Associations between Body Mass Index, Gait Mechanics and Trochlear Cartilage Thickness in those with ACL Reconstruction.

PURPOSE: High body mass index (BMI) is a strong predictor of post-traumatic osteoarthritis (OA) after anterior cruciate ligament reconstruction (ACLR). Altered gait mechanics are independently affected by BMI and ACLR, and influence OA risk. Yet, evidence directly assessing the impact of high BMI on gait or cartilage characteristics after ACLR are limited. Here, we evaluated if high BMI moderates associations between gait and trochlear cartilage structure in individuals with ACLR. METHODS: Treadmill walking biomechanics were evaluated in forty normal BMI and twenty-four high BMI participants with ACLR at self-selected speeds. Normalized and absolute peak and cumulative loads (i.e., impulse) were extracted for peak knee flexion and adduction moments (KFM, KAM) and vertical ground reaction force (GRF). Medial and lateral femoral cartilage thickness and medial: lateral thickness ratios were assessed via ultrasound. RESULTS: Those with ACLR and high BMI walked with reduced normalized peak vertical GRFs, and greater absolute peak and cumulative loads compared to normal BMI individuals with ACLR. Those with ACLR and high BMI also exhibited thinner cartilage and greater medial: lateral ratios in ACLR limbs compared to contralateral limbs whereas normal BMI individuals with ACLR exhibited thicker ACLR limb cartilage. Lastly, greater peak KAM and KAM cumulative load were associated with thicker lateral cartilage and lesser medial: lateral thickness ratios, but only in the high BMI group. CONCLUSIONS: We observed those with high BMI after ACLR exhibited trochlear cartilage structural alterations not observed in normal BMI patients, while differential associations between loading outcomes and cartilage thickness in ACLR knees were observed between groups. Those with high BMI after ACLR may require different therapeutic strategies to optimize joint health in this subset of patients.

Development of a Low-cost Epimysial Electromyography Electrode: A Simplified Workflow for Fabrication and Testing.

Electromyography (EMG) is a valuable diagnostic tool for detecting neuromuscular abnormalities. Implantable epimysial electrodes are commonly used to measure EMG signals in preclinical models. Although classical resources exist describing the principles of epimysial electrode fabrication, there is a sparsity of illustrative information translating electrode theory to practice. To remedy this, we provide an updated, easy-to-follow guide on fabricating and testing a low-cost epimysial electrode. Electrodes were made by folding and inserting two platinum-iridium foils into a precut silicone base to form the contact surfaces. Next, coated stainless steel wires were welded to each contact surface to form the electrode leads. Lastly, a silicone mixture was used to seal the electrode. Ex vivo testing was conducted to compare our custom-fabricated electrode to an industry standard electrode in a saline bath, where high levels of signal agreement (sine [intraclass correlation - ICC= 0.993], square [ICC = 0.995], triangle [ICC = 0.958]), and temporal-synchrony (sine [r = 0.987], square [r = 0.990], triangle [r= 0.931]) were found across all waveforms. Low levels of electrode impedance were also quantified via electrochemical impedance spectroscopy. An in vivo performance assessment was also conducted where the vastus lateralis muscle of a rat was surgically instrumented with the custom-fabricated electrode and signaling was acquired during uphill and downhill walking. As expected, peak EMG activity was significantly lower during downhill walking (0.008 ± 0.005 mV) than uphill (0.031 ± 0.180 mV, p = 0.005), supporting the validity of the device. The reliability and biocompatibility of the device were also supported by consistent signaling during level walking at 14 days and 56 days post implantation (0.01 ± 0.007 mV, 0.012 ± 0.007 mV respectively; p > 0.05) and the absence of histological inflammation. Collectively, we provide an updated workflow for the fabrication and testing of low-cost epimysial electrodes.

Open-sourced semi-automatic program for ultrasound assessments of femoral trochlea cartilage health.

We developed an open-sourced program that accounts for the current limitations of B-mode ultrasound and extends the clinical utility of ultrasound for assessing femoral trochlear cartilage thickness. Images were collected on 18 patients with a history of knee surgery. By failing to account for ultrasound acoustics and beam refraction, cartilage thickness was underestimated by 26% and overestimated by 0-4%, respectively (p < 0.001). Comprehensive thickness measurements achieved by measuring the Euclidean distance between every point were significantly different than traditional single-location measurements or by using the area/length (p = 0.004-0.006). Sub-regions were significantly different than all whole regions of interest (p = 0.001-0.012).

