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Results for “Skeletal muscle dysfunction”

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At least 235 records · Page 13Linked to original sources

PubMed1989

Prolonged degeneration of muscle spindles in the masseter muscle after treatment of developing mice with the local anesthetic lidocaine hydrochloride.

The effect of lidocaine-HCl on muscle spindles in the masseter muscle of developing mice was investigated. Repeated injections of mice with anesthetic in the short term decreased the diameters of primary endings, intrafusal muscle fibers and outer capsules in the equatorial regions of muscle spindles, and caused a drop in the succinic dehydrogenase activity in intrafusal muscle fibers of the muscle spindles. In addition, the diameters did not recover to the control value even after about 10 weeks following cessation of anesthetic treatment. Thus, the present results suggest that repeated use of lidocaine-HCl in developing animals may cause dysfunction of the skeletal muscles.

Animals↗

PubMed1997

Mechanisms and implications of endothelial dysfunction in congestive heart failure.

The pathogenesis of heart failure is determined by the ventricular and vascular responses to myocellular injury. Experimental and clinical studies suggest that the vascular endothelium may play an important role in modulating progression of ventricular and vascular remodeling in heart failure. Endothelial cell dysfunction has been described in the coronary and skeletal muscle circulations of patients with heart failure and appears to be characterized by decreased endothelial synthesis of nitric oxide and increased production of endothelin-1. The pathogenesis of endothelial dysfunction in heart failure is unknown, but may be related to increased oxidative stress, abnormal regional flow conditions, and cytokine and neurohormonal activation. The specific role of endothelial dysfunction in the pathogenesis of heart failure remains to be determined. If endothelial dysfunction does contribute to progression of disease in early heart failure, specific therapies to enhance endothelial dysfunction may improve long-term morbidity and mortality.

Animals↗

PubMed2002

Mitochondrial respiratory chain function in skeletal muscle of ALS patients.

Evidence implicating mitochondrial dysfunction in the central nervous system of patients with sporadic amyotrophic lateral sclerosis (SALS) has recently been accumulating. In contrast, data on mitochondrial function in skeletal muscle in SALS are scarce and controversial. We investigated the in situ properties of muscle mitochondria in patients with early-stage SALS and sedentary (SED) controls using the skinned fiber technique to determine whether respiration of muscle tissue is altered in early-stage SALS in comparison with SED. Musculus vastus lateralis biopsies were obtained from 7 SED group members and 14 patients with early-stage SALS (mean disease duration, 9 months). Muscle fibers were permeabilized with saponine and then skinned and placed in an oxygraphic chamber to measure basal (V(0)) and maximal (V(max)) adenosine diphosphate-stimulated respiration rates and to assess mitochondrial regulation by adenosine diphosphate. Muscle oxidative capacity, evaluated with V(max), was identical in patients in the SALS and SED groups (V(0): SALS, 1.1 +/- 0.1; SED, 0.8 +/- 0.1, micromol 0(2). min(-1). gm(-1)dw and V(max): SALS, 3.1 +/- 0.3; SED, 2.5 +/- 0.3, micromol 0(2). min(-1). gm(-1)dw). This study shows an absence of large mitochondrial damage in skeletal muscle of patients with early-stage SALS, suggesting that mitochondrial dysfunction in the earlier stages of SALS is almost certainly not systemic.

Amyotrophic Lateral Sclerosis↗

PubMed2005

Activation of the endoplasmic reticulum stress response in autoimmune myositis: potential role in muscle fiber damage and dysfunction.

