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.
Clinical Pharmacology Unit and Research Centre, The University of Edinburgh, Western General Hospital, EH4 2XU, Edinburgh, UK.
Stephen J
SJ
Leslie
Jonathan
J
Affolter
Martin A
MA
Denvir
David J
DJ
Webb
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