Early recovery from large‐strain lengthening contractions is not compromised in dysferlin‐null skeletal muscle

The recovery of dysferlin‐null skeletal muscles from injurious large‐strain lengthening contractions is delayed due to extensive necrosis and inflammation that peaks 3 days after injury. Here we test the hypothesis that muscles of dysferlin‐null A/J mice and control A/WySnJ mice recover during the first few hours after large‐strain injury, but that A/J muscle subsequently undergoes secondary damage leading to a loss of contractile torque. METHODS We studied the response to injury from 15 large‐strain lengthening contractions in the tibialis anterior muscle of A/J and A/WySnJ mice. We measured contractile torque and assessed morphological changes in muscle ~ 10 min and 3, 6, 12, 24, 48 and 72 hrs after injury. RESULTS Changes in torque and counts of necrotic fibers after injury are shown in Table 1 (*, p<0.05 A/W Vs A/J; † , p<0.05 compared to 3 hrs). 1 Contractile torque and counts of necrotic fibers after injuryMouse Uninjured ~ 10 min 3 hrs 6 hrs 12 hrs 24 hrs 48 hrs 72 hrsTorque (% Pre‐injury) Mean ± S.D. A/WySnJ 100 62 ± 2 87 ± 2 92 ± 5 85 ± 10 89 ± 5 85 ± 5 95 ± 6 A/J 100 66 ± 4 78 ± 7 75 ± 0 * 70 ± 5 * 70 ± 5 * 62 ± 1 *† 64 ± 9 *†Necrotic fibers(% total # fibers counted) Mean ± S.D. A/WySnJ 0.2 ± 0.5 1 ± 2 2 ± 1 2 ± 1 2 ± 3 3 ± 2 3 ± 4 2 ± 2 A/J 1 ± 1 2 ± 2 7 ± 4 * 9 ± 6 * 8 ± 4 * 18 ± 14 *† 19 ± 9 *† 23 ± 8 *†CONCLUSIONS Dysferlin‐null muscle recovers as well as control by 3 hrs following injury, after which it gradually loses contractile torque and necrotic fibers appear. This work was funded by the Jain Foundation Inc.