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At least 721 records · Page 40Linked to original sources
PubMed1998

Role of nitric oxide on diaphragmatic contractile failure in Escherichia coli endotoxemic rats.

Contractile dysfunction of the respiratory muscles plays an important role in the genesis of respiratory failure during sepsis. Nitric oxide (NO), a free radical that is cytotoxic and negatively inotropic in the heart and skeletal muscle, is produced in large amounts during sepsis by a NO synthase inducible (iNOS) by LPS and/or cytokines. The aim of this study was to investigate whether iNOS was induced in the diaphragm of Escherichia coli endotoxemic rats and whether inhibition of iNOS induction or of NOS synthesis attenuated diaphragmatic contractile dysfunction. Rats were inoculated intravenously (IV) with 10 mg/kg of E. coli endotoxin (LPS animals) or saline (C animals). Six hours after LPS inoculation animals showed a significant increase in diaphragmatic NOS activity (L-citrulline production, P < 0.005). Inducible NOS protein was detected by Western-Blot in the diaphragms of LPS animals, while it was absent in C animals. LPS animals had a significant decrease in diaphragmatic force (P < 0.0001) measured in vitro. In LPS animals, inhibition of iNOS induction with dexamethasone (4 mg/kg IV 45 min before LPS) or inhibition of NOS activity with N(G)-methyl-L-arginine (8 mg/kg IV 90 min after LPS) prevented LPS-induced diaphragmatic contractile dysfunction. We conclude that increased NOS activity due to iNOS was involved in the genesis of diaphragmatic dysfunction observed in E. coli endotoxemic rats.

Animals↗
PubMed2006

Skeletal muscle mitochondrial functions, mitochondrial DNA copy numbers, and gene transcript profiles in type 2 diabetic and nondiabetic subjects at equal levels of low or high insulin and euglycemia.

We investigated whether previously reported muscle mitochondrial dysfunction and altered gene transcript levels in type 2 diabetes might be secondary to abnormal blood glucose and insulin levels rather than an intrinsic defect of type 2 diabetes. A total of 13 type 2 diabetic and 17 nondiabetic subjects were studied on two separate occasions while maintaining similar insulin and glucose levels in both groups by 7-h infusions of somatostatin, low- or high-dose insulin (0.25 and 1.5 mU/kg of fat-free mass per min, respectively), and glucose. Muscle mitochondrial DNA abundance was not different between type 2 diabetic and nondiabetic subjects at both insulin levels, but the majority of transcripts in muscle that are involved mitochondrial functions were expressed at lower levels in type 2 diabetes at low levels of insulin. However, several gene transcripts that are specifically involved in the electron transport chain were expressed at higher levels in type 2 diabetic patients. After the low-dose insulin infusion, which achieved postabsorptive insulin levels, the muscle mitochondrial ATP production rate (MAPR) was not different between type 2 diabetic and nondiabetic subjects. However, increasing insulin to postprandial levels increased the MAPR in nondiabetic subjects but not in type 2 diabetic patients. The lack of MAPR increment in response to high-dose insulin in type 2 diabetic patients occurred in association with reduced glucose disposal and expression of peroxisome proliferator-activated receptor-gamma coactivator 1alpha, citrate synthase, and cytochrome c oxidase I. In conclusion, the current data supports that muscle mitochondrial dysfunction in type 2 diabetes is not an intrinsic defect, but instead a functional defect related to impaired response to insulin.

Biopsy↗
PubMed2001

Physical training in patients with chronic heart failure enhances the expression of genes encoding antioxidative enzymes.

