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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: sbina@usuhs.mil; 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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References

1.Gronert, GA, Antognini, JF, Pessah, I. In: Miller, RD, ed. Anesthesia, 5th edn. New York: Churchill Livingstone, 2000: 1033–1052.Google Scholar
2.Heffron, JJA. Malignant hyperthermia: Biochemical aspects of the acute episode. Br J Anaesth 1988; 60: 274–278.CrossRefGoogle ScholarPubMed
3.Nelson, TE, Flewellen, EH. The malignant hyperthermia syndrome. N Engl J Med 1983; 309: 416–418.CrossRefGoogle ScholarPubMed
4.Rosenberg, H. Clinical presentation of malignant hyperthermia. Br J Anaesth 1988; 60: 268–273.CrossRefGoogle ScholarPubMed
5.Allen, GC, Larach, MG, Kunselman, AR. The sensitivity and specificity of the caffeine-halothane contracture test. The North American Malignant Hyperthermia Registry of MHAUS. Anesthesiology 1998; 88: 579–588.CrossRefGoogle ScholarPubMed
6.Bina, S, Cowan, G, Karaian, J, Muldoon, S, Mongan, P, Bunger, R. Effects of caffeine, halothane, and 4-chloro-m-cresol on skeletal muscle lactate and pyruvate in malignant hyperthermia-susceptible and normal swine as assessed by microdialysis. Anesthesiology 2006; 104: 90–100.CrossRefGoogle ScholarPubMed
7.Schuster, F, Scholl, H, Hager, M, Muller, R, Roewer, N, Anetseder, M. The dose–response relationship and regional distribution of lactate after intramuscular injection of halothane and caffeine in malignant hyperthermia-susceptible pigs. Anesth Analg 2006; 102: 468–472.CrossRefGoogle ScholarPubMed
8.Anetseder, M, Hager, M, Muller, CR, Roewer, N. Diagnosis of susceptibility to malignant hyperthermia by use of a metabolic test. Lancet 2002; 359: 1579–1580.CrossRefGoogle ScholarPubMed
9.Anetseder, M, Hager, M, Muller, CR, Roewer, N. Regional [Lactate] and carbon dioxide concentrations in a metabolic test for malignant hyperthermia. Lancet 2003; 362: 494.CrossRefGoogle Scholar
10.Ungerstedt, U. Microdialysis – principle and applications for studies in animals and human. J Intern Med 1991; 230: 365–373.CrossRefGoogle Scholar
11.Bunger, R, Mukohara, N, Kang, YH, Mallet, RT. Combined glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase in catecholamine-stimulated guinea-pig cardiac muscle. Comparison with mass-action ratio of creatine kinase. Eur J Biochem 1991; 202: 913–921.CrossRefGoogle ScholarPubMed
12.Veech, RL, Lawson, JW, Cornell, NW, Krebs, HA. Cytosolic phosphorylation potential. J Biol Chem 1979; 254: 6538–6547.CrossRefGoogle ScholarPubMed
13.Bunger, R, Mallet, RT, Hartman, DA. Pyruvate-enhanced phosphorylation potential and inotropism in normoxic and postischemic isolated working heart. Near-complete prevention of reperfusion contractile failure. Eur J Biochem 1989; 180: 221–233.CrossRefGoogle ScholarPubMed
14.Schulze, K, Duschek, C, Lasley, RD, Bünger, R. Adenosine enhances cytosolic phosphorylation potential and ventricular contractility in stunned guinea pig heart: receptor-mediated and metabolic protection. J Appl Physiol 2007; 102: 1202–1213.CrossRefGoogle ScholarPubMed
15.Mallet, RT, Bünger, R. Energetic modulation of cardiac inotropism and sarcoplasmic reticular Ca2+ uptake. Biochim Biophys Acta 1994; 1224: 22–32.CrossRefGoogle ScholarPubMed
16.Martin, BJ, Valdivia, HH, Bünger, R, Lasley, RD, Jr.Mentzer, RM. Pyruvate augments calcium transients and cell shortening in rat ventricular myocytes. Am J Physiol 1998; 274: H8–H17.Google ScholarPubMed
17.Larach, MG. Standardization of the caffeine halothane muscle contracture test: north American Malignant Hyperthermia Group. Anesth Analg 1989; 69: 511–515.CrossRefGoogle ScholarPubMed
18.Pette, D, Dölken, G. Some aspects of regulation of enzyme levels in muscle energy-supplying metabolism. Adv Enzyme Regul 1975; 13: 355–377.CrossRefGoogle ScholarPubMed
19.Hasselbach, W, Oetliker, H. Energetics and electrogenicity of the sarcoplasmic reticulum calcium pump. Annu Rev Physiol 1983; 45: 325–339.CrossRefGoogle ScholarPubMed