Mean Muscle Fiber Cross-sectional Area Research Articles

HDAC4 Genomic Methylation and Subsequent DNA Binding Following Joint Injury Confers a Sustained Epigenetic Memory of Disrupted Muscle Plasticity

Joint injury is associated with protracted atrophy and weakness that poorly recovers; our objective was to define molecular effectors of lost muscle size, strength, and plasticity following joint injury. We hypothesized that epigenetic imprinting of joint injury in muscle impairs muscle plasticity and contributes to poor functional recovery following surgical repair. We recruited a total of sixteen ACL-injured participants from whom we obtained vastus lateralis muscle biopsies Pre-, 7-days post-, and 4-months post- reconstruction surgery (Sx) and strength measures up to 6-months post-Sx. We performed immunohistochemistry, RNA-seq, reduced representation bisulfite sequencing (RRBS), and HDAC4 chromatin immunoprecipitation sequencing (HDAC4 ChIP-seq) to determine the impact of epigenetics and gene expression on histological profiles, muscle size and muscle strength following injury. Binding and Expression Target Analysis (BETA) of DNA methylation revealed a conserved 985bp regulatory genomic region that was differentially methylated upstream of the HDAC4 promoter. We observed 108 (Pre-Sx), 111 (7d post-Sx), and 110 (4-months post-Sx) differentially methylated promoter sites of which 95 sites were common across all timepoints in the injured limb. Additionally, we observed 1293 differentially methylated intragenic sites within the HDAC4 locus that were also common across all timepoints following injury. Altered HDAC4 methylation was associated with a 2.2 and 4.3 fold change in HDAC4 transcript abundance Pre-Sx and 7d post-Sx, respectively (FDR < 0.05). Notably, HDAC4 binding to critical contractile genes coincided with their downregulation 7d post-Sx (Log2 fold change: ACTA1: -2.02; CKM: -0.97; ATP2A1: -2.34; HOMER2: -1.09; all FDR<0.05). Altered transcript abundance of these genes coincided with lower mean muscle fiber cross-sectional area in the injured limb compared to Healthy (Healthy: 4845 ± 213.4μm2; pre-Sx: 4313 ± 190.6μm2, p<0.05; 7d post-Sx: 3685 ± 228.1μm2, p<0.05; 4-months post-Sx: 3422 ± 142.8μm2, p<0.05) and lower peak torque compared to Healthy (Healthy: 174.8 ± 10.72nm; pre-Sx: 135.2 ± 10.19nm, p<0.05; 4-months post-Sx: 82.64 ± 6.80nm, p<0.05; 6-months post-Sx: 105.9 ± 8.26nm, p<0.05) that was sustained throughout follow-up. Our results suggest that joint injury confers HDAC4 promoter-proximal and intragenic epigenetic imprinting by DNA methylation that increases HDAC4 transcript abundance and HDAC4-DNA binding to represses expression of genes regulating muscle contractile function. This HDAC4 gene regulatory program likely contributes to prolonged deficits in muscle size and strength following joint injury. This work was supported by NIH-NIAMS R01 AR072061. 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.

Peripheral artery disease patients with chronic kidney disease have lower muscle strength and mitochondrial function compared to those with normal kidney function

Introduction: Chronic kidney disease is a significant risk factor for both the development of peripheral artery disease (PAD) and major adverse limb events. However, little is known about how the coalescence of these two conditions impacts limb muscle pathophysiology. The objective of the current study was to determine the impact of CKD on skeletal muscle strength and mitochondrial health in patients with and without PAD. Methods: A cross-sectional prospective study design was employed to assess plantar flexor muscle strength, muscle fiber cross-sectional area (CSA), and mitochondrial health in four groups of patients (61 males and 29 females): PAD only (Toe brachial index, TBI<0.5 and eGFR>60 mL/min), CKD only (TBI>0.75 and eGFR:15-45 mL/min), PAD with CKD (TBI<0.5 and eGFR:15-45 mL/min), and adult controls without PAD and CKD (TBI>0.75 and eGFR>60 mL/min). Results: Plantar flexor muscle strength was lowest in PAD patients with CKD compared to adult controls ( P<0.0001), PAD only ( P=0.001), and CKD only ( P=0.003). No differences in the mean muscle fiber CSA were detected. The percentage of COX+ fibers was significantly lower in PAD patients with CKD compared to adult controls ( P=0.03). High resolution respirometry analysis of mitochondrial oxidative phosphorylation (OXPHOS) function demonstrated that CKD has a significant negative impact on muscle bioenergetics. PAD patients with CKD had lower OXPHOS function than adult controls ( P=0.0016) and PAD patients without CKD ( P=0.0015). Notably, CKD patients without PAD also had lower OXPHOS function than adult controls ( P=0.0054) and PAD patients without CKD ( P=0.005). Conclusion: The current results demonstrate a profound negative impact of CKD on the associated myopathy of PAD patients. This study was supported by National Institutes of Health (NIH) grant R01-HL149704 (T.E.R.). 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.

