The ryanodine contracture test may help diagnose susceptibility to malignant hyperthermia

Purpose: The ryanodine contracture test (RCT) using the plant alkaloid ryanodine as the triggering agent has been proposed to reduce equivocal results of the in vitro caffeine-halothane-contracture test (IVCT), which is the accepted and standardized procedure to diagnose malignant hyperthermia (MH). However, the response of skeletal muscle of non-MH affected patients (controls) to ryanodine has not yet been characterized. Methods: Skeletal muscle biopsies were studied in 33 controls and in six patients with a history of fulminant MH, Following the lVCT, the RCT was performed in all specimens using ryanodine 1 muM. Onset time of contracture and time to reach a contracture level of 10 mN above lowest resting tension and above predrug tension were calculated. Results: With the standard lVCT, all controls were labelled MH non-susceptible; all clinically diagnosed MH patients were labelled MH susceptible. With ryanodine, control muscle differed from MH susceptible muscle regarding onset time of contracture (26 vs 3.8 min, P < 0.05) and time to reach a contracture of 10 mN ( 49 vs 12.5 min, P < 0.05; all median). Tissue viability and patient's age significantly influenced contracture times. Conclusions: Despite the highly specific binding of ryanodine at the myocytic sarcoplasmic reticulum, the wide range of contracture times of the controls points toward heterogeneity of ryanodine receptors within physiologic limits. This may also be caused in part by tissue viability and the patients' age. The ryanodine contracture test performed in addition to the lVCT may add clarity into diagnosing a patient as MH-susceptible or not.