MALIGNANT HYPERTHERMIA (MH) DIAGNOSTICS - A COMPARISON BETWEEN THE HALOTHANE-CAFFEINE-TEST AND THE RYANODINE-CONTRACTURE-TEST RESULTS IN MH-SUSCEPTIBLE, NORMAL AND CONTROL MUSCLE

Recent studies demonstrated different contracture responses in muscle from malignant hyperthermia susceptible (MHS) compared to normal (MHN) individuals following exposure to the plant alkaloid ryanodine in-vit ro. To confirm if ryanodine has a specific action in MHS muscle, the e ffect of a single concentration was investigated in skeletal muscle fr om MHS, MHN and control subjects using a new evaluation technique. In- vitro contracture test (IVCT) and MH diagnosis were per formed accordi ng to the European Protocol in 86 patients sent to us for MH diagnosti c testing and in 24 controls. Viable fresh muscle bundles were exposed to a single bolus of ryanodine 1.0 mu M. Contracture onset time (OTp: defined as the time (min) from administration of ryanodine to the sta rt of a contracture as measured by a contracture exceeding predrug bas eline height), and the time to an increase of the baseline height to 1 0 mN above the predrug level (10Tp) were recorded. 29 patients were id entified by IVCT to be MHS, 50 MHN, 7 MHE (equivocal) and 24 controls MHN. The indices from the ryanodine test separated all MHS (OTp: <16 m in; 10Tp <27.4 min) from MHN (>18 and >27.7 min) and control subjects (>17.4 and >29 min). Values for MHE (equivocal) individuals ranged fro m 17.1 to 27.8 min for the OTp and from 32 to 49.2 min for the 10Tp. 5 patients with fulminant MH crises were included in the MHS group and showed the 95% confidence intervals (Ct) of the median value less than or equal to 8.05min (OTp) and less than or equal to 13.35min (10TP) f or MHS. In contrast, CI of the median value for the control group were found to be greater than or equal to 25.2min (OTp) and 43.15min (10Tp ) for normal muscle. Thus the ryanodine test protocol showed markedly different contractures in MHS and MHN or control muscle. These results suggest that MHS muscle has a higher sensitivity to ryanodine. Howeve r, the protocol should be investigated for reproducibility and validat ion of thresholds by other laboratories. Ryanodine can help to improve MH diagnostic tests.