MODULATION OF RYANODINE-INDUCED CONTRACTURES IN HUMAN SKELETAL-MUSCLEPRETREATED WITH DANTROLENE

Dantrolene seems to be the causal therapy in malignant hyperthermia (M H) crisis but the complex mechanisms of MH and dantrolene therapy are still not fully understood The influence of dantrolene on ryanodine-in duced contractures has been reported in animal studies only. In the pr esent study 20 patients from 17 families were tested for MH using the protocol of the European Malignant Hyperthermia Group. In addition rya nodine induced contractures were evaluated following bolus application of 10.0 mu mol . l(-1) ryanodine. Alter pretreatment with 1 mu mol . l(-1) dantrolene ryanodine-provoked contractures developed significant ly later in MHS (15.8+/-1.8 min) and MHN (46.0+/-4.2 min) muscle speci mens than after ryanodine alone (MHS 4.8+/-0.7 min), (MHN 13.7+/-0.9 m in). They were no longer observed in either group after pretreatment w ith 5 mu mol . l(-1) dantrolene. We conclude that dantrolene is able t o attenuate ryanodine-induced contractures dose-dependently, and there fore it is speculated that dantrolene could specifically act at the ry anodine receptor binding site.