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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to examine the Ca2+-Mg2+ myofibrillar ATPase and protein composition of cardiac and skeletal muscle following strenuous activity to voluntary exhaustion. Sprague-Dawley rats (200 g) were assigned to a control and exercised group, with the run group completing 25 m.min-1 and 8% grade for 1 hour. Following activity, the myocardial Ca2+-Mg2+ myofibrillar ATPase activity -pCa relationship had undergone a rightward shift in the curve. Electrophoretic analysis revealed a change in the pattern of cardiac myofibrillar protein bands, particularly in the 38-42 Kdalton region. Enzymatic analysis of myofibrillar proteins from plantaris muscle, revealed no change in Ca2+ regulation following exercise. Electronmicrographic and electrophoretic analysis revealed extensively disrupted sarcomeric structure and a change in the ratio of several plantaris myofibrillar proteins. No difference was observed for myosin: Actin: tropomyosin ratios; however a dramatic reduction in 58 and 95 Kdalton proteins were evident. The results indicate that prolonged running is associated with similar responses in cardiac and skeletal muscle myofibrillar protein compositions. The abnormalities in myofibrillar ultrastructure may implicate force transmission failure as a factor in exercised-induced muscle damage and/or fatigue.
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PMID:Influence of exercise on cardiac and skeletal muscle myofibrillar proteins. 297 50

Creatine kinase (CK) provides ATP buffering in skeletal muscle and is expressed as 1) cytosolic myofibrillar CK (M-CK) and 2) sarcomeric mitochondrial CK (ScCKmit) isoforms that differ in their subcellular localization. We compared the isometric contractile and fatigue properties of 1) control CK-sufficient (Ctl), 2) M-CK-deficient (M-CK[-/-]), and 3) combined M-CK/ScCKmit-deficient null mutant (CK[-/-]) diaphragm (Dia) to determine the effect of the absence of M-CK activity on Dia performance in vitro. Baseline contractile properties were comparable across groups except for specific force, which was approximately 16% lower in CK[-/-] Dia compared with M-CK[-/-] and Ctl Dia. During repetitive activation (40 Hz, (1)/(3) duty cycle), force declined in all three groups. This decline was significantly greater in CK[-/-] Dia compared with Ctl and M-CK[-/-] Dia. The pattern of force decline did not differ between M-CK[-/-] and Ctl Dia. We conclude that Dia isometric muscle function is not absolutely dependent on the presence of M-CK, whereas the complete absence of CK acutely impairs isometric force generation during repetitive activation.
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PMID:Absence of myofibrillar creatine kinase and diaphragm isometric function during repetitive activation. 951 80

Relaxed striated muscle cells exhibit mechanical fatigue when exposed to repeated stretch and release cycles. To understand the molecular basis of such mechanical fatigue, single molecules of the giant filamentous protein titin, which is the main determinant of sarcomeric elasticity, were repetitively stretched and released while their force response was characterized with optical tweezers. During repeated stretch-release cycles titin becomes mechanically worn out in a process we call molecular fatigue. The process is characterized by a progressive shift of the stretch-force curve toward increasing end-to-end lengths, indicating that repeated mechanical cycles increase titin's effective contour length. Molecular fatigue occurs only in a restricted force range (0-25 pN) during the initial part of the stretch half-cycle, whereas the rest of the force response is repeated from one mechanical cycle to the other. Protein-folding models fail to explain molecular fatigue on the basis of an incomplete refolding of titin's globular domains. Rather, the process apparently derives from the formation of labile nonspecific bonds cross-linking various sites along a pre-unfolded titin segment. Because titin's molecular fatigue occurs in a physiologically relevant force range, the process may play an important role in dynamically adjusting muscle's response to the recent history of mechanical perturbations.
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PMID:Mechanical fatigue in repetitively stretched single molecules of titin. 1115 52

Inspiratory muscle weakness in patients with chronic obstructive pulmonary disease (COPD) is of major clinical relevance; maximum inspiratory pressure generation is an independent determinant of survival in severe COPD. Traditionally, inspiratory muscle weakness has been ascribed to hyperinflation-induced diaphragm shortening. However, more recently, invasive evaluation of diaphragm contractile function, structure, and biochemistry demonstrated that cellular and molecular alterations occur, of which several can be considered of pathologic nature. Although the fiber-type shift toward oxidative type I fibers in COPD diaphragm is regarded as beneficial, rendering the overloaded diaphragm more resistant to fatigue, the reduction of diaphragm fiber force generation in vitro likely contributes to diaphragm weakness. The reduced diaphragm force generation at single-fiber level is associated with loss of myosin content. Moreover, the diaphragm in COPD is exposed to oxidative stress and sarcomeric injury. The current Pulmonary Perspective postulates that the oxidative stress and sarcomeric injury activate proteolytic machinery, leading to contractile protein wasting and, consequently, loss of force-generating capacity of diaphragm fibers in patients with COPD. Interestingly, several of these presumed pathologic alterations are already present early in the course of the disease (GOLD I/II), although these patients do not appear to be limited in their daily-life activities. Therefore, investigating in vivo diaphragm function in mild to moderate COPD should be the focus of future research. Treatment of diaphragm dysfunction in COPD is complex because its etiology is unclear, but recent findings show promise for the use of proteasome inhibitors in syndromes associated with muscle wasting, such as the diaphragm in COPD.
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PMID:Diaphragm muscle fiber dysfunction in chronic obstructive pulmonary disease: toward a pathophysiological concept. 1741 28

