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Tissue viability imaging: Microvascular response to vasoactive drugs induced by iontophoresis
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Berzelius Clinical Research Center AB.
Berzelius Clinical Research Center AB.
Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
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2009 (English)In: Microvascular Research, ISSN 0026-2862, Vol. 78, no 2, 199-205 p.Article in journal (Refereed) Published
Abstract [en]

When one is studying the physiology of the cutaneous microcirculation there is a need for relevant non-invasive and versatile techniques. In this study we used a new optical device, the tissue viability imager (TiVi), to map changes in cutaneous microvascular concentrations of red blood cells during iontophoresis of vasoactive substances (noradrenaline (NA) and phenylephrine (Phe) for vasoconstriction and acetylcholine (ACh) and sodium nitroprusside (SNP) for vasodilatation). We aimed to present data both individually and pooled, using a four-variable logistic dose response model that is commonly used in similar in vitro vascular studies. The accuracy of the TiVi was also investigated by calculating the coefficient of variation and comparing it with similar tests previously done using laser Doppler imaging.

Tests were also performed using the TiVi and LDPI simultaneously to further compare the two methods. Results showed that the TiVi is capable of quantifying vascular responses to iontophorised noradrenaline and phenylephrine without the need to increase background flow first. Fitting the TiVi data to the dose response model resulted in ED50-values with narrow confidence intervals and acceptable r2 values. Mean ED50-values for the TiVi did not differ significantly from similar values obtained using laser Doppler.

Results further seem to suggest that when the blood perfusion increases during vasodilatation in skin the initial phase relies mainly on an increase in red blood cell concentration whereas the further perfusion increase is due to an increase in red blood cell velocity.

Place, publisher, year, edition, pages
2009. Vol. 78, no 2, 199-205 p.
Keyword [en]
Cutaneous microcirculation; Iontophoresis; Laser Doppler; Tissue viability imager
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-21238DOI: 10.1016/j.mvr.2009.04.008OAI: diva2:240986
Original Publication: Joakim Henricson, Anders Nilsson, Erik Tesselaar, Gert Nilsson and Folke Sjöberg, Tissue viability imaging: Microvascular response to vasoactive drugs induced by iontophoresis, 2009, Microvascular Research, (78), 2, 199-205. Copyright: Elsevier Science B.V., Amsterdam Available from: 2009-09-30 Created: 2009-09-30 Last updated: 2009-10-30Bibliographically 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.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1125
National Category
Medical and Health Sciences
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)
Available from: 2009-10-13 Created: 2009-10-13 Last updated: 2009-10-13Bibliographically approved

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