Curcumin counteracts loss of force and atrophy of hindlimb unloaded rat soleus by hampering neuronal nitric oxide synthase untethering from sarcolemma.

Antioxidant administration aimed to antagonize the development and progression of disuse muscle atrophy provided controversial results. Here we investigated the effects of curcumin, a vegetal polyphenol with pleiotropic biological activity, because of its ability to upregulate glucose-regulated protein 94 kDa (Grp94) expression in myogenic cells. Grp94 is a sarco-endoplasmic reticulum chaperone, the levels of which decrease significantly in unloaded muscle.

Stem-cell therapy in an experimental model of pulmonary hypertension and right heart failure: role of paracrine and neurohormonal milieu in the remodeling process.

Background: In this study we investigated the effect of human amniotic fluid stem (hAFS) cells and rat adipose tissue stromal vascular fraction GFP-positive cell (rSVC-GFP) therapy and the contribution of the paracrine and neurohormonal milieu to cardiac and pulmonary vascular remodeling in a rat model of pulmonary hypertension (PH) and right heart failure (RHF).

Methods: Sprague-Dawley rats were injected with monocrotaline (MCT). Four million hAFS or rSVC-GFP cells were injected via the tail vein 3 weeks after MCT.

Exercise intolerance in chronic heart failure: mechanisms and therapies. Part I.

Muscular fatigue and dyspnoea on exertion are among the most common symptoms in chronic heart failure; however their origin is still poorly understood. Several studies have shown that cardiac dysfunction alone cannot fully explain their origin, but the contribution of the multiorgan failure present in this syndrome must be highlighted. In this study, divided in two parts (see part II: pp.

Exercise intolerance in chronic heart failure: mechanisms and therapies. Part II.

Muscular fatigue and dyspnoea on exertion are among the most common symptoms in chronic heart failure; however their origin is still poorly understood. Several studies have shown that cardiac dysfunction alone cannot fully explain their origin, but the contribution of the multiorgan failure present in this syndrome must be highlighted. We aimed to summarize the existing evidence and the most controversial aspects of the complex interplay of different factors involved in the symptom generation.

Effects of inactivity on human muscle glutathione synthesis by a double-tracer and single-biopsy approach.

Oxidative stress is often associated to inactivity-mediated skeletal muscle atrophy. Glutathione is one of the major antioxidant systems stimulated, both at muscular and systemic level, by activation of oxidative processes. We measured changes in glutathione availability, oxidative stress induction and the extent of atrophy mediated by 35 days of experimental bed rest in vastus lateralis muscle of healthy human volunteers.

A transient antioxidant stress response accompanies the onset of disuse atrophy in human skeletal muscle.

It is presently unknown whether oxidative stress increases in disused skeletal muscle in humans. Markers of oxidative stress were investigated in biopsies from the vastus lateralis muscle, collected from healthy subjects before [time 0 (T0)], after 1 wk (T8), and after 5 wk (T35) of bed rest. An 18% decrease in fiber cross-sectional area was detected in T35 biopsies (P<0.

Skeletal muscle proteins oxidation in chronic right heart failure in rats: can different beta-blockers prevent it to the same degree?

Background: Skeletal muscle atrophy and decreased expression of slow fibers contribute to exercise capacity limitation in Chronic Heart Failure (CHF). Pro-inflammatory cytokines and free radicals worsen muscle damage. In CHF sarcomeric proteins are oxidized with reduction of muscle twitch efficiency, and VO(2)-max.

Physiological basis for contractile dysfunction in heart failure.

The purpose of this review is to enlighten the mechanisms of skeletal muscle dysfunction in heart failure. The muscle hypothesis suggests that chronic heart failure (CHF) symptoms, dyspnoea and fatigue are due to skeletal muscle alterations. Hyperventilation due to altered ergoreflex seems to be the cause of shortness of breath.

Skeletal muscle myofibrillar protein oxidation and exercise capacity in heart failure.

Background: Heart failure is characterized by limited exercise tolerance and by a skeletal muscle myopathy with atrophy and shift toward fast fibres. An inflammatory status with elevated pro-inflammatory cytokines and exaggerated free radicals production can worsen muscle damage. We have previously demonstrated in a model of heart failure, the monocrotaline treated rat, that oxidation of skeletal muscle actin, tropomyosin and myosin produces a reduction of contractile efficiency, which may further depress muscle function and exercise capacity.

Carnitine-mediated improved response to erythropoietin involves induction of haem oxygenase-1: studies in humans and in an animal model.

Background: Carnitine improves erythropoetin (EPO) response and anaemia in haemodialysis patients (HD); however, the mechanism(s) responsible remain unidentified. We have reported that carnitine induces haem oxygenase (HO)-1, which is an antioxidant and antiapoptotic that acts via pathways shared with EPO. Therefore carnitine's effect on these pathways may account for the improved EPO response.

Trophic action of sphingosine 1-phosphate in denervated rat soleus muscle.

Sphingosine 1-phosphate (S1P) mediates a number of cellular responses, including growth and proliferation. Skeletal muscle possesses the full enzymatic machinery to generate S1P and expresses the transcripts of S1P receptors. The aim of this work was to localize S1P receptors in rat skeletal muscle and to investigate whether S1P exerts a trophic action on muscle fibers.

Skeletal muscle wastage in Crohn's disease: a pathway shared with heart failure?

