Modeling Perfusion Dynamics in the Skin During Iontophoresis of Vasoactive Drugs Using Single-Pulse and Multiple-Pulse Protocols

Microcirculation. 2015 Aug;22(6):446-53. doi: 10.1111/micc.12211.


Objective: After iontophoresis of vasoactive drugs into the skin, a decrease in perfusion is commonly observed. We delivered vaso-active drugs by iontophoresis using different delivery protocols to study how these affect this decrease in perfusion as measured using LDF.

Methods: We measured skin perfusion during iontophoresis of (ACh), MCh, and NA using a single pulse or separate pulses at different skin sites, and during repeated delivery of ACh at the same site.

Results: Perfusion half-life was 6.1 (5.6-6.6) minutes for ACh and 41 (29-69) minutes for MCh (p < 0.001). The maximum response with multiple pulses of ACh iontophoresis was lower than with a single pulse, 30 (22-37) PU vs. 43 (36-50) PU, p < 0.001. Vasoconstriction to NA was more rapid with a single pulse than with multiple pulses. The perfusion half-life of ACh decreased with repeated delivery of ACh at the same site-first 16 (14-18), second 5.9 (5.1-6-9) and third 3.2 (2.9-3.5) minutes, p < 0.001.

Conclusions: The drug delivery protocol affects microvascular responses to iontophoresis, possibly as a result of differences in the dynamics of local drug concentrations. Perfusion half-life may be used as a measure to quantify the rate of perfusion recovery after iontophoresis of vasoactive drugs.

Keywords: acetylcholine; iontophoresis; methacholine; microcirculation; noradrenaline; skin.

MeSH terms

  • Acetylcholine* / administration & dosage
  • Acetylcholine* / pharmacokinetics
  • Adult
  • Female
  • Humans
  • Iontophoresis*
  • Male
  • Methacholine Chloride* / administration & dosage
  • Methacholine Chloride* / pharmacokinetics
  • Microcirculation / drug effects*
  • Models, Cardiovascular*
  • Norepinephrine* / administration & dosage
  • Norepinephrine* / pharmacokinetics
  • Skin / blood supply*


  • Methacholine Chloride
  • Acetylcholine
  • Norepinephrine