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

Study Objectives: To define threshold times for ryanodine contracture testing (RCT) using skeletal muscle specimens from malignant hyperthermia-susceptible (MHS) and control individuals.

Design: Prospective study.

Setting: Malignant hyperthermia (MH) laboratory at a university hospital.

Patients: 8 patients with previous fulminant MH and 53 control patients undergoing in vitro contracture test (IVCT) for diagnosis of MH susceptibility.

Interventions: Biopsies of the quadriceps femoris muscle were performed with a 3-in-1 nerve block, with spinal anesthesia, or with trigger-free general anesthesia.

Measurements And Main Results: Patients were classified as MHS, MH normal (MHN), or MH equivocal (MHE) by the IVCT according to the protocol of the European MH Group (EMHG). Ryanodine 1 microM was added as a bolus to the organ bath to extra vital muscle specimens. Contracture levels were defined as: 1 = start of contracture (OT; min); 2 = time (min) to reach a contracture of 2 mN, and 3 = time (min) to reach a contracture of 10 mN. The effects of ryanodine on contracture responses were measured. Ryanodine induced contractures in all specimens. MHS specimens reached all defined contracture levels significantly sooner than did the controls. Ryanodine contracture test enables a clear discrimination of MHS specimens from controls at contracture levels of OT and 2 mN, whereas at 10 mN a small overlap was observed.

Conclusions: Using this test, which is an experimental approach from a single laboratory, an assignment to MHS or MHN is possible. To define contracture levels for RCT more precisely and to agree on commonly used thresholds, multicenter studies with larger numbers of patients are required.