Dose-dependent increase of transcapillary diffusion of sodium fluorescein after histamine microinjections.
BACKGROUND
To study the dose-dependent effects of histamine on capillary permeability in human skin, using the microinjection technique.


METHODS
Eight healthy volunteers (2 w, 6 m; mean age 33 years) were included in the study. On two separate occasions, glass microcannulas with a tip diameter of 7 to 9 microns were inserted into the subepidermal layer of the skin at the distal medial tibia surface of each lower limb with a micromanipulator. In each subject, 0.5 microliter of 3 different concentrations of histamine solution (0.1/1000, 0.01/1000 and 0.001/1000) were injected and compared to the solvent (0.9% NaCl). Transcapillary diffusion of intravenously administered Na-fluorescein was assessed simultaneously using two fluorescence videomicroscopy systems. Off-line video densitometry was performed in an area of 0.56 mm2 around the injection sites and fluorescence light intensities were measured in arbitrary units (AU) at 10, 30, 60, 120 and 600 s after dye appearance.


RESULTS
Compared to the solvent histamine microinjections resulted in a dose-dependent increase of mean fluorescence light intensities (FLI). Whereas mean FLI for the 0.001/1000 histamine injection was only significantly elevated 10 min after dye appearance (p < 0.05) an increase of mean FLI was already observed 10 s after dye appearance following the 0.1/1000 histamine injection (p < 0.05), which was more pronounced at later time points (p < 0.001). Mean FLI's for the 0.01/1000 histamine solution were in between and resulted in significantly elevated values 1 min to 10 min after dye appearance (p < 0.05).


CONCLUSIONS
We conclude that the microinjection technique together with fluorescence videomicroscopy described previously [6] is able to document a dose-dependent effect of histamine microinjections on skin capillary permeability. The technique may facilitate to determine appropriate dosages not only of histamine in order to test the effect of antagonists on human skin capillary permeability.
Department of Internal Medicine, University Hospital Zurich, Switzerland.
S
S
Läuchli
U K
UK
Franzeck
A J
AJ
Leu
U
U
Hoffmann
D000328:Adult; D002199:Capillary Permeability / Q000187:drug effects*; D003720:Densitometry; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D005260:Female; D019793:Fluorescein / Q000493:pharmacokinetics*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008845:Microinjections; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D008875:Middle Aged; D012867:Skin / Q000098:blood supply*
D006632:Histamine; D019793:Fluorescein