Effects of dantrolene on myoplasmic free [Ca2+] measured in vivo in patients susceptible to malignant hyperthermia

J. R. Lopez, A. Gerardi, M. J. Lopez, P. D. Allen

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Malignant hyperthermia (MH) is a genetic disease characterized by hypermetabolism in skeletal muscle following a triggering stimulus and can be reversed or pretreated with dantrolene sodium. The myoplasmic free [Ca2+] was measured, using Ca2+ selective microelectrodes in vivo in the superficial fibers of the sartorius muscle of eight MH-susceptible and eight control subjects. Both groups received continuous epidural anesthesia with chloroprocaine 3%. In both the control and MH muscle fibers, the myoplasmic free [Ca2+] was measured before and after the intravenous administration of a cumulative dantrolene dose of 0.5, 1.5, and 2.5 mg/kg. The mean resting myoplasmic free [Ca2+] was 0.112 ± 0.004 μM (mean ± SEM n = 32) in the control and 0.485 ± 0.022 μM (n = 33) in the MH subjects. In the MH subjects, dantrolene induced a dose-dependent reduction in myoplasmic free [Ca2+]. The 0.5-mg/kg dose reduced it to 0.326 ± 0.017 μM (n = 22), the 1.5-mg/kg dose to 0.233 ± 0.015 μM (n = 25), and the 2.5-mg/kg dose to 0.092 ± 0.008 μM (n = 26). In controls, dantrolene also reduced resting myoplasmic free [Ca2+] but to a lesser extent. The 0.5-mg/kg dose reduced it to 0.096 ± 0.004 μM (n = 22), the 1.5-mg/kg dose to 0.077 ± 0.003 μM (n = 23), and the 2.5-mg/kg dose to 0.068 ± 0.002 μM (n = 27). The results of the study extend our previous findings in humans and swine and demonstrate that it is possible to measure myoplasmic free [Ca2+] in vivo in humans. They also demonstrate that the effect of administration dantrolene on human skeletal muscle in vivo is associated with a dose-dependent reduction in the myoplasmic free [Ca2+].

Original languageEnglish (US)
Pages (from-to)711-719
Number of pages9
JournalAnesthesiology
Volume76
Issue number5
StatePublished - 1992
Externally publishedYes

Fingerprint

Dantrolene
Malignant Hyperthermia
Skeletal Muscle
Muscles
Inborn Genetic Diseases
Epidural Anesthesia
Microelectrodes
Intravenous Administration
Swine

Keywords

  • Malignant hyperthermia, ions: calcium
  • Measurement techniques, calcium: microelectrodes
  • Neuromuscular relaxants: dantrolene

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Effects of dantrolene on myoplasmic free [Ca2+] measured in vivo in patients susceptible to malignant hyperthermia. / Lopez, J. R.; Gerardi, A.; Lopez, M. J.; Allen, P. D.

In: Anesthesiology, Vol. 76, No. 5, 1992, p. 711-719.

Research output: Contribution to journalArticle

Lopez, J. R. ; Gerardi, A. ; Lopez, M. J. ; Allen, P. D. / Effects of dantrolene on myoplasmic free [Ca2+] measured in vivo in patients susceptible to malignant hyperthermia. In: Anesthesiology. 1992 ; Vol. 76, No. 5. pp. 711-719.
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AU - Allen, P. D.

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N2 - Malignant hyperthermia (MH) is a genetic disease characterized by hypermetabolism in skeletal muscle following a triggering stimulus and can be reversed or pretreated with dantrolene sodium. The myoplasmic free [Ca2+] was measured, using Ca2+ selective microelectrodes in vivo in the superficial fibers of the sartorius muscle of eight MH-susceptible and eight control subjects. Both groups received continuous epidural anesthesia with chloroprocaine 3%. In both the control and MH muscle fibers, the myoplasmic free [Ca2+] was measured before and after the intravenous administration of a cumulative dantrolene dose of 0.5, 1.5, and 2.5 mg/kg. The mean resting myoplasmic free [Ca2+] was 0.112 ± 0.004 μM (mean ± SEM n = 32) in the control and 0.485 ± 0.022 μM (n = 33) in the MH subjects. In the MH subjects, dantrolene induced a dose-dependent reduction in myoplasmic free [Ca2+]. The 0.5-mg/kg dose reduced it to 0.326 ± 0.017 μM (n = 22), the 1.5-mg/kg dose to 0.233 ± 0.015 μM (n = 25), and the 2.5-mg/kg dose to 0.092 ± 0.008 μM (n = 26). In controls, dantrolene also reduced resting myoplasmic free [Ca2+] but to a lesser extent. The 0.5-mg/kg dose reduced it to 0.096 ± 0.004 μM (n = 22), the 1.5-mg/kg dose to 0.077 ± 0.003 μM (n = 23), and the 2.5-mg/kg dose to 0.068 ± 0.002 μM (n = 27). The results of the study extend our previous findings in humans and swine and demonstrate that it is possible to measure myoplasmic free [Ca2+] in vivo in humans. They also demonstrate that the effect of administration dantrolene on human skeletal muscle in vivo is associated with a dose-dependent reduction in the myoplasmic free [Ca2+].

AB - Malignant hyperthermia (MH) is a genetic disease characterized by hypermetabolism in skeletal muscle following a triggering stimulus and can be reversed or pretreated with dantrolene sodium. The myoplasmic free [Ca2+] was measured, using Ca2+ selective microelectrodes in vivo in the superficial fibers of the sartorius muscle of eight MH-susceptible and eight control subjects. Both groups received continuous epidural anesthesia with chloroprocaine 3%. In both the control and MH muscle fibers, the myoplasmic free [Ca2+] was measured before and after the intravenous administration of a cumulative dantrolene dose of 0.5, 1.5, and 2.5 mg/kg. The mean resting myoplasmic free [Ca2+] was 0.112 ± 0.004 μM (mean ± SEM n = 32) in the control and 0.485 ± 0.022 μM (n = 33) in the MH subjects. In the MH subjects, dantrolene induced a dose-dependent reduction in myoplasmic free [Ca2+]. The 0.5-mg/kg dose reduced it to 0.326 ± 0.017 μM (n = 22), the 1.5-mg/kg dose to 0.233 ± 0.015 μM (n = 25), and the 2.5-mg/kg dose to 0.092 ± 0.008 μM (n = 26). In controls, dantrolene also reduced resting myoplasmic free [Ca2+] but to a lesser extent. The 0.5-mg/kg dose reduced it to 0.096 ± 0.004 μM (n = 22), the 1.5-mg/kg dose to 0.077 ± 0.003 μM (n = 23), and the 2.5-mg/kg dose to 0.068 ± 0.002 μM (n = 27). The results of the study extend our previous findings in humans and swine and demonstrate that it is possible to measure myoplasmic free [Ca2+] in vivo in humans. They also demonstrate that the effect of administration dantrolene on human skeletal muscle in vivo is associated with a dose-dependent reduction in the myoplasmic free [Ca2+].

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