Cross-sectional Muscle Research Articles

The effect of lumbar multifidus muscle degeneration on upper lumbar disc herniation.

This study aimed to investigate the effect of lumbar multifidus muscle (MF) degeneration on upper lumbar disc herniation (ULDH). This study used 3.0T magnetic resonance imaging (MRI) T2 axial weighted images to retrospectively analyze 93 ULDH patients and 111 healthy participants. Sixty-five pairs of participants were included in this study using propensity score matching (PSM). Cross-sectional area, fat infiltration area, anteroposterior diameter (APD), lateral diameter (LD), cross-sectional area of the bilateral multifidus muscles at the corresponding level, intervertebral disc area at the corresponding section, and visual analog scale (VAS) score for low back pain (LBP). For inter-group comparisons, we used the t-test, analysis of variance (ANOVA), Mann-Whitney U test, Kruskal-Wallis test, chi-square test, or Fisher's exact test, according to the type of data. We used Pearson correlation analysis to study the correlation between the VAS score and related indicators, and established a predictive model for upper lumbar disc herniation using the receive operative characteristic (ROC) curve analysis method. Finally, univariate and multivariate logistic regression analyses were performed to establish a predictive model for the risk of high lumbar disc herniation. We compared the fat areas at the lumbar vertebral levels L1/2, L2/3, and L3/4, as well as the left lateral diameter (LD) (MF), L1/2 left lumbar multifidus muscle index (LMFI), and L1/2 total fat infiltration cross-section area (TFCSA), and found significant differences between the case and control groups (P < 0.001). Furthermore, we observed a significant positive correlation (P < 0.05) between the VAS scores and multiple muscle indicators. Additionally, we developed ROC prediction models to assess the risk of lumbar intervertebral disc protrusion at the L1/2, L2/3, and L3/4 levels, with the results identifying L1/2 TFCSA, L2/3 TFCSA, and L3/4 relative psoas major muscle cross-section area (rPMCSA) as the most predictive indicators. Finally, univariate and multivariate logistic regression analyses showed that the L1/2 rPMCSA, L2/3 TFCSA were significantly associated with the risk of lumbar intervertebral disc protrusion in both models. Degeneration of the MF is significantly correlated with the occurrence of ULDH, and the larger the area of fat infiltration in the MF, the more obvious the lower back pain in ULDH patients. In addition, TFCSA can serve as an indicator of the occurrence of ULDH.

The Use of Grayscale Muscle Ultrasound to Indicate Muscle Recovery After Peripheral Nerve Reconstruction.

This study aimed to validate the use of grayscale muscle ultrasound by measuring echo intensity to longitudinally evaluate functional muscle reinnervation in a rabbit peroneal nerve defect model. Eighteen New Zealand White rabbits underwent a 30-mm peroneal nerve reconstruction with autografts or decellularized allografts. Ultrasound measurements of tibialis anterior muscles were performed before surgery and at 4, 8, 12, 16, 20, and 24 weeks postoperatively and included cross-sectional muscle area, mean gray value (MGV), and mean gray value normalized for area (MGVA). At 24 weeks, functional motor recovery was evaluated with isometric tetanic force (ITF) and compound muscle action potential (CMAP). MGVA data was compared with ITF and CMAP measurements by calculating the Spearman correlation coefficient. Muscle area (Left/Right Ratio (L/R)) of autografts was superior to allografts at 4, 12, 16, 20 and 24 weeks (p<0.03 for all comparisons). MGVs of the operated side were significantly higher for autografts at 4, 8, and 12 weeks and at 12, 16, 20, and 24 weeks for allografts (p<0.01 for all comparisons), compared to their unoperated sides. Similar patterns were seen in both groups for MGVA (operated versus control side). MGVA (L/R) demonstrated a strong correlation with ITF (L/R) for autografts (ρ = -0.7) and allografts (ρ = -0.87), but inconsistent with CMAPs (L/R). Quantitative muscle ultrasound demonstrated a reliable, non-invasive tool for evaluating motor recovery in a rabbit peroneal nerve reconstruction model. Clinical translation could provide valuable insights into muscle health and structural changes following nerve reconstruction.

Evaluating the Role of Rectus Abdominis Fat Transfer (RAFT) in Improving Muscle Thickness: Does it Really Work? A 12-Month Follow-Up Cohort Study.

