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 523 records · Page 29Linked to original sources

PubMed1999

Ag+ alters cell growth, neurite extension, cardiomyocyte beating, and fertilized egg constriction.

BACKGROUND: The Russian Space Agency uses electrochemically generated silver ions (Ag+) to purify drinking water for their space station, Mir, and their portion of the International Space Station. U.S. EPA guidelines allow 10.6 micromol x L(-1) Ag+ in human drinking water for up to 10 d. Studies correlate Ag+ exposure with tissue dysfunction in humans, rats, and mice, and with altered ion transport, skeletal muscle contraction, and embryonic cell constriction in other animal cells. Ag+ effects on cell shape change-related functions have not been assessed. METHODS: Immortalized embryonic human intestinal epithelial cells, freshly explanted embryonic avian nerve cells and cardiomyocytes, and marine fertilized eggs were grown in vitro in medium containing AgNO3. RESULTS: Intestinal cells detach from the substratum and viable cell number decreases by 5-6 d at 5 micromol x L(-1) AgNO3, and faster at higher concentrations. Microtubules appear unaltered in adherent cells. Detached cells are nonviable. Neurite outgrowth and glial cell migration from dorsal root ganglia are inhibited by 3 d at 15 micromol x L(-1) AgNO3 or greater. Contractions stop temporarily in most cardiomyocytes by 5 min at 5 micromol x L(-1) AgNO3 or more, but some cardiomyocytes beat 3 times faster than normal at 7.5-20 micromol x L(-1) AgNO3. Picomolar Ag+ increases marine egg polar lobe constriction within an hour, even in the absence of microtubules. CONCLUSION: Ag+ alters animal cell growth and shape changes by a MT-independent mechanism. This is the first report of Ag+ effects on vertebrate neurite outgrowth, glial cell migration, or cardiomyocyte beat rate.

Animals↗

PubMed2007

Postulated role of interdomain interaction between regions 1 and 2 within type 1 ryanodine receptor in the pathogenesis of porcine malignant hyperthermia.

We have demonstrated recently that CICR (Ca2+-induced Ca2+ release) activity of RyR1 (ryanodine receptor 1) is held to a low level in mammalian skeletal muscle ('suppression' of the channel) and that this is largely caused by the interdomain interaction within RyR1 [Murayama, Oba, Kobayashi, Ikemoto and Ogawa (2005) Am. J. Physiol. Cell Physiol. 288, C1222-C1230]. To test the hypothesis that aberration of this suppression mechanism is involved in the development of channel dysfunctions in MH (malignant hyperthermia), we investigated properties of the RyR1 channels from normal and MHS (MH-susceptible) pig skeletal muscles with an Arg615-->Cys mutation using [3H]ryanodine binding, single-channel recordings and SR (sarcoplasmic reticulum) Ca2+ release. The RyR1 channels from MHS muscle (RyR1MHS) showed enhanced CICR activity compared with those from the normal muscle (RyR1N), although there was little or no difference in the sensitivity to several ligands tested (Ca2+, Mg2+ and adenine nucleotide), nor in the FKBP12 (FK506-binding protein 12) regulation. DP4, a domain peptide matching the Leu2442-Pro2477 region of RyR1 which was reported to activate the Ca2+ channel by weakening the interdomain interaction, activated the RyR1N channel in a concentration-dependent manner, and the highest activity of the affected channel reached a level comparable with that of the RyR1MHS channel with no added peptide. The addition of DP4 to the RyR1MHS channel produced virtually no further effect on the channel activity. These results suggest that stimulation of the RyR1MHS channel caused by affected inter-domain interaction between regions 1 and 2 is an underlying mechanism for dysfunction of Ca2+ homoeostasis seen in the MH phenotype.

Adenosine Triphosphate↗

PubMed1988

Characterization of a myopathy caused by prostaglandin dysfunction.

