Assessing High‐ and Low‐intensity Physical Rehabilitation Approaches to Address Skeletal Muscle Dysfunction Following Volumetric Muscle Loss

Abstract

INTRODUCTIONVolumetric muscle loss (VML), the removal of a large volume of muscle tissue due to surgery or severe trauma is characterized by persistent contractile and metabolic deficits. There is a need to identify clinically translatable physical rehabilitation approaches to address VML; however, optimal parameters of physical rehabilitation strategies such as intensity, progression, and volume have not been well‐established. The primary objective of this study was to determine if the prescribed intensity of two clinically translatable rehabilitation strategies, i.e., whole‐body vibration and voluntary wheel running, influenced skeletal muscle mass and function after VML. We hypothesized that physical rehabilitation would improve muscle function versus leaving the injury untreated, and that magnitude of improvement would be influenced by intensity of physical rehabilitation. METHODS: 12‐week‐old, male C57BL/6 mice (N=55) were assigned to one of 5 groups: uninjured, VML with no rehabilitation (VML), high‐resistance wheel running (HR), low‐resistance wheel running (LR), high‐magnitude vibration (H‐Vib, 1.0g), and low‐magnitude vibration (L‐Vib, 0.6g). Mice underwent unilateral VML injury to the primary ankle plantarflexors (gastrocnemius, soleus, plantaris muscles). Physical rehabilitation strategies were administered for 8‐weeks starting 3‐days after VML injury. To determine rehabilitation effectiveness, muscle mass, muscle strength (i.e., in vivopeak‐isometric torque), and muscle metabolic function (permeabilized muscle fibers oxygen consumption and electron conductance) were assessed. RESULTS: Compared to uninjured mice, VML without rehabilitation resulted in 27% less muscle mass (p<0.01), 36% less peak‐isometric torque (p<0.01), 22% less maximal oxygen consumption (p<0.01) and 36% less electron conductance (p<0.01). Vibration: There were no statistically significant differences among groups for muscle mass or mitochondrial function (p≥0.50). Peak‐isometric torque was 24% greater in H‐Vib (p<0.01), but not L‐Vib mice, compared to VML. Wheel running:HR, but not LR, had 11% greater muscle mass compared to VML (p<0.05). Peak‐isometric torque was 22% greater in both HR and LR compared to VML (p<0.05). Metabolic function was not statistically different among groups. CONCLUSION: Our primary finding is that vibration and wheel running are capable of producing positive adaptations in VML‐injured muscle. Furthermore, results from this study suggest that intensity as a rehabilitation variable should be considered when developing and validating strategies to address functional deficits in VML‐injured muscle. Ongoing and future research is needed to determine the molecular signaling pathways affected by these rehabilitation strategies, and more importantly, why metabolic adaptations are lacking.