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Vitamin E and Porcine Malignant Hyperthermia

  • Khay S. Cheah
Conference paper

Summary

In malignant hyperthermia (MH), an increase in the level of myoplasmic free Ca2+ is generally accepted to be the initiator of the syndrome, but the primary cause responsible for this increase has yet to be fully characterized. In MH-susceptible pigs, which are widely used as a model for understanding human MH syndrome, an excess formation of fatty acids [1,2], an abnormality in the excitation-contraction coupling mechanism [3], a defect in the Ca2+ release channel of the sarcoplasmic reticulum [4,5], a defect in membrane integrity [6,7], free radical-mediated peroxidation of membrane lipids [8], and a lower than normal Mg2+ inhibition of the Ca2+ release channel of the sarcoplasmic reticulum [9] have all been postulated to be responsible for the development of porcine MH. Vitamin E supports the idea that porcine MH syndrome is associated with an alteration in membrane permeability induced by fatty acids. Dietary supplementation of vitamin E in the form of dl-alpha-tocopheryl acetate reduces the increased leakage of pyruvate kinase and creatine kinase, and normalizes the membrane permeability of skeletal muscle and the rate of glycolysis, and the amount of Ca2+ released in skeletal muscle of MH-susceptible pigs. Vitamin E also reduces the enhanced level of endogenous fatty acids and phospholipase A2 activity of skeletal muscle mitochondria of MH-susceptible pigs to normal, in addition to preventing the formation of meat quality deficiencies associated with the halothane gene. The principal beneficial effect of vitamin E results from its ability to prevent the destabilization of membrane permeability by fatty acids, and probably also from inhibiting phospholipase A2 activity, thereby preventing the increase in the level of myoplasmic Ca2+.

