Volume loss during muscle reinnervation surgery is correlated with reduced CMAP amplitude but not reduced force output in a rat hindlimb model.

Introduction: Muscle reinnervation (MR) surgery offers rehabilitative benefits to amputees by taking severely damaged nerves and providing them with new denervated muscle targets (DMTs). However, the influence of physical changes to muscle tissue during MR surgery on long-term functional outcomes remains understudied. Methods: Our rat hindlimb model of MR surgery utilizes vascularized, directly neurotized DMTs made from the lateral gastrocnemius (LG), which we employed to assess the impact of muscle tissue size on reinnervation outcomes, specifically pairing the DMT with the transected peroneal nerve. We conducted MR surgery with both DMTs at full volume and DMTs with partial volume loss of 500 mg at the time of surgery (n = 6 per group) and measured functional outcomes after 100 days of reinnervation. Compound motor action potentials (CMAPs) and isometric tetanic force production was recorded from reinnervated DMTs and compared to contralateral naïve LG muscles as positive controls. Results: Reinnervated DMTs consistently exhibited lower mass than positive controls, while DMTs with partial volume loss showed no significant mass reduction compared to full volume DMTs (p = 0.872). CMAP amplitudes were lower on average in reinnervated DMTs, but a broad linear correlation also exists between muscle mass and maximum CMAP amplitude irrespective of surgical group (R2 = 0.495). Surprisingly, neither MR group, with or without volume loss, demonstrated decreased force compared to positive controls. The average force output of reinnervated DMTs, as a fraction of the contralateral LG's force output, approached 100% for both MR groups, a notable deviation from the 9.6% (±6.3%) force output observed in our negative control group at 7 days post-surgery. Tissue histology analysis revealed few significant differences except for a marked decrease in average muscle fiber area of reinnervated DMTs with volume loss compared to positive controls (p = 0.001). Discussion: The results from our rat model of MR suggests that tissue electrophysiology (CMAPs) and kinesiology (force production) may recover on different time scales, with volumetric muscle loss at the time of MR surgery not significantly reducing functional outcome measurements for the DMTs after 100 days of reinnervation.

Simulated altitude is medicine: intermittent exposure to hypobaric hypoxia and cold accelerates injured skeletal muscle recovery.

Muscle injuries are the leading cause of sports casualties. Because of its high plasticity, skeletal muscle can respond to different stimuli to maintain and improve functionality. Intermittent hypobaric hypoxia (IHH) improves muscle oxygen delivery and utilization. Hypobaria coexists with cold in the biosphere, opening the possibility to consider the combined use of both environmental factors to achieve beneficial physiological adjustments. We studied the effects of IHH and cold exposure, separately and simultaneously, on muscle regeneration. Adult male rats were surgically injured in one gastrocnemius and randomly assigned to the following groups: (1) CTRL: passive recovery; (2) COLD: intermittently exposed to cold (4°C); (3) HYPO: submitted to IHH (4500 m); (4) COHY: exposed to intermittent simultaneous cold and hypoxia. Animals were subjected to these interventions for 4 h/day for 9 or 21 days. COLD and COHY rats showed faster muscle regeneration than CTRL, evidenced after 9 days at histological (dMHC-positive and centrally nucleated fibre reduction) and functional levels after 21 days. HYPO rats showed a full recovery from injury (at histological and functional levels) after 9 days, while COLD and COHY needed more time to induce a total functional recovery. IHH can be postulated as an anti-fibrotic treatment since it reduces collagen I deposition. The increase in the pSer473Akt/total Akt ratio observed after 9 days in COLD, HYPO and COHY, together with the increase in the pThr172AMPKα/total AMPKα ratio observed in the gastrocnemius of HYPO, provides clues to the molecular mechanisms involved in the improved muscle regeneration. KEY POINTS: Only intermittent hypobaric exposure accelerated muscle recovery as early as 9 days following injury at histological and functional levels. Injured muscles from animals treated with intermittent (4 h/day) cold, hypobaric hypoxia or a simultaneous combination of both stimuli regenerated histological structure and recovered muscle function 21 days after injury. The combination of cold and hypoxia showed a blunting effect as compared to hypoxia alone in the time course of the muscle recovery. The increased expression of the phosphorylated forms of Akt observed in all experimental groups could participate in the molecular cascade of events leading to a faster regeneration. The elevated levels of phosphorylated AMPKα in the HYPO group could play a key role in the modulation of the inflammatory response during the first steps of the muscle regeneration process.