OBJECTIVE: The etiology and pathogenesis of human inflammatory myopathies remain unclear. Findings of several studies suggest that the degree of inflammation does not correlate consistently with the severity of clinical disease or of structural changes in the muscle fibers, indicating that nonimmune pathways may contribute to the pathogenesis of myositis. This study was undertaken to investigate these pathways in myositis patients and in a class I major histocompatibility complex (MHC)-transgenic mouse model of myositis. METHODS: We examined muscle tissue from human myositis patients and from class I MHC-transgenic mice for nonimmune pathways, using biochemical, immunohistochemical, and gene expression profiling assays. RESULTS: Up-regulation of class I MHC in skeletal muscle fibers was an early and consistent feature of human inflammatory myopathies. Class I MHC staining in muscle fibers of myositis patients showed both cell surface and a reticular pattern of internal reactivity. The pathways of endoplasmic reticulum (ER) stress response, the unfolded protein response (glucose-regulated protein 78 pathway), and the ER overload response (NF-kappaB pathway) were significantly activated in muscle tissue of human myositis patients and in the mouse model. Ectopic expression of wild-type mouse class I MHC (H-2K(b)) but not degradable glycosylation mutants of H-2K(b) induced ER stress response in C(2)C(12) skeletal muscle cells. CONCLUSION: These results indicate that the ER stress response may be a major nonimmune mechanism responsible for skeletal muscle damage and dysfunction in autoimmune myositis. Strategies to interfere with this pathway may have therapeutic value in patients with this disease.

Animals↗

PubMed2006

PGC-1beta down-regulation is associated with reduced ERRalpha activity and MCAD expression in skeletal muscle of senescence-accelerated mice.

Mitochondrial dysfunction is involved in the development of aging. Here, we examined the effect of aging on the skeletal muscle expression of two isoforms of the transcriptional peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 (PGC-1) in an experimental murine model of accelerated aging, the senescence-accelerated mouse (SAM). The senescence-accelerated prone mice (SAM-P8) showed no changes in PGC-1alpha, but a decrease in PGC-1beta expression (52% reduction, p <.001) was observed compared to the senescence-accelerated resistant mice (SAM-R1). In agreement with the proposed role of PGC-1beta as an estrogen-related receptor (ERR) protein ligand, the expression of the ERRalpha target gene medium-chain acyl-coenzyme A dehydrogenase was strongly suppressed (85%, p <.001) in SAM-P8. The decrease in the expression of medium-chain acyl-coenzyme A dehydrogenase was consistent with the reduction in ERRalpha DNA-binding activity of SAM-P8. These findings indicate that the age-mediated decrease in PGC-1beta expression in SAM-P8 skeletal muscle affects the expression of genes involved in mitochondrial fatty acid oxidation.

Acyl-CoA Dehydrogenase↗

PubMed1995

[Physiologic, biochemical and genetic aspects of malignant hyperthermia].

Malignant hyperthermic syndrome (MHS) is based on a metabolic dysfunction of the skeletal muscle. It is characterized by an elevation of muscle metabolism and rigidity, accompanied by an increase of arterial pCO2, lactate and potassium plasma concentration, and body temperature. In sensitive individuals, MHS can be evoked pharmacologically. To identify substances that evoke this syndrome or those useful for its therapy, MHS is modelled in pigs. The primary defect attributed to MHS is the impairment of sarcoplasmic calcium homeostasis based on a dysfunction of one of calcium ion channels. In some cases, genetic mapping has shown that MHS is related to changes in 19 chromosome (in humans). Abnormal function of the ion channel is probably not sufficient for the expression of MHS. The syndrome manifests only when several modifying factors coincide.

Animals↗

PubMed1995

[Physiologic, biochemical and genetic aspects of malignant hyperthermia].

Animals↗

PubMed2006

Intrauterine growth restriction induces increased capillary density and accelerated type I fiber maturation in newborn pig skeletal muscles.