Looking for an adequate solution for those patients who desire abdominal definition, but are not candidates for liposuction alone, Danilla developed a technique, using selective fat grafting into the rectus abdominis (RAFT) to increase the muscle volume in addition to selective liposuction and abdominoplasty to provide an optimal body contouring. To determine whether intramuscular fat grafting in the rectus abdominis muscles leads to an increase in muscle thickness after one year. This is a prospective cohort study, from a single center, carried out over 24 months (October 2021-September 2023). Sixty-two patients who underwent lipoabdominoplasty and RAFT, had their rectus abdominis cross section measured by ultrasound pre- and 12 months postoperatively. To compare the muscle thickness, a paired t-test statistic was used. A p-value of 0.05 was considered statistically significant (IBM SPSS Statistics V26). After 1 year, all 62 patients showed an increase in the size of the rectus muscle cross section, although only 58 (94%) had fat identifiable in the US. Preoperatively, the mean muscle cross-sectional size was 1, 4cm. After RAFT, overall mean muscle cross section was 2, 3cm (0, 9cm/66.9% increase). When stratified into groups with and without identifiable fat, the group in which the graft remained showed greater increase than the group with no visible fat (69, 9% vs 19,6%). The RAFT provided a significant increase in the muscle cross section in most cases after 1 year. The presence of fat is related to a statistically significant increase in the muscle compartment (pack). This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Sarcopenic obesity in patients with head and neck cancer is predictive of critical weight loss during radiotherapy.

The impact of computed tomography-defined sarcopenia on outcomes in head and neck cancer has been well described. Sarcopenic obesity (SO) (depleted muscle mass combined with obesity) may pose a more serious risk than either condition alone. We investigated SO and its impact on survival and critical weight loss (≥ 5 %) in patients with head and neck cancer who received curative radiotherapy (± other modalities). Retrospective analysis of computed tomography cross-sectional muscle at cervical (C3), thoracic (T2) and lumbar (L3) regions was conducted. Patients were grouped by BMI and sarcopenia status based on established thresholds. A total of 413 patients were included for analysis, the majority having oropharyngeal carcinoma (52 %), and 56 % received primary concurrent chemoradiotherapy. The majority of the cohort (65 %) was overweight or obese (BMI ≥ 25 kg/m2). Sarcopenia was found in 43 %, with 65 % having SO (n 116), equating to 28 % of the whole cohort. Critical weight loss was experienced by 58 % (n 238). A significantly higher proportion of patients with SO experienced critical weight loss (n 70 v. 19, P < 0·001) and were four times more likely to do so during treatment (OR 4·1; 95 % CI 1·5, 7·1; P = 0·002). SO was not found to impact on overall or cancer-specific survival; however, in patients with sarcopenia, those with SO had better overall survival (median 9·1 v. 7·0 years; 95 % CI 5·2, 16·8; P = 0·021). SO at the time of presentation in patients with head and neck cancer is predictive of critical weight loss during treatment, and muscle evaluation can be useful in identifying patients at nutritional risk regardless of BMI and obvious signs of wasting.

An Analysis of Age-Related Body Composition Changes and Metabolic Patterns in Korean Adults Using FDG-PET/CT Health Screening Data.

F-18-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) can be used to measure bone mineral density (BMD), cross-sectional muscle area (CSMA), Hounsfield units (HU) of liver and muscle, subcutaneous adipose tissue (SAT), abdominal visceral adipose tissue (VAT), and glucose metabolism. The present study aimed to identify age-related changes in body composition and glucose metabolism in Korean using opportunistic FDG-PET/CT imaging. We analyzed FDG-PET/CT, clinical history, and laboratory data abstracted from the medical records of patients who underwent health screening at a single institute between 2017 and 2022. In total, 278 patients were included in the analysis (male:female=140:138). Age and body mass index were positively correlated in female, but negatively correlated in male. BMD decreased with age more in female, and CSMA decreased with age more in male. Muscle HU decreased with age for both sexes. In female, SAT and VAT increased with age; and in male, SAT decreased slightly while VAT remained stable. Muscle glucose metabolism showed no association with age in male but increased with age in female. CSMA correlated positively with BMD overall; and positively correlated with VAT and SAT in male only. In female only, both SAT and VAT showed negative correlations with glucose metabolism and correlated positively with muscle glucose metabolism. Liver HU values were inversely correlated with VAT, especially in female; and positively correlated with muscle glucose metabolism in female only. FDG-PET/CT demonstrated distinct patterns of age-related changes in body composition and glucose metabolism, with significant differences between sexes.

