PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Skeletal muscle dysfunction”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37Linked to original sources
PubMed2004

Insulin resistance does not diminish eNOS expression, phosphorylation, or binding to HSP-90.

Previously, using an animal model of syndrome X, the obese Zucker rat (OZR), we documented impaired endothelium-dependent vasodilation. The aim of this study was to determine whether reduced expression or altered posttranslational regulation of endothelial nitric oxide synthase (eNOS) underlies the vascular dysfunction in OZR rats. There was no significant difference in the relative abundance of eNOS in hearts, aortas, or skeletal muscle between lean Zucker rats (LZR) and OZR regardless of age. There was no difference in eNOS mRNA levels, as determined by real-time PCR, between LZR and OZR. The inability of insulin resistance to modulate eNOS expression was also documented in two additional in vivo models, the ob/ob mouse and the fructose-fed rat, and in vitro via adenoviral expression of protein tyrosine phosphatase 1B in endothelial cells. We next investigated whether changes in the acute posttranslational regulation of eNOS occurs with insulin resistance. Phosphorylation of eNOS at S632 (human S633) and T494 was not different between LZR and OZR; however, phosphorylation of S1176 was significantly enhanced in OZR. Phosphorylation of S1176 was not different in the ob/ob mouse or in fructose-fed rats. The association of heat shock protein 90 with eNOS, a key regulatory step controlling nitric oxide and aberrant O2- production, was not different between OZR and LZR. Taken together, these results suggest that changes in eNOS expression or posttranslation regulation do not underlie the vascular dysfunction seen with insulin resistance and that other mechanisms, such as altered localization, reduced availability of cofactors, substrates, and the elevated production of O2-, may be responsible.

Animals↗
PubMed1997

Effect of increased maxillo-mandibular relationship on isometric strength in TMD patients with loss of vertical dimension of occlusion.

The effect on isometric strength of the shoulders and limbs while biting in habitual occlusion, on a bite-elevating appliance and on a placebo appliance was analyzed. Twenty female volunteer patients, presenting with temporomandibular pain dysfunction syndrome and obvious loss of vertical dimension, served as subjects. All were weaker to the manual application of the isometric Deltoid Press (IDP) when biting, as opposed to maintaining the mandible in an unsupported rest position. Two intraoral appliances were fabricated for each subject: a bite-elevating appliance (BEA) set by a functional criterion of peak strength to the IDP and a placebo appliance which did not interfere with occlusion but was "set" with a mock IDP procedure. Testing was carried out by the Neuromuscular Research Testing Laboratory of the Neurology Department of Tufts New England Medical Center. Testing was independent of the dentist who fabricated and set the appliances. A standard neuromuscular test with the Maximal Voluntary Isometric Contraction apparatus was used to assess strength of right and left shoulder, elbow and knee flexion and extension as is routinely performed with all neuromuscular disease patients. Twelve strength tests were carried out for each of three conditions: 1. Baseline-biting in habitual occlusion; 2. Elevated-biting on the BEA; and 3. Placebo-biting with the placebo appliance inserted. The order of conditions 2 and 3 was counterbalanced without knowledge of the subjects. Twelve repeated measures ANOVAs (each subject as their own control) were conducted for each of the 12 strength measures. All F-tests indicated a significant main effect for treatment differences (p < 0.0001). Mean strength biting on the BEA was consistantly greater (p < 0.001) than Baseline or Placebo strength. Baseline and Placebo condition were equivalent. These findings confirmed previous observations at this TMD Center: individuals with loss of vertical dimension of occlusion respond to a bite raising appliance by increased isometric-strength.

Analysis of Variance↗
PubMed1995

Mechanical dysfunction in the border zone of an ovine model of left ventricular aneurysm.

