CLASSIFICATION OF MALIGNANT HYPERTHERMIA EQUIVOCAL PATIENTS BY 4-CHLORO-M-CRESOL

To clarify the contracture response to 4-chloro-m-cresol (4-CmC) in ma lignant hyperthermia (MH) equivocal (MHE) muscle, we studied the effec t of cumulative concentrations of 4-CmC. In vitro contracture test (IV CT) was performed in 35 probands according to the European MH test pro tocol Surplus muscle bundles were exposed to 4-CmC (25-200 mu mol/L), maintaining each concentration for 4 and 8 min. After 4 min exposure, the contracture increase of MH susceptible (MHS) (n = 7) muscle specim ens was significantly (P = 0.05) greater at 50 mu mol/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 mu mol/L. Exposure for 8 min yielded signif icant differences at 50 mu mol/L only between MHS and MHEh. MHEh muscl es revealed a dose-response curve similar to that found in MHN specime ns. MHS muscles showed a significantly higher sensitivity to 4-CmC tha n 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. Th erefore, 4-CmC might reduce the frequency of MHEh diagnosis based on s tandard halothane-caffeine IVCT. However, since MHE individuals may al so represent an aberrant genetic status, with MH causing defects linke d to unknown mutations, it is premature to consider 4-CmC as a solutio n to the diagnostic uncertainty of the true status of MHE probands. Pr esently, 4-CmC may provide supplementary information for a more precis e phenotypic categorization of MHE individuals.