INOSITOL 1,4,5-TRISPHOSPHATE IN BLOOD AND SKELETAL-MUSCLE IN HUMAN-MALIGNANT HYPERTHERMIA

The in vitro contracture test (IVCT) is the only available diagnostic method at present for evaluation of malignant hyperthermia (MH) suscep tibility. However, the disadvantage of the IVCT is that it is invasive . Several studies suggest that an altered inositol phosphate system is involved in the development of MH. A greater concentration of inosito l 1,4,5-trisphosphate (1,4,5-IP3) was found in MH susceptible (MHS) th an in normal (MHN) skeletal muscles. In this study the concentrations of 1,4,5-IP3 in blood samples and skeletal muscle specimens of identic al patients were measured in an attempt to define susceptibility to MH . Muscle biopsies were obtained from 34 patients with clinical suspici on of MH. Patients were first classified as MHS (n=19), MHN (n=8) or M H equivocal (MHE; n=7) by the standard IVCT. For detection of 1,4,5-IP 3 concentrations, blood samples were obtained and an additional muscle specimen was excised. After sample preparation, concentrations of 1,4 ,5-IP3 were measured using radioimmunoassay. In blood samples, concent rations of 1,4,5-IP3 were similar in all individuals tested for MH sus ceptibility and in control patients not tested for MH susceptibility ( n=44). In skeletal muscle, 1,4,5-IP3 concentrations were significantly higher in MHS than in MHE or MHN patients, respectively. Each MHS sam ple contained more 1,4,5-IP3 than the highest concentration measured i n MHN muscle. Defining arbitrary thresholds for 1,4,5-IP3 concentratio n in skeletal muscles in order to discriminate between MHS and MHN sta tus, it was possible to assign three MHE patients to MHS and four to M HN. This study supports the hypothesis that an altered inositol phosph ate system might be involved in MH. However, measurement of 1,4,5-IP3 concentration in a simple blood sample preparation is not reliable for MH susceptibility screening.