509. DOES SARCOPENIA AFFECT THE OUTCOME OF PATIENTS WITH ESOPHAGEAL CARCINOMA AFTER ESOPHAGECTOMY?

Abstract Background Sarcopenia is increasingly recognized as an independent predictor of clinical outcomes of cancer patients such as post-operative complications and prolonged hospital stays. Additionally, sarcopenia can also negatively impact overall survival because of reduced ability to tolerate treatments like neoadjuvant therapy and surgery. At particular risk among cancer patients is the esophageal cancer population because of tumor stenosis leading to dysphagia and impossibility of oral feeding in many patients. The purpose of the current study was to investigate the effect of preoperative sarcopenia on postoperative complications in patients undergoing esophagectomy for esophageal cancer. Methods This retrospective study includes all patients who underwent full-robotic abdominothoracic esophageal resection because of esophageal cancer at our institution between 06/2020 and 12/2022. The skeletal muscle index (SMI) was assessed using the preoperative computed tomographic staging scans by measuring the cross-sectional muscle area at the third lumbar vertebral level. Following cut off SMI values were used to define sarcopenia: men: 52,4 cm2/m2, women: 38,5 cm2/m2 according to Prado et al (Lancet Oncol, 2008). Recorded parameters included demographic data, neo-adjuvant treatment, histologic findings, postoperative course and overall- and disease-free survival. Results A total of 113 cases were included in this preliminary analysis. 97 patients (86%) were classified as having sarcopenia. Of these, 38 patients (40%) had a preoperatively or during esophageal resection implemented percutaneous endoscopic jejunostomy (PEJ) tube to ensure enteral nutrition. Despite age, groups were comparable regarding neoadjuvant treatment and histologic findings (mean age sarcopenic patients: 66y vs. 61y non-sarcopenic patients, p = 0.03). There was no difference in the incidence of occurrence of anastomotic leakage, pulmonary complications, need for re-operation, length of (ICU) stay and overall- and disease-free survival between sarcopenic and non-sarcopenic patients. Conclusion Incidence of sarcopenia is very high among esophageal cancer patients. In our study population, however, preoperative sarcopenia failed to predict complications or long-term outcome after esophagectomy for esophageal cancer. 40% of the sarcopenic patients received a PEJ. This relatively high proportion of implemented PEJ could have contributed to the observed comparable outcomes between sarcopenic and non-sarcopenic patients. This observation underlines the importance of prehabilitation and nutritional support for patients with preoperative sarcopenia.

Functional study of the ST6GAL2 gene regulating skeletal muscle growth and development

ST6GAL2, a member of the sialoglycosyltransferase family, primarily localizes within the cellular Golgi apparatus. However, the role of the ST6GAL2 gene in skeletal muscle growth and development remains elusive. In this study, the impact of the ST6GAL2 gene on the proliferation, differentiation, and apoptosis of primary chicken myoblasts at the cellular level was investigated. Quantitative fluorescent PCR was used to measure the expression levels of genes. Subsequently, using gene knockout mice, we assessed its effects on skeletal muscle growth and development in vivo. Our findings reveal that the ST6GAL2 gene promotes the expression of cell cycle and proliferation-related genes, including CCNB2 and PCNA, and apoptosis-related genes, such as Fas and Caspase-9. At the individual level, double knockout of ST6GAL2 inhibited the formation of both fast and slow muscle fibers in the quadriceps, extensor digitorum longus, and tibial anterior muscle, while promoting their formation in the gastrocnemius and soleus. These results collectively demonstrate that the ST6GAL2 gene facilitates the proliferation, apoptosis, and fusion processes of primary chicken myoblasts. Additionally, it promotes the enlargement of cross-sectional muscle fiber areas and regulates the formation of fast and slow muscle fibers at the individual level, albeit inhibiting muscle fusion. This study provides valuable insights into the role of the ST6GAL2 gene in promoting proliferation of skeletal muscle.

Sarcopenia as a prognostic factor in patients with hepatocellular carcinoma treated with transcatheter arterial chemoembolization plus sorafenib.