BACKGROUND: The pathophysiology of regional mechanical dysfunction in the border zone (BZ) region of left ventricular aneurysm was studied in an ovine model using magnetic resonance imaging tissue-tagging and regional deformation analysis. METHODS: Transmural infarcts were created in adult Dorsett sheep (n = 8) by ligation of the distal homonymous coronary artery and were allowed to mature into left ventricular aneurysms for 8 to 12 weeks. Animals were imaged subsequently using double oblique magnetic resonance imaging with radiofrequency tissue tagging. Short axis slices were selected for analysis that included predominantly the septal component of the aneurysm as well as adjacent BZ regions in the anterior and posterior ventricular walls. Dark grid patterns of magnetic presaturations were placed on the myocardium and tracked as they deformed during the diastolic, isovolumic systolic, and systolic ejection phases of the cardiac cycle. Regional ventricular wall strains were calculated in BZ regions and regions remote from the aneurysm and compared with strains measured in corresponding regions from normal control sheep (n = 6). RESULTS: Diastolic midwall circumferential strains (fiber extensions) were relatively preserved, but abnormal circumferential lengthening strains were observed in the BZ regions during isovolumic systole. Peak circumferential strains ranged from 0.04 to 0.07 in the BZ regions but averaged -0.05 in the normal hearts (p = 0.002 for the anterior BZ and p = 0.001 for the posterior BZ). Midwall end-systolic fiber strains were depressed in the anterior BZ (-0.03 to -0.09 for the BZ versus -0.11 for the normal heart, p < 0.0001) but not in the posterior BZ (p = 0.19). CONCLUSIONS: Our data support the theory that the stretching of BZ fibers during isovolumic systole contributed to a reduction in fiber shortening during systolic ejection and thus reduced the overall contribution of these fibers to forward ventricular output.

Animals↗
PubMed2000

Tubular aggregates in the skeletal muscle of the senescence-accelerated mouse; SAM.

We investigated the skeletal muscles of nine strains of senescence accelerated mouse (SAM), DDD, AKR/J, C57BL/6J, A/J and BALB/c mice. We found that male SAMP8, SAMP7, C57BL/6J, A/J and BALB/c mice expressed tubular aggregates (TAs) in their skeletal muscle. Among these strains, the SAMP8 strain, which exhibits a short life span and various age-associated neurodegenerative disorders plus mitochondrial dysfunction, showed TAs more markedly than the others. Thus, we compared SAMP8 mice against SAMR1 mice, an accelerated senescence-resistant strain. Light- and electron micrographs showed that male SAMP8 mice exhibited an age-dependent aggravation of TA accumulation. There were no significant differences in the serum lactate/pyruvate levels between the SAMP8 and SAMR1 mice. However, the serum creatine kinase (CK) levels of the 3 and 6-month-old SAMP8 mice were higher than that of the corresponding SAMR1 mice. Considering the serum CK levels and the mitochondrial dysfunction of SAMP8 mice, we conclude that the TAs may be involved in the homeostasis of energy metabolism that is not appropriately regulated in the SAMP8 mouse mitochondrion.

Aging↗
PubMed2005

Peripheral nerve and skeletal muscle involvement in CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by degeneration of vascular smooth muscle cells (VSMC) of nearly all tissues studied so far. The clinical phenotype of CADASIL shows great variability. The disease is caused by mutations of the Notch3 gene encoding the transmembrane receptor Notch3, which is expressed predominantly in VSMC. In some patients, neuromuscular symptoms have been described. To investigate the fine structural features of peripheral nerve and muscle biopsy specimens in more cases and greater detail, seven electron microscopically confirmed CADASIL patients showing a variable amount of granular osmiophilic material on the surface of VSMC were included in this study. Pathogenic mutations within the cluster region (exon 3 and 4) of the Notch3 gene were identified in six cases. Degeneration and regeneration of nerve fibers in the sural nerves, studied in four cases, was present, although moderate, in all nerve biopsy specimens, whereas an intramuscular nerve fascicle showed more severe changes. Enlarged mitochondria with needle-like calcium precipitates were repeatedly seen. In muscle biopsy specimens, some degree of neurogenic atrophy was apparent in addition to myopathic changes, including occasional ragged red fibers with abnormally large mitochondria, focal tubular aggregates, abnormal terminal cisternae, and myofibrillary abnormalities. Automated sequence analysis of the whole mitochondrial DNA performed in one patient revealed several nucleotide polymorphisms, which were not considered pathogenic. The findings suggest that in CADASIL degeneration of small blood vessels is initiated by defects of the surface membrane of VSMC. Dysfunction of these blood vessels may cause low-grade chronic ischemia with secondary hypoxidosis and a large variety of structural changes noted in skeletal muscle and peripheral nerves, although a primary influence of the underlying genetic defect can not be excluded.

