Different patterns of mast cell activation by muscle relaxants in human skin

Background: Activation of mast cells and systemic release of histamine are major side effects of intravenously administered muscle relaxants. In the c urrent study, dermal microdialysis was used for the investigation of mast c ell activation by muscle relaxants. Dermal microdialysis enabled simultaneo us assessment of mediator release, vascular reactions, and sensory effects induced by intradermal application of muscle relaxants without systemic sid e effects. Methods: Succinylcholine, the isoquinotines cisatracurium, atracurium, and mivacurium, and the steroids pancuronium, vecuronium, rocuronium, and rapac uronium were tested in human volunteers (n = 6 each). After intradermal ins ertion of microdialysis capillaries (0.4 mm diameter, cutoff 3,000 kd) and a 60-min equilibration period, the muscle relaxants were delivered via the capillaries for 30 min, followed by a 30-min washout period. Dialysate was sampled at 15-min intervals, and histamine, mast cell tryptase, and protein extravasation were determined. Changes in skin blood flow were measured us ing a laser Doppler imager. Potency and efficacy were derived from nonlinea r fittings of the dose-response curves. Results. For succinylcholine and the isoquinolines, dose-response curves fo r the vascular and sensory effects paralleled the histamine and tryptase re lease. In contrast, aminosteroids evoked a rapid histamine release that was accompanied by a delayed increase in tryptase. Conclusions: Dermal microdialysis has been successfully used to simultaneou sly assess mediator release, vascular reactions, and sensory effects. The d ifferent pattern of tryptase release by isoquinolines and aminosteroids sug gests different mechanisms of mast cell activation.