OBJECTIVES: We sought to determine whether the benefit of training for vasodilation in the skeletal muscle vasculature of patients with chronic heart failure (CHF) is likely to be caused at the molecular level primarily by increased nitric oxide (NO) production or decreased inactivation of NO. BACKGROUND: Physical training reverses endothelium dysfunction in patients with CHF, mediated by increased NO bioactivity. Some animal studies support a mechanism whereby training results in increased vascular NO levels by sustained transcriptional activation of the endothelial NO synthase (eNOS) gene, presumably due to shear stress. The mechanism has not been addressed in patients with CHF. METHODS: The steady state transcript levels for eNOS and two other shear stress regulated genes (angiotensin-converting enzyme [ACE] and prostacyclin synthase [PGI2S]) were measured in samples of skeletal muscle from patients with CHF before and after 12 weeks of training. Transcript levels were measured in the same samples for two genes encoding antioxidant enzymes, copper zinc superoxide dismutase (Cu/Zn SOD) and glutathione peroxidase (GSH-Px). Untrained patients served as controls. RESULTS: As expected, training significantly enhanced peak oxygen uptake in the patients with CHF. Training did not increase steady-state transcript levels for eNOS, ACE or PGI2S. In striking contrast, training increased the expression of the antioxidative enzyme genes by approximately 100%. CONCLUSIONS: Our results do not support a model of benefit from training by increased eNOS expression. However, the data are entirely consistent with the alternative hypothesis, that reduced oxidative stress may account for the increase in vascular NO-mediated vasodilation. Insight into the mechanism may be relevant when considering therapies for exercise-intolerant patients with CHF.

Aged↗
PubMed1998

Peak systolic stress-rate-corrected mean velocity of fiber shortening in preterm and fullterm infants.

The relation of rate-corrected mean velocity of fiber shortening (mVcfc)-end-systolic wall stress (ESS) is a load-independent index of left ventricular contractility, but involves simultaneous M-mode echocardiography, carotid or axillary pulse tracing and blood pressure determination, which may be impractical in younger infants. We examined whether the relation of the peak systolic wall stress (PSS)-mVcfc could be used as a simpler method of assessing left ventricular contractility in preterm and fullterm infants. In 45 preterm and fullterm infants, mVcfc, ESS, and PSS were determined using echocardiography, axillary pulse tracing and blood pressure measurement. Five patients with left ventricular dysfunction or low cardiac output state were also studied. The relation of PSS and ESS was PSS=5.19+1.04 ESS (r=0.98, p<0.01). The slope of mVcfc=1.58-0.012 ESS (r=-0.78, p<0.01) was nearly identical to that of mVcfc=1.60-0.011 PSS (r=-0.75, p<0.01), with no difference in the regression coefficients. The relationship of PSS and ESS in 5 patients was very close and the slope of the regression line was nearly identical to that of 45 infants. The relation of mVcfc PSS correlates well with the relation using ESS and can be used as a simple method of assessing left ventricular contractility.

Blood Pressure↗
PubMed2002

Hereditary neuronal intranuclear inclusion disease with autonomic failure and cerebellar degeneration.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID), a multiple-system degeneration, occurs usually as a sporadic disorder with onset in childhood. The disease has been found in monozygotic twins and in siblings. In 2 previously described families, the disorder has affected 2 generations. OBJECTIVE: To investigate the clinical, anatomical, and electrophysiological characteristics of NIID that affect the central nervous system and the central and peripheral components of the autonomic nervous system in 2 successive generations of a family. DESIGN: Case report. SETTING: Tertiary care hospital. PATIENTS: A 53-year old woman and her sons, aged 28 and 25 years. Symptoms began in childhood in 2 of the 3 cases, and consisted of urinary and fecal incontinence, erectile dysfunction in the men, and recurrent orthostatic hypotension. METHODS: We used results of clinical neurological evaluations; cranial magnetic resonance imaging; skeletal muscle and sphincter electromyography (EMG); peripheral nerve conduction and bulbocavernosus reflex studies; autonomic function tests; brainstem, visual, somatosensory, and motor evoked potentials; auditory and vestibular testing; metabolic and molecular genetic testing; and muscle and rectal biopsy with immunohistochemistry. RESULTS: We found variable degrees of ocular dysmetria in 2 cases, ataxic dysarthria and limb ataxia in 1, and hyperreflexia in 2. Magnetic resonance imaging revealed cerebellar atrophy in all 3 cases and diffuse cerebral cortical atrophy in 1. Results of peripheral nerve conduction studies were normal. Sphincter EMG findings were abnormal in 2 of the 3 cases, and results of autonomic function tests were abnormal in the same 2. The EMG in 1 case revealed a chronic neurogenic pattern in the distal limb muscles. Metabolic and molecular genetic testing revealed no abnormal findings. Results of the muscle biopsy were negative, but results of the rectal biopsy revealed eosinophilic ubiquitinated intranuclear inclusions in neurons. CONCLUSION: Transmission of NIID in 2 generations presenting with autonomic failure and cerebellar ataxia was hereditary.

