Factors critical to iontophoretic assessment of vascular reactivity: implications for clinical studies of endothelial dysfunction

Skin microvascular responses to iontophoresis of acetylcholine, an endothelium-dependent vasodilator, and sodium nitroprusside, an endothelium-independent vasodilator, were measured using a laser Doppler imager whose software controlled iontophoretic current delivery in an integrated fashion. A novel feature involved monitoring voltage across the iontophoresis chambers during current application (total charge: 8 mC). Both drugs elicited vasodilatation but with differing magnitudes and time courses, whereas current delivery with only vehicle (0.5% NaCl) present was ineffective. During drug delivery a three-to fourfold difference in calculated skin resistance was observed between subjects, with higher resistance being associated with lower dilator responses to both drugs. There was a significant (p < 0.0001) linear inverse correlation between perfusion.time and resistance.time integrals for both acetylcholine ( r = -0.86) and sodium nitroprusside ( r = -0.96). This was corrected in individual subjects by multiplying individual perfusion values by the resistance.time integral, which reduced response variability. Cyclooxygenase inhibition by aspirin apparently attenuated acetylcholine and sodium nitroprusside vasodilator responses but after correcting for skin resistance there was no longer any difference. Monitoring voltage across the iontophoretic circuit is critical, as effective drug delivery in individual subjects is influenced by the circuit resistance that can be corrected for. These findings have implications for clinical studies that use the iontophoresis technique for assessing vascular function.