Beyond the first bout: Adaptations to repeated injuries across physiological and pathological conditions

Skeletal muscle exhibits remarkable plasticity following injury, yet most research has focused on responses to a single bout of eccentric contractions. This review addresses adaptations to repeated eccentric contraction-induced injuries across physiological and pathological conditions, with emphasis on insights from preclinical rodent models. In healthy muscle, the repeated bout effect (RBE) reduces strength loss and accelerates recovery after subsequent bouts. However, these adaptations are highly condition dependent. Aging can attenuate the RBE, while dystrophic muscle remains vulnerable to repeated injury despite compensatory remodeling. Other factors, including but not limited to, chronic alcohol intake and malignant hyperthermia can influence these responses, though their effects vary and do not universally abolish adaptation. Collectively, these findings highlight that the trajectory of muscle adaptation depends on its physiological state and underlying pathology. Understanding these condition-specific mechanisms is essential for developing targeted strategies to optimize recovery, maximize adaptations, and preserve muscle health across diverse populations.