Adult↗
PubMed1988

Lethal autosomal recessive arthrogryposis multiplex congenita with whistling face and calcifications of the nervous system.

Three children from a sibship of four had congenital contractures, scarce facial expressions, central nervous system dysfunction, and early death. Extensive deposits of calcium compounds were found at postmortem examination of the nervous system and of skeletal muscle. The disorder in these sibs is presumably inherited as an autosomal recessive trait. The metabolic basis for the calcium deposition has yet to be discovered.

Arthrogryposis↗
PubMedDate not supplied

Three-dimensional ultrasound and magnetic resonance imaging of pelvic anatomy: potential for complications from minimally invasive procedures.

OBJECTIVE: Several new minimally invasive therapies have recently been popularized for both malignant and benign prostate disorders, including interstitial implantation of radioactive seeds and high-radiofrequency wires, cryoablation, transurethral thermotherapy, and laser prostatectomy. Complications can be incurred during the various procedures, often as a result of injury to adjacent anatomic structures. Some of the complications are inadvertent, whereas others are inherent in the particular treatment process. We hope to increase awareness and understanding of some of the potential complications. METHODS AND MATERIALS: Magnetic resonance (MR) and three-dimensional transrectal ultrasonography (TRUS) imaging were utilized to illustrate the relevant pelvic anatomy in, respectively, a healthy volunteer and four patients undergoing evaluation for prostate symptoms. In addition, data from the Visible Human dataset (the Visible Human Project is part of the National Library of Medicine 1986 Long-Range Plan) were used. RESULTS: The potential complications relating to urinary sphincter and anal sphincter control, sexual function, pelvic musculature, and pelvic nerve physiology could be explained on the basis of the MR and TRUS findings using cryoablation for illustrative purposes. CONCLUSION: A clear understanding of the relevant anatomy and physiology is essential for the physician to provide patient counseling preoperatively regarding anticipated sequelae and to avoid preventable intraoperative complications related to minimally invasive therapeutic procedures for the prostate.

Adult↗
PubMed2005

Altered reflex cardiovascular control during exercise in heart failure: animal studies.

This brief review summarizes recent studies describing the potential role of the muscle metaboreflex in mediating the altered cardiovascular responses to dynamic exercise in heart failure and the interaction between the muscle metaboreflex and the arterial baroreflex in these responses. In normal dogs, activation of the muscle metaboreflex (via partial reductions in hindlimb blood flow) during submaximal exercise, elicits a powerful pressor response. This increase in arterial pressure is mediated by an increase in cardiac output with little, if any, peripheral vasoconstriction. The metaboreflex pressor response is buffered by the arterial baroreflex via baroreflex-mediated inhibition of metaboreflex-induced peripheral vasoconstriction. In contrast, after induction of heart failure, the mechanisms involved in the muscle metaboreflex are shifted to vasoconstriction with little, if any, increase in cardiac output. The loss of the cardiac output response of the metaboreflex in heart failure probably stems from inability to improve ventricular function. The shift towards vasoconstriction in this setting may be due to depressed ability of the arterial baroreflex to buffer metaboreflex-induced peripheral vasoconstriction. The relative underperfusion of active skeletal muscle in heart failure may tonically activate the metaboreflex and this probably contributes to the enhanced sympatho-excitation seen during exercise in heart failure.

Animals↗
PubMed2005

[Primary Sjogren's syndrome: clinical and serological feature of a single centre].