AIMS: Humans with low birth weight exhibit evidences of vascular dysfunction. Recent findings indicate a microvascular rarefaction in skeletal muscles soon after postnatal development in rats suffered by intrauterine protein restriction. METHODS: To examine the effects of intrauterine growth restriction on capillary density, muscle fiber distribution and accompanying muscular and systemic circulation immediately after birth, studies were conducted on 1-day-old anesthetized normal weight (n = 7) and intrauterine growth restricted (n = 6) piglets. Cardiac output and hind limb muscle blood flow were measured by colored microspheres. Counting of type I fibers and skeletal capillary numbers was done by immunohistochemical staining. RESULTS: Increased proportion of type I fibers and capillary density was found in the flexor digitalis superficialis and gastrocnemius medialis (P < 0.05) in newborn IUGR piglets. Furthermore, a marked correlation was shown between capillary density and type I fiber fraction for all flexor muscles studied (P < 0.05). Moreover, cardiac output and muscular blood flow were markedly increased in IUGR piglets (P < 0.05). Correspondingly, total peripheral resistance, as well as vascular resistance, of hind limb flexors appeared significantly decreased (P < 0.05). CONCLUSIONS: Compromised intrauterine environmental conditions leading to fetal growth restriction provokes coordinated structural and functional adaptation of skeletal muscles.

Animals↗

PubMed2006

Local and distant burn injury alter immuno-inflammatory gene expression in skeletal muscle.

BACKGROUND: Severe burn trauma mediates immune dysfunction, infection, and multiple organ dysfunction syndrome. We are investigating the immuno-inflammatory response by characterizing gene expression changes in skeletal muscle after local and distant burn injury. METHODS: Male CD1 mice in three experimental groups, control (unburned), hind limb (local burn), and 30% total body surface area (distant burn), were killed between 6 hours and 10 days postburn; and changes in gastrocnemius muscle global gene expression were assessed using microarrays. RESULTS: The 35 immuno-inflammatory genes are differentially expressed in both models, with an additional 20 and 30 genes specific to distant and local burn, respectively. These genes encode chemokines, oxidative-stress, complement, and defense/immune functions. CONCLUSION: Burn mediates a common systemic response, independent of the site or extent of injury, and also specific responses to local versus distant trauma. A transcriptome profile of genes that initiate and sustain systemic inflammation has been identified.

Animals↗

PubMed1997

Cardiopulmonary bypass alters vasomotor regulation of the skeletal muscle microcirculation.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with alterations in the regulation of organ perfusion and vascular permeability. The purpose of this study was to examine the effects of hypothermic CPB on the regulation of the skeletal muscle microcirculation and the modulating influence of the priming solution. METHODS: Sheep were placed on hypothermic CPB with a prime of either Pentastarch hydroxylethyl starch (HS) solution (n = 7), a solution in which HS is conjugated with deferoxamine (n = 7), or Ringer's lactate solution (n = 7). Sheep were placed on hypothermic CPB (27 degrees C) for 90 minutes while the heart was protected with cold blood cardioplegia. Sheep were then separated from CPB and perfused for an additional 3 hours off CPB. Hemodynamics and total water content were measured. RESULTS: In vitro relaxation responses of gracilis muscle arterioles (70 to 180 microns) to the endothelium-dependent agent acetylcholine, the endothelium-independent cyclic GMP-mediated vasodilator sodium nitroprusside, the beta-adrenergic agonist isoproterenol, and the adenylate cyclase activator forskolin were studied. No statistically significant hemodynamic differences were observed between groups. However, weight gain was significantly less when the priming solution was HS or HS-deferoxamine compared to when Ringer's lactate was used. Skeletal muscle arteriolar relaxations to the endothelium-dependent vasodilator acetylcholine and the beta-adrenergic agonist isoproterenol were impaired after CPB in the HS and Ringer's lactate groups. Acetylcholine response was preserved in the HS-deferoxamine group, whereas the response to isoproterenol remained impaired. The responses to sodium nitroprusside and forskolin were similar in all groups. CONCLUSIONS: Skeletal muscle microvascular endothelium-dependent relaxation and beta-adrenergic relaxation are reduced after CPB using either a crystalloid or HS prime. Skeletal muscle microvascular endothelial dysfunction may be attributable to oxygen-derived free radical-mediated injury, whereas altered beta-adrenergic regulation is attributable to mechanisms other than the generation of oxygen-derived free radicals during CPB.

