Vitamin E and Skeletal Muscle Contracture in Vitro CHARLENE A. HON AND DENNIS F. LANDERS Department of Anesthesiology University of Nebraska Medical Center Omaha, Nebraska 68198-4455
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that is triggered by halogenated anesthetics, such as halothane (Hal), and by succinylcholine (Sch).' An MH episode is characterized by tachycardia, increased core temperature, widespread skeletal muscle rigidity, and severe metabolic acidosis. The cause for MH appears to be an underlying membrane dysfunction that impairs regulation of myoplasmic calcium. Diagnosis of susceptibility to MH is based on clinical presentation and confirmed by in vitrn skeletal muscle contracture tests. Dantrolene, the specific therapeutic agent for an MH episode, may be used to relieve skeletal muscle spasms and pain in MH-susceptible patients, but not without serious side effects. Vitamin E (VE) functions in membranes as a lipid soluble antioxidant* and structural stabilizer and, in addition, has few side effects, even at very high doses.' The purpose of this study was to examine the effect of dietary supplementation with VE on skeletal muscle contracture in an in vitro preparation of rat diaphragm exposed to the contracture-inducing agents, caffeine, Hal, and Sch. Male Sprague-Dawley rats (250 g; N = IO/group) were fed either a standard diet or a purified VE-supplemented (VE-S) diet (200 IU VE/kg diet) for 1 month and for 6 months. The animals were then weighed and decapitated, and blood was
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FIGURE 1. Mean maximum tension, Sch and 3% Hal. I Control; k&' ~ VE( I mo); m Control; VE(h mo); Ir, significantly different from control (p < 0.05). 358
HON & LANDERS: SKELETAL MUSCLE
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FIGURE 2. Mean maximum tension (g) after caffeine. IControl; m VE(I mo); m Control; m VE (6 mo); Ir, significantly different from control (p < 0.05).
collected. The diaphragm was removed and placed in Krebs’ solution (pH 7.4) bubbled with O2 : CO, (95 : 5). Strips of diaphragm were prepared, mounted vertically under tension (1 g) on glass-platinum electrodes, and placed in carbogenated Krebs in a tissue bath at 37°C. The muscle fascicles were directly stimulated with 0.2 Hz. After equilibration for 30 minutes, muscle was exposed to incremental caffeine (0.5, 1.0, 2.0, 4.0, 8.0, and 32.0 mM) or to Sch (50 mM) and Hal (3%) either individually or in combination. The maximum increase in baseline tension for each muscle strip was recorded and mean values analyzed using a t test. Serum VE concentrations were confirmed with HPLC. There were no differences in weight gain between groups at 1 month or 6 months; serum VE content (29 pgimL) confirmed the status of the VE-S group. After 1 month of VE-S, there were significant reductions in contractures produced by 3% Hal alone and by caffeine at concentrations 2 2 mM: after 6 months of VE-S, there were significant reductions in contractures induced by the combination of 3% Hal and Sch and by 4.0 and 8.0 mM caffeine (FIGURES 1 and 2). The twitch response and contracture tension were reduced in both control and VE-S groups maintained for 6 months. Results of this study suggest that supplemental VE may act as a protective agent for pharmacologically induced skeletal muscle contracture. This effect may be dependent on the mechanism and site of action of the contracture-inducing agent as well as the age of the animals. REFERENCES 1 . GRONERT, G. A. 1980. Malignant hyperthermia. Anesthesiology 53: 395-423. 2. TAPPEL,A. L. 1962. Vitamin E is the biological lipid antioxidant. Vitam. Horm. (NY) 20: 493-502. 1988. Safety of oral intake of vitamin E. Am. J. Clin. 3. BERDICHA. & L. J. MACHLIN. Nutr. 48: 612-619.