Effect of Veau Class on Levator Veli Palatini Muscle Composition.

To examine levator veli palatini muscle composition in patients with nonsyndromic cleft palate and investigate the impact of Veau class. Prospective cohort study. Tertiary care academic hospital. Thirteen patients with nonsyndromic cleft palate were recruited. During primary palatoplasty, a sample of levator veli palatini muscle was excised and prepared for histological analysis. Fat and collagen content were determined utilizing Oil Red and Sirius red stains, respectively, while muscle fiber cross-sectional areas were calculated from H&E-stained samples, with analysis using histomorphometric methods. Immunofluorescent staining of myosin heavy chain isoforms was performed. Patients underwent repair at 10.8 months of age (interquartile range [IQR] 10.2-12.9). Fat content of the levator veli palatini muscle was low in both groups, ranging from 0% to 5.2%. Collagen content ranged from 8.5% to 39.8%; neither fat nor collagen content showed an association with Veau classes. Mean muscle fiber cross-sectional area decreased with increasing Veau class, from 808 µm2 (range 692-995 µm2) in Veau II to 651 µm2 (range 232-750 µm2) in Veau III (P = .02). There was also a nonsignificant decrease in proportion of type I muscle fibers with increasing Veau class (44.3% [range 31.4%-84.4%] in Veau II vs 35.3% [range 17.4%-61.3%] in Veau III). Muscle fiber area in levator veli palatini muscles decreases in Veau III clefts in comparison to Veau II. The impact of these differences in velopharyngeal dysfunction requires further analysis of a larger cohort.

Dietary zinc deficiency disrupts skeletal muscle proteostasis and mitochondrial biology in rats

ObjectivesZinc deficiency is related to reduced growth, mass, and work capacity of skeletal muscle. However, the underlying mechanisms in connection with skeletal muscle proteostasis and mitochondrial biology are not clear. The aim of this study was to investigate the consequences of dietary zinc deficiency on skeletal muscle proteostasis and mitochondrial biology in growing rats. MethodsThree-wk-old male Wistar/Kyoto weanling rats were fed either a zinc-deficient diet (<1 mg/kg; ad libitum) or a control diet pair-fed with zinc-deficient group (47.5 mg/kg) for a 7-wk period. Skeletal (gastrocnemius) muscle myofiber cross-sectional area was measured on hematoxylin and eosin-stained sections. Real-time quantitative reverse transcription polymerase chain reaction and immunoblotting were performed to study the target gene and protein expression, respectively. The chymotrypsin-like proteasomal activity was analyzed by fluorescence method. ResultsResults showed a decreased mean muscle fiber cross-sectional area and increased apoptosis in the muscle of zinc-deficient rats. Activation of the ubiquitin-proteasome system as indicated by increased levels of the E1 enzyme, MuRF1 (muscle-specific E3 ligase; muscle atrophy marker) and proteasomal activity was observed in the zinc-deficient rats. Declined autophagy (Beclin1, ATG5, and LC3), and increased endoplasmic reticulum stress markers were observed. Zinc deficiency also affected mitochondrial biology including fission, fusion, transcription, and oxidative phosphorylation components. ConclusionZinc deficiency disturbed the skeletal muscle proteostasis, and mitochondrial biology, causing decreased cell size and increased cell death.

Dieckol Attenuated Glucocorticoid-Induced Muscle Atrophy by Decreasing NLRP3 Inflammasome and Pyroptosis.

