Assessment of Blood Flow Changes in Human Skin by Microdialysis Urea Clearance

Farnebo, Simon; Zettersten, Erik; Samuelsson, Kersti; Tesselaar, Erik; Sjöberg, Folke

doi:10.1111/j.1549-8719.2010.00077.x

Cited by 26 publications

(39 citation statements)

References 29 publications

(46 reference statements)

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“…Ethanol in perfusates and in microdialysates was determined as previously described (12). Ethanol dilution and microdialysate urea concentrations served to assess changes in tissue blood flow (13,14).…”

Section: Methodsmentioning

confidence: 99%

Limited Acute Influences of Electrical Baroreceptor Activation on Insulin Sensitivity and Glucose Delivery: A Randomized, Double-Blind, Crossover Clinical Study

et al. 2014

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Arterial baroreflexes may regulate resistance vessels supplying glucose to skeletal muscle by modulating efferent sympathetic nervous system activity. We hypothesized that selective manipulation of baroreflex activity through electrical carotid sinus stimulation influences insulin sensitivity by changing muscular glucose delivery. We enrolled 16 hypertensive patients who responded to treatment with an electrical carotid sinus stimulator. Patients were submitted to a frequently sampled intravenous glucose tolerance test (FSIGT) with the stimulator on and with the stimulator off on separate days in a randomized, double-blind, crossover study. We monitored interstitial glucose, lactate, and pyruvate in the vastus lateralis muscle using microdialysis. Glucose and insulin concentrations in arterialized venous blood before and during FSIGT were virtually identical with the stimulator on and with the stimulator off. Insulin sensitivity, the primary end point of this study, was 3.3 6 1.0 (mU/L) 21 $ min 21 and 4.4 6 2.6 (mU/L) 21 $ min 21 (on vs. off; P = 0.7). Interstitial glucose, lactate, and pyruvate increased similarly during FSIGT regardless of the stimulator settings. In conclusion, acute changes in baroreceptor stimulation did not elicit significant changes in muscular glucose delivery and whole-body insulin sensitivity. Baroreflex-mediated changes in sympathetic vasomotor tone may have a limited acute effect on muscle glucose metabolism in patients with treatment-resistant hypertension.

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Section: Methodsmentioning

confidence: 99%

Limited Acute Influences of Electrical Baroreceptor Activation on Insulin Sensitivity and Glucose Delivery: A Randomized, Double-Blind, Crossover Clinical Study

et al. 2014

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“…Similarly, endogenous substances can diffuse from the tissue into the catheter and be collected as dialysate into microvials. Microdialysis has been used in humans to monitor substances such as inflammatory markers (Mellergard et al, 2008;Sjögren & Anderson, 2009), energy metabolites (Rosdahl et al, 1998;2000), hormones (Desvigne et al, 2005;Sandqvist et al, 2011) and to study the local effects of vasoactive drugs on tissue blood flow (Farnebo et al, 2011).…”

Section: Microdialysismentioning

confidence: 99%

“…Ethanol clearance (Hickner et al, 1991) and urea clearance (Farnebo et al, 2011) have been used within microdialysis studies (described under 1.6.1) and are based on the principle that a marker, with a known concentration, added to the perfusate, diffuses through the semipermeable membrane of the microdialysis catheter into the interstitium, and this diffusion is partly dependent on the local blood flow. An estimate of the blood flow is then obtained by measuring the concentration of the marker in the dialysate, which is inversely proportional to local blood flow (Farnebo et al, 2010a).…”

Section: Clearance Techniquesmentioning

confidence: 99%

“…In study IV local blood flow was indirectly assessed by urea clearance, a recently presented technique for tissue blood flow monitoring (Farnebo et al, 2011), that has not found widespread application. An alternative would have been the more established ethanol clearance technique.…”

Section: Limitationsmentioning

confidence: 99%

“…In study IV local blood flow was also indirectly measured by urea clearance. The relative loss of added urea is proportional to local blood flow (Farnebo et al, 2011). The concentration of urea in the dialysate was analysed with a CMA 600 measurement system (CMA Microdialysis, Stockholm).…”

Section: Provocationsmentioning

confidence: 99%

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Assessment of microvascular and metabolic responses in the skin