The Effect of Potassium Nitrate Supplementation on the Force and Properties of Extensor digitorum longus (EDL) Muscles in Mice.

Adding potassium nitrate (KNO3) to the diet improves the physiological properties of mammalian muscles (rebuilds weakened muscle, improves structure and functionality). The aim of this study was to investigate the effect of KNO3 supplementation in a mouse model. BALB/c mice were fed a KNO3 diet for three weeks, followed by a normal diet without nitrates. After the feeding period, the Extensor digitorum longus (EDL) muscle was evaluated ex vivo for contraction force and fatigue. To evaluate the possible pathological changes, the histology of EDL tissues was performed in control and KNO3-fed groups after 21 days. The histological analysis showed an absence of negative effects in EDL muscles. We also analyzed 15 biochemical blood parameters. After 21 days of KNO3 supplementation, the EDL mass was, on average, 13% larger in the experimental group compared to the controls (p < 0.05). The muscle-specific force increased by 38% in comparison with the control group (p < 0.05). The results indicate that KNO3 has effects in an experimental mouse model, showing nitrate-diet-induced muscle strength. This study contributes to a better understanding of the molecular changes in muscles following nutritional intervention and may help develop strategies and products designated to treat muscle-related issues.

Preying dangerously: black widow spider venom resistance in sympatric lizards.

Lizards and spiders are natural adversaries, yet little is known of adaptations that lizards might possess for dealing with the venomous defences of spider prey. In the Western USA, two lizard species (Elgaria multicarinata and Sceloporus occidentalis) are sympatric with and predate western black widow spiders (Latrodectus hesperus). The consequences of black widow spider venom (BWSV) can be severe, and are well understood for mammals but unknown for reptiles. We evaluated potential resistance to BWSV in the lizards that consume black widows, and a potentially susceptible species (Uta stansburiana) known as prey of widows. We investigated BWSV effects on whole-animal performance (sprint) and muscle tissue at two venom doses compared with control injections. Sprint speed was not significantly decreased in E. multicarinata or S. occidentalis in any treatment, while U. stansburiana suffered significant performance reductions in response to BWSV. Furthermore, E. multicarinata showed minimal tissue damage and immune response, while S. occidentalis and U. stansburiana exhibited increased muscle damage and immune system infiltration in response to BWSV. Our data suggest predator-prey relationships between lizards and spiders are complex, possibly leading to physiological and molecular adaptations that allow some lizards to tolerate or overcome the dangerous defences of their arachnid prey.

Repeated botulinum treatment of rabbit masseter causes cumulative tissue damage.

OBJECTIVE: Botulinum neurotoxins (BoNT) are used in masticatory muscles for pain relief, unloading of the mandible, and cosmetic facial contouring. Treatment is often repeated every few months as function returns. This study assessed masticatory function and musculoskeletal structure after multiple BoNT treatment of the rabbit masseter. DESIGN: Female rabbits received 3 injections of BoNT (n = 13) or saline (n = 5) into one masseter muscle at intervals of 12 weeks. The contralateral side served as control. Periodic measurements of masticatory electromyography (EMG) and stimulated anterior bite force were made. After the final 12-week recovery interval, neuromuscular connection was investigated by stimulating the masseteric nerve to elicit an evoked EMG response. Mandibular specimens were collected for microCT analysis, and masseters were collected for histomorphometry and counts of replicating cells. RESULTS: Control and saline-injected muscles maintained consistent masticatory EMG and anterior bite force throughout the study. BoNT-injected masseters showed strong declines after each injection; during the 12-week recovery period, masticatory EMG and anterior bite force improved, although only electrical activity reached normal levels. Multiple injection resulted in persistently atrophied muscle fibers with fibrosis, and notable loss of bone from the mandibular body and condyle. The uninjected masseters of the BoNT group also showed evidence of mild toxin-related changes. CONCLUSIONS: Although muscle function is mostly regained after each injection, masseters receiving multiple doses of BoNT show extensive damage. In addition, mandibular bone density is decreased on the injected side.

Diallel Cross Application and Histomolecular Characterization: An Attempt to Develop Reference Stock of Labeo ariza.

