Research Paper J Vasc Res 2002;39:447–455 Elimination of Electrically Induced Iontophoretic Artefacts: Implications for Non-Invasive Assessment of Peripheral Microvascular Function William R. Ferrell a Jane E. Ram say b Naomi Brooks b John C. Lockhart d Sylvia Dickson d Grainne M. McNeece d Ian A. Greer b Naveed Sattar c Departments of a Medicine, b Obstetrics and Gynaecology, and c Pathological Biochemistry, Royal Infirmary, Glasgow, and d Division of Biological Sciences, University of Paisley, Paisley, UK Received: December 20, 2001 Accepted after revision: April 11, 2002 Prof. W.R. Ferrell Department of Medicine, Royal Infirmary 10 Alexandra Parade Glasgow G31 2ER (UK) Tel. +44 141 211 4688, Fax +44 141 211 0414, E-Mail w.ferrell@bio.gla.ac.uk ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2002 S. Karger AG, Basel 1018–1172/02/0395–0447$18.50/0 Accessible online at: www.karger.com/journals/jvr Key Words Iontophoresis W Laser Doppler imaging W Galvanic response W Electrically induced hyperaemia W Endothelium W Acetylcholine W Sodium nitroprusside W Prostaglandins W Vasodilatation W Resistance Abstract Iontophoretic assessment of skin microvascular function is complicated by the occurrence of electrically induced hyperaemia, especially at the cathode. Studies were per- formed to identify means of reducing such effects. Skin vasodilator responses were measured using a laser Doppler imager that controlled iontophoretic current de- livery. A novel feature involved monitoring voltage across the iontophoresis chambers. Comparison be- tween responses to vehicle (distilled H 2 O), acetylcholine (ACh) and sodium nitroprusside (SNP) showed electrical- ly induced hyperaemia at the cathode associated with the vehicle, whose time course overlapped with that of the SNP response. Voltage across the chambers contain- ing drugs dissolved in H 2 O was significantly (p = 0.018, n = 7) lower than the voltage profile of H 2 O alone. H 2 O iontophoresis was associated with cathodal hyperaemic responses in most subjects, whereas a 0.5% NaCl vehicle produced lower voltages and eliminated this artefact. Voltage W time integral rather than charge was the prime determinant of electrically induced hyperaemic re- sponses. No significant correlation was found between skin fold thickness and either calculated skin resistance (r 2 = 0.0002) or vascular response to ACh (r 2 = 0.13). Smaller chamber size led to higher voltages and greater electrically induced hyperaemic responses. These ap- pear to be prostaglandin dependent as they were ablated by cyclooxygenase inhibition. Use of a low-resistance vehicle combined with larger chamber sizes and lower currents can prevent such artefacts, thereby increasing the robustness of this methodology for clinical assess- ment of endothelial function. Copyright © 2002 S. Karger AG, Basel Introduction There is considerable evidence relating impaired endo- thelial vasomotor function to coronary heart disease [1]. Such endothelial dysfunction also occurs in the peripheral circulation proportionate to the degree of dysfunction