Modulating Physical Activity to Enhance Rehabilitative Outcomes

Abstract

Skeletal muscle is the primary organ for human movement. In this way, muscle is highly organized by architecture, fiber type, excitation-contraction coupling, and metabolism to supply energy, contract, and transmit force. When any of these aspects is disrupted, for example resulting from injury, there can be decreased force production capacity and impaired movement. Skeletal muscle is remarkable in its ability to repair, regenerate and adapt. Therefore, most injuries are recoverable. Though, in severe cases of muscle injury (i.e., volumetric muscle loss injury; VML), there is a permanent loss of function. For recoverable muscle injuries, rehabilitation improves recovery. However, rehabilitation remains minimally effective for VML injury and lacks physiologic rationale as to why. Preclinical models for rehabilitation of VML are limited and must expand to test a broader scope of rehabilitation variables (i.e., timing, type, intensity, and duration). One variable that may impact the response to rehabilitation is physical activity. Currently, extreme methods of activity restriction (i.e., hindlimb unloading, immobilization, and denervation) dominate activity restriction studies. Chapter one of this thesis is a review of the literature relating to skeletal muscle, skeletal muscle injury, physical rehabilitation, VML injury, and physical activity. The second chapter of this thesis evaluates a combined electrical stimulation and range of motion as a rehabilitation approach, and an underutilized model of restricting activity that limits housing space instead of completely unloading skeletal muscle. Collectively the data indicate that this rehabilitation impaired muscle function. Restricting activity recovered some impairment, suggesting restricted activity might improve response to rehabilitation. However, restricting activity also resulted in whole body metabolic impairment, a side effect that should be seriously considered if restricting activity is to be used as an adjuvant to enhance rehabilitation. Finally, chapter three dives into conclusions and future directions of this work. Future studies should be aimed at expanding the repertoire of rehabilitation models used for the rehabilitation of VML injury and explore other variables, particularly when to commence rehabilitation, what mode of rehabilitation might be best and most translatable, and how restricting activity may play a role.