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Results for “Skeletal muscle dysfunction”

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At least 343 records · Page 19Linked to original sources
PubMed1997

Inhibition of the activity of poly(ADP ribose) synthetase reduces ischemia-reperfusion injury in the heart and skeletal muscle.

Reperfusion of the ischemic myocardium results in the generation of oxygen-derived free radicals, NO, and presumably peroxynitrite. These, in turn, may cause strand breaks in DNA, which activate the nuclear enzyme poly(ADP ribose) synthetase (PARS). This results in a rapid depletion of intracellular NAD and ATP. When this reaction is excessive, there is ultimately cell death. Here we demonstrate that 3-aminobenzamide (and several other, chemically distinct, inhibitors of PARS activity) reduces the infarct size caused by ischemia and reperfusion of the heart or skeletal muscle of the rabbit. Inhibition of PARS activity also attenuates the myocardial dysfunction caused by global ischemia and reperfusion in the isolated, perfused heart of the rabbit. In skeletal muscle, inhibition of the activity of neuronal NO synthase reduces infarct size, indicating that the formation of NO contributes to the activation of PARS there. There is no significant neuronal NO synthase activity in the heart, and hence NO synthase inhibitors did not reduce myocardial infarct size. Thus, activation of PARS contributes to the cell death caused by ischemia-reperfusion, and PARS inhibitors may constitute a novel therapy for ischemia-reperfusion injury.

Animals↗
PubMed2001

Effect of tumor necrosis factor-alpha on skeletal muscle metabolism.

Over the past year, considerable progress has been made in our understanding of biologic actions by which tumor necrosis factor-alpha (TNF-alpha) may influence skeletal muscle metabolism. Reports published during this period highlighted three general actions with metabolic consequences: accelerated catabolism (protein loss, insulin resistance), contractile dysfunction, and disruption of myogenesis. Recent research also indicates that skeletal muscle myocytes synthesize TNF-alpha and that the cytokine functions as an endogenous mediator of muscle adaptation via autocrine/paracrine effects. These advances demonstrate the fundamental importance of TNF-alpha effects on skeletal muscle myocytes and provide a focus for future studies of intracellular mechanism.

Animals↗
PubMedDate not supplied

Ischemia-reperfusion and cell membrane dysfunction.

One to 3 hours of partial skeletal muscle ischemia-reperfusion in dogs and rats causes cell membrane depolarization. Intracellular levels of adenosine triphosphate remain normal, suggesting that direct membrane injury rather than electrogenic pump failure occurs. Membrane depolarization can be prevented by superoxide dismutase and catalase, or by neutrophil depletion. Oxygen free radicals may be one type of mediator causing membrane damage, and it appears that leukocytes release these toxic species.

Adenosine Triphosphate↗
PubMed2003

Eccentric exercise in coronary patients: central hemodynamic and metabolic responses.

PURPOSE: With lengthening (eccentric) muscle contractions, the magnitude of locomotor-muscle mass and strength increase has been demonstrated to be greater compared with shortening (concentric) muscle contractions. In healthy subjects, energy demand and heart rate responses with eccentric exercise are small relative to the amount of muscle force produced. Thus, eccentric exercise may be an attractive alternative to resistance exercise for patients with limited cardiovascular exercise tolerance. METHODS: We tested the cardiovascular tolerance of eccentric exercise in 13 coronary patients (ages 40-66) with preserved and/or mild reduced left ventricular function. Patients were randomly assigned to either an eccentric (ECC; N = 7) or a concentric (CON; N = 6) training group and trained for 8 wk. Training workload was increased progressively (from week 1 to 5) to an intensity equivalent to 60% [OV0312]O(2peak). RESULTS: On average, maximum power output achieved with ECC was fourfold compared with CON (357 +/- 96 W vs 97 +/- 21 W; P < 0.005), whereas measures of oxygen uptake and blood lactate were significantly lower (P < 0.05 each), and ratings of perceived exertion were similar for ECC and CON. During a 20-min session of ECC and CON, central hemodynamics was measured by means of right heart catheterization. During ECC, responses of mean arterial blood pressure, systemic vascular resistance, pulmonary capillary pressure, cardiac index, and stroke work of the left ventricle on average were in the normal range of values and similar to those observed during CON. Compared with baseline, after 8 wk of training, echocardiographic left ventricular function was unchanged. CONCLUSION: The results indicate uncoupling of skeletal muscle load and cardiovascular stress during ECC. For low-risk patients with coronary heart disease without angina, inducible ischemia, or left ventricular dysfunction, ECC can be recommended as a safe new approach to perform high-load muscular exercise training with minimal cardiovascular stress.