Keywords

Sarcoplasmic Reticulum Malignant Hyperthermia Malignant Hyperthermia PLA2 Activity Longissimus Dorsi 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Cheah KS, Cheah AM (1981) Skeletal muscle mitochondria) phospholipase A2 and the interaction of mitochondria and sarcoplasmic reticulum in porcine malignant hyperthermia. Biochim Biophy Acta 638: 40–49CrossRefGoogle Scholar
  2. 2.
    Cheah KS (1987) Mitochondria and malignant hyperthermia. In: Britt BA (ed) Malignant hyperthermia. Nijhoff, Boston, pp 79–102CrossRefGoogle Scholar
  3. 3.
    Okumura F, Crocker BD, Denborough MA (1980) The site of the muscle cell abnormality in swine susceptible to malignant hyperpyrexia. Br J Anaesth 52: 377–383PubMedCrossRefGoogle Scholar
  4. 4.
    Mickelson JR, Gallant EM, Litterer LA, Johnson KM, Rempel WE, Louis CF (1988) Abnormal sarcoplasmic reticulum ryanodine receptor in malignant hyperthermia. J Biol Chem 263: 9310–9315PubMedGoogle Scholar
  5. 5.
    Ohnishi ST (1994) How was the abnormal calcium release channel from the sarcoplasmic reticulum identfied? In: Ohnishi ST, Ohnishi T (eds) Malignant hyperthermia-a genetic membrane disease. CRC Press, Boca Raton, pp 45–66Google Scholar
  6. 6.
    Cheah KS, Cheah AM (1985) Malignant hyperthermia: molecular defects in membrane permeability. Experientia (Basel) 41: 656–661CrossRefGoogle Scholar
  7. 7.
    Britt BA (1987) Aetiology and pathophysiology of malignant hyperthermia In: Britt BA (ed) Malignant hyperthermia. Nijhoff, Boston, pp 11–42Google Scholar
  8. 8.
    Duthie GG, Arthur JR (1993) Free radicals and calcium homeostasis: relevance to malignant hyperthermia. Free Radical Biol & Med 14: 435–442CrossRefGoogle Scholar
  9. 9.
    Lamb GD (1993) Ca2+ inactivation, Mg2+ inhibition and malignant hyperthermia. J Muscle Res Cell Motil 14: 554–556PubMedCrossRefGoogle Scholar
  10. 10.
    Britt BA, Kalow W (1970) Malignant hyperthermia: a statistical review. Can Anaesth Soc J 17: 293–315PubMedCrossRefGoogle Scholar
  11. 11.
    Gronert GA (1980) Malignant hyperthermia. Anesthesiology 53: 395–423PubMedCrossRefGoogle Scholar
  12. 12.
    Mitchell G, Heffron JJA (1982) Porcine stress syndromes. In: Chichester CO (ed) Advances in food research. Academic Press, New York, pp 167–230Google Scholar
  13. 13.
    Cheah KS, Cheah AM (1984) Membrane permeability in porcine malignant hyperthermia. In: Kates M, Manson LA (eds) Membrane fluidity. Biomembranes, vol 12. Plenum, New York, pp 661–687CrossRefGoogle Scholar
  14. 14.
    Harrison GG (1987) Porcine malignant hyperthermia-the saga of the “hot” pig. In: Britt BA (ed) Malignant hyperthermia. Nijhoff, Boston, pp 103–136CrossRefGoogle Scholar
  15. 15.
    O’Brien PJ (1994) Canine malignant hyperthermia/canine stress syndrome. In: Ohnishi ST, Ohnishi T (eds) Malignant hyperthermia-a genetic membrane disease. CRC Press, Boca Raton, pp 105–116Google Scholar
  16. 16.
    Allen WM, Hebert CN, Smith LP (1974) Deaths during and after transportation of pigs in Great Britian. Vet Rec 94: 212–215PubMedCrossRefGoogle Scholar
  17. 17.
    Williams CH, Houchins C, Shanklin MD (1975) Pigs susceptible to energy metabolism in the fulminant hyperthermia stress syndrome. Br Med J 3: 411–413PubMedCrossRefGoogle Scholar
  18. 18.
    Lopez-Padrino JR (1994) Free calcium concentration in skeletal muscle of malignant hyperthermia susceptible subjects: effects of ryanodine. In: Ohnishi ST, Ohnishi T (eds) Malignant hyperthermia-a genetic membrane disease. CRC Press, Boca Raton, pp 133–150Google Scholar
  19. 19.
    Mickelson JR, Louis CF (1992) Calcium regulation in porcine skeletal muscle-review. In: Puolanne E, Demeyer DI, Ruusunen M, Ellis S (eds) Pork quality: genetic and metabolic factors. CAB International, Wallingford, UK, pp 160–184Google Scholar
  20. 20.
    Fujii J, Otsu K, Zorzato F, De Leon S, Khanna VK, Weiler JE, O’Brien PJ, MacLennan DH (1991) Identification of a mutation in the porcine ryanodine receptor that is associated with malignant hyperthermia. Science 253: 448–451PubMedCrossRefGoogle Scholar
  21. 21.
    Hogan K (1994) Molecular genetic diagnosis of human malignant hyperthermia. In: Ohnishi ST, Ohnishi T (eds) Malignant hyperthermia-a genetic membrane disease. CRC Press, Boca Raton, pp 293–317Google Scholar
  22. 22.
    Otsu K, Philips MS, Khanna VK, De Leon S, MacLennan DH (1992) Refinement of diagnostic assays for a probable causal mutation for porcine and human malignant hyperthermia. Genomics 13: 835–837PubMedCrossRefGoogle Scholar
