Micromechanical modeling of the epimysium of the skeletal muscles

A micromechanical model has been developed to investigate the mechanical properties of the epimysium. In the present model, the collagen fibers in the epimysium are embedded randomly in the ground substance. Two parallel wavy collagen fibers and the surrounding ground substance are used as the repeat unit (unit cell), and the epimysium is considered as an aggregate of unit cells. Each unit cell is distributed in the epimysium with some different angle to the muscle fiber direction. The model allows the progressive straightening of the collagen fiber as well as the effects of fiber reorientation. The predictions of the model compare favorably against experiment. The effects of the collagen fiber volume fraction, collagen fiber waviness at the rest length and the mechanical properties of the collagen fibers and the ground substance are analyzed. This model allows the analysis of mechanical behavior of most soft tissues if appropriate experimental data are available.     

Age-related changes in the composition and mechanical properties of human nasal cartilage

Mutations in the tuberous sclerosis 2 (TSC2) gene product have been genetically linked to the pathology of both tuberous sclerosis (TSC) and the gender-specific lung disease, lymphangioleiomyomatosis (LAM). Both diseases are classified as disorders of cellular migration, proliferation, and differentiation. Earlier studies from our laboratory (1) linked TSC2 with steroid/nuclear receptor signaling. Studies presented here provide evidence for calmodulin (CaM) signaling in the propagation of this TSC2 activity. Far Western screening of a lambda phage human brain cDNA library to identify interacting proteins for the TSC2 gene product (tuberin) yielded multiple clones encoding human CaM. Direct binding with 32P-labeled tuberin demonstrated Ca2+-dependent binding to CaM-Sepharose which was lost upon deletion of the C-terminal 72 residues. The sequence (1740)WIARLRHIKRLRQRIC(1755) was identified as one capable of forming a basic amphipathic helix indicative of CaM binding domains in known calmodulin binding proteins. Studies with a synthetic peptide of this sequence demonstrated very tight Ca2+-dependent binding to CaM as judged by tryptophan fluorescence perturbation studies and phosphodiesterase activation by CaM. Deletion mutagenesis studies further suggested that this CaM binding domain is required for tuberin modulation of steroid receptor function and that mutations in this region may be involved in the pathology of TSC and LAM.     

Age-related changes in contractile properties of single skeletal fibers from the soleus muscle.

Peak absolute force, specific tension (peak absolute force per cross-sectional area), cross-sectional area, maximal unloaded shortening velocity (Vo; determined by the slack test), and myosin heavy chain (MHC) isoform compositions were determined in 124 single skeletal fibers from the soleus muscle of 12-, 24-, 30-, 36-, and 37-mo-old Fischer 344 Brown Norway F1 Hybrid rats. All fibers expressed the type I MHC isoform. The mean Vo remained unchanged from 12 to 24 mo but did decrease significantly from the 24- to 30-mo time period (from 1.71 +/- 0.13 to 0.85 +/- 0.09 fiber lengths/s). Fiber cross-sectional area remained constant until 36 mo of age, at which time there was a 20% decrease from the values at 12 mo of age (from 5,558 +/- 232 to 4,339 +/- 280 micrometer2). A significant decrease in peak absolute force of single fibers occurred between 12 and 24 mo of age (from 51 +/- 2 x 10(-5) to 35 +/- 2 x 10(-5) N) and then remained constant until 36 mo, when another 43% decrease occurred. Like peak absolute force, the specific tension decreased significantly between 12 and 24 mo by 20%, and another 32% decline was observed at 37 mo. Thus, by 24 mo, there was a dissociation between the loss of fiber cross-sectional area and force. The results suggest time-specific changes of the contractile properties with aging that are independent of each other. Underlying mechanisms responsible for the time-dependent and contractile property-specific changes are unknown. Age-related changes in the molecular dynamics of myosin may be the underlying mechanism for altered force production. The presence of more than one beta/slow MHC isoform may be the mechanism for the altered Vo with age.     

Ultrastructural changes in the skeletal muscles after physical exertion in rats of various ages

The white rats of the age 1, 3 and 12 months ran in the treadmill at a speed 45 m/min for 20, 40, 60 and 90 days. There is not any linear dependence of muscular transformations and the intensity of physical loading. Changes of the material components of muscular fibers are of undulated character, depending on the age, increase in quantity of myofibrils is always accompanied with a decrease in the quantity of mitochondria. When the total share of myofibrils and mitochondria increases, the quantity of other ultrastructural elements of the muscular fibers and hyaloplasm decreases.     

Age-related changes of the stretch reflex excitability in human ankle muscles

The purpose of this study was to characterize the effects of aging on the stretch reflex in the ankle muscles, and in particular to compare the effects on the ankle dorsi-flexor (tibialis anterior: TA) and the plantar-flexor (soleus: SOL). Stretch reflex responses were elicited in the TA and SOL at rest and during weak voluntary contractions in 20 elderly and 23 young volunteers. The results indicated that, in the TA muscle, the elderly group had a remarkably larger long-latency reflex (LLR), whereas no aging effect was found in the short latency reflex (SLR). These results were very different from those in the SOL muscle, which showed significant aging effects in the SLR and medium latency reflex (MLR), but not in the LLR. Given the fact that the LLR of the TA stretch reflex includes the cortical pathway, it is probable that the effects of aging on the TA stretch reflex involve alterations not only at the spinal level but also at the cortical level. The present results indicate that the stretch reflexes of each of the ankle antagonistic muscles are affected differently by aging, which might have relevance to the neural properties of each muscle.     