The objective of the present study was to evaluate the growth performance and genetic variation in diallel crosses of Ariza labeo (Labeo ariza) originating from three geographically separated rivers (Atrai, Jamuna and Kangsha) in Bangladesh. Intra (G1K♀K♂, G2J♀J♂, and G3A♀A♂) and inter (G4K♀A♂, G5K♀J♂, G6A♀K♂, G7A♀J♂, G8J♀K♂, and G9J♀A♂) stocks were produced following diallel cross (sex ratio-1:1 and n = 48; 16 from each river). Reproductive and growth performance, muscle cellularity and genetic variation following genotyping of eight microsatellite markers (Lr1, Lr2, Lr3, Lr22, Lr24, Lr27, Lr28 and Lr29) and analysis of all crossbreeds was performed. The fertilization (95% ± 2.11%), hatching (88% ± 1.03%), and survival rates (82% ± 1.88%) of G4K♀A♂ were higher compared to other groups. With respect to length and weight gains (2.67 ± 0.4 cm and 3.39 ± 0.2 g), SGR (3.23% ± 0.20%), and heterosis (8.87% and 24.74%) G4K♀A♂ was the superior group. A higher number of hyperplastic muscle fibers, mean number of alleles (2.75) and mean observed heterozygosity (0.417) from G4K♀A♂ could be interpreted to mean that G4K♀A♂ comprise better performance efficiency compared to others and are considered for continuing the L. ariza stock improvement program.

The Interaction of Dried Distillers Grains With Solubles (DDGS) Type and Level on Growth Performance, Health, Texture, and Muscle-Related Gene Expression in Grass Carp (Ctenopharyngodon idellus).

The aim of this study was to estimate the possible synergetic effects of the two levels of dietary dried distillers grains with solubles (DDGS) from different sources (US-imported and native) on the growth, health status, muscle texture, and muscle growth-related gene expression of juvenile grass carp. Four treatments of fish were fed with 4 isonitrogenous diets, namely, native DDGS20, native DDGS30, US-imported DDGS20, and US-imported DDGS30 for 60 days. The US-imported DDGS30 group showed the better growth and feed efficiency. Additionally, we observed a significant increase in hepatopancreatic total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in native DDGS groups. Moreover, raw muscle collagen increases considerably in the US-imported DDGS30 compared with the native DDGS30 group. In comparison with the native DDGS groups, the US-imported DDGS groups showed significantly decrease in all textural properties and fiber density, while increased fiber diameter. Dietary native DDGS inclusion significantly showed the upregulation of myog, myhc, and fgf6a expression in muscle, while the downregulation of the expression of myod and myf5. Overall, US-imported DDGS30 had a beneficial influence on growth via regulating genes involved in myogenesis and hypertrophy, the formation of collagen, but had negative impacts on antioxidant capacity and cooked muscle texture.

Enhancing Interrogation of Skeletal Muscle Samples for Informative Quantitative Data.

Careful quantitative analysis of histological preparations of muscle samples is crucial to accurate investigation of myopathies in man and of interpretation of data from animals subjected to experimental or potentially therapeutic treatments. Protocols for measuring cell numbers are subject to problems arising from biases associated with preparative and analytical techniques. Prominent among these is the effect of polarized structure of skeletal muscle on sampling bias. It is also common in this tissue to collect data as ratios to convenient reference dominators, the fundamental bases of which are ill-defined, or unrecognized or not accurately assessable. Use of such 'floating' denominators raises a barrier to estimation of the absolute values that assume practical importance in medical research, where accurate comparison between different scenarios in different species is essential to the aim of translating preclinical research findings in animal models to clinical utility in Homo sapiens.This review identifies some of the underappreciated problems with current morphometric practice, some of which are exacerbated in skeletal muscle, and evaluates the extent of their intrusiveness into the of building an objective, accurate, picture of the structure of the muscle sample. It also contains recommendations for eliminating or at least minimizing these problems. Principal among these, would be the use of stereological procedures to avoid the substantial counting biases arising from inter-procedure differences in object size and section thickness.Attention is also drawn to the distortions of interpretation arising from use of undefined or inappropriate denominators.

Consequences of ankle joint immobilisation: insights from a morphometric analysis about fibre typification, intramuscular connective tissue, and muscle spindle in rats.