OBJECTIVE: To describe clinical and serological features of a large series of patients affected by primary Sjogren's syndrome (pSS), assessing the evolution of the disease in a long-term follow-up study. METHODS: Clinical and laboratory data of 250 patients with pSS attending our Unit for a mean follow-up period of 140 months were retrospectively collected and analysed. In all the cases the diagnosis was made according with the recent international criteria. RESULTS: Glandular involvement was almost universally present, typically as the first manifestation of the disease and a slow progression of the salivary and lachrymal dysfunction was seen during the observation period. Extraglandular involvement was mild, quite rare and delayed. The respective percentages for muscle-skeletal disease, urogenital, haematological, skin, pulmonary, gastrointestinal, neurological and renal involvement were 60%, 40%, 24%, 20%, 11%, 7%, 8% and 3%. Only 6 patients developed a lymphoma. The serological pattern of the majority of patients remained constant throughout the follow-up period. CONCLUSIONS: pSS is often a benign condition. Since some patients may develop lymphoid malignancies, clinical follow-up is recommended.

Adult↗
PubMed1997

[Lactic acidosis and hepatic mitochondrial changes during a treatment with zidovudine].

Adverse effects of zidovudine, which mainly result in myopathies and hematological disorders, could be due to multitissular mitochondrial toxicity of the drug. During zidovudine treatment, most cases of lactic acidosis have been attributed to mitochondrial myopathy. We report a case of hepatocellular failure with lactic acidosis in a 33 year-old patient with the human immunodeficiency virus infection and treated with zidovudine for 8 months. Liver biopsy showed massive macrovacuolar steatosis and ultrastructural mitochondrial abnormalities similar to those previously described in the skeletal muscle. This is the second reported case of lactic acidosis and hepatocellular failure which is probably related to hepatic mitochondrial dysfunction caused by zidovudine.

Acidosis, Lactic↗
PubMed2005

Anaphylactic shock: a form of distributive shock without inhibition of oxygen consumption.

BACKGROUND: The pathophysiology of anaphylactic shock during anesthesia is incompletely characterized. It is described as distributive by analogy with septic shock (anaerobic metabolism, high tissue oxygen pressure [Ptio2] values). The Ptio2 profile and its metabolic consequences during anaphylaxis are not known. METHODS: Ovalbumin-sensitized anaphylactic shock rats (n = 11) were compared to nicardipine-induced hypotension rats (n = 12) for systemic hemodynamics, Ptio2, sympathetic nervous system activation, skeletal muscle blood flow, and interstitial lactate and pyruvate concentrations using combined microdialysis and polarographic Clark-type oxygen probes. RESULTS: In both groups, the time course and the magnitude of arterial hypotension were similar. The ovalbumin group but not the nicardipine group displayed decreased skeletal muscle blood flow (from 45 +/- 6.2 ml x 100 g(-1) x min(-1) to 24.3 +/- 5 ml x 100 g(-1) x min(-1); P < 0.0001) and Ptio2 values (from 42 +/- 5 to 5 +/- 2; P < 0.0001). The ovalbumin group had more intense sympathetic nervous system activation with higher plasma epinephrine and interstitial norepinephrine concentrations. For the ovalbumin group, there was skeletal muscle anaerobic metabolism (lactate concentration increased from 0.446 +/- 0.105 to 1.741 +/- 0.459 mm; P < 0.05) and substrate depletion (pyruvate concentration decreased from 0.034 +/- 0.01 mm to 0.006 +/- 0.002 mm; P < 0.05) leading to increased interstitial lactate/pyruvate ratios (from 17 +/- 6 to 311 +/- 115; P < 0.05). CONCLUSIONS: This profile suggests decreased skeletal muscle blood flow and oxygen delivery. Persistent energy consumption results in decreased Ptio2 and substrate depletion through anaerobic glycolysis leading to complete failure of cellular energy production. This could explain rapid organ dysfunction and resuscitation difficulties.

Anaphylaxis↗
PubMed2003

[Do syndromes X, cardiac and metabolic, have any similar characteristics?].