Water and electrolyte changes in skeletal and cardiac muscles of rats during prolonged hypokinesia

The objective of this study was to show that hypokinesia (diminished movement) could affect differently water and electrolyte content in muscles having minimum differences in their function and morphology. To this end, we studied water and electrolyte content in skeletal and cardiac muscles, fluid excretion, electrolyte absorption, and electrolyte levels in plasma, urine and feces of rats during prolonged hypokinesia (HK). Studies were conducted on one-hundred-twenty-six 13-weeks old male Wister rats during a pre-hypokinetic period and a hypokinesia period. Animals were equally divided into two groups: vivarium control rats (VCR) and hypokinetic rats (HKR). Hypokinetic animals were kept in small individual cages which restricted their movements in all directions without hindering food and water intake. Control rats were housed in individual cages under vivarium control conditions. Sodium (Na+) and potassium (K+) absorption, electrolyte and water content in cardiac muscles (right and left ventricle), thigh extensor (quadriceps femoris muscle) and long muscle of the back (biceps femoris muscle), urine volume, and electrolyte levels in plasma and urine and feces did not change in VCR when compared to their pre-hypokinetic levels. The absorption of Na+ and K+, water and electrolyte content in cardiac and skeletal muscles decreased significantly, while urine volume, plasma electrolyte levels and urine and fecal electrolyte excretion increased significantly in HKR compared with their pre-HK values and with their respective vivarium control (VCR). Water and electrolyte content decreased more significantly in skeletal than in cardiac muscles. Water and electrolyte levels decreased more in the thigh extensor and in the right ventricle than in the long muscle of the back, the left ventricle or the septum. Muscles suffering from higher water and electrolyte loss against the background of lower water and electrolyte content show lower water and electrolyte deposition. Lower electrolyte and water content in skeletal than in cardiac muscle shows that water and electrolyte content decreases more in skeletal than cardiac muscles. Skeletal muscle showed lower water and electrolyte content than cardiac muscle indicating that the risk for decreased muscle water and electrolyte content is inversely related to the muscle function and morphology, i.e., the more weight-bearing supporting function and morphology muscles have, the higher the risk for lower muscle water and electrolyte content. It was concluded that the greater muscle function and morphology, the lower electrolyte and water deposition, the higher water and electrolyte losses, and the lower water and electrolyte content.     

Glyconeogenic pathway in isolated skeletal muscles of rats

Although the conversion of lactate to glycogen (glyconeogenesis) in muscle was demonstrated a long time ago, the biochemical reactions responsible for this process are still a controversial matter. In the present study, advantage was taken from the specific inhibition induced by phenylalanine on muscle pyruvate kinase (PK) to investigate the role of reverse PK activity in muscle glyconeogenesis. Addition of phenylalanine to the incubation medium of a preparation of isolated, intact skeletal muscles that maintain metabolic activity for several hours reduced by 50% the rate of incorporation of [14C]lactate or [14C]bicarbonate into muscle glycogen. Muscle extracts presented high levels of maximal activity of PK in the reverse direction, which was completely blocked in the presence of phenylalanine. In contrast, mercaptopicolinic acid, an inhibitor of phosphoenolpyruvate carboxykinase (PEPCK), did not affect the incorporation of 14C from either lactate or bicarbonate into muscle glycogen. Maximal PEPCK activity was much lower in muscle extracts than in gluconeogenic or glyceroneogenic tissues and was suppressed in the presence of mercaptopicolinic acid. The data suggest that a reversal of the metabolic flux through the reaction catalyzed by PK contributes to the accumulation of lactate-derived glycogen that occurs in skeletal muscle under certain physiological conditions.     

Voltage-current relationships in skeletal muscles of rats.

(1) Thin sheets of fibres from gastrocnemius and lumbricalis muscles of rats were washed in Tris-proponiate solutions containing 0.67 to 60 mM K. The voltage-current relationship was measured by the two microelectrode technique. (2) The V-C curve was S-shaped. The steep region, sometimes including a "forbidden" voltage zone, occurred between about -40 and -70 mV when the solution contained 2 mM K. In some fibres the steep region was found to occur at more positive currents and voltages in "upward" runs (steps of increasing depolarizing currents) then in "downward" runs. The V-C curves thus revealed hysteresis loops presumably covering a negative conductance region. (3) The voltage at which the steep region occurred was a function of [K]0. The mid-point of the steep region was 50 to 60 mV more positive than EK for a particular [K]0 was about 6 mM the steep region of the V-C relationship was not conspicuous. The steep V-C region is considered to reflect depolarizing K inactivation. The near disappearance of the phenomenon at 6 mM K is thought to result from an interference of delayed rectification and depolarizing K inactivation.     

