Eccentric contractions induce rapid isometric torque drop in dystrophin-deficient dogs

Abstract

We tested the hypothesis that eccentric contractions (ECCs) rapidly induce greater-than-normal isometric torque drop in dystrophin-deficient golden retriever muscular dystrophy (GRMD) muscles. ECCs were imposed by forcibly stretching activated muscles. The results indicate that isometric torque drop was greater in GRMD versus controls (P < 0.0001). Our findings support the hypothesis that ECCs induce greater-than-normal isometric torque drop in GRMD muscles. The magnitude of ECC-induced isometric torque loss may be an ideal clinical endpoint in the GRMD model.

FIGURE 1

Dynamic force analysis of GRMD (n = 10), carrier (n = 7), and normal (n = 5) dogs. Representative twitch (top panel) and tetany (bottom panel) tracings from normal and GRMD dogs, respectively (A). Compared to normal and carrier dogs, affected GRMD dogs demonstrate lower twitch and tetanic torque values in tibiotarsal flexion (B) and extension (C). Note the y-axis scale. Representative torque tracings (D) during 10 ECCs. The darkest line displays the first contraction while the lightest line shows the tenth contraction. Following ECC, affected GRMD dogs rapidly lose strength as assessed by isometric torque. Temporal decrements in torque following eccentric injury (E). GRMD dogs display significantly greater-than-normal torque drop after the fifth ECC. Contractions were applied every 5 s. Broken lines through the x-axis indicate a 4-min rest period. Following completion of 30 ECCs, isometric torque varies among genotypes (F). GRMD dogs lose 63% of their original torque, whereas carriers lose 13% and normals lose 8%. Black = normal; gray = carrier; light = GRMD. *Significantly different (one-way ANCOVA) compared to the other genotypes (P < 0.05).