Orthosis immobilisations are routinely used in orthopaedic procedures. This intervention is applicable in bone fractures, ligament injuries, and tendonitis, among other disorders of the musculoskeletal system. We aimed to evaluate the effects of ankle joint functional immobilisation on muscle fibre morphology, connective tissue, muscle spindle and fibre typification triggered by a novel metallic orthosis. We developed a rodent-proof experimental orthosis able to hold the tibiotalar joint in a functional position for short and long terms. The tibialis anterior muscles of free and immobilised legs were collected and stained by histology and histochemistry techniques to investigate general muscle morphology, connective tissue and muscle fibre typification. Morphometric analysis of muscle cross-section area, fibre type cross-section area, fibre type density, percentage of intramuscular connective tissue, and thickness of the muscle spindle capsule were obtained to gain insights into the experimental protocol. We found that short- and long-term immobilisation decreased the cross-section area of the muscles and induced centralisation of myonuclei. The connective tissue of immobilised muscle increased after 2 and 4 weeks mainly by deposition of type III and type I collagen fibres in the perimysium and endomysium, respectively, in addition to muscle spindle capsule thickening. Type IIB muscle fibre was severely affected in our study; the profile assumed odd shapes, and our data suggest interconversion of these fibre types within long-term immobilisation. In conclusion, our protocol has produced structural and histochemical changes in muscle biology. This method might be applied to various rodent models that enable genetic manipulation for the investigation of muscle degeneration/regeneration processes.

Type-2 muscle fiber atrophy is associated with sarcopenia in elderly men with hip fracture.

Sarcopenia is a common geriatric syndrome and can lead to falls and fragility fractures. It is associated with a decline of muscle fiber numbers and size. Muscle biopsies of the vastus lateralis muscle were taken from thirty-two patients with hip fracture (18 women and 14 men; mean age: 82.2 ± 6.2 years). Serial cross sections of skeletal muscle were labeled with myosin heavy chain slow (fiber type-1) and fast (fiber type-2) antibodies in order to measure the size, ratio and percentage of mixed fiber types. The presence of sarcopenia was defined according to the EWGSOP2 criteria by using BIA and handgrip strength measurement. Sarcopenia was identified in 5 patients (3 women and 2 men), probable-sarcopenia in 11 patients (4 women and 7 men). Significant differences in fiber diameter were found for fiber type-2 in men but not in women. Only 1-3% mixed fiber types were found in sarcopenic patients, indicating a final stage where reinnervation is not possible to occur anymore. Muscle fiber type-2 atrophy seems to be a histological marker for sarcopenia in men.

Accelerometry predicts muscle ultrastructure and flight capabilities in a wild bird.

Muscle ultrastructure is closely linked with athletic performance in humans and lab animals, and presumably plays an important role in the movement ecology of wild animals. Movement is critical for wild animals to forage, escape predators and reproduce. However, little evidence directly links muscle condition to locomotion in the wild. We used GPS-accelerometers to examine flight behaviour and muscle biopsies to assess muscle ultrastructure in breeding black-legged kittiwakes (Rissa tridactyla). Biopsied kittiwakes showed similar reproductive success and subsequent over-winter survival to non-biopsied kittiwakes, suggesting that our study method did not greatly impact foraging ability. Muscle fibre diameter was negatively associated with wing beat frequency, likely because larger muscle fibres facilitate powered flight. The number of nuclei per fibre was positively associated with average air speed, likely because higher power output needed by faster-flying birds required plasticity for muscle fibre recruitment. These results suggest the potential for flight behaviour to predict muscle ultrastructure.

Skeletal muscle transcriptional networks linked to type I myofiber grouping in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder impacting cognition, movement, and quality of life in >10 million individuals worldwide. We recently characterized and quantified a skeletal muscle pathology in PD represented by exaggerated type I myofiber grouping presumed to result from denervation-reinnervation processes. Our previous findings indicated that impaired neuromuscular junction integrity may be involved in type I grouping, which is associated with excessive motor unit activation during weight-bearing tasks. In this study, we performed transcriptional profiling to test the hypothesis that type I grouping severity would link to distinct gene expression networks. We generated transcriptome-wide poly(A) RNA-Seq data from skeletal muscle of individuals with PD [n = 12 (9 men, 3 women); 67 ± 2 yr], age- and sex-matched older adults (n = 12; 68 ± 2 yr), and sex-matched young adults (n = 12; 30 ± 1 yr). Differentially expressed genes were evaluated across cohorts. Weighted gene correlation network analysis (WGCNA) was performed to identify gene networks most correlated with indicators of abnormal type I grouping. Among coexpression networks mapping to phenotypes pathologically increased in PD muscle, one network was highly significantly correlated to type I myofiber group size and another to percentage of type I myofibers found in groups. Annotation of coexpressed networks revealed that type I grouping is associated with altered expression of genes involved in neural development, postsynaptic signaling, cell cycle regulation and cell survival, protein and energy metabolism, inflammation/immunity, and posttranscriptional regulation (microRNAs). These transcriptomic findings suggest that skeletal muscle may play an active role in signaling to promote myofiber survival, reinnervation, and remodeling, perhaps to an extreme in PD.NEW & NOTEWORTHY Despite our awareness of the impact of Parkinson's disease (PD) on motor function for over two centuries, limited attention has focused on skeletal muscle. We previously identified type I myofiber grouping, a novel indicator of muscle dysfunction in PD, presumably a result of heightened rates of denervation/reinnervation. Using transcriptional profiling to identify networks associated with this phenotype, we provide insight into potential mechanistic roles of skeletal muscle in signaling to promote its survival in PD.