A finite-element model for the mechanical analysis of skeletal muscles

In the present paper, a finite-element model for simulating muscle mechanics is described. Based on nonlinear continuum mechanics an algorithm is proposed that includes the contractile active and passive properties of skeletal muscle. Stress in the muscle is assumed to result from the superposition of a passive and an active part. The passive properties are described by a hyperelastic constitutive material law whereas the active part depends on the fibre length, shortening velocity and an activation function. The constraint of approximate incompressibility of the muscle element is satisfied as a property of the constitutive equations. Because of the nonlinear behaviour of the material and the highly dynamical performance an incremental procedure including iterative methods is used. The advantage of the model over previous formulations is the possibility to integrate the element into an engineering standard finite-element programme ANSYS using advanced numerical tools. The model allows simulations of muscle recruitment, calculations of stress and strain distributions and predictions of muscle shape. Other possible applications are studies of the muscle architecture, the effect of inertia and impacts. First, simple examples are presented.     

Age-related thermodynamic and mechanical properties of the rat collagen

The age peculiarities of cross-linking degree, thermodynamic and mechanic properties of rat tail tendon collagen fibres were investigated. It is shown that during the period from 1 to 3 months the melting temperature decreases and the enthalpy difference increases, from 3 to 24 months the melting temperature increases and the enthalpy difference decreases. The strength of fibres increases during the whole life. The maximal relative extension increases during the first 12 months and tends to decrease in after-life. The Young's module in the elastic deformation region decreases during the period from 1 to 3 months, then increases. It is shown tht those changes in fibre properties may be connected with the age dynamics of collagen cross-linking degree observed here: its decreasing during the period from 1 to 3 months and its following continuous increasing in after-life.     

Age-related changes in plasma proteins of analbuminemic rats

A mutant strain, Nagase analbuminemia rats (NAR), was established from Sprague-Dawley rats. Age-related changes in plasma proteins of NAR were investigated to obtain information of their abnormalities of protein metabolism. The total protein concentration in the serum of NAR of various ages was almost the same as that of normal rats of the same age. The albumin level of NAR was less than 0.05 mg/ml at all ages examined. The concentrations of serum alpha 1-antitrypsin, alpha-X protein, alpha 2-macroglobulin, transferrin, ceruloplasmin, IgG, IgA and IgM were higher in NAR than in normal rats except for the perinatal stage, but alpha 1-acid glycoprotein level in NAR was normal. The serum transferrin and ceruloplasmin levels were especially high in female adult NAR. The plasma fibrinogen concentration was also increased in NAR. These findings indicate that the normal total serum protein level of NAR was maintained by increase in the globulin concentration.     

Morphological changes in continuously stretched skeletal muscles in sheep

The effects of continuous elongation of skeletal muscles were studied on six sheep who underwent a lengthening osteotomy of the right tibia. Open muscle biopsies were taken from the biceps femoris muscle preoperatively (Group A), after 5 weeks of bone distraction (Group B) and after another 5 weeks without further distraction (Group C). The size and distribution of type 1 (slow-twitch) and type 2 (fast-twitch) muscle fibres were determined from sections stained for myofibrillar ATPase activity. All sections were also evaluated by light microscopy, especially with regard to myopathic changes. The type 2 fibres showed a significant decrease in size from group A to B and from group B to C. The reduction in fibre size from group A to C was 44.2%. The type 1 fibres, on the other hand, showed no significant differences in mean fibre size between the groups. However, there were considerable individual variations in type 1 fibre size between the groups. The distribution of both fibre types was similar in groups A and B (appr. 17% type 1 fibres) whereas the relative number of type 1 fibres was reduced to 12.4% in group C (P less than 0.01). Myopathic changes, i.e. muscle fibre necroses, were not seen in any of the groups. It is concluded that the type 2 fibre atrophy is mainly caused by muscular inactivity during the postoperative period, but an additional effect of continuous stretching of the muscle cannot be excluded.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-related changes of serum lipoprotein oxidation in rats

Oxidation of low-density lipoprotein (LDL) may be a prelude to atherogenesis and directly age related. To assess whether there may be relationship between age and plasma lipoprotein (LP) oxidation, we studied copper-mediated LP oxidation isolated from the blood of 2 months, 7 months, and 15 months old rats. We determined whether the susceptibility of LP to oxidation might be related to vitamin C levels in serum, vitamin E levels in LP, or the total antioxidant capacity (TAC) of serum or LP. Serum vitamin C content was inversely related to age, malondialdehyde (MDA) propagation rate, and maximum change of MDA concentrations. However, there were no significant relationships between age and serum TAC, LP TAC, serum vitamin E, or the ratio of LP vitamin E to serum vitamin C content. The lag phase of MDA formation was significantly decreased with age and the ratio of LP vitamin E content to serum vitamin C content, increased with age. Maximum change of MDA concentration was positively correlated with the ratio of LP vitamin E contents to serum vitamin C concentration. Thus, as the rat ages, vitamin C status decreases with an increased LP susceptibility to oxidation. It is tempting to speculate that enhanced LP oxidation in older rats may reflect a reduced amount of recycling of LDL vitamin E by serum vitamin C.