. First the local effects of insulin was studied, followed by a systemic provocation by an oral glucose load. Additionally, as control experiment, six subjects did not recieve local delivery of insulin or the oral glucose load. During microdialysis the local blood flow was measured by urea clearance and by laser speckle contrast imaging (LSCI).

Results: Within 15 minutes of local insulin delivery, microvascular blood flow in the skin increased (urea clearance: P=.047, LSCI: P=.002) paralleled by increases in pyruvate (P=.01) and lactate (P=.04), indicating an increase in glucose uptake. An oral glucose load increased urea clearance from the catheters, indicating an increase in skin perfusion, although no perfusion changes were detected with LSCI. The concentration of glucose, pyruvate and lactate increased in the skin after the oral glucose load.

Conclusion: Insulin has metabolic and vasodilatory effects in the skin both when given locally and after systemic delivery through an oral glucose load.
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http://dx.doi.org/10.1111/micc.12325DOI Listing
October 2016