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Validation of laser Doppler flowmetry coupled with intra-dermal injection for investigating effects of vasoactive agents on the skin microcirculation in man

  • Pharmacodynamics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

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.

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Acknowledgements

S.J.L. and J.T.A. were supported by British Heart Foundationships (FS/98040 and FS/2000021).

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Correspondence to David J. Webb.

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Leslie, S.J., Affolter, J., Denvir, M.A. et al. Validation of laser Doppler flowmetry coupled with intra-dermal injection for investigating effects of vasoactive agents on the skin microcirculation in man. Eur J Clin Pharmacol 59, 99–102 (2003). https://doi.org/10.1007/s00228-003-0577-3

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  • DOI: https://doi.org/10.1007/s00228-003-0577-3

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