Muscle Regrowth During Physical Rehabilitation and Amino Acid Supplementation

The goal of this translational research project is to identify key mechanisms involved in regulating skeletal muscle loss and regrowth following total knee arthroplasty (TKA). Total knee arthroplasty induces significant declines in muscle mass and strength, which is directly responsible for reduced function, specifically functional independence. Such declines in muscle strength and volume and activities of daily living (getting up from a chair, climbing stairs and walking) can persist for up to 2 years.

Atrophy is the direct result of an imbalance between muscle protein synthesis and breakdown. However, there are two quite distinct mechanisms leading to muscle loss: accelerated protein breakdown (e.g. burn injury), primarily resulting from the stress response, or decreased protein synthesis (e.g., immobilization). In case of severe stress, muscle protein synthesis actually increases, although not adequately to impede muscle loss, and anabolic stimuli, such as nutrition, cannot counteract muscle atrophy. On the other hand, decreased protein synthesis from inactivity can be stimulated by nutrition and exercise, thereby reducing or preventing atrophy. Currently, we do not know which condition predominates following TKA: surgical stress-induced catabolism or immobility-associated declines in synthesis . What is not known is which signaling pathway predominates following TKA; stress induced catabolism or immobility associated declines in synthesis. Our goal is to determine which model (stress or inactivity) accounts for the acute and rapid muscle loss following TKA in order to better focus rehabilitation efforts.

Our general hypothesis is that quadriceps atrophy following TKA surgery is primarily due to inactivity, which can be counteracted by physical therapy (PT) and essential amino acid (EAA) supplementation. Our goal is to delineate the basic mechanisms underlying muscle loss with TKA, and based on this new information, to find novel rehabilitation strategies to accelerate recovery of normal function from TKA.

Thus, our plan is to test in older adults the following specific hypothesis:

1. TKA induces an acute and severe net protein catabolism by reducing muscle protein synthesis
2. TKA induced catabolism is attenuated with the ingestion of EAA
3. EAA supplementation following PT will stimulate muscle protein synthesis and mTOR signaling to a greater extent than PT with Placebo
4. EAA supplementation during TKA PT rehabilitation will improve muscle strength, muscle volume and functional outcomes to a greater extent than PT with Placebo