  23. 23.
    Hughes IP, Moran C, Nicholas FW (1992) PCR genotyping of the ryanodine receptor gene for a putative casual mutation for malignant hyperthermia in Australian pigs. J Anim Breed Genet 109: 465–476CrossRefGoogle Scholar
  24. 24.
    Kasparek S (1980) Chemistry of tocopherols and tocotrienols. In: Machlin LJ (ed) Vitamin E-a comprehensive treatise. Dekker, New York, pp 7–65Google Scholar
  25. 25.
    Burton GW, Cheeseman KH, Doba D, Ingold KU, Slater TF (1983) Vitamin E as an antioxidant in vitro and in vivo. In: Porter R, Whelan J (eds) Ciba Found Symp Biol Vitamin E 101: 4–18Google Scholar
  26. 26.
    McCay PB (1985) Vitamin E: interactions with free radicals and ascorbate. Annu Rev Nutr 5: 323–340PubMedCrossRefGoogle Scholar
  27. 27.
    Sokol RJ (1988) Vitamin E deficiency and neurological disease. Annu Rev Nutr 8: 351–373PubMedCrossRefGoogle Scholar
  28. 28.
    Erin NE, Spirin MM, Tabidze LV, Kagan VE (1984) Formation of a-tocopherol complexes with fatty acids. A hypothetical mechanism of stabilization of biomembranes by vitamin E. Biochim Biophys Acta 774: 96–102PubMedCrossRefGoogle Scholar
  29. 29.
    McCay PB, King MM (1980) Vitamin E: its role as a biological free radical scavenger and its relationship to the microsomal mixed function oxidase system. In: Machlin LJ (ed) Vitamin E-a comprehensive treatise. Dekker, New York, pp 289–317Google Scholar
  30. 30.
    Duthie GG, Arthur JR (1989) The antioxidant abnormality in the stress susceptible pig: the effects of vitamin E supplementation. Ann NY Acad Sci 570: 322–234PubMedCrossRefGoogle Scholar
  31. 31.
    Duthie GG, Arthur JR, Nicol F, Walker M (1989) Increased indices of lipid peroxidation in stress susceptible pigs and effects of vitamin E. Res Vet Sci 46: 226–230Google Scholar
  32. 32.
    Duthie GG, McPhail DB, Arthur JR, Goodman BA, Morrice PC (1990) Spin trapping of free radicals and lipid peroxidation in microsomal preparations from malignant hyperthermia susceptible pigs. Free Radical Res Commun 8: 93–99CrossRefGoogle Scholar
  33. 33.
    Douglas CE, Chan AC, Choy PC (1986) Vitamin E inhibits platelet phospholipase A2. Biochim Biophys Acta 876: 639–645PubMedGoogle Scholar
  34. 34.
    Cheah KS, Cheah AM, Krausgrill DI (1995) Effect of dietary supplementation of vitamin E on pig meat quality. Meat Sci 39: 255–264PubMedCrossRefGoogle Scholar
  35. 35.
    Cheah KS, Cheah AM, Fletcher JE, Rosenberg H (1989) Skeletal muscle mitochondrial respiration of malignant hyperthermia-susceptible patients. Calcium-induced uncoupling and free fatty acids. Int J Biochem 21: 913–920PubMedCrossRefGoogle Scholar
  36. 36.
    Fletcher JE, Tripolitis L, Rosenberg H, Beech J (1993) Malignant hyperthermia: halothane-and calcium-induced release in skeletal muscle. Biochem Mol Biol Int 29: 763–772PubMedGoogle Scholar
  37. 37.
    Behrens WA, Madere R (1987) Mechanisms of absorption, transport and tissue uptake of RRR-a-tocopherol and d-y-tocopherol in the white rat. J Nutr 117: 1562–1569PubMedGoogle Scholar
  38. 38.
    Jensen M, Essen-Gustaysson B, Hakkarainen J (1988) The effect of a diet with a high or low content of vitamin E on different skeletal muscles and myocardium in pigs. J Vet Med A35: 487–497CrossRefGoogle Scholar
  39. 39.
    Asghar A, Gray JI, Booren AM, Gomaa EA, Abouzied MM, Miller ER (1991) Effects of supranutritional dietary vitamin E levels on subcellular deposition of a-tocopherol in the muscle and on pork quality. J Sci Food Agric 57: 31–41CrossRefGoogle Scholar
  40. 40.
    Iyer SL, Katyare SS, Howland JL (1976) Elevated erythrocyte phospholipase A associated with Duchenne and myotonic muscular dystrophy. Neurosci Lett 2: 103–106PubMedCrossRefGoogle Scholar
  41. 41.
    Lloyd SJ, Nunn MG (1978) Osmotic fragility of erythrocytes in Duchenne muscular dystrophy. Br Med J 11: 252–259CrossRefGoogle Scholar
  42. 42.
    Van Deenen LLM (1981) Topology and dynamics of phospholipids in membranes. FEBS Lett 123: 3–15PubMedCrossRefGoogle Scholar
  43. 43.
    Kalofoutis A, Jullien G, Spanos V (1977) Erythrocyte phospholipids in Duchenne muscular dystrophy. Clin Chim Acta 74: 85–90PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 1996

Authors and Affiliations

  • Khay S. Cheah
    • 1
  1. 1.Agriculture DepartmentUniversity of MelbourneParkvilleAustralia

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