Accelerated Contractures After Administration of Ryanodine to Skeletal Muscle of Malignant Hyperthermia Susceptible Patients

Ryanodine contracture threshold times for diagnosis of malignant hyperthermia susceptibility: An experimental approach from a single laboratory

“…Following this investigation, further studies were performed to find the optimal administration technique. 9,10,13,16,17 The best discrimination was found with the use of high-purity ryanodine instead of a mixture of high-purity ryanodine and 9,21-dehydroryanodine. Further studies investigated different concentrations of ryanodine.…”

“…5,6 The diagnostic use of ryanodine in the IVCT has shown in several investigations to discriminate between MHS and MHN in swine and humans. [7][8][9][10] To improve MH diagnosis and to reduce the number of MHE results following IVCT, an additional optional ryanodine contracture test (RCT) has been implemented as part of the protocol of the EMHG. However, up to now, the EMHG has not defined or agreed on commonly used threshold times for ryanodine contracture testing to enable reliable differentiation between MHS and MHN patients.…”

The ryanodine contracture test may help diagnose susceptiblity to malignant hyperthermia

“…15 Ryanodine, devoid of these secondary effects, was proposed as a favourable substance to diagnose MHS by a contracture test and thus to reduce equivocal results (MHE) of the IVCT. [10][11][12]16 Published data comparing results of MHS, MHE and MHN patients support this contention. 13 Since the definition, validation and reproducibility of diagnostic thresholds as well as the identification of patient and testing procedure associated influences is of paramount importance for a diagnostic test, we investigated skeletal muscle of patients with no personal or family history of any neuromuscular disease or anesthesia complication.…”

“…However, the contracture data regarding the variables OT, 10T, OTp and 10Tp are comparable with published data from MHN patients. 11,12 We investigated the possible influence of methodological factors such as pre-testing viability of the muscle bundles, patients' sex and age on the RCT. Viability of the tested muscle bundles was ensured by applying the viability criterion of the European protocol, i.e., a minimum predrug twitch amplitude of 10 mN.…”

“…Hence, an in vitro contracture test using ryanodine as the pharmacological trigger (RCT) has been proposed to supplement the IVCT and thereby improve specificity and reduce equivocal results. [10][11][12] In an earlier study by our laboratory, primary results of the RCT in 24 healthy individuals have been compared to the range of contractures induced in skeletal muscle of five patients having survived a fulminant MH episode and the general usefulness of this test was demonstrated. 13 However, potential patient-or testing procedurerelated influences on the RCT have so far not been investigated, which is a prerequisite for the implementation of a new diagnostic test.…”