In vitro muscle contractures induced by halothane and suxamethonium. II: Human skeletal muscle from normal and malignant hyperthermia susceptible patients.
The role of lipolysis in halothane-induced contractures of human skeletal muscle was examined using three inhibitors of phospholipase A2 (PLA2) activity (quinacrine, spermine and indomethacin) and exogenously administered PLA2. In addition, we examined the effects of the same PLA2 inhibitors on contractures induced by halothane in combination with suxamethonium. The studies were conducted on directly stimulated muscle strips isolated from biopsies from patients diagnosed as MH susceptible, or not susceptible, by the halothane contracture test. The liberation of fatty acids from skeletal muscle homogenates was examined to determine whether PLA2 activity might be increased in MH susceptible patients. The three PLA2 inhibitors antagonized halothane-induced contractures of muscle from MH susceptible patients as well as induction of contractures by suxamethonium and halothane. Pre-exposing preparations that were previously unresponsive to halothane to bee venom PLA2 caused the muscle strips to respond with contractures upon subsequent challenge with halothane, but not with suxamethonium. Free fatty acid production during an in vitro incubation of skeletal muscle homogenates was greater in preparations from MH susceptible patients than in those from patients who were not susceptible. These results suggest that excess liberation of fatty acids may be involved in halothane-induced contractures of muscle from MH susceptible individuals, in the synergism observed between halothane and suxamethonium, and in human MH.
D004198:Disease Susceptibility; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008305:Malignant Hyperthermia / Q000378:metabolism / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000378:metabolism; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D013390:Succinylcholine / Q000494:pharmacology*
D005230:Fatty Acids, Nonesterified; D013096:Spermine; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D013390:Succinylcholine; D006221:Halothane; D007213:Indomethacin