CADASIL↗
PubMed2001

Development of lipophilic cations as therapies for disorders due to mitochondrial dysfunction.

Mitochondrial dysfunction causes or exacerbates a number of diseases. These include genetic disorders such as Friedreich's ataxia where the primary lesion is a defect in a nuclear gene and those diseases caused by mutations to mitochondrial DNA. Mitochondrial damage also contributes to neurodegenerative diseases, diabetes and ischaemia-reperfusion injury. Drug therapies to prevent or alleviate mitochondrial dysfunction use redox active compounds, anti-oxidants or mitochondrial co-factors, however, their effectiveness is limited. A promising approach to increase the selectivity and potency of these compounds is to modify them so that they concentrate within mitochondria. This can be done by incorporating a lipophilic cation which causes the molecules to concentrate several hundred-fold in mitochondria, driven by the membrane potential across the inner membrane. As lipophilic cations cross biological membranes easily, they can be delivered to mitochondria of the heart, brain and skeletal muscle, the organs most affected by mitochondrial damage. Mitochondria-targeted lipophilic cations may lead to improved therapies for diseases involving mitochondrial dysfunction.

Animals↗
PubMed2002

Vascular function, insulin resistance and fatty acids.

Over the past 10 years it has become clear that intact vascular function, especially at the level of the endothelium, is paramount in the prevention or delay of cardiovascular disease. It has also become clear that insulin itself, in addition to its metabolic actions, directly effects vascular endothelium and smooth muscle. Insulin, at normal physiologic concentrations, causes changes in skeletal muscle blood flow in healthy, insulin-sensitive subjects. Insulin's effect on the endothelium is mediated through its own receptor and insulin signalling pathways, resulting in the increased release of nitric oxide. Insulin's vascular actions are impaired in insulin-resistant conditions such as obesity, Type II (non-insulin-dependent) diabetes mellitus and hypertension, which could contribute to the excessive rates of cardiovascular disease in these groups. Insulin-resistant states of obesity and Type II diabetes show a multitude of metabolic abnormalities that could cause vascular dysfunction. Non-esterified fatty acid levels increase long before hyperglycaemia becomes present. Raised non-esterified fatty acids impair insulin's effect on glucose uptake in skeletal muscle and the vascular endothelium and thus could have detrimental effects on the vasculature, leading to premature cardiovascular disease.

Animals↗
PubMed2000

Adrenergic reactivity of visceral veins in hypoxia and hypothermia.

Adrenoreactivity of veins in skeletal muscle to norepinephrine decreased, while reactivity of intestinal veins remained virtually unchanged during combined exposure to hypoxia and hypothermia. In skeletal muscles cooling enhanced the direct effect of hypoxia on vascular smooth muscle cells, while in the intestine hypothermia prevented hypoxia-induced endothelial dysfunction, as it did under normothermic conditions. The results of experiments on the intestine indicated possible protective effect of hypothermia with respect to hypoxia-induced damage, and experimental findings on muscles showed potentiation of the direct effect of oxygen deficiency on venous smooth muscles.

Adrenergic alpha-Agonists↗
PubMed2004

Tissue energetics as measured by nuclear magnetic resonance spectroscopy during hemorrhagic shock.

