title: A human vascular model based on microdialysis for the assessment of the vasoconstrictive dose-response effects of norepinephrine and vasopressin in skin.
abstract: OBJECTIVE
  Microdialysis enables drug delivery in the skin and simultaneous measurement of their effects. The present study aimed to evaluate dose-dependent changes in blood flow and metabolism during microdialysis of norepinephrine and vasopressin.
  
  
  METHODS
  We investigated whether increasing concentrations of norepinephrine (NE, 1.8-59 μmol/L) and vasopressin (VP, 1-100 nmol/L), delivered sequentially in one catheter or simultaneously through four catheters, yield dose-dependent changes in blood flow (as measured using urea clearance) and metabolism (glucose and lactate).
  
  
  RESULTS
  We found a significant dose-dependent vasoconstriction with both drugs. Responses were characterized by a sigmoid dose response model. Urea in the dialysate increased from a baseline of 7.9 ± 1.7 to 10.9 ± 0.9 mmol/L for the highest concentration of NE (p < 0.001) and from 8.1 ± 1.4 to 10.0 ± 1.7 mmol/L for the highest concentration of VP (p = 0.037). Glucose decreased from 2.3 ± 0.7 to 0.41 ± 0.18 mmol/L for NE (p = 0.001) and from 2.7 ± 0.6 to 1.3 ± 0.5 mmol/L for VP (p < 0.001). Lactate increased from 1.1 ± 0.4 to 2.6 ± 0.5 mmol/L for NE (p = 0.005) and from 1.1 ± 0.4 to 2.6 ± 0.5 mmol/L for VP (p = 0.008). There were no significant differences between responses from a single catheter and from those obtained simultaneously using multiple catheters.
  
  
  CONCLUSIONS
  Microdialysis in the skin, either with a single catheter or using multiple catheters, offers a useful tool for studying dose response effects of vasoactive drugs on local blood flow and metabolism without inducing any systemic effects.
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Kim Tchou
authors.initials: KT
authors.lastname: Folkesson
authors.forename: Anders
authors.initials: A
authors.lastname: Samuelsson
authors.forename: Erik
authors.initials: E
authors.lastname: Tesselaar
authors.forename: Bengt
authors.initials: B
authors.lastname: Dahlström
authors.forename: Folke
authors.initials: F
authors.lastname: Sjöberg
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D006801:Humans; D008297:Male; D017551:Microdialysis; D008955:Models, Cardiovascular; D009638:Norepinephrine / Q000008:administration & dosage*; D012867:Skin / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*; D014667:Vasopressins / Q000008:administration & dosage*
chemical_list: D014662:Vasoconstrictor Agents; D014667:Vasopressins; D009638:Norepinephrine