In Vitro Diagnosis of Malignant Hyperthermia Susceptibility with Ryanodine-Induced Contractures in Human Skeletal Muscles

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Abstract
The in vitro contracture test with ryanodine is a new method to distinguish malignant hyperthermia (MH) susceptible (MHS) from normal (MHN) patients. The purpose of our investigation was to determine whether smaller concentrations of ryanodine than those used previously may result in a better differentiation. We performed a ryanodine contracture test (RCT) using concentrations of 1 and 2 microM in muscle specimens of 41 MHS, 58 MHN, and 19 MH-equivocal (MHE) patients. Nine patients were excluded from the study due to neuromuscular diseases. All contracture levels (i.e., start of contractures, contractures of 0.2 g and 1.0 g) were attained significantly earlier in MHS than in MHN muscles at both concentrations of ryanodine. Using a ryanodine concentration of 2 microM, all contracture levels were reached significantly faster than with 1 microM. There was no overlap in the range of times between groups at all contracture levels with ryanodine 1 and 2 microM. The median threshold times for all MHE patients were always between those of MHS and MHN. Defining arbitrarily threshold times for MHS and MHN, an assignment of MHE patients to either MHS or MHN using 1 or 2 microM ryanodine was possible in most cases. Ryanodine administration at a concentration of 1 microM led to a better distinction of MHS from MHN patients than 2 microM. The RCT with ryanodine 1 microM should therefore be added to the current diagnostic methods.