Dose-dependent increase of transcapillary diffusion of sodium fluorescein after histamine microinjections

Background: To study the dose-dependent effects of histamine on capillary p ermeability in human skin, using the microinjection technique. Patients and methods: Eight healthy volunteers (2 w, 6 m; mean age 33 years ) were included in the study. On two separate occasions, glass microcannula s with a rip diameter of 7 to 9 mu m were inserted into the subepidermal la yer of the skin at the distal medial tibia surface of each lower limb with a micromanipulator In each subject, 0.5 mu l of 3 different concentrations of histamine solution (0.1 parts per thousand 0.01 parts per thousand and 0 .001 parts per thousand) were injected and compared to the solvent (0.9% Na Cl). Transcapillary diffusion of intraveneously administered Na-fluorescein was assessed simultaneously using two fluorescence videomicroscopy systems . Off-line video densitometry was performed in art area of 0.56 mm(2) aroun d the injection sites and fluorescence light intensities were measured in a rbitrary units (AU) at 10, 30, 60, 120 and 600 s after dye appearance. Results: Compared to the solvent histamine microinjections resulted in a do se-dependent increase of mean fluorescence light intensities (FLI). Whereas mean FLI for the 0.001 parts per thousand histamine injection was only sig nificantly elevated 10 min after dye appearence (p < 0.05) an increase of m ean FLI was already observed 10 s after dye appearence following the 0.1 pa rts per thousand histamine injection (p < 0.05), which was more pronounced at later rime points (p < 0.001). Mean FLI's for the 0.01 parts per thousan d histamine solution were in between and resulted in significantly elevated values 1 min to 10 min after dye appearence (p < 0.05). Conclusions: We conclude that the microinjection technique together with fl uorescence videomicroscopy described previously [6] is able to document a d ose-dependent effect of histamine microinjections on skin capillary permeab ility. The technique may facilitate to determine appropriate dosages Mot on ly of histamine in order to test the effect of antagonists on human skin ca pillary permeability.