Loss of skeletal muscle volume is an important aspect of sarcopenia in hepatocellular carcinoma (HCC) patients treated by surgical resection, transcatheter arterial chemoembolization (TACE), or sorafenib. This study determined the influence of sarcopenia and other laboratory results on survival in patients with HCC treated with TACE plus sorafenib. The patients were divided into two groups based on the presence of sarcopenia. The skeletal muscle index was calculated by normalizing the cross-sectional muscle area at the L3 level on an abdominal computed tomography scan before embolization according to the patient's height. The clinical characteristics of the two groups were then compared. The progression-free survival (PFS) and overall survival (OS) rates after treatment were determined. Sarcopenia was present in 75 of the 102 (74%) patients with HCC included in this study. The albumin, prealbumin, and cholinesterase levels were lower in those with sarcopenia. The OS (P = 0.001) and PFS (P = 0.008) were significantly prolonged in the nonsarcopenia group compared to the sarcopenia group. Sarcopenia, ECOG (≥2), and prealbumin (<180 mg/L) were significantly associated with PFS. Sarcopenia, ECOG (≥2), Child-Pugh B, BCLC stage C, prealbumin (<180 mg/L), and cholinesterase (<5,320 U/L) were significantly associated with OS. The prognostic factors for OS included sarcopenia, ECOG (≥2), and cholinesterase (<5,320 U/L), whereas only ECOG (≥2) was identified as a prognostic factor for PFS. Sarcopenia may be an indicator of poor clinical outcome in patients with HCC receiving TACE plus sorafenib.

Impact of relative cisplatin dose to skeletal muscle mass on adverse events in patients with head and neck cancer undergoing chemoradiotherapy.

Chemoradiotherapy (CRT) with high-dose cisplatin (CDDP) is the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC). Although dosing is based on body surface area (BSA), some patients experience CDDP-related adverse events (AEs). We aimed to evaluate the impact of relative CDDP dose to skeletal muscle mass (SMM) on chemotherapy-associated AEs in patients with HNSCC undergoing CRT with high-dose CDDP. We retrospectively analyzed data of patients who underwent CRT with high-dose CDDP (80-100 mg/m2, triweekly) between 2010 and 2023. SMM was measured as the cross-sectional muscle area at the third cervical vertebra (C3-SMM) using computed tomography; the skeletal muscle index (SMI) was defined as SMM normalized by squared height. The CDDP index was defined as the prescribed CDDP dose divided by SMI. CDDP-related AEs were assessed during the first cycle using Common Terminology Criteria for Adverse Events v5.0. Overall, 306 patients were identified. The CDDP index cutoff value best associated with grade ≥ 3 AEs was 10.312. Grade ≥ 3 hematological toxicities exhibited stronger association with high CDDP index value than with low CDDP index value (26.9% vs 16.3%, P = .033). Multivariate analysis revealed that high CDDP index value and creatinine clearance < 70 mL/minute were predictive factors for grade ≥ 3 AEs (odds ratio [OR] 2.55, P = .008; OR 3.68, P = .002, respectively). The CDDP index based on C3-SMM was an independent predictive factor for grade ≥ 3 CDDP-related AEs. C3-SMM is potentially more useful than BSA for determining the optimal CDDP dose in patients with HNSCC.

Impact of functional electrical stimulation on nerve-damaged muscles by quantifying fat infiltration using deep learning.

Quantitative imaging in life sciences has evolved into a powerful approach combining advanced microscopy acquisition and automated analysis of image data. The focus of the present study is on the imaging-based evaluation of the posterior cricoarytenoid muscle (PCA) influenced by long-term functional electrical stimulation (FES), which may assist the inspiration of patients with bilateral vocal fold paresis. To this end, muscle cross-sections of the PCA of sheep were examined by quantitative image analysis. Previous investigations of the muscle fibers and the collagen amount have not revealed signs of atrophy and fibrosis due to FES by a laryngeal pacemaker. It was therefore hypothesized that regardless of the stimulation parameters the fat in the muscle cross-sections would not be significantly altered. We here extending our previous investigations using quantitative imaging of intramuscular fat in cross-sections. In order to perform this analysis both reliably and faster than a qualitative evaluation and time-consuming manual annotation, the selection of the automated method was of crucial importance. To this end, our recently established deep neural network IMFSegNet, which provides more accurate results compared to standard machine learning approaches, was applied to more than 300 H&E stained muscle cross-sections from 22 sheep. It was found that there were no significant differences in the amount of intramuscular fat between the PCA with and without long-term FES, nor were any significant differences found between the low and high duty cycle stimulated groups. This study on a human-like animal model not only confirms the hypothesis that FES with the selected parameters has no negative impact on the PCA, but also demonstrates that objective and automated deep learning-based quantitative imaging is a powerful tool for such a challenging analysis.