Administration of inhibitors of prostaglandin synthetase to chicken embryos produced myopathies in their skeletal muscles which were characterized by ringbinden, loss of Z-discs, M-bands, and thick and thin filaments and decreased myoblast proliferation and type 2 myotube formation. The effect of administration of prostaglandins on myoblast proliferation was also examined and PGE was found to suppress proliferation. There was also a tendency for PGF2 alpha to suppress and PGI2 to stimulate proliferation, although neither of these effects were statistically significant. PGA, PGB and PGD did not affect myoblast proliferation.

Adenosine Triphosphatases↗

PubMed2005

Autonomic neural functions in space.

Autonomic neural functions are important to regulate vital functions in the living body. There are different methods to evaluate indirectly and directly autonomic, sympathetic and parasympathetic, neural functions of human body. Among various methods, microneurography is a technique to evaluate directly sympathetic neural functions in humans. Using this technique sympathetic neural traffic leading to skeletal muscles (muscle sympathetic nerve activity; MSNA) can be recorded from human peripheral nerves in situ. MSNA plays essentially important roles to maintain blood pressure homeostasis against gravity. Orthostatic intolerance is an important problem as an autonomic dysfunction encountered after exposure of human beings to microgravity. There exist at least two different types of sympathetic neural responses, low and high responders to orthostatic stress in orthostatic hypotension seen in neurological disorders. To answer the question if post-spaceflight orthostatic intolerance is induced by low or high MSNA responses to orthostatic stress, MSNA was microneurographically recorded for the first time before, during and after spaceflight in 1998 under Neurolab international research project. The same activity has been recorded during and/or after ground-based short- and long-term simulations of microgravity. MSNA was rather enhanced on the 12(th) and 13(th) day of spaceflight and just after landing day. Postflight MSNA response to head-up tilt was well preserved in astronauts who were orthostatically well tolerant. MSNA was suppressed during short-term simulation of microgravity less than 2 hours but was enhanced after long-term simulation of microgravity more than 3 days. Orthostatic intolerance after exposure to long-term simulation of microgravity was associated with reduced MSNA response to orthostatic stress with impaired baroreflex functions. These findings obtained from MSNA recordings in subjects exposed to space as well as short- and long-term simulations of microgravity indicate that sympathetic neural control is lowered when exposed to short-term microgravity but becomes enhanced after exposure to long-term microgravity. A lack of enhanced sympathetic neural response to orthostatic stress may induce orthostatic intolerance. Based on these findings effective countermeasures should be developed to prevent autonomic dysfunctions induced by exposure to microgravity. These include development of prescription and devices of physical exercise, electrical and magnetic nerve stimulations, body vibration, elastic bandage and stocking, lower body negative pressure, artificial gravity, medical drugs, and combinations of them. These countermeasures will be beneficial to prevent autonomic dysfunctions related to gravitational stress such encountered in bedridden subjects as orthostatic hypotension, atrophy of antigravity muscles and so on. This is particularly important in the present aged-society with many bedridden elderly people. The knowledge accumulated from studies on autonomic neural functions in space should be very useful to establish effective countermeasures and preventive methods for gravity-dependent autonomic dysfunctions.

Aging↗

PubMed2004

The role of creatine in the management of amyotrophic lateral sclerosis and other neurodegenerative disorders.