Dexamethasone (Dexa), frequently used as an anti-inflammatory agent, paradoxically leads to muscle inflammation and muscle atrophy. Receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4) lead to nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome formation through nuclear factor-κB (NF-κB) upregulation. NLRP3 inflammasome results in pyroptosis and is associated with the Murf-1 and atrogin-1 upregulation involved in protein degradation and muscle atrophy. The effects of Ecklonia cava extract (ECE) and dieckol (DK) on attenuating Dexa-induced muscle atrophy were evaluated by decreasing NLRP3 inflammasome formation in the muscles of Dexa-treated animals. The binding of AGE or high mobility group protein 1 to RAGE or TLR4 was increased by Dexa but significantly decreased by ECE or DK. The downstream signaling pathways of RAGE (c-Jun N-terminal kinase or p38) were increased by Dexa but decreased by ECE or DK. NF-κB, downstream of RAGE or TLR4, was increased by Dexa but decreased by ECE or DK. The NLRP3 inflammasome component (NLRP3 and apoptosis-associated speck-like), cleaved caspase -1, and cleaved gasdermin D, markers of pyroptosis, were increased by Dexa but decreased by ECE and DK. Interleukin-1β/Murf-1/atrogin-1 expression was increased by Dexa but restored by ECE or DK. The mean muscle fiber cross-sectional area and grip strength were decreased by Dexa but restored by ECE or DK. In conclusion, ECE or DK attenuated Dexa-induced muscle atrophy by decreasing NLRP3 inflammasome formation and pyroptosis.

Muscle fiber hypertrophy in response to 6 weeks of high-volume resistance training in trained young men is largely attributed to sarcoplasmic hypertrophy.

Cellular adaptations that occur during skeletal muscle hypertrophy in response to high-volume resistance training are not well-characterized. Therefore, we sought to explore how actin, myosin, sarcoplasmic protein, mitochondrial, and glycogen concentrations were altered in individuals that exhibited mean skeletal muscle fiber cross-sectional area (fCSA) hypertrophy following 6 weeks of high-volume resistance training. Thirty previously resistance-trained, college-aged males (mean ± standard deviation: 21±2 years, 5±3 training years) had vastus lateralis (VL) muscle biopsies obtained prior to training (PRE), at week 3 (W3), and at week 6 (W6). Muscle tissue from 15 subjects exhibiting PRE to W6 VL mean fCSA increases ranging from 320–1600 μm2 was further interrogated using various biochemical and histological assays as well as proteomic analysis. Seven of these individuals donated a VL biopsy after refraining from training 8 days following the last training session (W7) to determine how deloading affected biomarkers. The 15 fCSA hypertrophic responders experienced a +23% increase in mean fCSA from PRE to W6 (p<0.001) and, while muscle glycogen concentrations remained unaltered, citrate synthase activity levels decreased by 24% (p<0.001) suggesting mitochondrial volume decreased. Interestingly, repeated measures ANOVAs indicated that p-values approached statistical significance for both myosin and actin (p = 0.052 and p = 0.055, respectively), and forced post hoc tests indicated concentrations for both proteins decreased ~30% from PRE to W6 (p<0.05 for each target). Phalloidin-actin staining similarly revealed actin concentrations per fiber decreased from PRE to W6. Proteomic analysis of the sarcoplasmic fraction from PRE to W6 indicated 40 proteins were up-regulated (p<0.05), KEGG analysis indicated that the glycolysis/gluconeogenesis pathway was upregulated (FDR sig. <0.001), and DAVID indicated that the following functionally-annotated pathways were upregulated (FDR value <0.05): a) glycolysis (8 proteins), b) acetylation (23 proteins), c) gluconeogenesis (5 proteins) and d) cytoplasm (20 proteins). At W7, sarcoplasmic protein concentrations remained higher than PRE (+66%, p<0.05), and both actin and myosin concentrations remained lower than PRE (~-50%, p<0.05). These data suggest that short-term high-volume resistance training may: a) reduce muscle fiber actin and myosin protein concentrations in spite of increasing fCSA, and b) promote sarcoplasmic expansion coincident with a coordinated up-regulation of sarcoplasmic proteins involved in glycolysis and other metabolic processes related to ATP generation. Interestingly, these effects seem to persist up to 8 days following training.

Pre-training Skeletal Muscle Fiber Size and Predominant Fiber Type Best Predict Hypertrophic Responses to 6 Weeks of Resistance Training in Previously Trained Young Men.