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

INTRODUCTION: Despite rigorous rehabilitation aimed at restoring muscle health, anterior cruciate ligament (ACL) injury is often hallmarked by significant long-term quadriceps muscle weakness. Derangements in mitochondrial function are a common feature of various atrophying conditions, yet it is unclear to what extent mitochondria are involved in the detrimental sequela of quadriceps dysfunction after ACL injury. Using a preclinical, non-invasive ACL injury rodent model, our objective was to explore the direct effect of an isolated ACL injury on mitochondrial function, muscle atrophy, and muscle phenotypic transitions. METHODS: A total of 40 male and female, Long Evans rats (16-week-old) were exposed to non-invasive ACL injury, while 8 additional rats served as controls. Rats were euthanized at 3, 7, 14, 28, and 56 days after ACL injury, and vastus lateralis muscles were extracted to measure the mitochondrial respiratory control ratio (RCR; state 3 respiration/state 4 respiration), mitochondrial reactive oxygen species (ROS) production, fiber cross sectional area (CSA), and fiber phenotyping. Alterations in mitochondrial function and ROS production were detected using two-way (sex:group) analyses of variance. To determine if mitochondrial characteristics were related to fiber atrophy, individual linear mixed effect models were run by sex. RESULTS: Mitochondria-derived ROS increased from days 7 to 56 after ACL injury (30-100%, P < 0.05), concomitant with a twofold reduction in RCR (P < 0.05). Post-injury, male rats displayed decreases in fiber CSA (days 7, 14, 56; P < 0.05), loss of IIa fibers (day 7; P < 0.05), and an increase in IIb fibers (day 7; P < 0.05), while females displayed no changes in CSA or phenotyping (P > 0.05). Males displayed a positive relationship between state 3 respiration and CSA at days 14 and 56 (P < 0.05), while females only displayed a similar trend at day 14 (P = 0.05). CONCLUSION: Long-lasting impairments in quadriceps mitochondrial health are present after ACL injury and play a key role in the dysregulation of quadriceps muscle size and composition. Our preclinical data indicate that using mitoprotective therapies may be a potential therapeutic strategy to mitigate alterations in muscle size and characteristic after ACL injury.

Relationship between altered knee kinematics and subchondral bone remodeling in a clinically translational model of ACL injury.

Abnormal joint kinematics are commonly reported in the acute and chronic stages of recovery after anterior cruciate ligament (ACL) injury and have long been mechanistically implicated as a primary driver in the development of posttraumatic osteoarthritis (PTOA). Though strongly theorized, it is unclear to what extent biomechanical adaptations after ACL injury culminate in the development of PTOA, as data that directly connects these factors does not exist. Using a preclinical, noninvasive ACL injury rodent model, our objective was to explore the direct effect of an isolated ACL injury on joint kinematics and the pathogenetic mechanisms involved in the development of PTOA. A total of 32, 16-week-old Long-Evans rats were exposed to a noninvasive ACL injury. Marker-less deep learning software (DeepLabCut) was used to track animal movement for sagittal-plane kinematic analyses and micro computed tomography was used to evaluate subchondral bone architecture at days 7, 14, 28, and 56 following injury. There was a significant decrease in peak knee flexion during walking (p < .05), which had a moderate-to-strong negative correlation (r = -.59 to -.71; p < .001) with subchondral bone plate porosity in all load bearing regions of the femur and tibia. Additional comprehensive analyses of knee flexion profiles revealed dramatic alterations throughout the step cycle. This occurred alongside considerable loss of epiphyseal trabecular bone and substantial changes in anatomical orientation. Knee flexion angle and subchondral bone microarchitecture are severely impacted after ACL injury. Reductions in peak knee flexion angle after ACL injury are directly associated with subchondral bone plate remodeling.

The Utility of Functional Data Analyses to Reveal Between-Limbs Asymmetries in Those With a History of Anterior Cruciate Ligament Reconstruction.