Creatine is consumed in the diet and endogenously synthesised in the body. Over the past decade, the ergogenic benefits of synthetic creatine monohydrate have made it a popular dietary supplement, particularly among athletes. The anabolic properties of creatine also offer hope for the treatment of diseases characterised by weakness and muscle atrophy. Moreover, because of its cellular mechanisms of action, creatine offers potential benefits for diseases involving mitochondrial dysfunction. Recent data also support the hypothesis that creatine may have a neuroprotective effect. Amyotrophic lateral sclerosis (ALS) is characterised by progressive degeneration of motor neurons, resulting in weakening and atrophy of skeletal muscles. In patients with this condition, creatine offers potential benefits in terms of facilitating residual muscle contractility as well as improving neuronal function. It may also help stabilise mitochondrial dysfunction, which plays a key role in the pathogenesis of ALS. Indeed, the likely multifactorial aetiology of ALS means the combined pharmacodynamic properties of creatine offer promise for the treatment of this condition. Evidence from available animal models of ALS supports the utility of treatment with creatine in this setting. Limited data available in other neuromuscular and neurodegenerative diseases further support the potential benefit of creatine monohydrate in ALS. However, few randomised, controlled trials have been conducted. To date, two clinical trials of creatine monohydrate in ALS have been completed without demonstration of significant improvements in overall survival or a composite measure of muscle strength. These trials have also posed unanswered questions about the optimal dosage of creatine and its beneficial effects on muscle fatigue, a measure distinct from muscle strength. A large, multicentre, clinical trial is currently underway to further investigate the efficacy of creatine monohydrate in ALS and address these unresolved issues. Evidence to date shows that creatine supplementation has a good safety profile and is well tolerated by ALS patients. The purpose of this article is to provide a short, balanced review of the literature concerning creatine monohydrate in the treatment of ALS and related neurodegenerative diseases. The pharmacokinetics and rationale for the use of creatine are described along with available evidence from animal models and clinical trials for ALS and related neurodegenerative or neuromuscular diseases.

Amyotrophic Lateral Sclerosis↗

PubMed2004

Role of peroxisome proliferator-activated receptor-gamma in the protection afforded by 15-deoxydelta12,14 prostaglandin J2 against the multiple organ failure caused by endotoxin.

OBJECTIVE: The cyclopentenone prostaglandin 15-deoxydelta-prostaglandin J2 (15 d-PGJ2) exerts potent anti-inflammatory effects in vivo, which are in part due to the activation of peroxisome proliferator-activated receptor (PPAR)-gamma. Here we investigate the effects of 15 d-PGJ2 on the multiple organ injury/dysfunction associated with severe endotoxemia. DESIGN: Prospective, randomized study. SETTING: University-based research laboratory. SUBJECTS: Seventy anesthetized male Wistar rats. INTERVENTIONS: Rats received either Escherichia coli lipopolysaccharide (endotoxin, 6 mg/kg intravenously) or vehicle (saline, 1 mL/kg intravenously). 15 d-PGJ2 (0.3 mg/kg intravenously) or vehicle (10% dimethyl sulfoxide) was administered 30 mins before endotoxin. The selective PPAR-gamma antagonist GW9662 (0.3 mg/kg intravenously) or its vehicle (10% dimethyl sulfoxide) was given 45 mins before endotoxin. MEASUREMENTS AND MAIN RESULTS: Endotoxemia for 6 hrs increased serum concentrations of creatinine (indicator of renal dysfunction), aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, bilirubin (markers for hepatic injury and dysfunction), lipase (indicator of pancreatic injury), and creatine kinase (an indicator of neuromuscular skeletal muscle or cardiac injury). The potent PPAR-gamma agonist 15 d-PGJ2 attenuated the increases in the serum concentrations of these variables, indicating a protective effect of 15 d-PGJ2 against the multiple organ injury/dysfunction caused by endotoxin. The specific PPAR-gamma antagonist GW9662 reduced the protective effects afforded by 15 d-PGJ2. 15 d-PGJ2 did not affect the biphasic decrease in blood pressure or the increase in heart rate caused by endotoxemia. CONCLUSIONS: The potent PPAR-gamma agonist 15 d-PGJ2 reduces the multiple organ injury and dysfunction, but not the hypotension, caused by endotoxin in the rat. The mechanisms of the protective effect of this cyclopentenone prostaglandin are--at least in part--PPAR-gamma dependent, as the protection afforded by 15 d-PGJ2 was reduced by the PPAR-gamma antagonist GW9662. We propose that 15 d-PGJ2 or other ligands for PPAR-gamma may be useful in treating organ injury associated with endotoxic shock.

