Vol. 282, Issue 3, 1331-1336, 1997

Changes in Ryanodine-Induced Contractures by Stimulus Frequency in Malignant Hyperthermia Susceptible and Malignant Hyperthermia Nonsusceptible Dog Skeletal Muscle

Roberto T. Sudo and Thomas E. Nelson

Departments of Basic and Clinical Pharmacology, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (R.T.S.) and Anesthesia, Bowman Gray School of Medicine, Winston-Salem, North Carolina (T.E.N.)

Elective diagnosis of malignant hyperthermia depends on halothane and caffeine contracture testing of biopsied skeletal muscle. Ryanodine-induced contractures may provide greater sensitivity and specificity for malignant hyperthermia (MH) diagnosis. This study investigated the effects of ryanodine concentration and stimulus frequency to distinguish between MH susceptible (MHS) and MH non-susceptible (MHN) dogs. Increasing ryanodine concentrations (1, 2.5 and 5 µM) increased peak isometric contracture tension, but similar responses in MHS and MHN muscle precluded use for diagnosis. Time to tension onset and to peak tension decreased with increasing ryanodine concentration, and these times were shorter in MH skeletal muscle. Increasing stimulus frequency (0.1, 0.5 and 1 Hz) decreased the time to tension onset and to peak tension, but the effect was greater in MHN muscle which decreased the difference between MHN and MHS muscle responses. When ryanodine contracture tension onset time was selected to detect MHS muscle, combinations of either 0.1 Hz and 1 µM ryanodine or 0.5 Hz and 1 µM ryanodine reduced the probabilty of a false diagnosis to less than 1%. Similar studies performed on human muscle might identify optimal stimulus frequency and ryanodine concentration for detecting MH in patients.