Background: Lean body mass wastage in active Crohn's disease is not only related to malnutrition, but also to local and systemic inflammation. Altered bowel permeability can represent a source of pro-inflammatory cytokines, that have been shown to produce muscle wastage by several mechanisms such as apoptosis. In our study we have evaluated the body composition and the pathological changes of skeletal muscle in patients with Crohn's disease to see whether a relationships between altered gut permeability, proinflammatory cytokines production and muscle wastage existed.

Skeletal muscle apoptosis in experimental heart failure: the only link between inflammation and skeletal muscle wastage?

Purpose Of Review: The purpose of this review is to enlighten the mechanisms of muscle wastage in experimental heart failure with attention to skeletal muscle apoptosis and the role of proinflammatory cytokines that trigger apoptosis.

Recent Findings: Mechanisms leading to muscle wastage in chronic heart failure include cytokine-triggered skeletal muscle apoptosis, but also ubiquitin/proteasome and non-ubiquitin-dependent pathways. The regulation of fibre type involves the growth hormone/insulin-like growth factor 1/calcineurin/transcriptional coactivator PGC1 cascade.

Inflammation and perturbation of the l-carnitine system in heart failure.

Background: Heart failure (HF) is accompanied by elevated levels of pro-inflammatory cytokines. Skeletal muscle myopathy with atrophy of fibres, decreased oxidative metabolism and preferential synthesis of fast myosin heavy chains (MHCs) occurs, which contributes to the worsening of symptoms. l-Carnitine has been shown to be protective against the apoptosis-induced atrophy of fibres and fast MHCs shift.

Skeletal muscle fibres synthesis in heart failure: role of PGC-1alpha, calcineurin and GH.

Background: Patients with congestive heart failure (CHF) have decreased exercise capacity because of muscle fatigability. Symptoms are due to a specific myopathy with increased expression of fast type II fibres, fast MHCs and muscle atrophy. PGC-1alpha, a potent transcriptional coactivator for nuclear receptors, induces mitochondrial myogenesis and the preferential synthesis of slow fibres.

Skeletal muscle myofibrillar protein oxidation in heart failure and the protective effect of Carvedilol.

Heart failure is characterized by limited exercise tolerance and by a skeletal muscle myopathy with atrophy and shift toward fast fibres. An inflammatory status with elevated pro-inflammatory cytokines and exaggerated free radicals production, can worsen muscle damage. In a well established model of heart failure, the monocrotaline treated rat, we show that CHF is accompanied by oxidation of the skeletal muscle actin, tropomyosin and myosin, which further depresses muscle function and exercise capacity.

Sphingosine 1-phosphate protects mouse extensor digitorum longus skeletal muscle during fatigue.

Sphingomyelin derivatives exert various second messenger actions in numerous tissues. Sphingosine (SPH) and sphingosine 1-phosphate (S1P) are two major sphingomyelin derivatives present at high levels in blood. The aim of the present work was to investigate whether S1P and SPH exert relevant actions in mouse skeletal muscle contractility and fatigue.

Muscle wastage in chronic heart failure, between apoptosis, catabolism and altered anabolism: a chimaeric view of inflammation?

Purpose Of The Review: The mechanisms involved in determining skeletal muscle wastage and cachexia in heart failure are complex and not unequivocal. There are however three different mechanisms that are in some way related to each other and play a very important role. These are inflammation, the catabolic/anabolic imbalance and apoptosis.

Beneficial effects of GH/IGF-1 on skeletal muscle atrophy and function in experimental heart failure.

Muscle atrophy is a determinant of exercise capacity in heart failure (CHF). Myocyte apoptosis, triggered by tumor necrosis factor-alpha (TNF-alpha) or its second messenger sphingosine (SPH), is one of the causes of atrophy. Growth hormone (GH) improves hemodynamic and cardiac trophism in several experimental models of CHF, but its effect on skeletal muscle in CHF is not yet clear.

Skeletal muscle abnormalities in rats with experimentally induced heart hypertrophy and failure.

Background: In congestive heart failure (CHF), function and metabolism of skeletal muscles are abnormal.

Aim: To evaluate whether the reduced oxidative capacity of skeletal muscles in CHF is due to impaired O(2) utilisation.

Methods: CHF was induced in rats by injecting 50 mg/Kg monocrotaline.

L-Carnitine: a potential treatment for blocking apoptosis and preventing skeletal muscle myopathy in heart failure.

Skeletal muscle in congestive heart failure is responsible for increased fatigability and decreased exercise capacity. A specific myopathy with increased expression of fast-type myosins, myocyte atrophy, secondary to myocyte apoptosis triggered by high levels of circulating tumor necrosis factor-alpha (TNF-alpha) has been described. In an animal model of heart failure, the monocrotaline-treated rat, we have observed an increase of apoptotic skeletal muscle nuclei.

Effect of thalidomide on the skeletal muscle in experimental heart failure.

Background: Tumour Necrosis Factor alpha (TNFalpha) has been shown to contribute to heart failure (CHF) progression.

Aims: We have tried to antagonise the detrimental effects of TNFalpha on skeletal muscle apoptosis, by using thalidomide, a drug that inhibits its biosynthesis.

Methods: CHF was induced in 20 rats by injecting monocrotaline, which determines right ventricle (RV) failure.