Muscle mass as a modifier of stress response in acute ischemic stroke patients

Stroke triggers a systemic inflammatory response over the ensuing days after the cerebral insult. The age and comorbidities of the stroke population make them a vulnerable population for low muscle mass and sarcopenia, the latter being another clinical condition that is closely associated with inflammation, as shown by increased levels of pro-inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR). In this study, we evaluated the relationship between post-stroke NLR changes and muscle mass in a prospective cohort of acute ischemic stroke patients (n = 102) enrolled in the Muscle Assessment in Stroke Study Turkey (MASS-TR). Admission lumbar computed tomography images were used to determine the cross-sectional muscle area of skeletal muscles at L3 vertebra level and calculate the skeletal muscle index (SMI). The median (IQR) SMI was 44.7 (39.1–52.5) cm2/m2, and the NLR at admission and follow-up were 4.2 (3.0–10.5) and 9.4 (5.7–16.2), respectively. While there was no relationship between SMI and admission NLR, a significant inverse correlation was observed between SMI and follow-up NLR (r = − 0.26; P = 0.007). Lower SMI remained significantly associated (P = 0.036) with higher follow-up NLR levels in multivariate analysis. Our findings highlight the importance of muscle mass as a novel factor related to the level of post-stroke stress response.

Accurate Identification of Motoneuron Discharges From Ultrasound Images Across the Full Muscle Cross-Section.

Non-invasive identification of motoneuron (MN) activity commonly uses electromyography (EMG). However, surface EMG (sEMG) detects only superficial sources, at less than approximately 10-mm depth. Intramuscular EMG can detect deep sources, but it is limited to sources within a few mm of the detection site. Conversely, ultrasound (US) images have high spatial resolution across the whole muscle cross-section. The activity of MNs can be extracted from US images due to the movements that MN activation generates in the innervated muscle fibers. Current US-based decomposition methods can accurately identify the location and average twitch induced by MN activity. However, they cannot accurately detect MN discharge times. Here, we present a method based on the convolutive blind source separation of US images to estimate MN discharge times with high accuracy. The method was validated across Ten participants using concomitant sEMG decomposition as the ground truth. 140 unique MN spike trains were identified from US images, with a rate of agreement (RoA) with sEMG decomposition of 87.4 ± 10.3%. Over 50% of these MN spike trains had a RoA greater than 90%. Furthermore, with US, we identified additional MUs well beyond the sEMG detection volume, at up to >30 mm below the skin. The proposed method can identify discharges of MNs innervating muscle fibers in a large range of depths within the muscle from US images. The proposed methodology can non-invasively interface with the outer layers of the central nervous system innervating muscles across the full cross-section.

TRIM Enhances Angiogenesis in Dystrophic Muscle 140 Days Post Treatment

Background: Duchenne Muscular Dystrophy (DMD) causes limb muscle dysfunction and impaired mobility while promoting ischemia in effected muscles. For treatment, we developed a novel biomaterial, Time Release Ion Matrix (TRIM), that promotes angiogenesis and enhances muscle structure and function in dystrophic (D2. mdx) mice at 14- and 70-days post injection (dpi). Whether TRIM remains effective at 140 dpi is unknown. Hypothesis: At 140 dpi in D2. mdx mice TRIM will: 1) enhance isometric force and myofiber cross-sectional area (CSA) of the tibialis anterior (TA) muscle; and 2) stimulate angiogenic growth factors and increase vascularity. Methods: The right and left TA of adult male D2. mdx mice (male, n=7-8, age 7 months) were injected with saline alone (control) or 250 μg of TRIM suspended in saline. At 140 dpi, the left TA muscle was isolated for in situ muscle force measurements and histological analysis; the right TA was frozen for biochemical analysis. Muscle cross-sections were immunostained for laminin (myofiber borders), DAPI (nuclei), and CD31 (endothelial cells). Vascular endothelial growth factor (VEGF) ELISA and immunoblots were performed on muscle homogenates. Results: No difference in peak isometric force was recorded between groups at 140 dpi (means ± SE: TRIM, 65.4 ± 2.7g; Saline, 62.7 ± 1.5g; P= 0.34). TRIM enhanced the relative frequency of myofibers &gt;1000 μm2 by 27% vs. saline (TRIM, 56 ± 2%; Saline, 44 ± 3%; P= 0.006). DAPI staining revealed a 36% increase in central nuclei indicating myofiber regeneration (TRIM, 30.0 ± 1.7%; Saline, 22.0% ± 2.5; P=0.02). Microvessel area (CD31 staining, μm2) was 2.5-fold greater in treated TA’s (TRIM, 131 ± 12 μm2; Saline, 53 ± 6 μm2, P=0.0001). In muscle homogenates, TRIM had no effect on [VEGF] (TRIM, 102 ± 5%; Saline, 100 ± 4%; P= 0.79), while STAT3 activation was greater (TRIM, 129 ± 11%; Saline, 100 ± 7%; P= 0.04). Conclusion: At 140 days following injection of TRIM into the TA muscle of dystrophic mice, peak isometric force was unchanged while myofiber CSA was enhanced. Furthermore, TRIM promotes angiogenic growth factors and muscle vascularity, which should promote the ability to sustain physical activity. University of Missouri Coulter Biomedical Accelerator (SSS), American Physiological Society SURF (AGN), Texas A&amp;M Department of Kinesiology and Sport Management (ABM). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

