Effects of the phosphodiesterase-III inhibitor enoximone on skeletal muscle specimens from malignant hyperthermia susceptible patients

Study Objectives: To study the in vitro effects of the phosphodiesterase-II I inhibitor enoximone on skeletal muscle specimens from malignant hyperther mia susceptible (MHS) and normal (MHN) patients. Design: Prospective study. Setting: Malignant hyperthermia (MH) laboratory at a university hospital. Patients: 47 patients with clinical suspicion for MH undergoing in vitro co ntracture test (IVCT) for diagnosis of MH susceptibility. Interventions: Biopsies of M. quadriceps femoris were performed in adult pa tients with a 3-in-1 nerve block and in children with trigger-free general anesthesia. Measurements and Main Result: Patients were first classified as MHS or MHN by the IVCT according to the protocol of the European il VI Group (EMHG). P atients with equivocal results (MHE) or with neuromuscular diseases were ex cluded from the study. Enoximone was added to the organ bath to surplus vit al muscle specimens in single bolus concentrations of 0.4, 0.6, 0.8, or 1.6 mmol/L. The in vitro effects of enoximone on muscle contractures and twitc h were measured. Seventeen patients were classified as MHS and 30 as MHN by the EMHG criteria. Enoximone induced contractures in skeletal muscles in a dose-dependent manner Contractures of MHS compared to MHN muscle specimens were significantly larger at all concentrations used in this study. No ove rlap in maximum contractures was seen between MHS and MHN muscles at a bath concentration of 0.6 mmol/L enoximone only. Conclusions: Diagnosis of MH by an IVCT test with a single bolus administra tion of enoximone seems to be possible using a concentration of 0.6 mmol/L. The findings of this study may indicate an involvement of the phosphodiest erase-III and cAMP system in pathogenesis of MH. Further in vivo investigat ion should determine the trigger potency of enoximone in MH susceptible ind ividuals. (C) 2000 by Elsevier Science Inc.