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OtherCELLULAR AND MOLECULAR PHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics September 1997, 282 (3) 1331-1336;
Roberto T. Sudo
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Thomas E. Nelson
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Abstract

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.

Footnotes

  • Send reprint requests to: Dr. Thomas E. Nelson, Department of Anesthesia, Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1009.

  • 1 This work was supported by National Institutes of Health Grant GM23875 and by CAPES/MEC/CNPq/Brazil.

  • Abbreviations:
    MHS
    malignant hyperthermia susceptible
    MHN
    malignant hyperthermia nonsusceptible
    Ry1
    ryanodine receptor calcium release channel
    CHCT
    caffeine-halotrane-contracture test
    RCT
    ryanodine-contracture test
    Pt
    maximal tension amplitude
    CSA
    cross-sectional area
    MHE
    malignant hyperthermia equivocal
    • Received January 27, 1997.
    • Accepted May 12, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 282, Issue 3
1 Sep 1997
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OtherCELLULAR AND MOLECULAR PHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics September 1, 1997, 282 (3) 1331-1336;

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OtherCELLULAR AND MOLECULAR PHARMACOLOGY

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
Journal of Pharmacology and Experimental Therapeutics September 1, 1997, 282 (3) 1331-1336;
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