TRIM Enhances Dystrophic Muscle Function 70 Days Post Treatment

Background: Duchenne Muscular Dystrophy (DMD) is associated with limb muscle dysfunction caused by progressive weakness and degeneration of skeletal muscle. Current FDA-approved therapeutic strategies are less effective than originally hoped. Our alternative approach was to develop a novel biomaterial, Time Release Ion Matrix (TRIM), shown to release angiogenic ions and enhance muscle structure and function at 14 days post injection (dpi) in dystrophic (D2. mdx) mice. However, the long-term effects of TRIM are unknown. Hypothesis: At 70 days post injection in D2. mdx mice TRIM will: 1) enhance isometric force and myofiber cross-sectional area (CSA) of the tibialis anterior (TA) muscle; and 2) promote vascular endothelial growth factor (VEGF) availability and muscle vascularity. Methods: The right and left TA of adult male D2. mdx mice (n=6-7, age 5 months) were injected with saline alone (control) or 250 μg of TRIM suspended in saline. At 70 dpi, the left TA was isolated for in situ muscle force measurements and histological analysis; the right TA was frozen for biochemical analysis. Muscle cross-sections were immunostained for laminin (myofiber borders), DAPI (nuclei), and CD31 (endothelial cells). An ELISA for VEGF was performed on homogenates of frozen muscles. Results: TA’s injected with TRIM increased peak isometric force (means ± SE: TRIM 70.9 ± 1.8 g; Saline, 65.9 ± 1.1 g; P= 0.04). TRIM-treated TA’s had a 2.2-fold increase in relative frequency of myofibers &gt;1000 μm2 (TRIM, 31.8 ± 3.7%; Saline, 14.4 ± 1.9%; P= 0.001), and reduced the frequency of myofibers &lt;400 μm2 by 32% (TRIM, 38.6% ± 2.8; Saline, 56.5% ± 3.5; P= 0.001). DAPI staining revealed a 50% increase in central myonuclei indicative of regenerated myofibers (TRIM, 30.2 ± 1.7%; Saline, 20.2 ± 1.3%; P=0.0006). Microvessel area (CD31 staining; μm2) was 2.1-fold greater in treated TA’s (TRIM, 135.6 ± 8.7 μm2; Saline, 63.6 ± 4.5 μm2; P=0.0001). In muscle homogenates, TRIM increased [VEGF] (TRIM, 139 ± 10%; Saline, 100 ± 6%; P= 0.009) Conclusion: Results support the hypothesis that 70 days following injection of TRIM into the TA of dystrophic mice, muscle force and myofiber CSA are enhanced. Moreover, TRIM enhances VEGF with increased vascularity, suggesting that the angiogenic effects of TRIM complement those on myogenesis and contractile function towards restoring muscle structure and function in DMD. University of Missouri Coulter Biomedical Accelerator (SSS), Texas A&amp;M Department of Kinesiology and Sport Management (ABM). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Muscle function and structure in a mouse model of dysfunctional central nervous system myelin

