Primary myotubes as an alternative to the calcium induced calcium release test in diagnosing malignant hyperthermia susceptibility.

Authors

Sachiko Otsuki, Keiko Mukaida, Hirotsugu Miyoshi, Kenshiro Kido, Ayako Sumii, Tsuyoshi Ikeda, Takahiro Kato, Toshimichi Yasuda, Yousuke T Horikawa, Yasuko Ichihara, Yasuo M Tsutsumi

Published in

Journal of anesthesia. Jul 06, 2026. Epub Jul 06, 2026.

Abstract

Malignant hyperthermia (MH) is caused by the dysregulation of calcium (Ca²⁺) in skeletal muscle cells. In this study, we evaluated the accuracy of a method for diagnosing susceptibility to MH using myotubes as an alternative to Ca²⁺-induced Ca²⁺ release rate (CICR) test.
In this retrospective study, we retrospectively analyzed Ca²⁺ kinetics data obtained using fura-2/AM from myotubes that had been cultured from remnant muscle fibers of 98 patients who had previously undergone CICR testing for MH susceptibility in Japan. The 50% effective concentrations (EC₅₀) of caffeine and 4-chloro-m-cresol (4-CmC) were calculated from the concentration response curves. The previously calculated cut-off values (caffeine: 3.62 mM, 4-CmC: 197 μM) were used to diagnose susceptibility to MH. The diagnostic accuracy of myotubes was compared with that of the CICR test. Statistical significance was tested using the Mann-Whitney U test.
The CICR test identified 76 patients as CICR-Positive and 22 patients as CICR-Negative. The EC₅₀ for caffeine was 2.9 (2.4-3.3) and 5.0 (4.5-5.5) mM in the CICR-Positive and CICR-Negative groups, respectively (p < 0.0001). The EC₅₀ of 4-CmC was 130 (116-148) and 249 (226-289) μM in the CICR-Positive and CICR-Negative groups, respectively (p < 0.0001). The sensitivity for caffeine for myotubes was 98.7% (95%CI 92.9-99.9). The specificity for caffeine was 100% (95%CI 85.1-100.0). The sensitivity and specificity for 4-CmC were 100% (95%CI 95.2-100.0) and 100% (84.5-100.0), respectively.
Myotubes responses to caffeine and 4-CmC can be regarded as a viable alternative to the conventional CICR test; however, further validation is needed before this test supersedes the CICR.

PMID:
42406112
Bibliographic data and abstract were imported from PubMed on 06 Jul 2026.

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