| 1. |
- Droog Tesselaar, Erik, et al.
(författare)
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A protocol for iontophoresis of acetylcholine and sodium nitroprusside that minimises nonspecific vasodilatory effects
- 2004
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Ingår i: Microvascular research. - : Elsevier BV. - 0026-2862. ; 67:2, s. 197-202
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Tidskriftsartikel (refereegranskat)abstract
- Iontophoresis of vasoactive substances is a promising tool for studying pharmacological aspects of the (patho)physiology of the microvasculature. However, nonspecific microvascular responses are a common problem in most protocols used. We studied the effect of current density (mA/cm2), charge density (mC/cm2), drug concentration (mass %) and vehicle concentration (M) on the nonspecific vasodilatation during iontophoresis of sodium chloride, acetylcholine (ACh) and sodium nitroprusside (SNP). We found that nonspecific vasodilatation depended on current density and charge density in both anodal and cathodal iontophoresis. The responses to ACh and SNP were dependent on current density, charge density and drug concentration. We found that by limiting current density (<0.01 mA/cm2) and charge density (<7.8 mC/cm2) and with adjusted concentrations for drugs and vehicles, it is possible to prevent nonspecific effects during iontophoresis of ACh and SNP, while maximum drug effects (plateaus in the dose–response curves) are still obtained. These new findings are important for future iontophoresis studies in which vasoactive drugs are used to assess microvascular function because the presented approach has advantages compared to older techniques, which mainly have attempted to suppress or compensate for the nonspecific responses during iontophoresis by the use of local anaesthetics or the measurement of drug-minus-vehicle responses, both of which present well-known experimental shortcomings.
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| 2. |
- Droog Tesselaar, Erik, et al.
(författare)
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Nonspecific vasodilatation during transdermal iontophoresis : the effect of voltage over the skin
- 2003
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Ingår i: Microvascular research. - 0026-2862. ; 65:3, s. 172-178
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Tidskriftsartikel (refereegranskat)abstract
- We used laser Doppler perfusion imaging (LDPI) to study nonspecific vasodilatation during iontophoresis. In iontophoresis studies, nonspecific vasodilatation occurs as a result either of galvanic currents or of the applied voltage over the skin. We made dose–response measurements to study the effect of ionic strength of the vehicle on the nonspecific vasodilatation during iontophoresis of sodium chloride and deionized water, while we monitored the voltage over the skin. We found that anodal and cathodal ionotophoresis induced a voltage over the skin that was dependent on the ionic strength of the test solution. The nonspecific vasodilatation during anodal iontophoresis was less pronounced than during cathodal iontophoresis, and was independent of the voltage over the skin. The nonspecific vasodilatation in cathodal iontophoresis was related to the voltage over the skin, and was possibly mediated by depolarization of local sensory nerves. In experiments using cathodal iontophoresis, therefore, the ionic strengths of the vehicle and the drug are important when vasoactive drugs are examined, as the nonspecific vasodilatation needs to be controlled for. As the vasodilatation that we observed was heterogeneously distributed within the area of iontophoresis, LDPI may provide more accurate measurements than conventional laser Doppler perfusion monitoring.
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| 3. |
- Horiuchi, Yoshihito, et al.
(författare)
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Role of histamine release in nonspecific vasodilatation during anodal and cathodal iontophoresis
- 2004
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Ingår i: Microvascular research. - : Elsevier BV. - 0026-2862. ; 67:2, s. 192-196
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Tidskriftsartikel (refereegranskat)abstract
- Nonspecific vasodilatation during iontophoresis is an important confounding factor in experimental pharmacology. In this investigation, we studied the involvement of sensory nerves and histamine-related reactions in causing nonspecific vasodilatation in a model of anodal and cathodal iontophoresis of sodium chloride. Firstly, we applied a mixture of local anesthetic (EMLA) cream to confirm its suppressive effect on nonspecific vasodilatation and to measure its efficacy in three different dosages (duration: 1, 2, and 3 h). We then investigated the role of histamine in nonspecific vasodilatation by giving an oral antihistamine drug (cetirizine) to subjects who had and had not been given EMLA. We found substantial suppression of the nonspecific vasodilatation in all EMLA-treated groups (all dosages) compared with untreated controls (with suppression rates of 60–65%). Dosage had no significant effect. A further suppression of nonspecific vasodilatation was seen after oral cetirizine during anodal and cathodal iontophoresis in both EMLA-treated and untreated groups. The antihistamine effect was most pronounced during anodal iontophoresis. These results suggest a histaminergic increase in perfusion that may be independent of neurogenic mechanisms and depend on polarity (anode or cathode). Local nerve blocks (EMLA) together with cetirizine may therefore be used to reduce nonspecific vasodilatation in both anodal and cathodal iontophoresis.
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