CONTEXT: Researchers have traditionally used motion capture to quantify discrete data points (peak values) during hop testing. However, these analyses restrict the evaluation to a single time point (ie, certain percentage of stance) and provide only a narrow view of movement. Applying more comprehensive analyses may help investigators identify important characteristics that are masked by discrete analyses often used to screen patients for activity. OBJECTIVE: To examine the utility of functional data analyses to reveal asymmetries that are undetectable using discrete (ie, single time point) evaluations in participants with a history of anterior cruciate ligament reconstruction (ACLR) who achieved clinical hop symmetry. DESIGN: Cross-sectional study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Fifteen participants with unilateral ACLR (age = 21 ± 3 years, time from surgery = 4 ± 3 years) and 15 control participants without ACLR (age = 23 ± 2 years). INTERVENTION(S): Lower extremity biomechanics during the triple-hop-for-distance task for the ACLR and contralateral limbs of patients and a representative limb of control participants were measured. MAIN OUTCOME MEASURE(S): Peak sagittal-plane joint power, joint work, and power profiles were determined. RESULTS: Using discrete analyses, we identified lower peak knee power and work in the ACLR limb compared with the contralateral and control limbs (P < .05) but were unable to demonstrate differences at the ankle or hip. Using functional data analyses, we observed asymmetries at the ankle, knee, and hip between the ACLR and contralateral or control limbs throughout stance (P < .05), and it was revealed that these asymmetries stemmed from knee power deficits that were prominent during early loading. CONCLUSIONS: Despite achieving hop-distance symmetry, the ACLR knees absorbed less power. Although this information was revealed using discrete analyses, underlying asymmetries at the ankle and hip were masked. Using functional data analyses, we found interlimb asymmetries at the ankle, knee, and hip. Importantly, we found that functional data analyses more fully elucidated the extent and source of asymmetries, which can be used by clinicians and researchers alike to aid in clinical decision making.

Morphology and Anabolic Response of Skeletal Muscles Subjected to Eccentrically or Concentrically Biased Exercise.

CONTEXT: Long-term eccentric exercise is known to promote muscle growth better than concentric exercise, but its acute effect on muscle is not well understood because of misinterpreted modeling and in situ and in vitro stretch protocols. Knowing if the initial bout of eccentric exercise promotes muscle growth and limits damage is critical to understanding the effect of this mode of exercise. OBJECTIVE: To directly evaluate the immediate effects of eccentric and concentric exercises on untrained muscle when fiber strains were physiological and exercise doses were comparable. DESIGN: Controlled laboratory study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 40 skeletally mature male Long-Evans rats (age = 16 weeks, mass = 452.1 ± 35.2 g) were randomly assigned to an eccentric exercise (downhill walking, n = 16), concentric exercise (uphill walking, n = 16), or control (no exercise, n = 8) group. INTERVENTION(S): Rats were exposed to a single 15-minute bout of eccentric or concentric exercise on a motorized treadmill and then were euthanized at 6 or 24 hours postexercise. We harvested the vastus lateralis muscle bilaterally. MAIN OUTCOME MEASURE(S): The percentage increase or decrease in protein abundance in exercised animals relative to that in unexercised control animals was evaluated as elevated phosphorylated p70S6k relative to total p70S6k. Fiber damage was quantified using immunoglobulin G permeability staining. One-way analysis of variance and post hoc Tukey tests were performed. RESULTS: Rats exposed to eccentric exercise and euthanized at 24 hours had higher percentage response protein synthesis rates than rats exposed to eccentric exercise and euthanized at 6 hours (P = .02) or to concentric exercise and euthanized at 6 (P = .03) or 24 (P = .03) hours. We assessed 9446 fibers for damage and found only 1 fiber was infiltrated (in the concentric exercise group euthanized at 6 hours). Furthermore, no between-groups differences in immunoglobulin G fluorescent intensity were detected (P = .94). CONCLUSIONS: Incorporating eccentric exercise is a simple, universally available therapeutic intervention for promoting muscle recovery. A single 15-minute dose of eccentric exercise to a novice muscle can better exert an anabolic effect than a comparable dose of concentric exercise, with very limited evidence of fiber damage.