Acetylcholine↗

PubMed2004

Double-blinded, placebo-controlled trial of midodrine for exercise performance enhancement in tetraplegia: a pilot study.

BACKGROUND/OBJECTIVE: Spinal cord injury (SCI) impairs cardiovascular autonomic responses to exercise and, depending on the level of injury, may result in hypotension and pathologic fatigue with exertion. Other clinical populations with sympathetic regulatory dysfunction, but without skeletal muscle paralysis, exhibit similar signs and symptoms. Their ability to engage in physical activity improves with elevation of blood pressure through pharmacologic treatment: Midodrine, an oral alpha-sympathomimetic agent, has been shown to be safe and efficacious for this purpose. Use of this medication in individuals with SCI merits investigation. METHODS: Double-blind, placebo-controlled, randomized, crossover, within-subjects protocol. Four participants with chronic, motor-complete injuries from C6 to C8 underwent 4 peak exercise tests (PXT) using a wheelchair ergometer, following administration of midodrine, 5 mg, 10 mg, and placebo, in random order. Heart rate, blood pressure, oxygen consumption (VO2), and perceived exertion were measured. RESULTS: Treatment with midodrine, 10 mg, was associated with elevated systolic blood pressure during peak exercise in 3 participants. Two participants showed a concurrent decrease in perceived exertion and increase in VO2. No adverse effects of midodrine were evident. CONCLUSION: Midodrine enhances exercise performance in some individuals with SCI, similar to other clinical populations with cardiovascular autonomic dysfunction.

Adrenergic alpha-Agonists↗

PubMed2004

Allopurinol mitigates muscle contractile dysfunction caused by hindlimb unloading in mice.

INTRODUCTION: Prolonged mechanical unloading induces skeletal muscle weakness, a major problem following extended bed rest or spaceflight. Antioxidants are reported to partially inhibit the weakness caused by limb immobilization. The current study tested allopurinol, a xanthine oxidase inhibitor with antioxidant properties, for its capacity to protect the function of unloaded antigravity muscles. METHODS: Adult mice conditioned by 12 d of hindlimb suspension, with or without allopurinol 50 mg x kg(-1) x d(-1), were compared with freely ambulating controls. Animals were anesthetized and soleus muscles were isolated for ex vivo analyses. RESULTS: Relative to control muscles, unloading decreased soleus weight (-44%; p < 0.05) and cross-sectional area (-38%; p < 0.05), increased cytosolic oxidant activity (-46%; p < 0.01), decreased absolute tetanic force (e.g., -64% at 250 Hz; p < 0.001 ) and force/area (-35%; p < 0.01), and increased passive compliance of the unstimulated muscle (p < 0.05). Allopurinol administration blunted the effects of unloading, partially inhibiting losses of absolute force (p < 0.05) and force/area (p < 0.05) without affecting muscle atrophy. The drug also blunted compliance changes in the passive muscle (p < 0.05). DISCUSSION: Allopurinol does not inhibit atrophy of skeletal muscle caused by prolonged unloading. However, allopurinol does lessen the contractile dysfunction caused by unloading, an action that may have potential benefit for astronauts and bedridden individuals.

Allopurinol↗

PubMed1998

Systolic ventricular dysfunction causes selective diaphragm atrophy in rats.

