Acl Injury Reduces Quadriceps Mitochondrial Oxidative Capacity That Does Not Recover With Rehabilitation

Abstract

Protracted quadriceps weakness and localized muscle fatigue after ACL reconstruction result in poor knee mechanics. The biological underpinnings of poor functional recovery are unknown, limiting the development of evidence-based therapies. Mitochondrial dysfunction contributes to muscle atrophy and fatigue, but the effect of ACL injury and reconstruction on quadriceps mitochondrial capacity are unknown. PURPOSE: To define quadriceps oxidative capacity in human participants following ACL reconstruction and at the conclusion of rehabilitation. METHODS: Muscle biopsies (vastus lateralis) were obtained from ACL-injured and Healthy limbs of 11 participants (6 M,5F; 20 ± 3 yr) prior to surgical reconstruction and following the completion of post-surgical rehabilitation (4-6 months following surgery). Integrative (relative to tissue wet weight) mitochondrial oxidative phosphorylation capacity with complex I substrates (PCI), PCI plus complex II substrate (PCI + II), uncoupled electron transfer system capacity (ECI + II), and electron transfer system capacity with functional complex II only (ECII) was determined in permeabilized fiber bundles using high-resolution respirometry within 24 hr of biopsy collection. Oxidative phosphorylation and electron transport system capacity were compared using a mixed model. RESULTS: Following ACL injury, PCI + II is 19% lower in the injured limb (Healthy: 124 ± 8; ACL-injured: 97 ± 8 pmol O2 per second per mg tissue, p < 0.05) and did not recover following reconstruction and rehabilitation (Post-Rehab: 109 ± 12 pmol O2 per second per mg tissue, p > 0.05). Additionally, ECI + II was 18% lower in the ACL-injured quadriceps (Healthy: 140 ± 9; ACL-injured: 112 ± 12 pmol O2 per second per mg tissue, p < 0.05) and did not recover following reconstruction and rehabilitation (Post-Rehab: 123 ± 16 pmol O2 per second per mg tissue, p > 0.05). CONCLUSIONS: ACL injury and reconstruction reduce quadriceps oxidative capacity, and these deficits are obstinate to current standard of care rehabilitation. Quadriceps fatigue resistance is critical for stability of the healing knee, and there is a need for therapies targeting deficits in mitochondrial capacity to enhance muscular endurance. Supported by NIH R01AR072061 and R01AR071398