Limited evidence exists regarding differentially expressed biomarkers between previously-trained low versus high hypertrophic responders in response to resistance training. Herein, 30 college-aged males (training age 5 ± 3 years; mean ± SD) partook in 6 weeks of high-volume resistance training. Body composition, right leg vastus lateralis (VL) biopsies, and blood were obtained prior to training (PRE) and at the 3-week (W3) and 6-week time points (W6). The 10 lowest (LOW) and 10 highest (HIGH) hypertrophic responders were clustered based upon a composite hypertrophy score of PRE-to-W6 changes in right leg VL mean muscle fiber cross-sectional area (fCSA), VL thickness assessed via ultrasound, upper right leg lean soft tissue mass assessed via dual x-ray absorptiometry (DXA), and mid-thigh circumference. Two-way ANOVAs were used to compare biomarker differences between the LOW and HIGH clusters over time, and stepwise linear regression was performed to elucidate biomarkers that explained significant variation in the composite hypertrophy score from PRE to W3, W3 to W6, and PRE to W6 in all 30 participants. PRE-to-W6 HIGH and LOW responders exhibited a composite hypertrophy change of +10.7 ± 3.2 and -2.1 ± 1.6%, respectively (p < 0.001). Compared to HIGH responders, LOW responders exhibited greater PRE type II fCSA (+18%, p = 0.022). Time effects (p < 0.05) existed for total RNA/mg muscle (W6 > W3 > PRE), phospho (p)-4EBP1 (PRE > W3&W6), pan-mTOR (PRE > W3 < W6), p-mTOR (PRE > W3 < W6), pan-AMPKα (PRE > W3 < W6), pan-p70s6k (PRE > W3), muscle ubiquitin-labeled proteins (PRE > W6), mechano growth factor mRNA (W6 > W3&PRE), 45S rRNA (PRE > W6), and muscle citrate synthase activity (PRE > W3&W6). No interactions existed for the aforementioned biomarkers and/or other assayed targets (muscle 20S proteasome activity, serum total testosterone, muscle androgen receptor protein levels, muscle glycogen, or serum creatine kinase). Regression analysis indicated PRE type II fiber percentage (R2 = 0.152, β = 0.390, p = 0.033) and PRE type II fCSA (R2 = 0.207, β = -0.455, p = 0.019) best predicted the PRE-to-W6 change in the composite hypertrophy score. While our sample size is limited, these data suggest: (a) HIGH responders may exhibit more growth potential given that they possessed lower PRE type II fCSA values and (b) possessing a greater type II fiber percentage as a trained individual may be advantageous for hypertrophy in response to resistance training.

Effects of Repeated Eyelid Injections with Botulinum Toxin A on Innervation of Treated Muscles in Patients with Blepharospasm

ABSTRACTPurpose: To assess changes in innervation and muscle morphology after repeated botulinum toxin A injections in subjects with benign essential blepharospasm.Methods: Surgical waste specimens were processed for histologic examination of nerve fibers, neuromuscular junctions, fiber size, and central nucleation and compared to age matched controls and to two subjects with blepharospasm that had not received botulinum toxin A injections.Results: There was a significant increase in amount of nerve fibers and numbers of neuromuscular junctions in the orbicularis oculi muscles from subjects with blepharospasm treated repetitively with botulinum toxin A. In addition there was a significant decrease in mean muscle fiber cross-sectional area and an increase in central nucleation. The specimens from the subjects with only blepharospasm had the same density of nerves but had intermediate levels of neuromuscular junctions.Conclusions: These data suggest that repeated injections of botulinum toxin A has an effect on nerve and neuromuscular junction numbers, which are partly mirrored in orbicularis oculi muscle from subjects with blepharospasm only. These studies suggest the potential for modulating these changes in order to extend the duration of effectiveness of botulinum toxin.

Complete adult neurogenesis within a Wallerian degenerating nerve expressed as an ectopic ganglion.

Neurogenesis in the adult peripheral nervous system remains to be demonstrated. We transplanted embryonic neural stem cells into a Wallerian degenerating nerve graft and observed development of a nodular structure consisting of neurons, glia, and Schwann cells. Histological analysis revealed a structure loosely resembling the spinal cord, including a synaptic network that formed along the neuron. Furthermore, the new axons reinnervated the paralysed muscle, forming both de novo and revived neuromuscular junctions. Reinnervation of the paralysed muscle resulted in significantly greater mean wet muscle weight and muscle fibre cross-sectional area on the cell transplantation side than on the surgical control side (body weight 0.071±0.011% vs. 0.051±0.007%, p=.006; area 355.6±345.2 vs. 114.0±132.0μm2 , p<.001). Electrophysiological experiments demonstrated a functional connection between the neurons and muscle; hence, we identified this nodule as an ectopic ganglion. Surprisingly, in green rat experiments, most of these glial cells, but none of the neurons, expressed enhanced green fluorescent protein, suggesting that the cells constituting the ectopic ganglion were derived from both transplanted stem cells and endogenous stem cells. Such adult neurogenesis in a peripheral nerve related to neural stem cell transplantation has not been reported previously, and these results form the basis for a novel regenerative medicine approach in paralysed muscle.