Adult↗
PubMed2006

Lack of flow-mediated dilation and enhanced angiotensin II-induced constriction in skeletal muscle arterioles of lupus-prone autoimmune mice.

Systemic lupus erythematosus (SLE) is associated with disturbances in the microcirculation of various tissues, yet the nature of arteriolar dysfunction has not been characterized. Thus, changes in diameter of isolated, pressurized skeletal muscle arterioles of mice with systemic autoimmune disease (lupus prone, MRL/lpr four-month old female) and control (MRL) mice were investigated by video-microscopy. Arteriolar responses to changes in intraluminal pressure, flow, and to vasoactive agents with known mechanisms of action were compared. The active and passive (in Ca2+ free solution) diameter of MRL/lpr arterioles were not significantly different compared to MRL and morphometric changes were not apparent. Compared to MRL mice the endothelium-dependent dilations to increase in flow, acetylcholine and bradykinin were markedly reduced in arterioles of MRL/lpr mice. Endothelium-independent dilations to sodium-nitroprusside and adenosine were similar in MRL and MRL/lpr arterioles. Furthermore, angiotensin II elicited greater constrictions in MRL/lpr arterioles, whereas serotonin-induced constrictions were similar in both groups. Thus, in arterioles of MRL/lpr mice endothelium-dependent dilator mechanisms are impaired and constriction to angiotensin II is enhanced, suggesting specific alterations in the vasomotor function of microvessels that are likely contribute to the disturbance of skeletal muscle blood flow observed in systemic lupus erythematosus.

Acetylcholine↗
PubMed2006

Mitochondrial dysfunction in COPD patients with low body mass index.

Patients with chronic obstructive pulmonary disease (COPD) show abnormal adaptations of skeletal muscle redox status after exercise training. Increased skeletal muscle oxidative stress in COPD patients may prompt mitochondrial dysfunction. The present study explores the association between body composition and mitochondrial respiration in seven COPD patients with low body mass index (BMI(L)), eight COPD patients with normal body mass index (BMI(N)) and seven healthy controls. All of them underwent a vastus lateralis biopsy in which muscle structure, in vitro mitochondrial respiratory function, uncoupling protein 3 (UCP3) mRNA expression and glutathione levels in both isolated mitochondria and the whole muscle were determined. Mitochondrial respiratory function (assessed by acceptor control ratio (ACR)) was impaired in BMI(L) (2.2+/-0.6) compared with both BMI(N) (5.3+/-1.3) and controls (8.2+/-1.3). ACR significantly correlated with arterial oxygen tension and with muscle endurance but it showed a negative association with exercise-induced increase in blood lactate levels. UCP3 mRNA expression was reduced in BMI(L) patients. In conclusion, chronic obstructive pulmonary disease patients with low body mass index show electron transport chain dysfunction, which may contribute to low muscle endurance in the current subgroup of patients.

Aged↗
PubMed1991

Hyperthyroid myopathy and the response to treatment.

Hyperthyroidism is accompanied by significant dysfunction of both proximal and distal skeletal muscles. The purpose of this study was to quantitate the degree of muscle weakness in newly diagnosed patients with Graves' disease and to assess the response to treatment. Ten patients were prospectively studied with objective measures of strength and endurance of proximal and distal muscles while hyperthyroid (stage I), after 2 weeks of propranolol (stage II), and about 6 months later when euthyroid (stage III). Propranolol treatment for 2 weeks resulted in a subjective decrease in weakness, which was accompanied by a statistically significant improvement in grip strength (P less than 0.01), shoulder strength (P less than 0.02), and grip endurance (P less than 0.01) but not shoulder endurance. Muscle function further improved and attained control levels when the patients were chemically and clinically euthyroid. In contrast, a control group subjected to the same muscle testing protocol before and after 1 week of propranolol treatment showed no improvement in grip, shoulder strength, or shoulder endurance but had decreased grip endurance (P less than 0.01) and increased subjective weakness. These results confirm that muscle weakness commonly is associated with hyperthyroidism and can be quantitatively profound. In contrast to the effects of beta-blockade in normal controls, propranolol partially improves muscle weakness in thyrotoxic patients. We conclude that thyroid hormone and catecholamines in concert mediate the muscle dysfunction of hyperthyroidism.

