Cutaneous microdialysis : a technique for human in vivo sampling

Abstract: Microdialysis enables in vivo sampling of endogenous and exogenous substances in the interstitial fluid. A probe equipped with a tubular semi-permeable dialysis membrane is inserted into the skin, and perfused with a physiological solution. Diffusion of molecules from the extracellular space to the perfusate takes place, and the perfusate is collected for analysis. In this thesis, experimental and clinical applications of human cutaneous microdialysis in the fields of skin inflammation and percutaneous absorption are presented.The in vivo absorption kinetics of the model solvents ethanol and isopropanol, applied in excess to the skin over the dialysis probe, could be demonstrated in all subjects. Ethanol levels increased in a linear fashion to reach a peak at about 100 min, then establishing a plateau level. Isopropanol absorption showed similar kinetics. The absolute levels detected were lower for isopropanol than for ethanol.Laser Doppler perfusion imaging visualized the skin circulatory response to the microdialysis probe insertion. An immediate increase in skin blood perfusion was observed. The response began to subside after 15 min and returned to near normal within 60 min after probe insertion.Histamine, a ubiquitous inflammatory mediator, was studied as a model. Following the skin trauma caused by probe insertion, peak histamine levels were observed in the first 10-min sample, then falling successively to reach baseline within 40-60 min. Multiple regression analysis did not reveal any correlation between probe depth, as measured by ultrasoundtechnique, and obtained histamine levels during the equilibration period following probe insertion. Provocation with compound 48/80 as a positive control for skin histamine release, resulted in increased histamine levels in the perfusate. Histamine release was followed in reactions provoked in the skin of patients with cold urticaria. An up to 80-fold increase of histamine levels was observed, with peak levels 20-30 min after start of ice provocation, returning to baseline within 50-60 min.Human, in vivo, cutaneous microdialysis has the potential to be an important sampling method in studies of skin inflammation and percutaneous absorption of noxious chemicals as well as in dennal and transdermal drug delivery studies.