Validation of laser Doppler flowmetry coupled with intra-dermal injection for investigating effects of vasoactive agents on the skin microcirculation in man.
OBJECTIVE
To determine the reproducibility of laser Doppler flowmetry coupled with intra-dermal saline delivery.


METHODS
Delivery of saline was judged visually by two operators ( n=100), using a graduated syringe (Becton-Dickinson), by expelling saline onto a weighing boat. Volume was assessed by weight. Skin blood flow following intra-dermal injection of saline was assessed in 18 healthy volunteers; 10 attended twice to assess between-day reproducibility, and 8 attended once to assess between-site reproducibility. Results are expressed as mean value+/-SEM and 95% confidence interval for mean differences.


RESULTS
There was no difference between operators in mean injection weight, both weights being 10.3+/-0.1 mg (mean difference 0.08, 95% confidence interval, CI -0.23 to 0.39 mg; n=100, P=0.9). Intra-dermal saline caused a nine-fold increase in blood flow (0.03+/-0.003 to 0.27+/-0.02 perfusion units, PU; n=18, P<0.001). This response had a rapid onset, with the maximal effect seen at 4 min and a duration of greater than 30 min. There was no difference in the magnitude of the response between the dominant and non-dominant arms, AUC was 2.9+/-0.4 and 2.9+/-0.4, respectively (mean difference -0.05, 95% CI -0.8 to 0.73 PU; n=18, P=0.93). However, there was a trend towards differences between study visits 1 and 2: AUC was 3.2+/-0.6 and 2.0+/-0.5, respectively (mean difference 1.2, 95% CI -0.03 to 2.43 PU; n=10, P=0.7). There was no difference in the magnitude of responses between different sites on the forearm ( n=64, P=0.6).


CONCLUSIONS
These studies demonstrate that the technique of laser Doppler flowmetry coupled with intra-dermal injection is a safe, well-tolerated technique with good reproducibility. A trend towards reduced between-day reproducibility emphasizes the importance of vehicle control sites when investigating the effects of vasoactive compounds. This technique provides a reliable method for the intra-dermal delivery of drugs, despite the direct effect of injection of saline on blood flow.
Leslie
Stephen J
SJ
Clinical Pharmacology Unit and Research Centre, The University of Edinburgh, Western General Hospital, EH4 2XU, Edinburgh, UK.
Affolter
Jonathan
J
Denvir
Martin A
MA
Webb
David J
DJ
D000328:Adult; D006801:Humans; D007271:Injections, Intradermal; D017078:Laser-Doppler Flowmetry / Q000379:methods*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D015203:Reproducibility of Results; D012867:Skin / Q000098:blood supply*; D012965:Sodium Chloride / Q000008:administration & dosage*; D013997:Time Factors
D012965:Sodium Chloride