title: Modeling Perfusion Dynamics in the Skin During Iontophoresis of Vasoactive Drugs Using Single-Pulse and Multiple-Pulse Protocols.
abstract: 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.
authors.affiliation: Department of Hand and Plastic Surgery, Burns and Intensive care and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Iredahl
authors.affiliation: Department of Hand and Plastic Surgery, Burns and Intensive care and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Veeranjaneyulu
authors.initials: V
authors.lastname: Sadda
authors.affiliation: Department of Hand and Plastic Surgery, Burns and Intensive care and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Ward
authors.affiliation: Department of Hand and Plastic Surgery, Burns and Intensive care and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.|Ludwig Boltzmann Institute for Clinical and Experimental Traumatology, University of Applied Sciences, Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hackethal
authors.affiliation: Department of Hand and Plastic Surgery, Burns and Intensive care and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Simon
authors.initials: S
authors.lastname: Farnebo
authors.affiliation: Department of Hand and Plastic Surgery, Burns and Intensive care and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Tesselaar
authors.affiliation: Department of Hand and Plastic Surgery, Burns and Intensive care and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Folke
authors.initials: F
authors.lastname: Sjöberg
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000493:pharmacokinetics; D000328:Adult; D005260:Female; D006801:Humans; D007478:Iontophoresis; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000493:pharmacokinetics; D008833:Microcirculation / Q000187:drug effects*; D008955:Models, Cardiovascular; D009638:Norepinephrine / Q000008:administration & dosage / Q000493:pharmacokinetics; D012867:Skin / Q000098:blood supply*
chemical_list: D016210:Methacholine Chloride; D000109:Acetylcholine; D009638:Norepinephrine
keywords: acetylcholine; iontophoresis; methacholine; microcirculation; noradrenaline; skin