Susceptibility to eccentric contractions-induced locomotor muscle injury in cigarette smoke-exposed mice

Chronic exposure to tobacco cigarette smoke (CS) leads to pulmonary damage, inflammation, exercise intolerance, and skeletal muscle contractile and repair dysfunction, as our group has shown that CS exposure also delays muscle repair after eccentric contractions. This study investigated whether chronic CS exposure increases the susceptibility of locomotor muscles to injury from a session of eccentric contractions, as previous studies have shown that smokers have a greater risk of muscle injuries. Methods: Young adult (8 weeks old) wild-type mice (C57BL/6J, IACUC 25-071, n=24) were exposed to daily periods of CS or air (as controls) for eight consecutive weeks. After the exposure period, mice were treated with Evans Blue Dye (EBD), and 24 hours later, the anterior crural muscles from one hindlimb were subjected to a nerve-stimulated lengthening contractions protocol (LCP). The contralateral hindlimb was tested for dorsiflexion ankle torque production, but was not injured by LCP. In vivo torque was measured immediately after LCP (Day 0 group) or the day after LCP (Day 1 group) on both legs, followed by tissue dissection. Ex vivo contractility of the extensor digitorum longus (EDL) muscle was measured. Myofiber cross-sectional area and injury were detected in the tibialis anterior (TA) muscles by immunohistochemistry (IHC). Results: Immediately after LCP, CS-exposed mice had a lower maximal in vivo torque compared to the Air group in the LCP legs (60 ± 18 % vs 79 ± 15 % of the uninjured leg, respectively, P < 0.05); however, this difference was absent at Day 1 post-LCP. Ex vivo EDL force of the LCP-subjected legs was equally decreased in both exposure groups at Day 0. However, maximal force was lower in the CS group vs. the Air group at Day 1 post-LCP (72 ± 20 % vs. 110 ± 27 % of the uninjured leg, respectively, P=0.07). TA images revealed EBD-positive myofibers only in the LCP-subjected muscles in the Day 1 group. Conclusion: Data indicate that smoke exposure accelerates EDL muscle contractile dysfunction, which may indicate an increased susceptibility to muscle injury the day after eccentric contractions.