Skeletal muscle cellular contractile dysfunction after anterior cruciate ligament reconstruction contributes to quadriceps weakness at 6‐month follow‐up

Abstract

Muscle dysfunction following anterior cruciate ligament reconstruction (ACLR) may evolve from alterations in muscle contractility at the myofilament protein level. Using a prospective, within‐subject case–control design, we evaluated cellular‐level contractility, cross‐sectional area (CSA), and myosin heavy chain (MHC) isoform expression on single muscle fibers 3 weeks post ACLR, and evaluated their relationship to whole muscle strength and patient‐oriented outcomes 6 months post operation. Biopsies of the vastus lateralis were performed 3 weeks post ACLR in 11 subjects (5 females, mean age ± SD = 24.7 ± 6.5 years, height = 172.7 ± 8.2 cm, mass = 75.7 ± 12.5 kg) following first‐time ACL rupture and whole muscle strength and self‐reported pain, function, and quality of life assessed 6 months post ACLR. At 3 weeks post ACLR, force production was reduced (p < 0.01) in MHC I (−36%) and IIA (−48%) fibers compared with the non‐injured leg. When force production was expressed relative to CSA to account for fiber atrophy, reductions remained in MHC IIA fibers (−40%; p < 0.001), but MHC I fibers showed only a trend toward being lower (−13%; p = 0.09). Finally, skeletal muscle fiber functional deficits at 3 weeks post ACLR were associated with whole muscle weakness and less favorable patient‐reported outcomes at 6‐month follow‐up. Thus, ACLR promotes early cellular contractile dysfunction that may contribute to decreased whole muscle strength and patient function, and increased patient‐reported symptoms, at 6‐month follow‐up.

The Duration of Thigh Tourniquet Use Associated With Anterior Cruciate Ligament Reconstruction Does Not Produce Cellular-Level Contractile Dysfunction of the Quadriceps Muscle at 3 Weeks After Surgery

“…Our results suggest, however, that normal variation in tourniquet time does not explain variability in single-muscle fiber CSA, contractility, or mitochondrial content or structure at 3 weeks after surgery. This is an important result in light of a recent report 44 showing that impaired muscle contractility at the cellular level at 3 weeks after ACLR was associated with persistent whole-muscle weakness at 6-month follow-up. Our current findings suggest that normal variability in the duration of tourniquet use during ACLR surgery is not associated with these cellular maladaptations that contribute to longer term functional deficits.…”

“…ACL trauma and reconstruction have early and direct effects in reducing muscle fiber size and contractile function. 18,35,44 To our knowledge, this is the first study to provide evidence that these effects are not associated with the duration of tourniquet use during ACLR surgery. This observation was made at the cellular level at 3 weeks after ACLR surgery (a time when measuring whole-muscle strength and function of the lower extremity is contraindicated due to risk of further injury) and at the whole-muscle level 6 months after reconstruction, when patients prepare to return to preinjury activities.…”

“…This study was based on additional analysis of data acquired from 2 investigations of patients who sustained their first ACL disruption and underwent ACLR. 41,44 All participants were selected based on the same entry criteria and underwent the same treatment protocol (data were acquired from participants randomized to the sham treatment in the clinical trial reported by Toth et al 41 and were combined with data acquired in the study presented by Tourville et al 44 ). For both studies, participants were recruited contemporaneously from the same orthopaedic clinic and were included if they sustained an acute, firsttime ACL injury; were between 18 and 50 years of age; had a body mass index 35; had no history of previous The American Journal of Sports Medicine injections or surgeries to either lower extremity; had no history of significant knee or lower extremity injury; demonstrated no abnormal laxity of the collateral or posterior cruciate ligaments; had no radiographic evidence of osteoarthritis or fracture to both knees; showed no symptoms or signs of autoimmune or inflammatory disease or diabetes; demonstrated normal lower limb alignment (evaluated with the 2000 International Knee Documentation Committee [IKDC] examination outcome); had an articular cartilage lesion of grade 3A or less (assessed at the time of arthroscopy with the International Cartilage Repair Society evaluation); and were scheduled to undergo ACLR with any type of graft material.…”

“…The purpose of this investigation was to evaluate whether the duration of tourniquet use during ACLR would explain variability in quadriceps muscle size and function at the cellular level 3 weeks after surgery as well as whole-muscle strength and patient outcomes at 6-month follow-up, as we have previously shown that cellular function predicts these outcomes at 6-month follow-up after ACLR. 44 We hypothesized that the duration of tourniquet use during ACLR would be associated with a reduction in size and contractile function of single muscle fibers as well as mitochondrial content and size at 3 weeks after ACLR. Moreover, we anticipated that increased time of tourniquet use would be associated with whole-muscle weakness and reduced limb function and patient-reported function and quality of life at 6 months after ACLR, when most patients begin to prepare to return to their preinjury activities.…”

Long-Lasting Impairments in Quadriceps Mitochondrial Health, Muscle Size, and Phenotypic Composition Are Present After Non-invasive Anterior Cruciate Ligament Injury

“…The apparent disruption of type IIa fibers in the present study is particularly interesting when considering the notable loss of type IIa contractile function which has been identified by others following ACL injury (Gumucio et al, 2018;Tourville et al, 2021). Specifically, biopsied type IIa fibers displayed an independent loss of force production which was unrelated to neurologic activation (Gumucio et al, 2018;Tourville et al, 2021).…”