Dystrophin-deficient Mdx Muscle Fibers Are Preferentially Vulnerable to Necrosis Induced by Experimental Lengthening Contractions

Lengthening contractions were induced in the right anterior tibialis muscles (ATM) of anaesthetized normal and mdx (dystrophic) mice by supramaximal, nonfatiguing stimulation of the sciatic nerve for 180 min. In the left ATM of the same animals identical stimulation caused shortening contractions because of a prestimulation Achilles tenotomy. The prevalence of recently necrotic fibers was determined in all stimulated ATM by demonstrating the presence of IgG in the necrotic fibers using immunoperoxidase staining of cryostat sections. The results were compared to unstimulated normal and mdx ATM. A significantly higher rate of necrosis was demonstrated after lengthening contractions in the mdx ATM than normal ATM. Unstimulated normal and mdx ATM have either no or extremely infrequent necrotic fibers. We suggest that the enhanced vulnerability of mdx muscle fibers to lengthening contractions is related to the deficiency of dystrophin, which renders the sarcolemma more susceptible to suffer focal breaks. A similar situation may occur in Duchenne muscular dystrophy.