CHANGES IN RYANODINE-INDUCED CONTRACTURES BY STIMULUS FREQUENCY IN MALIGNANT HYPERTHERMIA SUSCEPTIBLE AND MALIGNANT HYPERTHERMIA NONSUSCEPTIBLE DOG SKELETAL-MUSCLE
Rt. Sudo et Te. Nelson, CHANGES IN RYANODINE-INDUCED CONTRACTURES BY STIMULUS FREQUENCY IN MALIGNANT HYPERTHERMIA SUSCEPTIBLE AND MALIGNANT HYPERTHERMIA NONSUSCEPTIBLE DOG SKELETAL-MUSCLE, The Journal of pharmacology and experimental therapeutics, 282(3), 1997, pp. 1331-1336
Elective diagnosis of malignant hyperthermia depends on halothane and
caffeine contracture testing of biopsied skeletal muscle. Ryanodine-in
duced contractures may provide greater sensitivity and specificity for
malignant hyperthermia (MH) diagnosis. This study investigated the ef
fects of ryanodine concentration and stimulus frequency to distinguish
between MH susceptible (MHS) and MH non-susceptible (MHN) dogs. Incre
asing ryanodine concentrations (1, 2.5 and 5 mu M) increased peak isom
etric contracture tension, but similar responses in MHS and MHN muscle
precluded use for diagnosis. Time to tension onset and to peak tensio
n decreased with increasing ryanodine concentration, and these times w
ere 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 differe
nce between MHN and MHS muscle responses. When ryanodine contracture t
ension onset time was selected to detect MHS muscle, combinations of e
ither 0.1 Hz and 1 mu M ryanodine or 0.5 Hz and 1 mu M ryanodine reduc
ed the probabilty of a false diagnosis to less than 1%. Similar studie
s performed on human muscle might identify optimal stimulus frequency
and ryanodine concentration for detecting MH in patients.