Is a presymptomatic malignant hyperthermia in-vitro diagnosis with 4-chloro-3-ethyl phenol possible? A study using porcine skeletal preparations

The diagnosis of malignant hyperthermia is currently performed with the in-vitro contracture test (IVCT) with halothane and caffeine. This test has a sensitivity of 99.0 % but only a specificity of 93.6 %. A cumulative IVCT with 4-chloro-3-ethyl-phenole (CEP) has recently been shown to differentiate between MH susceptible (MHS) and MH normal (MHN) swine. The pur-pose of this study was to investigate the ability of bolus CEP-applications to distinguish between porcine MHS- and MHN-muscle specimens using the IVCT. After approval by the local animal care committee 8 MHS- and 8 MHN-swine were anaesthetized and muscle biopsies taken. For IVCT, muscle specimens were exposed to bolus administration of CEP in concentrations of 75 resp. 100 micro mol l (-1). Predefined parameters were: (1) onset time of the contracture development, (2) time to the achievement of the 2, 5 and 10 mN contracture level and (3) maximum contracture level. Data are expressed as medians and ranges. After 75 micro mol l (-1) CEP administration all MHS-muscles showed contractures after 0.5 min (0.2 min/0.9 min). The 2 mN contracture level was reached by all MHS-, the 5 mN level by four MHS- and the 10 mN level by one MHS-specimen. The maximum contracture was 5.3 mN (2.4 mN/12.9 mN). The onset time after 100 micro mol l (-1) CEP was registered as 0.3 min (0.1 min/0.7 min) in the MHS-preparations. Again, the 2 mN level was achieved by all MHS-specimens, the 5 mN level by 5 and the 10 mN level by one MHS-bundle. The maximum contracture was measured as 5.9 mN (2.8 mN/13.9 mN). In 7 MHN-specimens no contracture development was measured. After 75 micro mol l (-1) CEP one MHN-muscle showed a maximum contracture of 1.0 mN, after 100 micro mol l (-1) CEP one MHN-bundle demonstrated a maximum contracture of 1.1 mN. Hence, a significant difference between MHS and MHN without overlap was revealed with both CEP-concentrations in the onset time of contracture, in the 2 mN contracture level and the maximum contracture. Since a clear differentiation between MHS and MHN porcine specimens was achieved after bolus application of 75 and 100 micro mol l (-1) CEP, MH-diagnosis might be possible with a CEP-IVCT. It seems worthwhile to examine this hypothesis in men.