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Modeling Perfusion Dynamics in the Skin During Iontophoresis of Vasoactive Drugs Using Single-Pulse and Multiple-Pulse Protocols
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.ORCID iD: 0000-0002-4245-7565
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.
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.
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.
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2015 (English)In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 22, no 6, 446-453 p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Informa Healthcare / Wiley: 12 months , 2015. Vol. 22, no 6, 446-453 p.
Keyword [en]
microcirculation; iontophoresis; acetylcholine; metha choline; noradrenaline; skin
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-121138DOI: 10.1111/micc.12211ISI: 000359676500002PubMedID: 26016387OAI: oai:DiVA.org:liu-121138DiVA: diva2:852279
Available from: 2015-09-08 Created: 2015-09-08 Last updated: 2017-12-04
In thesis
1. Assessment of microvascular and metabolic responses in the skin
Open this publication in new window or tab >>Assessment of microvascular and metabolic responses in the skin
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 51 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1534
National Category
Pharmaceutical Sciences Clinical Medicine Medical Laboratory and Measurements Technologies Bioengineering Equipment Medical Biotechnology Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:liu:diva-132167 (URN)10.3384/diss.diva-132167 (DOI)9789176857021 (ISBN)
Public defence
2016-11-18, Hugo Theorellsalen, Campus US, Linköping, 09:00 (Swedish)
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Available from: 2016-10-19 Created: 2016-10-19 Last updated: 2016-11-01Bibliographically approved

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Iredahl, FredrikWard, LiamFarnebo, SimonTesselaar, ErikSjöberg, Folke

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