Background. By the year 2030, 3.48 million older U.S. adults are projected to undergo total knee arthroplasty (TKA). Following this surgery, considerable muscle atrophy occurs, resulting in decreased strength and impaired functional mobility. Essential amino acids (EAAs) have been shown to attenuate muscle loss during periods of reduced activity and may be beneficial for TKA patients.Methods. We used a double-blind, placebo-controlled, randomized clinical trial with 28 older adults undergoing TKA. Patients were randomized to ingest either 20 g of EAAs (n = 16) or placebo (n = 12) twice daily between meals for 1 week before and 2 weeks after TKA. At baseline, 2 weeks, and 6 weeks after TKA, an MRI was performed to determine mid-thigh muscle and adipose tissue volume. Muscle strength and functional mobility were also measured at these times.Results. TKA patients receiving placebo exhibited greater quadriceps muscle atrophy, with a -14.3 ± 3.6% change from baseline to 2 weeks after surgery compared with -3.4 ± 3.1% for the EAA group (F = 5.16, P = 0.036) and a -18.4 ± 2.3% change from baseline to 6 weeks after surgery for placebo versus -6.2 ± 2.2% for the EAA group (F = 14.14, P = 0.001). EAAs also attenuated atrophy in the nonoperated quadriceps and in the hamstring and adductor muscles of both extremities. The EAA group performed better at 2 and 6 weeks after surgery on functional mobility tests (all P < 0.05). Change in quadriceps muscle atrophy was significantly associated with change in functional mobility (F = 5.78, P = 0.021).Conclusion. EAA treatment attenuated muscle atrophy and accelerated the return of functional mobility in older adults following TKA.Trial registration. Clinicaltrials.gov NCT00760383.

Total knee arthroplasty (TKA) utilizes a tourniquet to reduce blood loss, maintain a clear surgical “bloodless” field, and to ensure proper bone-implant cementing. In 2007, over 600,000 TKAs were performed in the United States, and this number is projected to increase to 3.48 million procedures performed annually by 2030. The acute effects of tourniquet-induced ischemia-reperfusion (I/R) on human skeletal muscle cells are poorly understood and require critical investigation, as muscle atrophy following this surgery is rapid and represents the most significant clinical barrier to long-term normalization of physical function. To determine the acute effects of I/R on skeletal muscle cells, biopsies were obtained at baseline, maximal ischemia (prior to tourniquet release), and reperfusion (following tourniquet release). Quadriceps volume was determined before and 2 wk post-TKA by MRI. We measured a 36% decrease in phosphorylation of Akt Ser473during ischemia and 37% during reperfusion ( P < 0.05). 4E-BP1 Thr37/46phosphorylation decreased 29% during ischemia and 22% during reperfusion ( P < 0.05). eEF2 Thr56phosphorylation increased 25% during ischemia and 43% during reperfusion ( P < 0.05). Quadriceps volume decreased 12% in the TKA leg ( P < 0.05) and tended to decrease (6%) in the contralateral leg ( P = 0.1). These data suggest cap-dependent translation initiation, and elongation may be inhibited during and after TKA surgery. We propose that cap-dependent translational events occurring during surgery may precipitate postoperative changes in muscle cells that contribute to the etiology of muscle atrophy following TKA.

Following total knee arthroplasty (TKA) surgery, persistent muscle atrophy and weakness are the greatest clinical barriers to functional recovery. Essential amino acid (EAA) ingestion has been shown to be a potent stimulator of muscle anabolism and to acutely stimulate amino acid transporter mRNA and protein levels in muscle. We examined the effect of twice‐daily EAA supplementation on amino acid transporter gene expression and total protein levels. In this placebo controlled study muscle biopsies were obtained after an overnight fast, under anesthesia immediately prior to TKA surgery following seven days of twice‐daily ingestion of 20g EAA (n=9) or placebo (n=7). Biopsies were analyzed for transcript and protein expression of amino acid transporters using quantitative PCR and Western blotting and compared to placebo. Preliminary results indicate significantly higher mRNA levels for SNAT2 (p<0.01), SNAT4 (p<0.05), and LAT3 (p<0.01) and suggest trends toward increased mRNA for LAT1 (p<0.10) and PAT2 (p<0.10) and decreased mRNA for CAT2 (p<0.10). Total protein levels for CD98 and LAT1 were unchanged between groups. Total protein levels for CD98 and LAT1 were unchanged between groups. These preliminary data suggest EAA supplementation may up‐regulate amino acid transporters at the transcriptional level and regulation of these transporters may involve independent pathways. Support: NICHD K01HD057332

BACKGROUND: Americans over the age of 65 represent the fastest growing segment of the U.S. population, thus it is not surprising to learn that the number of total knee arthroplasty (TKA) surgeries is predicted to increase as much as 673% by 2030, to 3.48 million procedures per year. By far the most significant clinical barrier following TKA surgery is persistent muscle atrophy and weakness. During TKA a tourniquet is used to reduce blood loss and maintain a clear surgical field. The tourniquet-induced ischemia-reperfusion (I/R) injury that results may contribute to the extensive muscle atrophy observed following this surgery. Additional research is necessary in order to better understand the effects of ischemia-reperfusion (I/R) on human skeletal muscle.