CHANGES IN RYANODINE-INDUCED CONTRACTURES BY STIMULUS FREQUENCY IN MALIGNANT HYPERTHERMIA SUSCEPTIBLE AND MALIGNANT HYPERTHERMIA NONSUSCEPTIBLE DOG SKELETAL-MUSCLE

Authors
Citation
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
Citations number
31
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00223565
Volume
282
Issue
3
Year of publication
1997
Pages
1331 - 1336
Database
ISI
SICI code
0022-3565(1997)282:3<1331:CIRCBS>2.0.ZU;2-M
Abstract
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.