N. Bigot1, E. Owen2, T. Kirkpartick2, A. Poluso2, M. Bremer2, L. Strycker3, K. Smolkowski3, B. Lantz4, S. Shah4, C. Mohler4, B. Jewett4, J. Muyskens1, H. Dreyer1

1University of Oregon; 2Slocum Research and Education Foundation; 3Oregon Research Institute;4Slocum Center for Orthopedics and Sports Center, Eugene, OR

PURPOSE: More than 600,000 Americans receive total knee arthroplasty (TKA) annually. Our goal is to improve functional outcomes following TKA by mitigating the extensive muscle loss that occurs during the first two weeks post surgery. Previously, we showed that essential amino acid supplementation (EAAs) improves function and reduces muscle atrophy as measured by MRI. This study aimed to determine muscle cell-level changes related to regenerative potential in TKA patients receiving EAAs compared to Placebo. METHODS Using a double-blind Placebo-controlled randomized clinical trial, 39 older adults (age 50-80 y) having TKA were randomized to ingest either 20 g of EAA (n = 19) or Placebo (n = 20) 2x/d between meals for 1 wk before, and 6 wk after TKA. Bilateral muscle biopsies (vastus lateralis (VL)) were obtained prior to surgery and at 1 or 2 weeks post TKA. Histological analysis determined cross-sectional area (CSA) of VL cells (anti-laminin), number of myonuclei per muscle cell (DAPI), fiber type composition (anti-MHC1), and satellite cell number (anti-Pax7). In addition, we assayed for shifts in inflammatory (M1) vs regenerative (M2) macrophage populations. RESULTS: Our preliminary results reveal satellite cell numbers are elevated in the EAA group vs Placebo for Type I cells (0.127±.02 vs, 0.073±.01, respectively, p=.054) and Type II cells (0.084±.02 vs. 0.039±.01, p=.64) after just 7 days of twice-daily EAA prior to surgery. After surgery in the EAA group, satellite cell numbers were reduced relative to baseline for both Type I (-37%) and II (-27%) fibers (p<0.05). No changes in the satellite cell populations were measured in either leg for the Placebo group. Muscle CSA was reduced (-12%) in the Placebo group in the operative leg (p =.017). The treatment group did not display the corresponding decrease in CSA (p =.098). M1 macrophage populations were reduced in the operative leg of the treatment group at 1-week post surgery (p =.017). No changes in macrophage populations were measured for the Placebo group. CONCLUSIONS: Our data suggest that amino acid supplementation may attenuate muscle atrophy through preservation of satellite cells and a reduction in inflammatory macrophage numbers.


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