Proteins regulating cap-dependent translation are downregulated during total knee Arthroplasty

Stephen M. Ratchford, Ashley N. Bailey, Hilary A. Senesac, Austin D. Hocker, Keith Smolkowski, Brick A. Lantz, Brian A. Jewett, Jeffrey S. Gilbert, Hans C. Dreyer

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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 Ser 473 during ischemia and 37% during reperfusion (P < 0.05). 4E-BP1 Thr 37/46 phosphorylation decreased 29% during ischemia and 22% during reperfusion (P < 0.05). eEF2 Thr 56 phosphorylation 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 capdependent translational events occurring during surgery may precipitate postoperative changes in muscle cells that contribute to the etiology of muscle atrophy following TKA.

Original languageEnglish (US)
Pages (from-to)702-711
Number of pages10
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume302
Issue number6
DOIs
StatePublished - Mar 2012

Keywords

  • 4E-binding protein 1
  • Activating transcription factor 4
  • Arrest
  • Atrophy
  • DNA damage
  • Growth
  • Muscle
  • Tourniquet

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