Functional Motor Nerve Regeneration Without Motor-Sensory Specificity Following End-to-Side Neurorrhaphy: An Experimental Study

To evaluate the quality of regenerating myelinated axons and motor-sensory specificity in an end-to-side nerve repair model. We divided 20 rats into 3 groups: (1) end-to-side neurorrhaphy using the ulnar nerve as donor nerve and the musculocutaneous nerve as recipient nerve; (2) normal control; and (3) transected nerve with the stumps buried. At 5 months, we monitored the grooming test, the electrophysiological response, and the histologic changes in nerve and muscle. Grooming recovered successfully, and electrophysiological investigations revealed that the target muscles had been reinnervated in the end-to-side group. The mean wet weight of the reinnervated biceps brachii muscle was 72% of the normal muscle, and the mean muscle fiber cross-sectional area of the reinnervated muscle was similar to the normal muscle. The implanted musculocutaneous nerve contained varying but satisfactory numbers of axons (end-to-side group: 596 ± 348 vs normal group: 1,340 ± 241). Acetylcholinesterase staining revealed a similar percentage of myelinated fibers in the musculocutaneous nerve (39%) and the biceps brachii branch of the musculocutaneous nerve (38%) in the end-to-side group. This was similar to the number of myelinated fibers in the donor ulnar nerve (37%). The present study confirms that limited but functional reinnervation can occur on the basis of collateral sprouting of intact axons from the ulnar nerve. The motor-sensory specificity is not important.

Muscle sparing in muscle RING finger 1 null mice: response to synthetic glucocorticoids

Skeletal muscle atrophy occurs under a variety of conditions and can result from alterations in both protein synthesis and protein degradation. The muscle-specific E3 ubiquitin ligases, MuRF1 and MAFbx, are excellent markers of muscle atrophy and increase under divergent atrophy-inducing conditions such as denervation and glucocorticoid treatment. While deletion of MuRF1 or MAFbx has been reported to spare muscle mass following 14 days of denervation, their role in other atrophy-inducing conditions is unclear. The goal of this study was to determine whether deletion of MuRF1 or MAFbx attenuates muscle atrophy after 2 weeks of treatment with the synthetic glucocorticoid dexamethasone (DEX). The response of the triceps surae (TS) and tibialis anterior (TA) muscles to 14 days of DEX treatment (3 mg kg(-1) day(-1)) was examined in 4 month-old male and female wild type (WT) and MuRF1 or MAFbx knock out (KO) mice. Following 14 days of DEX treatment, muscle wet weight was significantly decreased in the TS and TA of WT mice. Comparison of WT and KO mice following DEX treatment revealed significant sparing of mass in both sexes of the MuRF1 KO mice, but no muscle sparing in MAFbx KO mice. Further analysis of the MuRF1 KO mice showed significant sparing of fibre cross-sectional area and tension output in the gastrocnemius (GA) after DEX treatment. Muscle sparing in the MuRF1 KO mice was related to maintenance of protein synthesis, with no observed increases in protein degradation in either WT or MuRF1 KO mice. These results demonstrate that MuRF1 and MAFbx do not function similarly under all atrophy models, and that the primary role of MuRF1 may extend beyond controlling protein degradation via the ubiquitin proteasome system.