Adrenergic beta-Antagonists↗
PubMed2006

Effect of aging on the structure and function of skeletal muscle microvascular networks.

Humans are active creatures, yet physical activity and activity tolerance decline over the life span. One prevailing theme in the literature to account for a portion of the reduced activity tolerance with aging is the observation that the capacity to augment blood flow to skeletal muscle may be impaired with advancing age. This dysfunction may be due to adaptations in the structure or function of their microvascular networks, which collectively determine blood flow resistance. The intent of this review is to present the current knowledge of structure and function of microvascular networks from skeletal muscle with special regard to how these may adapt to, or persist through, the aging process. Skeletal muscles are supplied by an intricate branching network of arterioles and venules. The consistency of findings among available studies suggests that the overall arteriolar and venular network branching topology establishes early in development and varies little, if at all, over the life span. Microvascular networks are not a series of functionally isolated segmental branches. Rather, these networks transmit and communicate vasomotor signals along their lengths and among their branches. Current evidence suggests that aging is associated with a decrement in the capacity of upstream vessels to respond to downstream vasodilation and signals transmitted cell-to-cell along the vascular wall.

Aging↗
PubMed1992

Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy.

BACKGROUND: Previous study of patients with chronic fatigue syndrome (CFS) has demonstrated a markedly reduced dynamic exercise capacity, not limited by cardiac performance and in the absence of clinical neuromuscular dysfunction, suggesting the possibility of a subclinical defect of skeletal muscle. METHODS: The in vivo metabolism of the gastrocnemius muscles of 22 CFS patients and 21 normal control subjects was compared during rest, graded dynamic exercise to exhaustion and recovery, using 31P nuclear magnetic resonance (NMR) spectroscopy to reflect minute-to-minute intracellular high-energy phosphate metabolism. RESULTS: Duration of exercise was markedly shorter in the CFS patients (8.1 +/- 2.8 min) compared with the normal subjects (11.3 +/- 4.3 min) (p = 0.005). There were large changes in phosphocreatine (PCr), inorganic phosphate (Pi), and pH from rest to clinical fatigue in all subjects, reflecting the high intensity of the exercise. The temporal metabolic patterns were qualitatively similar in the CFS patients and normal subjects. There were early and continuous changes in PCr and Pi that peaked at the point of fatigue and rapidly reversed after exercise. In contrast, pH was relatively static in early exercise, not declining noticeably until 50 percent of total exercise duration was achieved, and reaching a nadir at 2 min postexercise, before rapidly reversing. There were no differences in pH at rest (7.08 +/- 0.04 vs 7.10 +/- 0.04), exhaustion (6.85 +/- 0.17 vs 6.76 +/- 0.17) or early (6.64 +/- 0.25 vs 6.56 +/- 0.24) or late recovery (7.09 +/- 0.04 vs 7.10 +/- 0.05), CFS patients vs normal subjects, respectively (NS). Neither were there intergroup differences (NS) in PCr or Pi. Although, quantitatively, the changes in PCr, Pi, and pH were marked and similar in both groups from rest to exhaustion, the changes all occurred much more rapidly in the CFS patients. Moreover, adenosine triphosphate (ATP) was significantly (p = 0.007) less at exhaustion in the CFS group. CONCLUSIONS: Patients with CFS and normal control subjects have similar skeletal muscle metabolic patterns during dynamic exercise and reach similar clinical and metabolic end points. However, CFS patients reach exhaustion much more rapidly than normal subjects, at which point they also have relatively reduced intracellular concentrations of ATP. These data suggest a defect of oxidative metabolism with a resultant acceleration of glycolysis in the working skeletal muscles of CFS patients. This metabolic defect may contribute to the reduced physical endurance of CFS patients. Its etiology is unknown. Whether CFS patients' overwhelming tiredness at rest has a similar metabolic pathophysiology or etiology also remains unknown.