The defect in energy production in an organism during shock states may be related to the impairment of mitochondrial respiration early in shock. The aim of this study was to investigate the timing and degree of cellular energetic changes during hemorrhagic shock in real time. Instrumented, splenectomized swine were randomized to undergo hemorrhagic shock, induced by a 35% blood volume bleed, for 90 min with (n = 10) or without (n = 9) subsequent resuscitation. Resuscitated animals received shed blood in two increments followed by two normal saline boluses (20 mL/kg/bolus). Throughout experimentation, tissue phosphoenergetics of liver and skeletal muscle were monitored using 31P nuclear magnetic resonance (NMR) spectroscopy via NMR coils on the liver and hindlimb. Near-infrared spectroscopy probes were used to measure liver, stomach, and skeletal muscle oxyhemoglobin saturation (StO2). Hemorrhagic shock induced an increase in phosphomonoesters in skeletal muscle (baseline: 7.09%, 90 min: 9.94% (P < 0.05); expressed as percent total phosphorus). This increase resolved in animals receiving resuscitation (n = 10) but remained elevated in those in unresuscitated shock (n = 9). Inorganic phosphate levels increased and betaATP levels decreased significantly in the liver of animals in shock as compared with baseline. StO2 in skeletal muscle, stomach, and liver correlated with whole organism oxygen delivery (r2 = 0.356, 0.368, and 0.432, respectively). We conclude that hemorrhagic shock induces early elevation of phosphomonoesters in skeletal muscle, which correlates with the severity of shock. This implies an early transition to anaerobic glycolysis during hemorrhagic shock, which may be indicative of early mitochondrial dysfunction.

Adenosine Triphosphate↗
PubMed2005

Nitric oxide and skeletal muscle reperfusion injury: current controversies (research review).

Nitric oxide (NO) has been implicated in a large number of disease processes, including ischemia-reperfusion injury following the restoration of oxygenated blood to previously ischemic muscle, which is a recognized significant complication of vascular surgery. Altered metabolism of NO is implicated in the endothelial dysfunction that forms part of the pathophysiology of ischemia-reperfusion injury. However, NO can demonstrate either protective or cytotoxic effects during reperfusion injury. The use of transgenic mice, either NO synthase (NOS) gene knockout animals, or animals that over-express NOS isoforms, along with direct NO measurements and NO donor or inhibitor studies, have all demonstrated a role for NO in skeletal muscle reperfusion injury. There appears to be an initial stimulation of NO production in the first 20-min of ischemia, with a gradual decline through early reperfusion and a second higher peak of NO commencing in the later stages of reperfusion. The absolute levels of NO in the reperfused tissue and its regulation by the subtle interplay with superoxide and the subsequent production of the highly toxic peroxynitrite anion, are important factors in determining whether NO, in the context of ischemia-reperfusion injury, has damaging or protective effects in the body.

Animals↗
PubMed1989

Effect of liver disease on the kinetics of lactate removal after heavy exercise.

Recovery from heavy exercise requires clearance of lactic acid from the blood and body tissues. Although it has long been felt that the liver plays the major role in lactate removal, it has more recently been asserted that skeletal muscle plays the dominant role. We felt it relevant to this controversy to determine whether patients with liver dysfunction have slowed lactate removal following heavy exercise. Eight patients with alcoholic liver disease and 5 normal subjects were studied. Liver function was measured by the 14C-aminopyrine breath test; the results were expressed as the rate of appearance of 14CO2 in the breath two hours after ingestion, as a fraction of the ingested 14C dose (%.h-1). Each participant exercised on a cycle ergometer for 7 min at a work rate which was moderately heavy for that subject (mean peak lactate is 5.3 mmol.L-1). During, and for 45 minutes after exercise, blood was drawn from a hand vein catheter. The time required for blood lactate to decrease halfway toward resting levels (t1/2 LA) was determined. Compared to the normal subjects and historical controls, seven of the patients had distinctly slowed lactate removal. The t1/2 LA was as long as 46 min (as compared to approximately 15 min seen normally). Further, among the patients the 2 h breath excretion of 14C was well correlated with the rate constant of lactate removal (r 0.82, P less than 0.01). Four of the patients with severe liver dysfunction performed a second exercise test in which, instead of resting after heavy exercise, low level exercise was continued. The t1/2 LA of the averaged responses decreased by 29%.2+

Adult↗
PubMed2005

[Facioscapulohumeral muscle dystrophy and heart disease].

