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Effects of ryanodine on skeletal muscle lactate and pyruvate in malignant hyperthermia-susceptible and normal swine as assessed by microdialysis

Published online by Cambridge University Press:  01 January 2008

S. Bina ,
S. Muldoon  and
R. Bünger
S. Bina*
Affiliation:
Uniformed services University of the Health Sciences, Department of Anesthesiology, Bethesda, MD, USA
S. Muldoon
Affiliation:
Uniformed services University of the Health Sciences, Department of Anesthesiology, Bethesda, MD, USA
R. Bünger
Affiliation:
Uniformed services University of the Health Sciences, Department of Anatomy, Physiology and Genetics, Bethesda, MD, USA
*
Correspondence to: Saiid Bina, Department of Anesthesiology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA. E-mail: [email protected]; Tel: +1 301 295 3142; Fax: +1 301 295 2200
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Summary

Background

The caffeine/halothane contracture test in North America and the in vitro contracture test in Europe are currently the only validated bioassays for diagnosing malignant hyperthermia susceptibility and phenotyping families. Both tests are invasive requiring surgical muscle biopsy. Here, we report first use of the selective ryanodine receptor type I agonist ryanodine in a percutaneous microdialysis protocol designed to test whether microdialysis-induced local metabolic responses of skeletal muscle due to ryanodine receptor activation can differentiate between malignant hyperthermia-sensitive and normal pigs.

Methods

Six microdialysis catheters were implanted percutaneously into the adductor muscles of the right and left thighs of malignant hyperthermia-susceptible (n = 9) and normal (n = 8) anaesthetized (ketamine/propofol) and mechanically ventilated swine. Systemic blood gases, haemodynamic parameters and creatine kinase levels were measured before, during and after microdialysis perfusion of ryanodine. After a post-implantation equilibration period of 30 min, one catheter perfused (2 μL min−1) with 0.9% NaCl (control) and was compared with the remaining five catheters perfused with increasing concentrations of ryanodine (0.2–100 μmol). Lactate and pyruvate levels were measured enzymatically.

Results

Continuous perfusion with ryanodine revealed dose-dependent sigmoidal increases in the dialysate lactate and lactate–pyruvate ratio parameters; these effects were greatly augmented in malignant hyperthermia-susceptible pigs compared to normal pigs (two- to threefold): estimated EC50 greatly decreased (>19-fold) while the maximum effect increased (>twofold) in the malignant hyperthermia-susceptible group.

Conclusion

The in vivo percutaneous microdialysis protocol for skeletal muscle, using ryanodine as the ryanodine receptor type I agonist and dialysed lactate–pyruvate parameters as metabolic index, can reproducibly differentiate between malignant hyperthermia-susceptible and normal swine.

Keywords

MALIGNANT HYPERTHERMIASWINERYANODINERYANODINE RECEPTOR CALCIUM RELEASE CHANNELMICRODIALYSIS TECHNIQUESLACTATEPYRUVATE
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 1 , January 2008 , pp. 48 - 57
Copyright
Copyright © European Society of Anaesthesiology 2007

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