Primary and secondary cardiac tumours are extremely rare in humans and domestic animals. This case describes the gross, light microscopical and immunohistochemical examination of a cardiac myxoma arising from the tricuspid valve in a 13-year-old female terrier dog. Clinically, long-term respiratory distress, progressive ascites, fatigue and exercise intolerance were observed in the animal. At necropsy, the right ventricular chamber was mildly dilated and a soft, whitish mass, 0.7 x 1.5 x 2.1 cm in size was observed arising from the ventricular surface of the septal leaflet of the tricuspid valve of the heart. Histologically, the mass was composed of a faintly eosinophilic myxoid matrix and spindle shaped fibroblast-like cells with elongated nuclei and stellate cells. The extracellular matrix was stained with periodic acid Schiff and alcian blue and the tumour cells were reactive with anti-vimentin and anti-alpha-sarcomeric actin antibodies. The authors believe that this is the first detailed description of a myxoma in this breed.
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PMID:Valvular cardiac myxoma in a dog. 1771 8

Inspiratory muscle weakness in patients with COPD is of major clinical relevance. For instance, maximum inspiratory pressure generation is an independent determinant of survival in severe COPD. Traditionally, inspiratory muscle weakness has been ascribed to hyperinflation-induced diaphragm shortening. However, more recently, invasive evaluation of diaphragm contractile function, structure, and biochemistry demonstrated that cellular and molecular alterations occur, of which several can be considered pathologic of nature. Whereas the fiber type shift towards oxidative type I fibers in COPD diaphragm is regarded beneficial, rendering the overloaded diaphragm more resistant to fatigue, the reduction of diaphragm fiber force generation in vitro likely contributes to diaphragm weakness. The reduced diaphragm force generation at single fiber level is associated with loss of myosin content in these fibers. Moreover, the diaphragm in COPD is exposed to oxidative stress and sarcomeric injury. This review postulates that the oxidative stress and sarcomeric injury activate proteolytic machinery, leading to contractile protein wasting and, consequently, loss of force generating capacity of diaphragm fibers in patients with COPD. Interestingly, several of these presumed pathologic alterations are already present early in the course of the disease (GOLD I/II), although these patients appear not limited in their daily life activities. Treatment of diaphragm dysfunction in COPD is complex since its etiology is unclear, but recent findings indicate the ubiquitin-proteasome pathway as a prime target to attenuate diaphragm wasting in COPD.
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PMID:Diaphragm adaptations in patients with COPD. 1821 29

Human resting muscle (myofascial) tone (HRMT) is the passive tonus or tension of skeletal muscle that derives from its intrinsic (EMG-silent) molecular viscoelastic properties. The word tone has been used to convey varying clinical and physiological features that have led to confusion and controversy. HRMT is the vital low-level, passive tension, and resistance to stretch that contributes importantly to maintain postural stability in balanced equilibrium positions. In contrast, co-contraction of muscle is an active neuromotor control that provides greater levels of tonus for increased stabilization. Functionally, HRMT is integrated with other passive fascial and ligamentous tensional networks of the body to form a biotensegrity system. This review aims to achieve better understandings of HRMT and its functional roles. Nature is frugal and man's adaptations to gravitational forces and erect postures seemingly evolved mechanisms in skeletal muscle tissues to economically enhance stability. Normal passive muscle tone helps to maintain relaxed standing body posture with minimally increased energy costs (circa 7% over supine), and often for prolonged durations without fatigue. Available data infer polymorphic variations in normal myofascial tone. However, few quantitative studies have been performed to establish normal frequency distributions of degrees of myofascial tone. Clinical experience indicates that persons with certain symptomatic musculoskeletal conditions may have palpably increased resting muscle firmness or hardness (EMG-silent), such as that of the upper trapezius in tension-type headache, and the lumbodorsal extensors (hartspann) in degenerative lumbar disc disease and ankylosing spondylitis. In summary, resting skeletal muscle tone is an intrinsic viscoelastic tension exhibited within the body's kinematic chains. It functions inseparably from fascial (i.e., myofascial) tissues and ligamentous structures. Thus, HRMT is a passive myofascial property which operates within networks of tensional tissues, i.e., biotensegrity. This passive tension is the CNS-independent component resulting from intrinsic molecular interactions of the actomyosin filaments in sarcomeric units of skeletal muscle and myofibroblast cells. The overarching CNS-activated muscle contractions generate far greater tensions transmitted by fascial elements. Interdisciplinary research on HRMT and its biodynamics promises greater effectiveness of clinical practitioners and productivity of investigators, which warrants priority attention.
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PMID:Human resting muscle tone (HRMT): narrative introduction and modern concepts. 1932 46