Analysis of Variance↗

PubMed1994

Insulin sensitivity in cystic fibrosis.

Cystic fibrosis (CF) patients demonstrate a spectrum of pancreatic beta-cell abnormalities. Those with no exocrine insufficiency (NEXO) have normal insulin secretion. Exocrine-insufficient CF patients with overt diabetes (EXO-IT) have impaired insulin secretion and fasting hyperglycemia. Exocrine-insufficient patients without diabetes (EXO) have impaired insulin secretion but maintain normoglycemia. We postulated that EXO individuals compensate for insulin deficiency by increasing insulin sensitivity and investigated glucose utilization in CF. To examine hepatic and peripheral insulin sensitivity, euglycemic-hyperinsulinemic clamp studies were performed by using the hot GINF isotope dilution technique. Insulin was sequentially infused at 0.25, 1.0, and 10.0 mU.kg-1.min-1. Glucose-mediated glucose uptake (GMGU) was assessed on another day with hyperglycemic clamp studies, during which insulin and somatostatin were infused to hold insulin-mediated glucose uptake constant between the two clamp studies. Skeletal muscle GLUT4 levels were assessed in EXO and control patients with Western blotting. Three patterns of peripheral and hepatic insulin sensitivity were seen that were related to the degree of pancreatic beta-cell dysfunction. NEXO individuals had normal peripheral and hepatic insulin sensitivity. EXO individuals had enhanced peripheral insulin sensitivity that was not associated with a change in skeletal muscle glucose transporter abundance compared with control patients; paradoxically, EXO subjects demonstrated hepatic insulin resistance. EXO-IT had peripheral and hepatic insulin resistance. GMGU was diminished in both EXO and EXO-IT subjects. The unique combination of increased hepatic glucose production and increased peripheral glucose utilization seen in EXO may be a metabolic adaptation to increased peripheral energy needs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2003

Anti-monocyte chemoattractant protein-1 gene therapy attenuates left ventricular remodeling and failure after experimental myocardial infarction.

BACKGROUND: Increased expression of monocyte chemoattractant protein-1 (MCP-1) has recently been described in clinical and experimental failing heart. However, its pathophysiological significance in heart failure remains obscure. We thus determined whether MCP-1 is increased in post-myocardial infarction (MI) hearts and its blockade can attenuate the development of left ventricular (LV) remodeling and failure. METHODS AND RESULTS: Anterior MI was produced in mice by ligating the left coronary artery. After 4 weeks, MI mice exerted LV dilatation and contractile dysfunction in association with myocyte hypertrophy and interstitial fibrosis of noninfarcted LV. MCP-1 mRNA levels were increased by 40-fold in noninfarcted LV 1 day after ligation, which persisted until 28 days. To block the MCP-1 signals, an N-terminal deletion mutant of the human MCP-1 gene was transfected into the limb skeletal muscle 3 days before and 14 days after ligation. This method improved the survival rate of mice with MI at 4 weeks (61% versus 87%, P<0.05) as well as attenuated LV cavity dilatation and contractile dysfunction, interstitial fibrosis, recruitment of macrophages, and myocardial gene expression of tumor necrosis factor-alpha and transforming growth factor-beta compared with the nontreated MI mice despite the comparable infarct size calculated as percent LV circumference. CONCLUSIONS: The activation of MCP-1 expression contributes to the LV remodeling and failure after MI. An anti-MCP-1 gene therapy can be a useful novel strategy for preventing post-MI heart failure.

Angiotensin II↗

PubMed2000

NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia.

