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Assessment of microvascular response to iontophoresis ofnoradrenaline and phenylephrine using local heating andlaser Doppler flowmetry
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Laser-Doppler flowmetry (LDF) is an attractive method to assess blood flow responses butlacks sensitivity to accurately measure low perfusion values during iontophoresis of vasoconstricting drugs without predilatation of the microvascular bed.

The aim of this study was to develop a protocol for iontophoresis of noradrenaline (NA) andphenylephrine (Phe) in the skin, using local heating to predilate the microvascular bed andLDF to measure blood flow responses. Three protocols with the same electrical charge (12mC) but different durations and current strengths (100 s x 0.12 mA, 200 s x 0.06 mA, 300 s x0.04 mA) were used to study the effect of pulse duration and current strength on the responses.

Skin perfusion decreased to 68-78% of the predilatated state with both NA and Phe. Doseresponse plateaus were not obtained with any protocol. The extent of the vasoconstriction depended on the protocol used.

These results suggest that predilatation by local heating appears less suitable duringiontophoresis of NA and Phe, due to limited vascular responses and especially absence of response plateaus, even at high current strengths. The latter leads to difficulties in performing proper dose response analyses. Another interesting finding was that the actual dose of NA and Phe given to the tissue was affected not only by the size of the electrical charge, but local blood flow as well.

National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-50639OAI: oai:DiVA.org:liu-50639DiVA: diva2:271812
Available from: 2009-10-13 Created: 2009-10-13 Last updated: 2010-01-14Bibliographically approved
In thesis
1. Assessment of microvascular effects of vasoactive drugs: Methodological in vivo studies in humansbased on iontophoresis
Open this publication in new window or tab >>Assessment of microvascular effects of vasoactive drugs: Methodological in vivo studies in humansbased on iontophoresis
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cardiovascular disease is the leading cause of death in western societies and endothelial dysfunction is one of the earliest signs seen in the development of such conditions. Thedevelopment of prognostic tools to aid in the prediction of micro- and macrovascular diseasebased on assessment of vascular reactivity is therefore of paramount importance.

Transdermal iontophoresis offers a quick, non-invasive and relatively straightforward way todeliver vasoactive substances in order to provoke a vascular response in man. When combined with either laser Doppler flowmetry (LDF) or tissue viability imaging (TiVi) for quantification of these responses the methodology offers a potentially powerful tool forvascular investigations. The technique has, however, not been established in clinical practice yet and is mostly used in experimental settings. The lack of consensus in what data analysistechnique to use, uncertainty concerning the actual drug dose applied, and the difficulties associated with the assessment of responses to vasoconstrictors may have contributed to thisfact. The aim of this thesis is therefore to address these issues and thus facilitate the use and improve the applicability of transdermal iontophoresis for assessment of cutaneous microvascular function.

More specifically, a non-linear dose-response model (Emax-model) that is commonly used in in vitro investigations of vascular function was applied to the iontophoresis data. The resultsshow that the Emax-model accurately describes the cutaneous vascular responses totransdermally iontophoresed acetylcholine (ACh) and, sodium nitroprusside (SNP). The Emaxmodelgenerates variables that can be used for quantitative statistical analysis of data andenables a more powerful analysis compared to the methods presently used. It is furtherdemonstrated that the maximal dose effect and vascular responses vary between differentprotocols with the same total iontophoretic charge but with different current strengths anddurations. This finding implies that the assumption that the local drug dose is linearlyproportional to the iontophoretic charge (used for estimation of delivered drug dose to themicrovascular bed) may be inaccurate in in vivo investigations and that there is need for amore refined model.

It is also demonstrated that in a vasoconstrictive setting (iontophoresis of noradrenaline andphenylephrine) TiVi is the favourable technique for measuring vascular responses as it issensitive enough to generate data that can be fitted to the Emax-model even without predilatationof the vessels.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 47 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1125
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-50642 (URN)978-91-7393-638-5 (ISBN)
Public defence
2009-11-06, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (English)
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Available from: 2009-10-13 Created: 2009-10-13 Last updated: 2009-10-13Bibliographically approved

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Henricson, JoakimDroog Tesselaar, ErikNilsson, GertSjöberg, Folke

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Department of Clinical and Experimental MedicineFaculty of Health SciencesDepartment of Biomedical EngineeringThe Institute of TechnologyBurn Unit Department of Plastic Surgery, Hand surgery and Burns
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