In order to examine the relative impairment of the diaphragm and other skeletal muscles in systolic ventricular dysfunction (VD), their structure and function were compared between rats with VD induced by left coronary artery ligation (n = 17) and sham-operated rats (Co, n = 10). In addition, in an attempt to unravel the mechanism of the observed impairment, we examined alterations in insulin-like growth factor-I (IGF-I) serum levels and IGF-I expression in the liver, diaphragm, and gastrocnemius. In a second series of rats (VD, n = 5 and Co, n = 5) hemodynamic measurements were performed. All measurements were performed 3 mo after the operation. Infarct size averaged 32 +/- 10 and 44 +/- 20% in the two series, respectively (NS). Hemodynamic measurements revealed a decrease in left ventricular peak systolic pressure of 19% (p < 0. 05). Significant diaphragm atrophy (weight: 622 +/- 52 mg in VD versus 750 +/- 54 mg in Co, p < 0.0005), without alterations in diaphragm contractile properties was present in VD animals. For all animals combined, the reduction in diaphragm weight was related to infarct size (r = -0.74, p < 0.001). No alterations were observed in the other inspiratory and peripheral muscles. ATPase staining of the diaphragm showed atrophy of type I and type IIx/b fibers, their cross-sectional area (CSA) being reduced by 13 and 16%, respectively (p < 0.05). There were no signs of myopathic alterations. IGF-I expression was increased by 55% in the diaphragm of rats with VD (p < 0.05). IGF-I expression in the liver and gastrocnemius and serum IGF-I levels were unaltered. These data suggest the presence of compensatory mechanisms aimed at minimizing diaphragmatic fiber atrophy. We conclude that systolic VD caused: (1) selective diaphragm atrophy, which was related to infarct size; (2) a decrease in diaphragm type I and IIx/b CSA not associated with myopathic changes; (3) an increase in the IGF-I mRNA content of the diaphragm. The selective diaphragm involvement in the present study may be related to the moderate degree of ventricular dysfunction induced.

Adenosine Triphosphatases↗

PubMed1998

Optimizing exercise training for subgroups of patients with chronic heart failure.

Patients with heart failure and severe left ventricular dysfunction are limited in their ability to tolerate exercise. Recent research has demonstrated that it is not a restricted cardiac output which limits exercise but an abnormality in the performance of a more peripheral component in the pathway of delivery of oxygen to the exercising muscles. Deficiencies in peripheral blood flow and skeletal muscle function and an exaggerated sensitivity to exercise-derived metabolic signals lead to early and profound exercise-induced fatigue and dyspnoea, the mechanisms of which we are only now beginning to understand. These findings raise the possibility of improving exercise tolerance by peripherally acting therapies such as exercise training of skeletal muscles in left ventricular dysfunction and chronic heart failure. Training has been shown to improve exercise tolerance at least as much as angiotensin-converting enzyme inhibitors in these syndromes; additionally, training improves ventilatory control, skeletal muscle metabolism and autonomic nervous system activity. As yet, the most appropriate forms of exercise therapy are not known nor is how best to choose the most suitable patients for this form of treatment. There is evidence that patients with at least moderate, and possibly severe but stable, heart failure can benefit from exercise rehabilitation, provided it is tailored to the capacity of the patient and certain safety considerations are taken into account.

Exercise Therapy↗

PubMed2005

Molecular clues into the pathogenesis of statin-mediated muscle toxicity.

The pathophysiology of statin-mediated muscle dysfunction is poorly defined. Reductions in skeletal muscle membrane cholesterol were initially thought to account for the range of myopathic reactions, e.g., myalgia, elevated serum creatine kinase, or rhabdomyolysis. This assumption however, does not consider a potential role of the isoprenoids in the pathophysiology of statin myopathy. The observation that derangements in mevalonate kinase (MK), but not more distal enzymes of cholesterologenesis, are associated with a skeletal myopathy suggests a critical role for the isoprenoids in the maintenance of muscle. Statins also deplete the isoprenoid pool by inhibiting the enzyme, beta-hydroxy-beta-methylglutaryl coenzyme A reductase, which is upstream of MK. Identifying candidate proteins that are both dependent on isoprenoid-mediated modification and associated with muscle disease, when genetically mutated, offers further insight into potential mechanisms of statin myopathy. For example, lamin A/C, selenoprotein N, alpha- and beta-dystroglycan, and cytoskeletal G-proteins all require isoprenylation for optimal function. Understanding the pleiotropic effects of protein prenylation, and the potential consequences of a generalized insufficiency of this form of protein modification, may help clarify the molecular pathogenesis of statin myopathy.

Animals↗

PubMed2026

Treatment updates in myotonic disorders.