Clinical Response to Personalized Exercise Therapy in Heart Failure Patients with Reduced Ejection Fraction is Accompanied by Skeletal Muscle Histological Alterations.

Abstract: Heart failure (HF) is associated with skeletal muscle wasting and exercise intolerance. This study aimed to evaluate the exercise-induced clinical response and histological alterations. One hundred and forty-four HF patients were enrolled. The individual training program was determined as a workload at or close to the lactate threshold (LT1); clinical data were collected before and after 12 weeks/6 months of training. The muscle biopsies from eight patients were taken before and after 12 weeks of training: histology analysis was used to evaluate muscle morphology. Most of the patients demonstrated a positive response after 12 weeks of the physical rehabilitation program in one or several parameters tested, and 30% of those showed improvement in all four of the following parameters: oxygen uptake (VO2) peak, left ventricular ejection fraction (LVEF), exercise tolerance (ET), and quality of life (QOL); the walking speed at LT1 after six months of training showed a significant rise. Along with clinical response, the histological analysis detected a small but significant decrease in both fiber and endomysium thickness after the exercise training course indicating the stabilization of muscle mechanotransduction system. Together, our data show that the beneficial effect of personalized exercise therapy in HF patients depends, at least in part, on the improvement in skeletal muscle physiological and biochemical performance.

Does partial muscle reinnervation preserve future re-innervation potential?

INTRODUCTION: Late revision nerve surgery for incomplete motor recovery due to partial reinnervation would improve muscle function if all muscle fibers were protected from developing denervation atrophy. METHODS: Sixty immature Sprague-Dawley rats underwent the following tibial nerve manipulations (n = 15/group): group A, partial denervation (two thirds of nerve resected and the remaining one third crushed), revision repair at 8 months; group B, partial denervation; group C, complete denervation, immediate reconstruction; group D, complete denervation, reconstruction at 8 months; and group E, control. Final testing at 11 months included muscle force, weight, and histology. RESULTS: Muscle weight was significantly (P < 0.05) different among all groups (highest to lowest: E > B > C > A > D), and force was significantly lower in groups A and D compared with E. Muscle fiber cross-sectional area was statistically smaller in group A than in groups B, C, or E. DISCUSSION: Partial reinnervation still allowed substantial muscle recovery, but it did not preserve the non-innervated muscle fibers. Muscle Nerve 56: 1143-1148, 2017.

Physiological tradeoffs may underlie the evolution of hypoxia tolerance and exercise performance in sunfish (Centrarchidae).

Tradeoffs between hypoxia tolerance and aerobic exercise performance appear to exist in some fish taxa, even though both of these traits are often associated with a high O2 transport capacity. We examined the physiological basis for this potential tradeoff in four species of sunfish from the family Centrarchidae. Hypoxia tolerance was greatest in rock bass, intermediate in pumpkinseed and bluegill and lowest in largemouth bass, based on measurements of critical O2 tension (Pcrit) and O2 tension at loss of equilibrium (PO2 at LOE). Consistent with there being a tradeoff between hypoxia tolerance and aerobic exercise capacity, the least hypoxia-tolerant species had the highest critical swimming speed (Ucrit) during normoxia and suffered the greatest decrease in Ucrit in hypoxia. There was also a positive correlation between Ucrit in normoxia and PO2 at LOE, which remained significant after accounting for phylogeny using phylogenetically independent contrasts. Several sub-organismal traits appeared to contribute to both hypoxia tolerance and aerobic exercise capacity (reflected by traits that were highest in both rock bass and largemouth bass), such as the gas-exchange surface area of the gills, the pH sensitivity of haemoglobin-O2 affinity, and the activities of lactate dehydrogenase and the gluconeogenic enzyme phosphoenolpyruvate carboxykinase in the liver. Some other sub-organismal traits were uniquely associated with either hypoxia tolerance (low sensitivity of haemoglobin-O2 affinity to organic phosphates, high pyruvate kinase and lactate dehydrogenase activities in the heart) or aerobic exercise capacity (capillarity and fibre size of the axial swimming muscle). Therefore, the cumulative influence of a variety of respiratory and metabolic traits can result in physiological tradeoffs associated with the evolution of hypoxia tolerance and aerobic exercise performance in fish.