MyoD regulates skeletal muscle differentiation (SMD) and is essential for repair of damaged tissue. The transcription factor nuclear factor kappa B (NF-kappaB) is activated by the cytokine tumor necrosis factor (TNF), a mediator of skeletal muscle wasting in cachexia. Here, the role of NF-kappaB in cytokine-induced muscle degeneration was explored. In differentiating C2C12 myocytes, TNF-induced activation of NF-kappaB inhibited SMD by suppressing MyoD mRNA at the posttranscriptional level. In contrast, in differentiated myotubes, TNF plus interferon-gamma (IFN-gamma) signaling was required for NF-kappaB-dependent down-regulation of MyoD and dysfunction of skeletal myofibers. MyoD mRNA was also down-regulated by TNF and IFN-gamma expression in mouse muscle in vivo. These data elucidate a possible mechanism that may underlie the skeletal muscle decay in cachexia.

Animals↗

PubMed2003

Chronic renal failure leads to reduced flow-dependent dilation in isolated rat skeletal muscle arterioles due to lack of NO mediation.

BACKGROUND: Chronic renal failure (CRF) is frequently accompanied by systemic vascular alterations which further increase the morbidity and mortality of these patients. However, the nature and the underlying mechanisms of vascular dysfunction are not completely understood. We hypothesized that--in addition to other factors--CRF alters local vasomotor mechanisms that are intrinsic to the vascular wall. METHODS: Changes in the diameter of isolated, pressurized (at 80 mm Hg) gracilis skeletal muscle arterioles (diameter approximately 150 microm) of female Wistar rats were investigated by videomicroscopy. Arteriolar responses to an increase in flow and vasoactive agents in partially nephrectomized (NX) and sham-operated (control) rats were compared. RESULTS: In NX rats, serum creatinine and urine protein excretion were increased. Compared to controls, increases in intraluminal flow (from 0 to 40 microl/min) resulted in significantly reduced dilation in arterioles of NX rats (maximum: 32 +/- 4 vs. 15 +/- 4 microm, p < 0.05). Inhibition of nitric oxide (NO) synthesis with L-NAME reduced the dilation of control arterioles but did not affect responses of NX arterioles. Also, dilations in response to histamine were significantly reduced in arterioles from NX rats as compared to control rats. L-NAME significantly decreased histamine-induced dilations of control arterioles, but it did not affect responses of NX arterioles. Dilations in response to the NO donor sodium nitroprusside were also significantly decreased in NX arterioles as compared to responses of control vessels, whereas responses to adenosine and norepinephrine were not significantly different in the two groups. CONCLUSIONS: We conclude that in rat skeletal muscle arterioles, CRF induced by renal mass reduction alters the mechanosensitive and agonist-induced responses of peripheral arterioles, in part by interfering with NO-signaling mechanisms. These alterations could contribute to increased peripheral vascular resistance and further aggravate the cardiovascular complications in CRF.

Adenosine↗

PubMed1998

Alterations in small arterioles precede changes in limb skeletal muscle after myocardial infarction.

We tested the hypothesis that alterations in arterioles in locomotor skeletal muscles in rats with myocardial infarction (MI), but before development of congestive heart failure (CHF), precede structural and functional changes commonly observed in limb muscle in association with CHF. Resting diameters of third- (A3) and fourth-order arterioles (A4) in extensor digitorum longus (EDL) muscle were significantly smaller in rats with nonfailing small and medium-sized MI compared with control animals. Dilation of A4 in response to 10(-4) M adenosine was significantly attenuated in both groups (P < 0.05), whereas dilation of A3 was unaltered. Microvessels from both groups of infarcted rats constricted to all doses of acetylcholine (10(-9), 10(-8), and 10(-7) M) and showed a significantly exaggerated vasoconstrictor response to norepinephrine (10(-9), 10(-8), and 10(-7) M) compared with microvessels in control rats (P < 0.05). Peak isometric tension of combined tibialis anterior and EDL muscles and muscle fatigue (final/peak tension x 100), measured during 5-min isometric supramaximal twitch contractions at 4 Hz, were similar in control and MI rats (218 +/- 7 vs. 213 +/- 15 g/g muscle and 52 +/- 1 vs. 51 +/- 9%, respectively; n = 5 for both). There was also no difference with respect to the proportion of oxidative fibers or capillary-to-fiber ratios. Our results indicate that, in rats with left ventricular dysfunction but without failure, decreased diameter and perturbations in reactivity of small arterioles precede alterations in skeletal muscle performance often seen at a later date in association with CHF. These findings are consistent with the notion of aberrant endothelial and smooth muscle function and may contribute to the maintenance of blood pressure after MI but before CHF.