Two syndromes are called syndromes X: cardiac (effort anginal pain, positive exercise tolerance test and absence of angiographically documented critical stenosis in coronary arteries) and metabolic (according to WHO definition: impaired glucose tolerance and insulin resistance and > or = 2 risk factors from the following list: hypertension, dyslipidaemia, visceral obesity and microalbuminuria). Hyperinsulinaemia and endothelial dysfunction are present in both syndromes. The contribution of endothelial nitric oxide synthase gene mutations to the etiology of these syndromes is also studied. Several mechanisms may be involved in the development of endothelial dysfunction, such as reduced synthesis and release of nitric oxide (NO), enhanced inactivation of NO after its release from endothelial cells or enhanced synthesis of vasoconstricting agents. It has been demonstrated that insulin exerts a direct hypertrophic effect on the vascular endothelium and the smooth muscle cells. The hemodynamic properties of insulin have also been discussed. Some findings suggest that in the skeletal muscle circulation, insulin stimulates both endothelin-1 (ET-1) and nitric oxide activity and an imbalance between the release of these two substances may be involved in the pathophysiology of endothelial dysfunction.

Albuminuria↗
PubMed1999

Oxidants and skeletal muscle function: physiologic and pathophysiologic implications.

Previous studies have demonstrated that skeletal muscles generate considerable reactive oxygen during intense muscle contraction. However, the significance of this phenomenon and whether it represents normal physiology or pathology are poorly understood. Treatment with exogenous antioxidants suggests that normal redox tone during contraction is influencing ongoing contractile function, both at rest and during intense exercise. This could represent the influence of redox-sensitive proteins responsible for excitation-contraction coupling or redox-sensitive metabolic enzymes. Some conditions associated with intense exercise, such as local tissue hypoxia or elevated tissue temperatures, could also contribute to reactive oxygen production. Evidence that muscle conditioning results in upregulation of antioxidant defenses also suggests a close relationship between reactive oxygen and contractile activity. Therefore, there appears to be a significant role for reactive oxygen in normal muscle physiology. However, a number of conditions may lead to an imbalance of oxidant production and antioxidant defense, and these, presumably, do create conditions of oxidant stress. Ischemia-reperfusion, severe hypoxia, severe heat stress, septic shock, and stretch-induced injury may all lead to oxidant-mediated injury to myocytes, resulting in mechanical dysfunction.

Animals↗
PubMed2006

Emerin-lacking mice show minimal motor and cardiac dysfunctions with nuclear-associated vacuoles.

Emery-Dreifuss muscular dystrophy is an inherited muscular disorder clinically characterized by slowly progressive weakness affecting humero-peroneal muscles, early joint contractures, and cardiomyopathy with conduction block. The X-linked recessive form is caused by mutation in the EMD gene encoding an integral protein of the inner nuclear membrane, emerin. In this study, mutant mice lacking emerin were produced by insertion of a neomycin resistance gene into exon 6 of the coding gene. Tissues taken from mutant mice lacked emerin. The mutant mice displayed a normal growth rate indistinguishable from their littermates and were fertile. No marked muscle weakness or joint abnormalities were observed; however, rotarod test revealed altered motor coordination. Electrocardiography showed mild prolongation of atrioventricular conduction time in emerin-lacking male mice older than 40 weeks of age. Electron microscopic analysis of skeletal and cardiac muscles from emerin-lacking mice revealed small vacuoles, which mostly bordered the myonuclei. Our results suggest that emerin deficiency causes minimal motor and cardiac dysfunctions in mice with a structural fragility of myonuclei.

Animals↗
PubMed1981

Influence of early phases of paralysis on microcirculation of rat skeletal muscle.

By combining tissue pO2 measurements with morphological visualization and counting of perfused capillaries, early microvascular changes were investigated in paralysis of skeletal muscle of the rat. The models included experimental allergic encephalomyelitis (EAE), experimental allergic neuritis (EAN), 6-aminonicotinamide intoxication, and peripheral denervation. The results showed that in all models tissue oxygenation was either normal or elevated. In most cases this was accompanied by a reduced perfusion of the capillary bed, supporting the hypothesis of a dysfunction in oxidative metabolism. The effects of paralysis on capillary perfusion were more marked in red than in white muscles, except in spastic paresis. Flaccid paralysis had more deleterious effects on muscle microcirculation than spastic paralysis. Our data suggest that: (1) microvascular changes occur very early after the onset of paralysis and (2) later developing changes in the skeletal muscle such as atrophy cannot be ascribed to a lack of oxygen supply but rather, at least in part, to a dysfunction in oxidative metabolism.