Cardiac involvement is well known in a number of skeletomuscular diseases but not in facio-scapulohumeral muscular dystrophy (FSHD). We report on a 71 year old woman with progressive cardiac insufficiency in FSHD, which was also confirmed by molecular analysis in one of the two daughters affected by the disease. Autopsy of the deceased patient showed the typical changes in skeletal muscles including focal inflammatory infiltrates in the diaphragm and, in addition, cardiac muscular involvement. The histological changes resembled those seen in primary cardiomyopathy despite the normal muscle mass volume. Both clinically and morphologically, the cardiac disease was the cause of death in this patient with FSHD.

Aged↗
PubMed2001

Abnormal elevation of resting pressure at the upper esophageal sphincter of Parkinson's disease patients.

We investigated the oral and pharyngeal swallowing function in seven Parkinson's disease (PD) patients, using videomanofluorometry, which is videofluorographic and manometric evaluation conducted simultaneously. Abnormal elevations of resting pressure were found at the upper esophageal sphincter (UES) in three of the seven cases, when they were asked to hold a bolus in the mouth and initiate swallowing. One of these three cases showed an abnormal elevation of resting pressure, intermingled with a normal pressure pattern. Since the UES showed complete relaxation in these three cases, it is inappropriate to suppose that irreversible pathophysiological changes at the level of peripheral nerves had occurred. Our results suggested that altered resting pressure resulted from dysfunction at a more central level, such as a lack of dopaminergic stimulation at the supramedullary level causing skeletal muscle rigidity. Since a tonic abnormality of the UES cannot be measured by only videofluorography, both videofluorographic and manometric evaluation will be necessary to assess the pharyngeal phase of swallowing in PD patients.

Aged↗
PubMed2003

Reduced length-dependent cross-bridge recruitment in skinned fiber preparations of human failing myocardium.

A depressed activity of myosin ATPase has been described in human failing myocardium. Since alterations in cross-bridge kinetics may affect both systolic and diastolic cardiac function, the present study simultaneously investigated Ca(2+)-dependent tension and actomyosin ATPase activity (MYO) in triton X-skinned fiber preparations of human non-failing (donor hearts, n=8) and failing (dilated cardiomyopathy, n=11) left ventricular myocardium at increasing sarcomeric length (1.9 and 2.1 microm, alpha-actinin staining). The MYO/tension ratio was analyzed as a parameter characterizing myofibrillar energetics. At a sarcomere length of 1.9 microm, the Ca(2+) sensitivity of tension was significantly increased in human failing compared to non-failing myocardium. In human non-failing myocardium, maximal Ca(2+)-activated tension [1.9 microm vs. 2.1 microm, 23.7 (1.9) vs. 28.3 (1.9) mN/mm(2)] and the Ca(2+) sensitivity of tension [EC(50)Ca(2+ )(pCa): 5.67 (0.06) vs. 7.07 (0.11)] were increased by increasing sarcomere length. This was accompanied by an enhancement in Ca(2+)-dependent MYO [+72 (11) vs. +101 (9) microM ADP/s] as well as an increase in the Ca(2+)-sensitivity of MYO [EC(50)Ca(2+ )(pCa): 5.84 (0.08) vs. 6.86 (0.08)]. In human failing myocardium, only Ca(2+) sensitivity of tension (but not of MYO) increased. Tension cost was increased in failing vs. non-failing tissue [1.9 microm: 4.18 (0.06) vs. 3.53 (0.06) (mN.s)/(mm(2). microM ADP); 2.1 microm: 4.28 (0.13) vs. 3.52 (0.05) (mN.s)/(mm(2). microM ADP)]. We concluded that, in human failing myocardium, the length-dependent force generation may be blunted due to an already increased Ca(2+) affinity of troponin C as well as an impairment of length-dependent cross-bridge recruitment.