Acetylcholine↗

PubMedDate not supplied

Can latissimus dorsi muscle stimulation benefit heart during training period after vascular delay?

We hypothesized that a two-stage vascular delay procedure followed by 5 weeks of conditioning of the latissimus dorsi muscle (LDM) could benefit the heart during the training period and greatly increase cardiac assistance when examined with maximum potential. In mongrel dogs (n = 10), left ventricle (LV) dysfunction was induced by intracoronary injections of latex microspheres [90 +/- 2 micro diameter]. Vascular delay of the LDM was performed in one group (n = 6), whereas the other group (control, n = 4) did not undergo vascular delay. After 2 weeks, CMP was performed in all animals followed by LDM conditioning. After 5 weeks of muscle training, we examined left ventricular function at 20 Hz-4 volts, 33 Hz-4 volts, and 50 Hz-10 volts stimulation by assessing peak aortic pressure (AoP), left ventricular pressure (LVP), maximum LV +dP/dt, stroke volume (SV), stroke work (SW), stroke power (SP), and aortic flow. LDM assisted beats were compared with nonstimulated beats. LDM stimulation caused significant increases in pressure and flow in the vascular delay group. At 20 Hz-4 volts, absolute increases were LVP (10.2 +/- 0.6) mm Hg, AoP (9.8 +/- 1.7) mm Hg, SV (1.8 +/- 0.4) ml, SW (5.3 +/- 1.0) gm x m, SP (40.8 +/- 12.7) gm x m/sec, max LV dP/dt (104.8 +/- 53.2) mm Hg/sec, and peak aortic flow (0.9 +/- 0.3) L/min. At 33 Hz-4 volts, the absolute increases were LVP (13.6 +/- 1.3) mm Hg, AoP (12.1 +/- 2.4) mm Hg, SV (2.7 +/- 0.7) ml, SW (7.4 +/- 1.4) gm x m, SP (72.7 +/- 16.5) gm x m/sec, max LV dP/dt (294 +/- 19) mm Hg/sec, and peak aortic flow (1.8 +/- 0.5) L/min. At 50 Hz-10 volts, the absolute increases were LVP (17.7 +/- 0.7) mm Hg, AoP (21.1 +/- 1.9) mm Hg, SV (6.0 +/- 1.1) ml, SW (14.6 +/- 2.2) gm.m, SP (128.2 +/- 15.3) gm x m/sec, max LV dP/dt (352 +/- 62) mm Hg/sec, and peak aortic flow (3.3 +/- 0.4) l/min (p < 0.05). The percentage increases were significantly larger in the vascular delay group compared with controls at 50 Hz-10 volts LDM stimulation. By using a two-stage vascular delay procedure, LDM stimulation can provide meaningful cardiac assistance during training periods. Furthermore, brief periods of maximal potential benefit (demand cardiomyoplasty) can be achieved during the training period.

Animals↗

PubMed2005

Epsilon-sarcoglycan compensates for lack of alpha-sarcoglycan in a mouse model of limb-girdle muscular dystrophy.

