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

• Published in: Anesthesiology (Philadelphia) 2001-09, Vol.95 (3), p.659-667
• Main Authors: KOPPERT, Wolfgang, BLUNK, James A, PETERSEN, Lars J, SKOV, Per, RENTSCH, Katharina, SCHMELZ, Martin
• Format: Article
• Language: English
• Subjects: Adult; Atracurium - analogs & derivatives; Atracurium - pharmacology; Biological and medical sciences; Dose-Response Relationship, Drug; Double-Blind Method; Drug toxicity and drugs side effects treatment; Female; Histamine Release - drug effects; Humans; Male; Mast Cells - drug effects; Mast Cells - physiology; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Neuromuscular Blocking Agents - pharmacology; Pharmacology. Drug treatments; Regional Blood Flow - drug effects; Serine Endopeptidases - metabolism; Skin - blood supply; Skin - drug effects; Succinylcholine - pharmacology; Tryptases
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-200109000-00019

Activation of mast cells and systemic release of histamine are major side effects of intravenously administered muscle relaxants. In the current study, dermal microdialysis was used for the investigation of mast cell activation by muscle relaxants. Dermal microdialysis enabled simultaneous assessment of mediator release, vascular reactions, and sensory effects induced by intradermal application of muscle relaxants without systemic side effects. Succinylcholine, the isoquinolines cisatracurium, atracurium, and mivacurium, and the steroids pancuronium, vecuronium, rocuronium, and rapacuronium were tested in human volunteers (n = 6 each). After intradermal insertion 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 using a laser Doppler imager. Potency and efficacy were derived from nonlinear fittings of the dose-response curves. For succinylcholine and the isoquinolines, dose-response curves for the vascular and sensory effects paralleled the histamine and tryptase release. In contrast, aminosteroids evoked a rapid histamine release that was accompanied by a delayed increase in tryptase. Dermal microdialysis has been successfully used to simultaneously assess mediator release, vascular reactions, and sensory effects. The different pattern of tryptase release by isoquinolines and aminosteroids suggests different mechanisms of mast cell activation.