INTRODUCTION. Claudin-11(CLDN11)-deficient mice have been reported to have dysfunctional central nervous system myelin, and altered motor control and muscle tone in their hindlimbs. OBJECTIVE. We compared CLDN11-deficient mice with strain-, age-, and sex-matched controls (CLDN11-suffent mice). We hypothesized that CLDN11-deficient mice will have reduced muscle strength and will show a greater resistance to high stretch velocities compared to their CLDN11-suffcient counterparts. METHODS. We studied the ankle dorsiflexor and plantarflexor muscles in a convenience sample of ten CLDN11-deficient and four CLDN11-suffcient mice (3-4 months, males). We recorded the maximum isometric contractile torque of the ankle plantarflexor and dorsiflexor muscles measured in milli-Newton-millimeter (mNmm), and the maximum contractile torque at low (100 °/s) and high (1200 °/s) muscle stretch velocities during eccentric contractions to assess spasticity. We also studied structural changes in muscle cross sections stained with hematoxylin and eosin. RESULTS. Data are reported as mean ± SD. Maximum plantarflexor contractile torque was 7800 ± 1651 mNmm and 9646 ± 2637 mNmm in CLDN11-deficient and -suffcient mice, respectively. Maximum dorsiflexor contractile torque was 1956 ± 347 mNmm and 2975 ± 195 mNmm in CLDN11-deficient and -suffcient mice, respectively. Spasticity assessed as the ratio of maximum eccentric torque measured at 1200 °/s to 100 °/s was 0.94 ± 0.07 and 0.93 ± 0.01 in the plantarflexors of CLDN11-deficient and -suffcient mice, respectively, and 1.41 ± 0.19 and 2.1 ± 0.33 in the dorsiflexors of CLDN11-deficient and -suffcient mice, respectively. One-way ANOVAs indicated that CLDN11-deficient and -suffcient mice were not statistically different (p&gt;0.05) in maximum torque production and spasticity. CLDN11-deficient mice showed no remarkable alterations in muscle structure. CONCLUSION. Claudin 11 deficiency in mice does not affect maximum contractile torque and stretch-velocity-dependent muscle tone when studied by robotic dynamometry under general anesthesia, nor does it prominently affect muscle structure. We thank the WSU UROP funding mechanism for supporting Ms. Iman Manzoor’s involvement on this project. We thank the Wayne State University Doctor of Physical Therapy (DPT) Program for supporting student research and providing research training through coursework and research experiences. We thank Dr. Alexander Gow for sharing mice and mentorship. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Chronic Hindlimb Ischemia Induces Alterations of Muscle Transcriptomes Based on Muscle Type

Introduction: Peripheral artery disease (PAD) is a progressive atherothrombotic disorder of the arteries supplying the lower limb and is the most prevalent cardiovascular disease, impacting over 230 million people worldwide. PAD is associated with lower extremity myopathy characterized by myofiber degeneration and fibrosis. Increased proportions of type I muscle fibers are associated with improved patient outcomes, but most studies, human and animal, only analyze the gastrocnemius (gastroc), which contains mixed amounts of type I and type II fibers. To elucidate the impacts of ischemia on muscles comprising mainly type I fibers, we evaluated the differential effect of hindlimb ischemia (HLI) on the soleus and gastroc, hypothesizing that chronic HLI would more severely impact the soleus. Methods: Chronic HLI was induced in Sprague-Dawley male rats with an endovascular iliofemoral artery occlusion approach. Time-dependent laser Doppler perfusion imaging assessed hindlimb perfusion before and after HLI up to 42 days. Myopathy was evaluated 28 days post-HLI by staining muscle cross-sections with Hematoxylin and Eosin (H&amp;E) and Masson trichrome. Quantification of muscle fibrosis, average fiber cross-sectional area, and presence of central nuclei were used to determine muscle pathology. RNAsequencing was used to determine the differences in transcriptomes of the gastroc and soleus in both sham and HLI conditions. Results: Histological analysis revealed that there were significantly increased levels of fibrosis after HLI, but only in the soleus (18.24±7.23 vs. 7.71±2.54 %, n = 8-16, p-value &lt;0.0001). The average fiber cross-sectional area was significantly reduced in the HLI soleus compared to the sham (1556.00±459.60 vs. 3072.00±831.50 μm, n = 8-16, p-value &lt;0.0001), but not between HLI and sham gastroc. Conversely, HLI increased the proportions of centralized nuclei in both muscles (soleus — 22.72±12.46 vs. 1.12±1.49 %, n = 8-16, p-value = 0.0002, gastroc — 12.75±10.17 vs. 0.00±0.00 %, n = 8-16, p-value = 0.0002), indicating prior muscle damage. The HLI soleus exhibited worse outcomes in all parameters compared to the HLI gastroc. These data were substantiated by RNAseq, which showed that the HLI soleus transcriptome contained more differentially expressed genes (DEGs, ~1000 altered genes) than its sham counterpart compared to HLI gastroc, which possessed &lt;100 DEGs (n = 5-6). Moreover, the HLI soleus transcriptome was highly fibrotic, pro-angiogenic, and promoted myoblast fusion, a combination that could explain the histological myopathy findings. Conclusions: Chronic HLI induces alterations of muscle ultrastructure and transcription. These effects occur predominantly in the soleus rather than the gastroc. The results of the present study implicate that the pathophysiology is different for distinct muscles and may result from varying fiber composition. This work can help identify the mechanisms responsible for the myopathy of PAD and may lead to the design of targeted interventions for the care of PAD patients. R01HL169205-01. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ex-vivo validation of spatial gain sonography for the quantification of echo intensity in fascicle-aligned ultrasound images in ten anatomical muscles in Bos taurus