Dystrophin and the dystrophin-associated protein (DAP) complex protect the sarcolemma against contraction-induced injury and serve as a mechanical link between the extracellular matrix and the actin cytoskeleton. Some of the functional properties of the DAP complex are mediated by its sarcoglycan (SG) subcomplex, which is composed of alpha-, beta-, gamma- and delta-SGs. Autosomal recessive limb-girdle muscular dystrophy type-2D (LGMD 2D) results from reduction in SG subcomplex levels caused by specific mutations in the muscle-specific alpha-SG gene. epsilon-SG is a widely expressed homolog of the muscle-specific alpha-SG, and expression of epsilon-SG may compensate for the pathologic changes in alpha-SG function. Thus, the goal of the present study was to investigate whether overexpression of epsilon-SG can compensate for dysfunction of alpha-SG. Several transgenic mouse lines that overexpress epsilon-SG in skeletal muscle were established. Overexpression of epsilon-SG in normal mice resulted in substitution of epsilon-SG for alpha-SG in the SG complex of skeletal muscle without any obvious abnormalities. To determine whether an increase in epsilon-SG expression may prevent muscular dystrophy in the context of alpha-SG-deficiency, these epsilon-SG transgenic mice were crossed with alpha-SG deficient mice. alpha-SG-deficient mice overexpressing epsilon-SG exhibited no skeletal muscle cell membrane damage or abnormal contraction. These data suggest that the overexpression of epsilon-SG may represent a therapeutic strategy for treatment of LGMD 2D.

Animals↗

PubMed2001

Skeletal muscle oxidative capacity and exercise tolerance in rats with heart failure.

PURPOSE: Past research has shown the development of exercise intolerance after myocardial infarction (MI). The purpose of this study was to test the hypothesis that reductions in oxidative enzyme activity, in a variety of skeletal muscles, coincide with the development of exercise intolerance in a rat model of chronic heart failure (CHF) induced by MI. METHODS: The animals were initially divided into two groups: sham-operated controls (Sham) and animals in which a MI was surgically induced. MI rats were then subdivided into two groups according to left ventricular end-diastolic pressure (LVEDP): <20 mm Hg [small MI (SMI)] and > 20 mm Hg [large MI (LMI)]. Exercise tolerance was measured by performing a progressive run to fatigue test (RTF). Citrate synthase (CS), 3-hydroxyacyl CoA dehydrogenase (HADH), and malate dehydrogenase (MDH) activities were measured in six hindlimb muscles. RESULTS: After approximately 6 wk of recovery, LVEDP differed among groups (P < 0.05): Sham (1 +/- 1 mm Hg, N = 7), SMI (7 +/- 2 mm Hg, N = 7), and LMI (30 +/- 2 mm Hg, N = 6). RTF was 20 +/- 1 min for Sham, 25 +/- 3 min for SMI, and 11 +/- 2 min for LMI (P < 0.05 for LMI vs Sham, SMI). Significant reductions in enzyme activity were found for all three enzymes in the red portion of the gastrocnemius muscles of LMI. However, no significant correlation was found between RTF and CS, HADH, or MDH in any muscle of the three groups of animals. DISCUSSION: The results of the present study demonstrate that severe left ventricular dysfunction is associated with reductions in exercise tolerance and modest decreases in oxidative enzyme activities in selected muscles. It does not appear, however, that the development of exercise intolerance in CHF and oxidative enzyme activities are mechanistically related to one another.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed2003

Ischemia/reperfusion injury of skeletal muscle: plasma taurine as a measure of tissue damage.