Iredahl¹

2016

Linköping University Medical Dissertations

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The general aim of this project was to develop experimental in vivo models that allow for minimally invasive investigations of responses in the skin to microvascular and metabolic provocations. The cutaneous microvasculature has emerged as a valuable model and been proposed to mirror the microcirculation in other organs. Dysfunction in the cutaneous microcirculation has thus been linked to systemic diseases such as hypertension and diabetes mellitus. Models for investigating skin responses could facilitate the understanding of pathophysiological mechanisms as well as effects of drugs. In the first study, three optical measurement techniques (laser Doppler flowmetry (LDF), laser speckle contrast imaging (LSCI) and tissue viability imaging (TiVi)) were compared against each other and showed differences in their ability to detect microvascular responses to provocations in the skin. TiVi was found more sensitive for measurement of noradrenaline-induced vasoconstriction, while LSCI was more sensitive for measurement of vascular occlusion. In the second study, microvascular responses in the skin to iontophoresis of vasoactive drugs were found to depend on the drug delivery protocol. Perfusion half-life was defined and used to describe the decay in the microvascular response to a drug after iontophoresis. In the third study, the role of nitric oxide (NO) was assessed during iontophoresis of insulin. The results showed a NO-dependent vasodilation in the skin by insulin. In the fourth study the vasoactive and metabolic effects of insulin were studied after both local and endogenous administration. Local delivery of insulin increased skin blood flow, paralleled by increased skin concentrations of interstitial pyruvate and lactate, although no change in glucose concentration was observed. An oral glucose load resulted in an increased insulin concentration in the skin paralleled by an increase in blood flow, as measured using the microdialysis urea clearance technique, although no changes in perfusion was measured by LSCI. The thesis concludes that when studying skin microvascular responses, the choice of measurement technique and the drug delivery protocol has an impact on the measurement results, and should therefore be carefully considered. The thesis also concludes that insulin has metabolic and vasodilatory effects in the skin both when administered locally and as an endogenous response to an oral glucose load. The vasodilatory effect of insulin in the skin is mediated by nitric oxide

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Swellable Gelatin Methacryloyl Microneedles for Extraction of Interstitial Skin Fluid toward Minimally Invasive Monitoring of Urea

Fonseca

Costa

Almeida

et al. 2020

Macromolecular Bioscience

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Kidney ailments, as chronic kidney disease, kidney stones and polycystic kidney disease, recognized as a comorbidity of diabetes and hypertension, are strongly linked to higher risk of cardiovascular diseases, infection and cancer. Therefore, they are considered a global public health problem, contributing to the global major burden of noncommunicable diseases, and having a direct impact on high global mortality and morbidity. [1,2] It is estimated that the prevalence and associated burden of kidney disease is responsible for 5-10 million deaths per year worldwide. [2] The quantification of biomarkers present in various body fluids represents a versatile tool for diagnosis, prognosis, monitoring, therapy and disease management. [3] Currently, the most common body fluids used for biomarkers detection are blood, urine and saliva. [3] However, interstitial skin fluid (ISF), which is formed by blood transcapillary filtration is gaining increasing relevance in this realm. [4] Surrounding the capillary beds in the connective tissue, the ISF contains systemic biomarkers and its composition varies along Urea, the main nitrogenous waste product of protein metabolism, is eliminated almost exclusively by the kidney, and hence, displays considerable clinical significance in the assessment of kidney disorders. The aim of this study is to prepare and investigate the potential of swellable cross-linked gelatin methacryloyl (c-GelMA) microneedles (MNs) as a platform for minimally invasive extraction of interstitial skin fluid (ISF) toward straightforward point-of-care healthcare monitoring of renal complaints, by quantification of urea. c-GelMA MNs are successfully prepared by photo-cross-linking and micromolding, faithfully replicating the master molds (387 ± 16 µm height, 200 µm base and 500 µm tip-to-tip distance). These MN patches display good mechanical properties, withstanding more than 0.15 N per needle without breaking. Ex vivo skin insertion assays reveal that the MNs penetrate up to 237 µm depth, reaching the dermis, where they should extract ISF considering a real application. In an in vitro application using an agarose skin model system, the c-GelMA MNs are able to efficiently recover urea (>98%). Additionally, these MNs exhibit noncytotoxic effects toward human keratinocytes. These findings suggest that c-GelMA MNs are promising devices for sampling ISF and offline analysis of urea, opening new avenues for simple point-of-care healthcare monitoring.

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Assessment of Blood Flow Changes in Human Skin by Microdialysis Urea Clearance

Cited by 26 publications

References 29 publications

Limited Acute Influences of Electrical Baroreceptor Activation on Insulin Sensitivity and Glucose Delivery: A Randomized, Double-Blind, Crossover Clinical Study

Limited Acute Influences of Electrical Baroreceptor Activation on Insulin Sensitivity and Glucose Delivery: A Randomized, Double-Blind, Crossover Clinical Study

Assessment of microvascular and metabolic responses in the skin

Swellable Gelatin Methacryloyl Microneedles for Extraction of Interstitial Skin Fluid toward Minimally Invasive Monitoring of Urea

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