Classification of malignant hyperthermia-equivocal patients by 4-chloro-M-cresol.

To clarify the contracture response to 4-chloro-m-cresol (4-CmC) in malignant hyperthermia (MH) equivocal (MHE) muscle, we studied the effect of cumulative concentrations of 4-CmC. In vitro contracture test (IVCT) was performed in 35 probands according to the European MH test protocol. Surplus muscle bundles were exposed to 4-CmC (25-200 micromol/L), maintaining each concentration for 4 and 8 min. After 4 min exposure, the contracture increase of MH susceptible (MHS) (n = 7) muscle specimens was significantly (P = 0.05) greater at 50 micromol/L compared with either MHE halothane sensitive (MHEh) (n = 13) or MH normal (MHN) (n = 15) classified patients. Statistically significant differences (P < 0.05) were also found at 75 micromol/L. Exposure for 8 min yielded significant differences at 50 micromol/L only between MHS and MHEh. MHEh muscles revealed a dose-response curve similar to that found in MHN specimens. MHS muscles showed a significantly higher sensitivity to 4-CmC than either MHEh or MHN, and, in the probands tested so far, MHEh and MHN muscles seem to identically respond to 4-CmC, which seems to indicate a normal response in MHEh probands, implying no MH susceptibility. Therefore, 4-CmC might reduce the frequency of MHEh diagnosis based on standard halothane-caffeine IVCT. However, since MHE individuals may also represent an aberrant genetic status, with MH causing defects linked to unknown mutations, it is premature to consider 4-CmC as a solution to the diagnostic uncertainty of the true status of MHE probands. Presently, 4-CmC may provide supplementary information for a more precise phenotypic categorization of MHE individuals.