6-Aminonicotinamide↗
PubMed1993

Effect of balloon mitral valvuloplasty on exercise capacity, ventilation and skeletal muscle oxygenation.

OBJECTIVES: The short- and long-term effects of valvuloplasty on exercise capacity, ventilation and skeletal muscle oxygenation were investigated to determine whether a dissociation between hemodynamic improvement and exercise capacity occurs in patients with mitral stenosis. BACKGROUND: Percutaneous balloon mitral valvuloplasty in patients with mitral stenosis results in immediate hemodynamic improvement at rest and with exercise. Improved exercise capacity has been described at 3 months after valvuloplasty. In patients with left ventricular dysfunction, acute therapeutic interventions that produce hemodynamic benefit do not immediately improve exercise capacity. METHODS: Maximal bicycle exercise with measurement of respiratory gases was performed in 11 patients with mitral stenosis before and at 48 h and 3 months after successful percutaneous balloon mitral valvuloplasty. Respiratory and leg skeletal muscle oxygenation were assessed by monitoring changes in light absorption of the serratus anterior and vastus lateralis muscles using near-infrared spectroscopy and were expressed as percent deoxygenation. RESULTS: Mitral valvuloplasty significantly increased mean mitral valve area from 1.0 +/- 0.2 to 1.7 +/- 0.3 cm2 (p < 0.05). Immediately after valvuloplasty, peak exercise oxygen consumption (VO2), VO2 at the anaerobic threshold, ventilation, peak respiratory and leg muscle deoxygenation all remained unchanged. At submaximal work loads, respiratory muscle deoxygenation was attenuated (25 W: before 12 +/- 4%; 48 h 4 +/- 3%; 50 W: before 10 +/- 5%; 48 h 5 +/- 4%; both p < 0.05). At 3 months, significant improvement in peak VO2 (before 10.9 +/- 5%; 3 months 14.6 +/- 6.2 ml/kg per min; p < 0.05) and VO2 at the anaerobic threshold (before 7.1 +/- 2.4; 3 months 8.4 +/- 2.3; p < 0.05) were observed, whereas ventilation remained unchanged. No further improvement was seen in respiratory muscle deoxygenation. Vastus lateralis deoxygenation at submaximal work loads tended to be decreased. CONCLUSIONS: Long-term changes in skeletal muscle and the lungs preclude immediate enhancement of exercise performance after balloon mitral valvuloplasty. Immediate symptomatic improvement probably results from an immediate decrease in the work of breathing. Long-term symptomatic improvement results from changes that occur in the peripheral skeletal musculature as well as from the reduced work of breathing.

Adult↗
PubMed2000

Morphological correlates of mitochondrial dysfunction in children.

Morphological studies have traditionally played a major role in the study of adults with suspected mitochondrial diseases. Here we review their role in the investigation of paediatric patients. The morphological changes may be macroscopic, such as developmental abnormalities of the brain in pyruvate dehydrogenase deficiency, including ectopic inferior olives and the absence of corpus callosum and pyramids. Other changes are histological, such as rarefaction of the neuropil and endothelial prominence in Leigh syndrome, and spongiosis with neuronal loss and gliosis in Alpers disease. The ragged-red fibres typical of mitochondrial disease in adults are only rarely seen in skeletal muscle biopsies from children. On the other hand, dramatic ultrastructural changes involving the mitochondria may be seen in many organs, including the liver, heart and intestine. In Alpers and lethal infantile mitochondrial diseases, the hepatocytes show marked accumulation of small droplets of lipid alternating with densely packed mitochondria with pale matrix and loss of granules. These changes are associated with a marked decrease in respiratory chain enzyme activity in the liver, often without similar decrease in the skeletal muscle or fibroblasts. Enlarged mitochondria with concentric cristae are prominent in the cardiac myocytes in Barth syndrome. For the assessment of children with a suspected disorder of mitochondrial dysfunction, detailed morphological studies of the brain (at autopsy) and of biopsies (especially of the liver), including ultrastructural assessment of the mitochondria, can be a very useful preliminary investigation. The findings should then be correlated with the clinical features and used as a guide for further biochemical and molecular studies, preferably on multiple tissues.

Adolescent↗