Adenosine Triphosphate↗
PubMed2006

Aging-induced adaptations of microvascular reactivity.

Control of blood flow to skeletal muscle depends on the vasomotor tone present in the resistance vasculature. Although muscle blood flow has been shown to decline with advancing age, our knowledge of how alterations of reactivity of the resistance vasculature contribute to reduced delivery or altered distribution of blood in the aged is limited. Recent work has demonstrated that age alters the reactivity of resistance arteries and arterioles from skeletal muscle, and that impairment of both vasodilator and vasoconstrictor responses occurs with advancing age. The alterations in cellular mechanisms that contribute to age-related impairment of vasoreactive responses encompass both the vascular endothelium and smooth muscle, and differ in muscles of varying function and fiber type. Current research suggests that some degree of age-induced endothelial dysfunction occurs in resistance arteries and arterioles from most skeletal muscle; however, the severity of endothelial impairment appears greater in resistance arteries and arterioles from highly oxidative locomotory muscles. Age-related impairment of vasoconstrictor responses to metabolites and endogenous constrictor agents has also been documented. These age-related reductions in vasoreactivity that occur in the skeletal muscle resistance vasculature may contribute to inadequate delivery or distribution of blood flow during exercise and ultimately be a factor in loss of exercise capacity that occurs with advancing age.

Aging↗
PubMed1995

Evaluation of the cardiomyopathy in Becker muscular dystrophy.

To evaluate the features and the course of cardiomyopathy in Becker muscular dystrophy, 68 patients--identified by clinical assessment and by reduced dystrophin labeling and/or DNA analysis--were followed in the years 1976-1993, for periods ranging from 3 to 18 years (mean 8). Patients periodically underwent clinical, electrocardiographic, echocardiographic, nuclear, and radiological assessments. Preclinical cardiac involvement was found in 67.4% of patients under 16 years of age, decreasing to 30% in patients older than 40. Clinically evident cardiomyopathy was found in 15% of patients under 16 years of age, increasing to 73% in patients older than 40. A real, dilated cardiomyopathy is the most frequent type of myocardial involvement after the age of 20. Results show that the severity of cardiac involvement can be unrelated to the severity of skeletal muscle damage and confirm that cardiac dysfunction is a primary feature of Becker muscular dystrophy.

Adolescent↗
PubMed1997

Oxidative phosphorylation dysfunction does not increase the rate of accumulation of age-related mtDNA deletions in skeletal muscle.

Several reports described an age-related accumulation of a particular mitochondrial DNA (mtDNA) deletion ('common deletion') in post-mitotic tissues. These findings led to the hypothesis that free radicals generated inside the mitochondria could damage mtDNA during a normal life span. The impaired electron transfer function resulting from mtDNA damage would increase the production of free radicals creating a vicious cycle. If this vicious cycle is an important player in the somatic accumulation of mtDNA deletions, patients with impaired oxidative phosphorylation (regardless of the primary defect) should have an accelerated accumulation of mtDNA deletions. We tested this hypothesis by performing three analyses: (a) comparing the amounts of the mtDNA 'common deletion' in normal controls and patients with genetically characterized mitochondrial disorders associated with pathogenic mtDNA point mutations or deletions other than the common deletion; (b) analyzing the co-segregation of the age-related mtDNA common deletion with a pathogenic mtDNA point mutation; and (c) by the detection of multiple mtDNA deletions by long PCR in controls and patients with mitochondrial disorders. We observed a positive correlation between age and common deletion levels in controls (r = 0.80) and patients (r = 0.69). The slopes of the curves were similar, suggesting that the rate of accumulation of the age-related common deletion was the same in both groups. We could not find a co-segregation of the pathogenic point mutated mtDNA molecules with the common deletion nor increased number of age-related deletions in patients. Our data do not support the hypothesis that a vicious cycle (damage to mtDNA would affect the respiratory function, leading to the generation of more free radicals, which in turn would provoke additional mtDNA damage) is an important factor in the accumulation of age-related mtDNA deletions.