The composition of cellular infiltrates in anti-HMG-CoA reductase-associated myopathy.

INTRODUCTION: To characterize cellular infiltrates in muscle biopsies from patients with anti-3-hydroxy-3-methyl-gulatryl-CoA reductase (HMGCR)-associated myopathy. METHODS: Biopsies from 18 anti-HMGCR myopathy and 7 control dermatomyositis patients were analyzed. RESULTS: CD4+ and CD8+ T-cells were scattered within the endomysium in 50% of anti-HMGCR biopsies. All anti-HMGCR biopsies included increased endomysial and/or perivascular CD163+ M2 macrophages; CD11c+ M1 macrophages were present in 18.8%. CD123+ plasmacytoid dendritic (PD) cells were observed within the endomysium and perivascular spaces in 62.5% of anti-HMGCR biopsies. Membrane attack complex was deposited on endothelial cells in 50% and on the sarcolemma of nonnecrotic muscle fibers in 85.7% of anti-HMGCR cases. Major histocompatibility complex class I antigen was up-regulated in 87.5% of the anti-HMGCR cases. CONCLUSIONS: In addition to necrosis, scattered CD4+, CD8+, and PD cells are characteristic of anti-HMGCR myopathy. Predominant M2 polarization suggests infiltrating macrophages are more likely to be involved with tissue repair than destruction.

Distinct physiological strategies are used to cope with constant hypoxia and intermittent hypoxia in killifish (Fundulus heteroclitus).

Many fish encounter hypoxia on a daily cycle, but the physiological effects of intermittent hypoxia are poorly understood. We investigated whether acclimation to constant (sustained) hypoxia or to intermittent diel cycles of nocturnal hypoxia (12 h normoxia:12 h hypoxia) had distinct effects on hypoxia tolerance or on several determinants of O2 transport and O2 utilization in estuarine killifish. Adult killifish were acclimated to normoxia, constant hypoxia, or intermittent hypoxia for 7 or 28 days in brackish water (4 ppt). Acclimation to both hypoxia patterns led to comparable reductions in critical O2 tension and resting O2 consumption rate, but only constant hypoxia reduced the O2 tension at loss of equilibrium. Constant (but not intermittent) hypoxia decreased filament length and the proportion of seawater-type mitochondrion-rich cells in the gills (which may reduce ion loss and the associated costs of active ion uptake), increased blood haemoglobin content, and reduced the abundance of oxidative fibres in the swimming muscle. In contrast, only intermittent hypoxia augmented the oxidative and gluconeogenic enzyme activities in the liver and increased the capillarity of glycolytic muscle, each of which should facilitate recovery between hypoxia bouts. Neither exposure pattern affected muscle myoglobin content or the activities of metabolic enzymes in the brain or heart, but intermittent hypoxia increased brain mass. We conclude that the pattern of hypoxia exposure has an important influence on the mechanisms of acclimation, and that the optimal strategies used to cope with intermittent hypoxia may be distinct from those for coping with constant hypoxia.

Interrelationship between bone substitution materials and skeletal muscle tissue.

Bone density and quantity are primary conditions for the insertion and stability of dental implants. In cases of a lack of adequate maxillary or mandibulary bone, bone augmentation will be necessary. The use of synthetic bioactive bone substitution materials is of increasing importance as alternatives to autogenously bone grafts. It is well known that bone can influence muscle function and muscle function can influence bone structures. Muscles have a considerable potential of adaptation and muscle tissue surrounding an inserted implant or bone surrogate can integrate changes in mechanical load of the muscle and hereupon induce signaling cascades with protein synthesis and arrangement of the cytoskeleton. The Musculus latissimus dorsi is very often used for the analyses of the in vivo biocompatibility of newly designed biomaterials. Beside macroscopically and histologically examination, biocompatibility can be assessed by analyses of the biomaterial influence of gene expression. This review discusses changes in the fiber type distribution, myosin heavy chain isoform composition, histological appearance and vascularization of the skeletal muscle after implantation of bone substitution materials. Especially, the effects of bone surrogates should be described at the molecular-biological and cellular level.