Utility for production of massaged products of selected wild boar muscles originating from wetlands and an arable area

Percentages of muscle fibre types, area of intramuscular fatty tissue (IMF) and changes in hardness, rheological properties as well as mean fibre cross-sectional area (CSA), and endomysium thickness of muscles from wild boars hunted in two different ecosystems (arable area vs. wetlands) were evaluated. Three muscles: Biceps femoris (BF), Semimembranosus (SM), and Longissimus (L) subjected to massaging (or not) for 4h were studied. Fibre type percentage and structural elements: mean muscle fibre cross-sectional area (CSA), endomysium thickness, and amount of intramuscular fat (IMF) were measured using a computer image analysis programme. Fibre properties of muscles from wild boars originating from arable areas did not differ from those of wild boars from wetlands. Muscles of wild boars hunted in the arable area of the forest contained significantly higher amounts of intramuscular fat and lower values of hardness, viscous and elastic moduli than the corresponding muscles of animals from the marshy area. Of the muscles tested, BF with its higher percentage of red fibres and fibre CSA, thicker endomysium and lower amount of IMF compared to SM and L muscles, was tougher and more elastic and viscous than the other two muscles. Muscle massaging resulted in an increase in the fibre CSA and decrease in thickness of the endomysium and as a consequence reduced hardness and augmented the viscous and elastic modules of the muscles. Muscles with higher amounts of intramuscular fat, lower values of textural parameters and percentage of red fibres as well as smaller structural elements showed higher susceptibility to massaging. Muscles from animals hunted on wetlands compared to those from wild boar shot on the arable land and BF compared to SM and L, were slightly less susceptible to mechanical tenderization.

Effect of pulmonary rehabilitation on muscle remodelling in cachectic patients with COPD

It is known that non-cachectic patients with chronic obstructive pulmonary disease (COPD) respond well to pulmonary rehabilitation, but whether cachectic COPD patients are capable of adaptive responses is both important and unknown. 10 cachectic and 19 non-cachectic COPD patients undertook high-intensity cycling training, at the same relative intensity, for 45 min x day(-1), 3 days x week(-1) for 10 weeks. Before and after rehabilitation vastus lateralis muscle biopsies were analysed morphologically and for the expression of muscle remodelling factors (insulin-like growth factor (IGF)-I, myogenic differentiation factor D (MyoD), tumour necrosis factor (TNF)-alpha, nuclear factor (NF)-kappaB and myostatin) and key components of ubiquitin-mediated proteolytic systems (muscle ring finger protein (MURF)-1 and Atrogin-1). Rehabilitation improved peak work-rate and the 6-min walk distance similarly in non-cachectic (18+/-3% and 42+/-13 m, respectively) and cachectic (16+/-2% and 53+/-16 m, respectively) patients, but quality of life only improved in non-cachectic COPD. Mean muscle fibre cross-sectional area increased in both groups, but significantly less in cachectic (7+/-2%) than in non-cachectic (11+/-2%) patients. Both groups equally decreased the proportion of type IIb fibres and increased muscle capillary/fibre ratio. IGF-I mRNA expression increased in both groups, but IGF-I protein levels increased more in non-cachectic COPD. MyoD was upregulated, whereas myostatin was downregulated at the mRNA and protein level only in non-cachectic patients. Whilst rehabilitation had no effect on TNF-alpha expression, it decreased the activation of the transcription factor NF-kappaB in both groups by the same amount. Atrogin-1 and MURF-1 expression were increased in cachectic COPD, but it was decreased in non-cachectic patients. Cachectic COPD patients partially retain the capacity for peripheral muscle remodelling in response to rehabilitation and are able to increase exercise capacity as much as those without cachexia, even if they exhibit both quantitative and qualitative differences in the type of muscle fibre remodelling in response to exercise training.

Heart size and mean muscle fibre cross-sectional area related to birth weight in pigs

One of the aims in domestic pig breeding has been to increase the size of litters resulting in variation in birth weight of piglets. Pig breeding has also resulted in increased body muscle mass. Muscles with the same size can consist either of large number of thin muscle fibres or small number of thick muscle fibres. Larger body muscle content means that in living animal the heart must pump blood to larger muscle mass than earlier. Our interest in this study was to investigate the relationship between the pig’s birth weight and (i) growth performance and carcass composition, (ii) the size of organs, and (iii) the mean muscle fibre cross-sectional area at slaughter. The study consisted of twenty pigs slaughtered at the age of 165±2 days. The day after the slaughter, the carcass composition was determined by dissecting the chilled carcass into lean, fat, bones, and skin and organs were weighed. The average cross sectional area of muscle fibres was determined from three fast-twitch muscles longissimus dorsi, semimembranosus, gluteus superficialis, and two slow-twitch muscles infraspinatus and masseter. The birth weight of pigs ranged from 0.9 to 2.2 kg. We found no clear relationships between the birth weight and the pig’s growth performance from birth to slaughter. When the birth weight increased the heart weight at slaughter increased as well (P &lt; 0.01). The heart weight was higher in those pigs with high carcass weight (P &lt; 0.05) and with the high weight of total muscle mass in the carcass (P &lt; 0.001). The cross sectional area of muscle fibres in M. longissimus dorsi (P &lt; 0.05), M. semimembranosus (P &lt; 0.10), and M. gluteus superficialis (P &lt; 0.05) was larger in those pigs with low birth weight compared to those found in pigs with high birth weight.;