Adolescent↗
PubMedDate not supplied

A technique for sequential segmental neuromuscular stimulation with closed loop feedback control.

In dynamic myoplasty, dysfunctional muscle is assisted or replaced with skeletal muscle from a donor site. Electrical stimulation is commonly used to train and animate the skeletal muscle to perform its new task. Due to simultaneous tetanic contractions of the entire myoplasty, muscles are deprived of perfusion and fatigue rapidly, causing long-term problems such as excessive scarring and muscle ischemia. Sequential stimulation contracts part of the muscle while other parts rest, thus significantly improving blood perfusion. However, the muscle still fatigues. In this article, we report a test of the feasibility of using closed-loop control to economize the contractions of the sequentially stimulated myoplasty. A simple stimulation algorithm was developed and tested on a sequentially stimulated neo-sphincter designed from a canine gracilis muscle. Pressure generated in the lumen of the myoplasty neo-sphincter was used as feedback to regulate the stimulation signal via three control parameters, thereby optimizing the performance of the myoplasty. Additionally, we investigated and compared the efficiency of amplitude and frequency modulation techniques. Closed-loop feedback enabled us to maintain target pressures within 10% deviation using amplitude modulation and optimized control parameters (correction frequency = 4 Hz, correction threshold = 4%, and transition time = 0.3 s). The large-scale stimulation/feedback setup was unfit for chronic experimentation, but can be used as a blueprint for a small-scale version to unveil the theoretical benefits of closed-loop control in chronic experimentation.

Algorithms↗
PubMedDate not supplied

Reperfusion injury in the human forearm is mild and not attenuated by short-term ischaemic preconditioning.

1. Ischaemia-reperfusion (IR) injury is an important contributor to tissue damage and has been shown to be attenuated by preconditioning (PC) in some animal models. A recent report has suggested that the forearm can be used for the study of this phenomenon in humans. We aimed to reproduce and further characterize this model. 2. Healthy young adult volunteers (mean (+/-SEM) age 32+/-6 years) were studied on two occasions. During one visit, IR alone was induced by 10 min of upper arm cuff occlusion, whereas on another occasion a PC stimulus (three 3 min cuff inflations) preceded IR. Endothelial function in the ischaemic arm was assessed by measuring arterial flow-mediated dilatation (FMD) and by calculation of forearm blood flow at baseline and 15 and 60 min after IR. Systemic venous blood was sampled from the non-ischaemic arm at baseline, after PC and at 2, 15 and 30 min after IR to assess neutrophil/leucocyte (CD11b) and platelet (bound glycoprotein IIb/IIIa and fibrinogen) activation, as well as numbers of platelet-leucocyte complexes, which were determined by flow cytometry. Because of a lack of measurable effects, the IR experiment was repeated with 20 min ischaemia in six subjects. 3. Five females and eight males completed the study. Flow-mediated dilatation was significantly impaired 30 min after IR (4.1 vs 6.2% at baseline; P<0.05);however, this was not significantly attenuated by ischaemic PC (FMD reduction at 30 min compared with baseline was 2.1+/-0.5% with IR alone and 2.6+/-1.4% with IR after PC; NS). No significant effect was seen on the number of platelet-leucocyte aggregates or on white cell or platelet activation after IR alone or after IR with PC (P>0.6 for all comparisons). Similar results were obtained in six subjects studied subjected to 20 min ischaemia. 4. In conclusion, in healthy young adults, brief periods of skeletal muscle ischaemia lead to arterial endothelial dysfunction, but no significant platelet or white cell activation. Preconditioning does not attenuate this effect on the endothelium. Further experiments with longer ischaemia times and varying PC stimuli may be necessary to produce measurable effects; however, this may prove difficult in conscious human subjects.

Adult↗
PubMed1982

Neurological involvement in legionellosis.

A study of the clinical, electrophysiological and biochemical features of 16 patients with legionellosis has been performed. Evidence of central and peripheral nervous system involvement has been found in the majority of patients. This is characterised by confusion out of keeping with the degree of toxic or metabolic upset, signs of anterior midline cerebellar dysfunction, grossly elevated creatinine kinase of skeletal muscle origin, and a subclinical peripheral neuropathy.

Adult↗