This study aimed to validate the concept of spatial gain sonography for quantifying texture-related echo intensity in B-mode ultrasound of skeletal muscle. Fifty-one bovine muscles were scanned postmortem using B-mode ultrasonography at varying fascicle probe angles (FPA). The relationship between mean gray values (MGV) and FPA was fitted with a sinusoidal and a linear function, the slope of which was defined as tilt echo gain (TEG). Macroscopic muscle cross sections were optically analyzed for intramuscular connective tissue (IMCT) content which was plotted against MGV at 0° FPA (MGV_00). MGV peaked at FPA 0°. Sine fits were superior to linear fits (adjusted r2-values 0.647 vs. 0.613), especially for larger FPAs. In mixed models, the pennation angle was related to TEG (P < 0.001) and MGV_00 (P = 0.035). Age was relevant for MGV_00 (P < 0.001), but not TEG (P > 0.10). The correlation between the IMCT percentage and MGV_00 was significant but weak (P = 0.026; adjusted r2 = 0.103). The relationship between fascicle probe angle and echo intensity in B-mode ultrasound can be modeled more accurately with a sinusoidal but more practically for clinical use with a linear fit. The peak mean gray value MGV_00 can be used to compare echo intensity across muscles without the bias of pennation angle.

The low cross-sectional muscle index at the third cervical vertebra is a marker for sarcopenia in patients with laryngopharyngeal cancer.

Muscle loss and sarcopenia play a significant role in head and neck cancer. In this study, the value of C3 cross-sectional skeletal muscle index was investigated to evaluate sarcopenia. Seventy-four patients were included in this retrospective study. Skeletal muscle index (SMI) was calculated using the paracervical muscles at the level of the third cervical vertebra. Survival rates and toxicities were compared. The 3-year overall survival rates were 33.3% in patients with low SMI (≤44.79) and 63.9% in patients with high SMI (>44.79) (P < 0.01). The 3-year progression-free survival rates were 25.9% in patients with low SMI and 63.2% in patients with high SMI (P < 0.01). Multivariate analyses found that advanced age (>65) was associated with a 2.9-fold increased risk of death and low SMI was associated with a 3.9-fold increased risk of death. Low SMI is associated with prolonged treatment time, increased toxicity, and decreased survival.

High-throughput Analysis of Capillary Density in Skeletal Muscle Cross Sections.

Capillary density in skeletal muscles is key to estimate exercise capacity in healthy individuals, athletes, and those with muscle-related pathologies. Here, we present a step-by-step, high-throughput semi-automated method for quantifying capillary density from whole human skeletal muscle cross-sections, in areas of the muscle occupied by myofibers. We provide a detailed protocol for immunofluorescence staining, image acquisition, processing, and quantification. Image processing is performed in ImageJ, and data analysis is conducted in R. The provided protocol allows high-throughput quantification of capillary density. Key features • This protocol builds upon the method and results described in Abbassi-Daloii et al. (2023b). • It includes step-by-step details on image acquisition and image processing of the entire muscle section. • It enables high-throughput and semi-automated image quantification of capillary density. • It provides a robust analysis for determining capillary density over the entire muscle cross section.

Immunostaining protocol of human 3D bioengineered skeletal muscle whole mounts and cross section for confocal microscopy

Immunostaining protocol of human 3D bioengineered skeletal muscle whole mounts and cross section for confocal microscopy