Early and Later Stage Muscle Recovery from Lengthening Contraction-Induced Injury in Cigarette Smoke-Exposed Mice

The use of tobacco products is associated with lower recovery from strenuous exercise, and mice exposed to cigarette smoke (CS) show impaired myofiber cross sectional area recovery from muscle injury. PURPOSE: To investigate the effects of short-term (i.e., 8 weeks) CS exposure on the early (7 days) and later stage (14 days) in vivo torque recovery of anterior crural muscles, EDL muscle force, and TA myofiber formation recovery after lengthening contractions (LCP). METHODS: Adult male (n=14) and female (n=13) mice expressing tdTomato fluorescent protein in satellite cells (Pax7CreER-Ai9, 8 weeks old) were daily exposed to smoke produced from 10 research cigarettes (1R6F), 5x per week for 8 consecutive weeks (CS group). Non-exposed mice were used as age-matched controls (VIV group, n=7 male and n=5 for female mice). On week 6, mice were treated with tamoxifen (2 mg/day, i.p.) to activate tdTomato expression in Pax7+ cells. On week 7, isometric dorsiflexion torque was measured on both legs by stimulating the peroneal nerve (200 ms trains, 0.2 ms pulses), and then one leg was subjected to LCP (1,0000/sec for 150 contractions) and torque was measured immediately after LCP. The contralateral leg was uninjured. On days 3, 7, and 14 post-LCP, torque was measured on both legs. Tissues were collected on either day 7 or day 14 after LCP for ex-vivo extensor digitorum longus (EDL) contractility and for tibialis anterior (TA) histology. Results are shown as Mean ± SD. RESULTS: Torque developed by the uninjured leg was not different between exposure groups at any time-point during the recovery period (94 ± 8 vs 94 ± 8 Nmm/kg for Pre-LCP; 78 ± 15 vs 96 ± 7 Nmm/kg at day 3; and 96 ± 6 vs 98 ± 2 Nmm/kg at day 7; VIV vs CS, respectively, P>0.05). In the LCP legs, in vivo torque pre-LCP (106 ± 5 and 76 ± 9 Nmm/kg) was decreased for both groups immediately after LCP (37 ± 3 and 30 ± 7 Nmm/kg) and at day 3 (65 ± 14 and 61 ± 8 Nmm/kg) (VIV and CS groups, respectively). At day 7, torque was recovered for CS group (78 ± 6 Nmm/kg) but not for VIV group (46 ± 3 Nmm/kg). At day 7, ex-vivo maximal force of EDL from uninjured leg was lower in CS group vs VIV group (365 ± 15 vs 456 ± 11 kPa, respectively) but not different from LCP legs (360 ± 56 vs 345 ± 38 kPa, for CS vs VIV, respectively). CONCLUSION: Mice exposed to CS over 8 weeks showed a faster recovery of in vivo torque at day 7 after lengthening contractions compared to non-exposed mice.