Performance of striated muscle relies on the nerve-driven activation of the sarcomeric motor and coupled energy supply lines. This biological engine is unique; its mechanical and metabolic characteristics are not fixed, but are tailored by functional demand with exercise. This remodelling is specific for the imposed muscle stimulus. This is illustrated by the increase in local oxidative capacity with highly repetitive endurance training vs. the preferential initiation of sarcomerogenesis with strength training regimes, where high-loading increments are imposed. The application of molecular biology has provided unprecedented insight into the pathways that govern muscle plasticity. Time-course analysis indicates that the adjustments to muscle work involve a broad regulation of transcript expression during the recovery phase from a single bout of exercise. Highly resolving microarray analysis demonstrates that the specificity of an endurance-exercise stimulus is reflected by the signature of the transcriptome response after muscle work. A quantitative match in mitochondrial transcript adjustments and mitochondrial volume density after endurance training suggests that the gradual accumulation of expressional microadaptations underlies the promotion of fatigue resistance with training. This regulation is distinguished from control of muscle growth via the load-dependent activation of sarcomerogenesis. Discrete biochemical signalling systems have evolved that sense metabolic perturbations during exercise and trigger a specific expression program, which instructs the remodelling of muscle makeup. A drop in muscle oxygen tension and metabolite perturbations with exercise are recognized as important signals in the genome-mediated remodelling of the metabolic muscle phenotype in humans.
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PMID:Tuning of mitochondrial pathways by muscle work: from triggers to sensors and expression signatures. 1944 13

The human sarcomeric alpha-actinins (ACTN2 and ACTN3) are major structural components of the Z line in skeletal muscle; they play a role in the maintenance of sarcomeric integrity and also interact with a wide variety of structural, signaling and metabolic proteins. ACTN2 is expressed in all muscle fibers, and expression of ACTN3 is restricted to the type 2 (fast glycolytic) fibers that are responsible for forceful contraction at high velocity. There is a common stop codon polymorphism R577X in the ACTN3 gene. Homozygosity for the R577X null-allele results in the absence of alpha-actinin-3 in fast muscle fibers with frequencies that vary from < 1% in Africans to approximately 18% in Caucasians. A number of association studies have demonstrated that the ACTN3 R577X genotype influences athletic performance in Caucasians; the frequency of the XX genotype is significantly lower than controls in sprint athletes, and it appears that alpha-actinin-3 deficiency is detrimental to sprint performance. In the general population, the ACTN3 genotype contributes to the normal variations in muscle strength and sprinting speed. In an Actn3 knockout mouse model, alpha-actinin-3 deficiency is associated with a shift in the characteristics of fast, glycolytic 2B muscle fibers towards a slow phenotype, with decreased muscle mass and fiber diameter, slower contractile properties, increased fatigue resistance, and an increase in oxidative enzyme activity. The shift towards a more efficient oxidative metabolism may underlie the selective advantage of the X-allele during evolution. In turn, the shift towards a 'slow' muscle phenotype in fast muscle fibers likely explains why loss of alpha-actinin-3 is detrimental to sprint performance.
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PMID:alpha-actinin-3 and performance. 1969 9

Barth syndrome is an X-linked genetic disorder caused by mutations in the tafazzin (taz) gene and characterized by dilated cardiomyopathy, exercise intolerance, chronic fatigue, delayed growth, and neutropenia. Tafazzin is a mitochondrial transacylase required for cardiolipin remodeling. Although tafazzin function has been studied in non-mammalian model organisms, mammalian genetic loss of function approaches have not been used. We examined the consequences of tafazzin knockdown on sarcomeric mitochondria and cardiac function in mice. Tafazzin knockdown resulted in a dramatic decrease of tetralinoleoyl cardiolipin in cardiac and skeletal muscles and accumulation of monolysocardiolipins and cardiolipin molecular species with aberrant acyl groups. Electron microscopy revealed pathological changes in mitochondria, myofibrils, and mitochondrion-associated membranes in skeletal and cardiac muscles. Echocardiography and magnetic resonance imaging revealed severe cardiac abnormalities, including left ventricular dilation, left ventricular mass reduction, and depression of fractional shortening and ejection fraction in tafazzin-deficient mice. Tafazzin knockdown mice provide the first mammalian model system for Barth syndrome in which the pathophysiological relationships between altered content of mitochondrial phospholipids, ultrastructural abnormalities, myocardial and mitochondrial dysfunction, and clinical outcome can be completely investigated.
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PMID:Cardiac and skeletal muscle defects in a mouse model of human Barth syndrome. 2106 80


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