Post‐ or Pre‐Injury Concentric Contractions Do Not Reduce Eccentric‐Contraction‐Induced Myofiber Damage in a Murine Model of Dysferlin‐linked Muscular Dystrophy

Abstract

BackgroundConcentric contractions have been shown to reduce delayed onset muscle soreness following eccentric contractions in healthy human subjects. Dysferlin‐deficient muscle undergoes severe delayed onset myofiber damage over several days after eccentric contractions. The goal of our study was to test the hypothesis that concentric contractions reduce eccentric‐contraction‐induced myofiber damage in dysferlin‐deficient muscle.MethodsWe studied the tibialis anterior (TA) muscle in 3–4 month old, male, dysferlin‐null BLAJ mice. We elicited TA muscle contractions by depolarizing the fibular nerve with an electrical stimulator; and used a custom‐built dynamometer to measure contractile torque and expose the TA muscle to eccentric contractions (one bout; 40 repetitions; 90–160 □ plantarflexion superimposed on maximal tetany of ankle dorsiflexors). We exposed one group of mice to a single bout of 20, maximal, unloaded concentric contractions soon after eccentric contractions (ConEx after EccEx; N = 4 mice); exposed a second group to 6 sessions of maximal, unloaded concentric contractions (40 repetitions/session) over 2 weeks (ConEx before EccEx; N = 4); and designated a third group as controls (Untreated; N =4). We studied contractile torque before, immediately after, and 3 days after eccentric contractions. We collected TA muscles 3 days after eccentric contractions to histologically assess myofiber damage through hematoxylin and eosin staining, and through immunoglobulin‐G (IgG) and desmin immunofluorescent labeling.ResultsSummarized in Table 1.ConclusionNeither post‐ nor pre‐injury concentric contractions reduce eccentric‐contraction‐induced myofiber damage in dysferlin‐deficient skeletal muscle.Support or Funding InformationFunded by a Faculty Startup Package to JAR. Dysferlin‐null BLAJ mice were a kind gift from the Jain Foundation Inc. Physiological and Histological Data Outcome Measure Untreated (Mean ± S.E.M.) ConEx after EccEx (Mean ± S.E.M.) ConEx before EccEx (Mean ± S.E.M.) Statistically Significant Difference Torque ‐ Immediately After Eccentric Contractions (% Pre) 52 ± 8 46 ± 1 49 ± 2 No Torque ‐ 3 Days After Eccentric Contractions (% Pre) 37 ± 9 34 ± 1 38 ± 2 No % Damaged Fibers ‐ 3 Days After Eccentric Contractions (H&E Staining) 42 ± 3 44 ± 2 41 ± 2 No % IgG+ and Desmin‐Fibers ‐ 3 Days After Eccentric Contractions 40 ± 3 43 ± 3 38 ± 3 No