Vitamin E and Porcine Malignant Hyperthermia

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⁺.