Assessing cutaneous microvascular function with iontophoresis: Avoiding non-specific vasodilation

Aim Iontophoresis of vasoactive agents is commonly used to assess cutaneous microvascular reactivity. However, it is known that iontophoresis can be limited by confounding non-specific vasodilatory effects. Despite this, there is still no standardization of protocols or data expression. Therefore, this study evaluated commonly used protocols of iontophoresis by assessing each for evidence of non-specific vasodilatory effects and examined the reproducibility of those protocols that are free of non-specific responses. Methods Twelve healthy participants were administered doses of acetylcholine (ACh) 1–2% and sodium nitroprusside (SNP) 1%, diluted in sodium chloride 0.9% or deionized water, and insulin 100 U/mL in a sterile diluent using iontophoresis coupled with laser speckle contrast imaging (LSCI). Increases in blood flux at a control electrode, containing the diluent only, indicated a non-specific response. Reproducibility of iontophoresis protocols that were free of non-specific vasodilatory effects were subsequently compared to that of post-occlusive reactive hyperemia (PORH), used as a standard, in 20 healthy participants. Results Iontophoresis of ACh or SNP in sodium choloride (0.02 mA for 200 and 400 s, respectively) and ACh in deionized water (0.1 mA for 30 s) mediated the least non-specific vasodilatory effects. Microvascular responses to insulin were mediated mainly by non-specific effects. Compared to PORH, the intraday and interday reproducibility for iontophoresis of ACh and SNP (0.02 mA for 200 and 400 s, respectively) with LSCI was weaker, but still deemed good to excellent when data was expressed, in perfusion units or cutaneous vascular conductance, as the absolute peak blood flux response to the vascular reactivity test or as the change in blood flux between peak and baseline values. Conclusion This study provides updated recommendations for assessing cutaneous microvascular function with iontophoresis.