Early initiation of electrical stimulation paired with range of motion after a volumetric muscle loss injury does not benefit muscle function

What is the central question of this study? First, how does physical rehabilitation influence recovery from traumatic muscle injury? Second, how does physical activity impact the rehabilitation response for skeletal muscle function and whole-body metabolism? What is the main finding and its importance? The most salient findings were that rehabilitation impaired muscle function and range of motion, while restricting activity mitigated some negative effects but also impacted whole-body metabolism. These data suggest that first, work must continue to explore treatment parameters, including modality, time, type, duration and intensity, to find the best rehabilitation approaches for volumetric muscle loss injuries; and second, restricting activity acutely might enhance rehabilitation response, but whole-body co-morbidities should continue to be considered.Volumetric muscle loss (VML) injury occurs when a substantial volume of muscle is lost by surgical removal or trauma, resulting in an irrecoverable deficit in muscle function. Recently, it was suggested that VML impacts whole-body and muscle-specific metabolism, which might contribute to the inability of the muscle to respond to treatments such as physical rehabilitation. The aim of this work was to understand the complex relationship between physical activity and the response to rehabilitation after VML in an animal model, evaluating the rehabilitation response by measurement of muscle function and whole-body metabolism. Adult male mice (n = 24) underwent a multi-muscle, full-thickness VML injury to the gastrocnemius, soleus and plantaris muscles and were randomized into one of three groups: (1) untreated; (2) rehabilitation (i.e., combined electrical stimulation and range of motion, twice per week, beginning 72 h post-injury, for ∼8 weeks); or (3) rehabilitation and restriction of physical activity. There was a lack of positive adaption associated with electrical stimulation and range of motion intervention alone; however, maximal isometric torque of the posterior muscle group was greater in mice receiving treatment with activity restriction (P = 0.008). Physical activity and whole-body metabolism were measured ∼6 weeks post-injury; metabolic rate decreased (P = 0.001) and respiratory exchange ratio increased (P = 0.022) with activity restriction. Therefore, restricting physical activity might enhance an intervention delivered to the injured muscle group but impair whole-body metabolism. It is possible that restricting activity is important initially post-injury to protect the muscle from excess demand. A gradual increase in activity throughout the course of treatment might optimize muscle function and whole-body metabolism.