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.