Fredrik Iredahl

Non-Invasive Measurement of Skin Microvascular Response during Pharmacological and Physiological Provocations

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; p<0.001) 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; p<0.001, LSCI: baseline 50.8±8.0 PU; max 151±22 PU; p<0.001) and RBC concentration (TiVi: baseline 49.2±32.9 AU; max 99.3±28.3 AU; p<0.001). After 5 minutes of forearm occlusion with prior exsanguination, a decrease was seen in perfusion (LDF: p = 0.027; LSCI: p<0.001) and in RBC concentration (p = 0.045). Only LSCI showed a significant decrease in perfusion after 5 minutes of occlusion without prior exsanguination (p<0.001). 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.

Microvascular blood flow in scalds in children and its relation to duration of wound healing: A study using laser speckle contrast imaging

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 6h after injury until complete reepithelialization or surgery. Duration of healing was defined as the time to complete reepithelialization. RESULTS Less perfusion, between 6 and 96h after injury, was associated with longer duration of healing with the strongest association occurring between 72 and 96h. 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.

The Microvascular Response to Transdermal Iontophoresis of Insulin is Mediated by Nitric Oxide

Insulin 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.

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

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.

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

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.

Modeling Perfusion Dynamics in the Skin During Iontophoresis of Vasoactive Drugs Using Single-Pulse and Multiple-Pulse Protocols.

After iontophoresis of vasoactive drugs into the skin, a decrease in perfusion is commonly observed. We delivered vaso‐active drugs by iontophoresis using different delivery protocols to study how these affect this decrease in perfusion as measured using LDF.