Abstract
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. PURPOSE: To determine the effects of I/R occurring in skeletal muscle during TKA. METHODS: Muscle biopsies were collected from older subjects (69Âą4.66 years) in the operating room following induction of anesthesia at baseline, during maximal ischemia (just prior to tourniquet release), and during reperfusion (following restoration of blood flow) during primary TKA. RESULTS: Phosphorylation status of Akt (Ser473), and 4E-BP1 (Thr37/46), were depressed during ischemia and reperfusion relative to baseline (p<0.05) and FoxO3a (Ser253) was decreased during ischemia (p<0.05). Total protein for HIF1Îą, REDD1, JNK, ATF4, and GADD34 were increased during ischemia (p<0.05). During reperfusion, HIF1Îą mRNA was elevated relative to baseline(p<0.05). During ischemia and reperfusion, REDD1, HSP 40, and MAFbx mRNA were elevated (p<0.05). CONCLUSIONS: Our data suggests that anabolic signaling is blunted and that proteins associated with stress pathways are being activated during TKA. Further, mRNA levels for several factors known to be involved in the stress activated signaling pathway are up-regulated during ischemia and reperfusion in muscles from older adults during TKA. These novel findings will help us to better understand the effects of I/R on muscle during TKA. This work was supported by the Eunice Kennedy Shriver National Institute for Child Health and Human Development K01HD057332 (HCD).
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