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J Appl Physiol 105: 1542-1553, 2008. First published September 11, 2008; doi:10.1152/japplphysiol.90926.2008
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Eccentric contractions do not induce rhabdomyolysis in malignant hyperthermia susceptible mice

Benjamin T. Corona,1 Clement Rouviere,1 Susan L. Hamilton,2 and Christopher P. Ingalls1

1Muscle Biology Laboratory, Department of Kinesiology and Health, Georgia State University, Atlanta, Georgia; and 2Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas

Submitted 18 July 2008 ; accepted in final form 4 September 2008

Recent studies suggest a link between exercise-induced rhabdomyolysis and mutations of the ryanodine receptor (RYR1) associated with malignant hyperthermia (MH). We hypothesized that MH-susceptible mice (RYR1Y522S/wt) would exhibit greater anterior crural muscle [tibialis anterior (TA) and extensor digitorum longus (EDL) muscles] damage and strength deficits following the performance of a single or repeated bouts of eccentric contractions compared with wild-type (WT) mice. After a single injury bout, RYR1Y522S/wt mice produced more isometric torque than WT mice immediately and 3 and 7 days postinjury. Moreover, EDL muscle isometric specific force deficits were fully recovered for RYR1Y522S/wt but not WT mice 14 days postinjury. The percentage of fibers in TA muscle exhibiting signs of muscle damage 7 and 14 days postinjury were at least three times less in RYR1Y522S/wt than in WT mice. Uninjured and injured EDL muscle from RYR1Y522S/wt mice also displayed greater S-glutathionylation of RYR1 than that from WT mice. During the weekly injury bouts, torque production by RYR1Y522S/wt mice was fully recovered before the third and fourth injury bouts, whereas torque was still reduced for WT mice. Three days after multiple injury bouts, there were ~50% fewer fibers exhibiting signs of muscle damage in RYR1Y522S/wt than in WT TA muscle. These findings indicate that the RYR1Y522S/wt mutation protects skeletal muscle from exercise-induced muscle injury and do not support a direct association between MH susceptibility and contraction-induced rhabdomyolysis when core temperature is maintained at lower physiological temperatures during exercise.

contraction-induced muscle injury/damage



Address for reprint requests and other correspondence: C. P. Ingalls, Georgia State Univ., Dept. of Kinesiology and Health, PO Box 3975, Atlanta, GA 30302-3975 (e-mail: cingalls{at}gsu.edu)




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Anesth. Analg.Home page
J. F. Capacchione and S. M. Muldoon
The Relationship Between Exertional Heat Illness, Exertional Rhabdomyolysis, and Malignant Hyperthermia
Anesth. Analg., October 1, 2009; 109(4): 1065 - 1069.
[Abstract] [Full Text] [PDF]




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