Resistance training alters the response of fed state mixed muscle protein synthesis in young men

Ten healthy young men (21.0 +/- 1.5 yr, 1.79 +/- 0.1 m, 82.7 +/- 14.7 kg, means +/- SD) participated in 8 wk of intense unilateral resistance training (knee extension exercise) such that one leg was trained (T) and the other acted as an untrained (UT) control. After the 8 wk of unilateral training, infusions of L-[ring-d(5)]phenylalanine, L-[ring-(13)C(6)]phenylalanine, and d(3)-alpha-ketoisocaproic acid were used to measure mixed muscle protein synthesis in the T and UT legs by the direct incorporation method [fractional synthetic rate (FSR)]. Protein synthesis was determined at rest as well as 4 h and 28 h after an acute bout of resistance exercise performed at the same intensity relative to the gain in single repetition maximum before and after training. Training increased mean muscle fiber cross-sectional area only in the T leg (type I: 16 +/- 10%; type II: 20 +/- 19%, P < 0.05). Acute resistance exercise increased muscle protein FSR in both legs at 4 h (T: 162 +/- 76%; UT: 108 +/- 62%, P < 0.01 vs. rest) with the increase in the T leg being significantly higher than in the UT leg at this time (P < 0.01). At 28 h postexercise, FSR in the T leg had returned to resting levels; however, the rate of protein synthesis in the UT leg remained elevated above resting (70 +/- 49%, P < 0.01). We conclude that resistance training attenuates the protein synthetic response to acute resistance exercise, despite higher initial increases in FSR, by shortening the duration for which protein synthesis is elevated.

Changes in expiratory muscle function following spinal cord section

Following spinal cord injury, muscles below the level of injury develop variable degrees of disuse atrophy. The present study assessed the physiological changes of the expiratory muscles in a cat model of spinal cord injury. Muscle fiber typing, cross-sectional area, muscle weight, and changes in pressure-generating capacity were assessed in five cats spinalized at the T(6) level. Airway pressure (P)-generating capacity was monitored during lower thoracic spinal cord stimulation before and 6 mo after spinalization. These parameters were also assessed in five acute animals, which served as controls. In spinalized animals, P fell from 41 +/- l to 28 +/- 3 cm H2O (means +/- SE; P < 0.001). Muscle weight of the external oblique, internal oblique, transversus abdominis, and internal intercostal muscles decreased significantly (P < 0.05 for each). Muscle weight of the external oblique, internal oblique, transversus abdominis, and internal intercostal, but not rectus abdominis (RA), correlated linearly with P (r > 0.7 for each; P < 0.05 for each). Mean muscle fiber cross-sectional area of these muscles was significantly smaller (P < 0.05 for each; except RA) and also correlated linearly with P (r > 0.55 for each; P < 0.05 for each, except RA). In spinalized animals, the expiratory muscles demonstrated a significant increase in the population of fast muscle fibers. These results indicate that, following spinalization, 1) the expiratory muscles undergo significant atrophy and fiber-type transformation and 2) the P-generating capacity of the expiratory muscles falls significantly secondary to reductions in muscle mass.

Increased muscle oxidative potential following resistance training induced fibre hypertrophy in young men