Adult↗
PubMed2000

Insulin resistance in chronic heart failure.

Insulin resistance is an important risk factor for the development of hypertension, atherosclerotic heart disease, left ventricular hypertrophy and dysfunction, and heart failure. It reflects a disturbance of glucose metabolism and potentially worsens metabolic efficiency of both skeletal muscle and cardiac muscle. The exact mechanisms of insulin resistance are not known, but the finding of significant insulin resistance occurring as a consequence of heart failure raises interesting possibilities as to its pathogenesis. While sympathetic nervous system overactivity can acutely reduce insulin sensitivity, it is not clear to what extent, in stable optimally treated chronic heart failure (CHF), the neurohormonal overactivity of this syndrome is the major cause of insulin resistance. Other potential mechanisms include the loss of skeletal muscle bulk, impaired endothelial function and reduced skeletal muscle blood flow, and a possible direct action of proinflammatory cytokines such as tumour necrosis factor-alpha. The consequences of insulin resistance in heart failure are not known, but the severity of the abnormality appears to parallel symptomatics and exercise limitation in this condition, and, in particular, be related to the impairment of gross skeletal muscle function. While specific therapies to correct insulin resistance in CHF have not been evaluated, there are several exciting possibilities on the horizon. Several nonpharmacological therapies have been shown to increase insulin sensitivity in patients with normal left ventricular function, and if these benefits could be duplicated in CHF, they may offer symptomatic benefit. These include weight reduction in the obese, regular exercise training and the use of dietary manipulation such as low-fat, high-fibre diets. Drug treatments with positive effects on insulin sensitivity include some angiotensin converting enzyme-inhibitors as well as newer drug groups, such as the glitazones and moxonidine, a centrally active agent with effects on the recently described imidazoline I-1 receptor that inhibits central sympathetic tone. The role of these agents in reversing the insulin resistance of chronic heart failure warrants further investigation.

Animals↗
PubMed2005

Sarcoplasmic reticulum adenosine triphosphatase overexpression in the L-type Ca2+ channel mouse results in cardiomyopathy and Ca2+ -induced arrhythmogenesis.

BACKGROUND: Overexpression of the L-type voltage-dependent calcium channel alpha(1C)-subunit (L-VDCC OE) in transgenic mice results in adaptive hypertrophy followed by a maladaptive phase associated with a decrease in sarcoplasmic reticulum adenosine triphosphatase (SERCA)2a expression at 8 to 10 months of age. Overexpressing SERCA to manipulate calcium (Ca(2+)) cycling and prevent pathologic phenotypes in some models of heart failure has been proven to be a promising genetic strategy. OBJECTIVE: In this study we investigated whether genetic manipulation that increases Ca(2+) uptake into the sarcoplasmic reticulum by overexpressing SERCA1a (skeletal muscle specific) into the L-VDCC OE background could restore or further deteriorate Ca(2+) cycling, contractile dysfunction, and electrical remodeling in the heart failure phenotype. RESULTS: We found that the survival rate of L-VDCC OE/SERCA1a OE double transgenic mice decreased by 50%. L-VDCC OE/SERCA1a OE mice displayed an accelerated phenotype of severe dilation of both ventricles associated with deteriorated left ventricular function. Voltage clamp experiments revealed enhanced increased inward Ca(2+) current density and decreased the transient outward potassium current. Action potential duration in double transgenic ventricular myocytes was prolonged, and isoproterenol induced early after depolarization. These mice demonstrated a high incidence of spontaneous left ventricular arrhythmia. Expression of the proarrhythmic signaling protein Ca(2+)/calmodulin-dependent kinase II (CaMKII) was increased while connexin43 expression was decreased, defining an important putative mechanism in the electrophysiologic disturbances and mortality. CONCLUSIONS: Despite previous reports of improved cardiac function in heart failure models after SERCA intervention, our results advocate the need to elucidate the involvement of augmented Ca(2+) cycling in arrhythmogenesis.

Action Potentials↗