Interplay Between Whole Body Metabolism, Physical Activity, and Muscle Function Following Volumetric Muscle Loss Injury

Abstract

Volumetric muscle loss (VML) injury occurs when a substantial volume of skeletal muscle is abruptly removed and results in significant long‐term functional limitations. Following VML injury, patients likely undergo periods of low or no mobility and are expected to have reduced physical activity. Immobility and lack of physical activity leads to impaired muscle function, and increased all‐cause mortality and risk for chronic disease. It is plausible that inactivity and immobility negatively affect outcomes following VML injury, exacerbating functional impairments. Our previous work supports an ~25% lower oxygen consumption rate in permeabilized muscle fibers of the muscle remaining after VML up to 4 months post‐injury, but how this may impact whole body metabolism is unclear. Therefore, the purpose of this study was to characterize whole body metabolic and physical activity following VML injury. We hypothesized that metabolism and physical activity would be impaired following VML. To elucidate the interplay between metabolism, activity, and muscle function following VML injury, adult male C57BL/6 mice (n=7) underwent a full‐thickness multi‐muscle VML injury (removal of ~22mg) to the gastrocnemius, soleus, and plantaris, or sham surgery (n=7). Twenty‐four hour whole body metabolic and physical activity was assessed pre‐, and 2 and 6 weeks post‐VML (or sham) injury. Contractile activity of the ankle plantarflexors was assessed terminally at 8 weeks post‐VML. Prior to randomization into experimental groups metabolic rate was ~18.5kcal/kg/hr and there was no difference in any metabolic or activity measure (p≥0.21), and both groups gained ~3g over the 8 week period. Whole body metabolism was evaluated for the 24‐hour period and isolated by the 12 hours of active and inactive time; respiratory exchange ratio (RER), an indirect measure of muscle oxidative capacity, was not different across experimental groups (p≥0.76) but was significantly decreased with time (main effect p≤0.01). Two weeks post‐VML mice tended to become hypermetabolic with a metabolic rate ~14% greater than sham. On average, mice ambulated ~1.2 km per 24‐hour period and contrary to the hypothesis, there was no difference in activity levels (p≥0.23) between sham and VML injured mice. Terminally the plantarflexor muscle group of the VML‐injured mice had ~1.4 fold greater maximal passive torque (indicator of muscle stiffness) and ~40% less maximal active isometric torque. These findings indicate limited changes whole body metabolic and physical activity levels in a model of VML injury, contrary to our hypothesis. Future studies will limit physical activity levels in this model to better recapitulate the low or no mobility expected following VML injury clinically.Support or Funding InformationSupported by W81XWH‐18‐1‐0710 & T32AR050938