Oxidative stress and muscle dysfunction following anterior cruciate ligament surgery Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/m613n143t

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  • Despite the advances in surgery, physical therapy, and pharmaceutical agents, muscle dysfunction (i.e., atrophy and weakness) continues to impair recovery from an anterior cruciate ligament (ACL) injury and surgery. Ischemia-reperfusion injury during surgery and the subsequent limb disuse are two events experienced by patients having ACL surgery. Oxidative stress and inflammation mediate muscle dysfunction; both of which can be modulated by antioxidants. The purpose of this project was to test the hypothesis that vitamin E and C supplementation would ameliorate muscle dysfunction following ACL surgery by attenuating the increase in mediators of muscle dysfunction. A randomized, double-blind, placebo-controlled study was conducted in men who received one of two supplements: 1) antioxidant (AO; 400 IU of vitamin E and 1000 mg vitamin C per day), or 2) matching placebo (PL) starting ~2-weeks prior to (baseline) and concluding 3-months post-surgery. Lower limb strength and skeletal muscle fiber cross-sectional area measurements were used to assess muscle dysfunction; markers of oxidative stress and inflammation were evaluated in the circulation and muscle. Plasma α-tocopherol (α-T) and ascorbic acid (AA) increased, while γ-T concentrations decreased significantly with AO supplementation. Following surgery, oxidative stress (F₂-isoprostanes), inflammation and muscle damage increased significantly in both groups. Compared to the PL group, AO supplementation ameliorated the increase in an anti-inflammatory cytokine (interleukin (IL)-10) and the depression of a pro- to anti-inflammatory cytokine ratio (IL-6:IL-10) immediately following surgery. Elevated AA decreased in the AO group and inversely correlated with a neutrophil chemoattractant cytokine immediately following surgery. In contrast to our expectations, a significant atrophy response from pre- to post-surgery was not observed in muscle biopsies, using histologic techniques. In fact, AO supplementation increased inducible nitric oxide synthase and myeloperoxidase expression in the muscle following surgery. Furthermore, and unlike the PL group, the recovery in peak isometric force of the injured limb within the AO group did not significantly increase from baseline to 3-months post-surgery. In summary, AO supplementation protected against immuno-suppression (increase in anti-inflammatory cytokines), but was ineffective in lowering oxidative stress induced by surgery. Moreover, AO supplementation did not minimize, and potentially contributed to muscle dysfunction following ACL reconstructive surgery.
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  • description.provenance : Submitted by Tyler Barker (barkert@onid.orst.edu) on 2009-04-03T20:23:45Z No. of bitstreams: 1 Dissertation Defense - Manuscript.pdf: 636783 bytes, checksum: 98cae3922834123892cb4e5379de4aa0 (MD5)
  • description.provenance : Made available in DSpace on 2009-04-17T21:08:47Z (GMT). No. of bitstreams: 1 Dissertation Defense - Manuscript.pdf: 636783 bytes, checksum: 98cae3922834123892cb4e5379de4aa0 (MD5)
  • description.provenance : Approved for entry into archive by Julie Kurtz(julie.kurtz@oregonstate.edu) on 2009-04-15T18:16:00Z (GMT) No. of bitstreams: 1 Dissertation Defense - Manuscript.pdf: 636783 bytes, checksum: 98cae3922834123892cb4e5379de4aa0 (MD5)
  • description.provenance : Approved for entry into archive by Laura Wilson(laura.wilson@oregonstate.edu) on 2009-04-17T21:08:47Z (GMT) No. of bitstreams: 1 Dissertation Defense - Manuscript.pdf: 636783 bytes, checksum: 98cae3922834123892cb4e5379de4aa0 (MD5)

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