Some evidence suggests that resistance training may lower relative muscle mitochondrial content via "dilution" of the organelle in a larger muscle fibre. Such an adaptation would reduce fatigue resistance, as well as compromise oxidative ATP synthesis and the capacity for fatty-acid oxidation. We investigated the effect of resistance training on mitochondrial enzymes of the citric acid cycle (citrate synthase; CS) and beta-oxidation (beta-hydroxyacyl CoA dehydrogenase; beta-HAD), as well as markers of the potential for glucose phosphorylation (hexokinase; HK) and glycolysis (phosphofructokinase; PFK). Twelve untrained men (21.9 +/- 0.5 y; 1.79 +/- 0.03 m; 83.2 +/- 3.2 kg) participated in a 12 week progressive resistance-training program. Muscle biopsies were taken from the vastus lateralis before (PRE) and after (POST) training. Training increased mean muscle fibre cross-sectional area (p < 0.05) and the activities of CS (PRE = 4.53 +/- 0.44 mol.kg protein(-1).h(-1); POST = 5.63 +/- 0.40 mol.kg protein(-1).h(-1); p < 0.001) and beta-HAD (PRE = 2.55 +/- 0.28 mol.kg protein(-1).h(-1); POST = 3.11 +/- 0.21 mol.kg protein(-1).h(-1); p < 0.05). The activity of HK increased 42% (p < 0.05), whereas the activity of PFK remained unchanged. We conclude that resistance training provides a stimulus for improving muscle oxidative potential, as reflected by the increased activities of CS and beta-HAD following resistance training induced hypertrophy.

Skeletal muscle adaptations to microgravity exposure in the mouse.

To investigate the effects of microgravity on murine skeletal muscle fiber size, muscle contractile protein, and enzymatic activity, female C57BL/6J mice, aged 64 days, were divided into animal enclosure module (AEM) ground control and spaceflight (SF) treatment groups. SF animals were flown on the space shuttle Endeavour (STS-108/UF-1) and subjected to approximately 11 days and 19 h of microgravity. Immunohistochemical analysis of muscle fiber cross-sectional area revealed that, in each of the muscles analyzed, mean muscle fiber cross-sectional area was significantly reduced (P < 0.0001) for all fiber types for SF vs. AEM control. In the soleus, immunohistochemical analysis of myosin heavy chain (MHC) isoform expression revealed a significant increase in the percentage of muscle fibers expressing MHC IIx and MHC IIb (P < 0.05). For the gastrocnemius and plantaris, no significant changes in MHC isoform expression were observed. For the muscles analyzed, no alterations in MHC I or MHC IIa protein expression were observed. Enzymatic analysis of the gastrocnemius revealed a significant decrease in citrate synthase activity in SF vs. AEM control.

Changes in capillary luminal diameter in rat soleus muscle after hind-limb suspension.

This study examined the time course change of the capillary luminal diameter and the number of capillaries in the rat soleus muscle during hind-limb suspension. Male Wistar rats were divided into 1 and 3 weeks of hind-limb suspension (HS) groups (HS-1 and HS-3). The HS groups were compared with age-matched control groups. All morphometric parameters with respect to capillary and muscle fibre cross-sectional area were determined in perfusion-fixed soleus muscles. After 1 and 3 weeks of hind-limb suspension, the mean muscle fibre cross-sectional area was significantly decreased in HS-1 (-32.0%) and HS-3 (-59.3%) compared with age-matched control groups. Despite a lower capillary-to-fibre ratio (HS-1, -19.3%; HS-3, -21.2%), the capillary density was unchanged in HS-1 and significantly increased in HS-3 compared with age-matched control groups. The mean capillary luminal diameter was significantly smaller in HS-1 (-19.9%) and HS-3 (-21.9%) than in the age-matched control groups. The capillary-to-fibre perimeter ratio which indicates the capillary surface area available for gas exchange between blood and tissue did not significantly differ between control groups and HS groups. In conclusion, the morphometrical adaptations in rat soleus with the suspension involved changes in both the capillary luminal diameter and number of capillaries, and the change in capillary surface area was proportional to the degree of muscle atrophy in HS groups.

Motor collateral sprouting through an end-to-side nerve repair

The outcome of end-to-side repair of peripheral nerves was investigated. The sciatic nerve in 10 male Sprague-Dawley rats was dissected to its tibioperoneal junction. The nerve to the medial gastrocnemius muscle, branching from the tibial nerve, was ligated at its origin and divided. Its distal end was sutured to an epineurial window on the side of the intact tibial nerve 1 cm distally. At 12 weeks, physiologic evaluation of the medial gastrocnemius muscle and analyses of histologic preparations of nerve and muscle were performed. The results showed that reinnervation successfully occurred in 8 rat media gastrocnemii. The mean weight of the reinnervated medial gastrocnemius was 73% of the contralateral normal muscle, the mean muscle fiber cross-sectional area of the reinnervated muscle was 72%, and the force of contraction was 60%. Analyses of histologic preparations revealed evidence of myelinated axons in the medial gastrocnemius nerve and no evidence of damage to axons of the donor tibial nerve.