The effects of extracellular magnesium on myoplasmic [Ca2+] in malignant hyperthermia susceptible swine

J. R. Lopez, V. Sanchez, I. Lopez, J. F. Ryan, M. Mendoza, F. A. Sreter, P. D. Allen

Research output: Contribution to journalArticle

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Abstract

It is now well established that the pathophysiology of the malignant hyperthermia (MH) sydrome is related to a malfunction of intracellular calcium homeostasis. Magnesium plays important roles in the basic contractile properties of muscle, and many of its actions are antagonistic to those of calcium. The aim of this study was to determine the effectiveness of magnesium sulphate to prevent the MH episode in susceptible animals and correlate this with its effects on the intracellular free calcium ([Ca2+](i)). The experiments were carried out using six control (Yorkshire) and ten MH-susceptible crossbred swine (Poland China x Pietrain). After determination of resting concentrations of [Ca2+](i) and [Mg2+](i), each animal was given either two iv bolus doses of 50 mg/kg or one iv bolus of 100 mg/kg of MgSO4. The resting [Ca2+](i) and [Mg2+](i) were determined by means of ion-selective microelectrodes. The resting [Ca2+](i) in normal muscle fibers was 0.11 ± 0.01 μM (mean ± SEM), whereas in the MH muscles the resting [Ca2+](i) was 0.36 ± 0.01 μM. In neither group was the resting [Ca2+](i) modified by MgSO4. This cumulative dose of MgSO4 (100 mg/kg) was not able to prevent the induction of an MH episode by 2% halothane. Although MgSO4 did not directly decrease [Ca2+](i) it did attenuate the increase in [Ca2+](i) associated with the syndrome from 7.29 ± 0.43 μM in untreated animals to 0.84 ± 0.03 μM in MgSO4 pretreated swine. In addition, the limb rigidity that accompanies this increase in calcium was prevented by MgSO4 pretreatment. Baseline measurements of [Mg2+](i) were not different in control and MH-susceptible muscles. Administration of MgSO4 (100 mg/kg) increased [Mg2+](i) 1.8-fold (P < 0.001). These results indicate that MgSO4 by itself was ineffective both in increasing resting [Ca2+](i) and in preventing the changes associated with the MH episode. However, MgSO4 was able to quantitatively reduce the increase in [Ca2+](i), prevent the limb rigidity, and reduce the increment in body temperature usually associated with the clinical syndrome.

Original languageEnglish (US)
Pages (from-to)109-117
Number of pages9
JournalAnesthesiology
Volume73
Issue number1
StatePublished - 1990
Externally publishedYes

Fingerprint

Malignant Hyperthermia
Magnesium
Swine
Calcium
Muscles
Extremities
Magnesium Sulfate
Microelectrodes
Halothane
Poland
Body Temperature
China
Homeostasis
Ions

Keywords

  • Malignant hyperthermia: calcium ions; skeletal muscle
  • Measurement technique: ion-selective microelectrode

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Lopez, J. R., Sanchez, V., Lopez, I., Ryan, J. F., Mendoza, M., Sreter, F. A., & Allen, P. D. (1990). The effects of extracellular magnesium on myoplasmic [Ca2+] in malignant hyperthermia susceptible swine. Anesthesiology, 73(1), 109-117.

The effects of extracellular magnesium on myoplasmic [Ca2+] in malignant hyperthermia susceptible swine. / Lopez, J. R.; Sanchez, V.; Lopez, I.; Ryan, J. F.; Mendoza, M.; Sreter, F. A.; Allen, P. D.

In: Anesthesiology, Vol. 73, No. 1, 1990, p. 109-117.

Research output: Contribution to journalArticle

Lopez, JR, Sanchez, V, Lopez, I, Ryan, JF, Mendoza, M, Sreter, FA & Allen, PD 1990, 'The effects of extracellular magnesium on myoplasmic [Ca2+] in malignant hyperthermia susceptible swine', Anesthesiology, vol. 73, no. 1, pp. 109-117.
Lopez JR, Sanchez V, Lopez I, Ryan JF, Mendoza M, Sreter FA et al. The effects of extracellular magnesium on myoplasmic [Ca2+] in malignant hyperthermia susceptible swine. Anesthesiology. 1990;73(1):109-117.
Lopez, J. R. ; Sanchez, V. ; Lopez, I. ; Ryan, J. F. ; Mendoza, M. ; Sreter, F. A. ; Allen, P. D. / The effects of extracellular magnesium on myoplasmic [Ca2+] in malignant hyperthermia susceptible swine. In: Anesthesiology. 1990 ; Vol. 73, No. 1. pp. 109-117.
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abstract = "It is now well established that the pathophysiology of the malignant hyperthermia (MH) sydrome is related to a malfunction of intracellular calcium homeostasis. Magnesium plays important roles in the basic contractile properties of muscle, and many of its actions are antagonistic to those of calcium. The aim of this study was to determine the effectiveness of magnesium sulphate to prevent the MH episode in susceptible animals and correlate this with its effects on the intracellular free calcium ([Ca2+](i)). The experiments were carried out using six control (Yorkshire) and ten MH-susceptible crossbred swine (Poland China x Pietrain). After determination of resting concentrations of [Ca2+](i) and [Mg2+](i), each animal was given either two iv bolus doses of 50 mg/kg or one iv bolus of 100 mg/kg of MgSO4. The resting [Ca2+](i) and [Mg2+](i) were determined by means of ion-selective microelectrodes. The resting [Ca2+](i) in normal muscle fibers was 0.11 ± 0.01 μM (mean ± SEM), whereas in the MH muscles the resting [Ca2+](i) was 0.36 ± 0.01 μM. In neither group was the resting [Ca2+](i) modified by MgSO4. This cumulative dose of MgSO4 (100 mg/kg) was not able to prevent the induction of an MH episode by 2{\%} halothane. Although MgSO4 did not directly decrease [Ca2+](i) it did attenuate the increase in [Ca2+](i) associated with the syndrome from 7.29 ± 0.43 μM in untreated animals to 0.84 ± 0.03 μM in MgSO4 pretreated swine. In addition, the limb rigidity that accompanies this increase in calcium was prevented by MgSO4 pretreatment. Baseline measurements of [Mg2+](i) were not different in control and MH-susceptible muscles. Administration of MgSO4 (100 mg/kg) increased [Mg2+](i) 1.8-fold (P < 0.001). These results indicate that MgSO4 by itself was ineffective both in increasing resting [Ca2+](i) and in preventing the changes associated with the MH episode. However, MgSO4 was able to quantitatively reduce the increase in [Ca2+](i), prevent the limb rigidity, and reduce the increment in body temperature usually associated with the clinical syndrome.",
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