Myotonia is delayed muscle relaxation after forceful contraction. It is due to hyperexcitability of the skeletal muscle membrane. It can arise from primary skeletal muscle ion channel dysfunction, involving chloride or sodium channels, but is also a prominent clinical feature in myotonic dystrophies where altered RNA splicing leads to secondary ion channel dysregulation amongst other systemic manifestations. Clinically, myotonia can range from delayed eye opening to a disabling symptom causing impaired mobility, functional difficulty and sometimes pain. It can also be a "hidden disability" with many patients feeling socially embarrassed by "looking healthy", yet being unable to do everyday physical tasks or to do them as effortlessly as their peers. It is a symptom that almost always indicates a genetic diagnosis, although it can occur in acquired conditions, including metabolic and drug-induced causes. To experience myotonia without knowing what it is can be baffling. To receive a genetic diagnosis associated with it can be life changing. Although there is no cure, there are many effective and available symptomatic treatments for myotonia and currently we are in an exciting era of clinical trials for new molecular disease-modifying therapies for myotonic dystrophy type 1. In this review, we consider recent developments in the treatment of myotonic disorders and how they may change clinical practice.

Humans↗

PubMed1995

Benefits of aortic and pulmonary counterpulsation using dynamic latissimus dorsi myoplasty.

BACKGROUND: Intraaortic and pulmonary artery counterpulsation are useful techniques to support circulation during either left or right ventricular dysfunction. Electrically stimulated skeletal muscles wrapped around the aorta, used as means of cardiac failure treatment, have proved to be an effective method of handling experimental left ventricular failure. In this article we report an induced cardiac failure model in acute open chest dogs and describe the hemodynamic improvement of simultaneous aortic and pulmonary artery counterpulsation. METHODS: This was achieved with a bilateral latissimus dorsi muscle flap, stimulated with a software written in C++ for Windows. Dynamic aortomyoplasty was performed using the left latissimus dorsi muscle flap around the descending aorta, and dynamic pulmonaromyoplasty was achieved wrapping the pulmonary trunk with the right latissimus dorsi muscle flap. In all animals blood pressures and cardiac output were measured after cardiac failure induced by a high-dose of propranolol hydrochloride (3 mg/kg intravenously) before and after latissimus dorsi muscle flap stimulation. RESULTS: Aortopulmonary counterpulsation resulted in a significant increase in mean aortic pressure, mean pulmonary pressure, and cardiac output. In addition, a significant decrease was observed in end-diastolic left ventricular pressure, systemic vascular resistance, and pulmonary vascular resistance. Subendocardial viability index (diastolic pressure-time index/systolic tension-time index) in aortomyoplasty and tension time index in pulmonaromyoplasty showed significant improvement when cardiac assistance was performed by electrical stimulation of both muscles (p = 0.037 and p = 0.001, respectively). CONCLUSIONS: Treatment of experimentally induced cardiac failure using aortopulmonary counterpulsation allows effective hemodynamic improvement in open-chest dogs.

Animals↗

PubMed1999

Treatment of potassium balance disorders.

Potassium is the predominant intracellular cation and is critical for the maintenance of resting cellular membrane potential. Abnormalities of potassium balance can manifest as skeletal and cardiac muscle dysfunction. Abnormalities of potassium concentration in plasma can result from changes in external potassium balance (intake vs. excretion) or internal balance (intracellular to extracellular). Hyperkalemia can result from renal failure, uroperitoneum, or severe dehydration and acidosis in calves with diarrhea. Hypokalemia occurs due to reduced forage intake, when increased gastrointestinal losses occur as with diarrhea, due to increased renal losses as with metabolic alkalosis or exogenous corticosteroid administration which promote kaliuresis, or with redistribution of potassium into the intracellular compartment with alkalosis or in association with insulin-mediated glucose uptake. Aggressive intravenous and oral therapy are often necessary to correct potassium balance disorders, in addition to therapy aimed at correcting any underlying disorder contributing to the potassium imbalance.

Animals↗