BACKGROUND: Cell membrane rupture by oxygen-derived free radicals is a systematic feature of ischemia/reperfusion (I/R) injury. High taurine concentration gradients in skeletal muscle prompted us to evaluate whether plasma taurine levels (pTau) are a useful marker of I/R injury after different periods of ischemia. METHODS: Rabbits were randomly assigned to either 1 or 2.5 hours of hind-limb ischemia followed by 2 hours of reperfusion (groups IR1 [n = 12] and IR2.5 [n = 13], respectively). Corresponding sham groups (SHAM1 [n = 8] and SHAM2.5 [n = 9]) were used as controls. Analyzed parameters included histomorphometry and electron microscopy of skeletal muscle biopsies, pTau, and plasma level of malondialdehyde. Skeletal muscle function was assessed 3 weeks after I/R injury. RESULTS: No significant morphologic changes were detectable at the end of ischemia. After reperfusion, mild interstitial edema with intact muscle cell membranes developed in IR1 group; pTau was not increased. IR2.5 group, by contrast, showed severe interstitial edema formation (interfiber area increased by 112%, P <.005), microvascular constriction (microvessel area decreased by 33%, P <.0005), and damage to the muscle cell membranes that was confirmed by the increased plasma malondialdehyde. pTau was higher than in the SHAM2.5 group (P <.0005). Pronounced cell damage in IR2.5 group resulted in impaired muscle function (maximal tetanic tension was reduced 2 times, P <.005) but not in IR1 group. CONCLUSION: Skeletal muscle tolerates 1 h/2 h but not 2.5 h/2 h of I/R, the latter resulting in interstitial edema formation, microvascular constriction, and a late muscle dysfunction. Cell membrane rupture through stimulated lipid peroxidation promotes leakage of intracellular taurine, leading to increased pTau after reperfusion and may be considered as prognostically unfavorable in terms of organ function reversibility. In the rabbit model, pTau seems to be a sensitive marker of I/R injury to skeletal muscle.

Animals↗

PubMed1996

Quality of life in older patients with congestive heart failure. Effects of ACE inhibitors.

Prolonged angiotensin converting enzyme (ACE) inhibition has been consistently demonstrated to increase life expectancy in symptomatic patients with congestive heart failure (CHF), and decrease morbidity in asymptomatic patients with left ventricular (LV) systolic dysfunction. However, prolonged ACE inhibition has not been shown to consistently improve the quality of life of patients with symptomatic CHF. The failure of ACE inhibition to improve quality of life cannot be readily explained, but several factors may contribute to this apparent lack of effect. First, endpoints such as death or hospitalisation are clearly easier to quantify and monitor than a patient's perception of how much CHF affects his/her life. Secondly, while ACE inhibition delays the progression of LV systolic dysfunction, which is the primary determinant of prognosis, it may not reverse the alterations in skeletal muscle vasculature, metabolism and mass, which are primarily responsible for exercise intolerance in patients with CHF. Lastly, patients with CHF, and particularly older patients, are also often incapacitated by other disease processes such as arthritis, loss of balance, pulmonary disorders and anaemia, which, to a large extent, affect the quality of their life more than LV systolic dysfunction and/or CHF.

Aged↗

PubMed1993

Deferoxamine prevents lipid peroxidation and attenuates reoxygenation injury in postischemic skeletal muscle.

In the presence of the transition metal iron, superoxide anion and H2O2 generated on reperfusion of postichemic tissue combine to form hydroxyl radical, which readily attacks membrane-associated polyunsaturated fatty acids in a free radical process, resulting in lipid peroxidation. To evaluate whether iron chelation with deferoxamine interrupts this process in postischemic skeletal muscle, high-grade partial hindlimb ischemia was created in Sprague-Dawley rats by clamping the infrarenal aorta for 90 min, after which period the clamp was removed and flow was reestablished for 60 min. Lipid peroxidation in skeletal muscle was assessed by determination of tissue thiobarbituric acid-reactive substances (TBARS); membrane dysfunction was assessed by measurement of resting membrane potential (Em). Ischemia was accompanied by an increase in muscle TBARS and depolarization of resting Em. On reperfusion, muscle TBARS continued to increase, whereas resting Em remained depolarized. Pretreatment with deferoxamine prevented lipid peroxidation during ischemia but had no effect on resting Em. On reperfusion in the deferoxamine-treated animals, there was still no increase in muscle TBARS, and partial repolarization of resting Em was noted. It is concluded that 1) high-grade partial ischemia in skeletal muscle is accompanied by iron-dependent lipid peroxidation via a mechanism that persists and accelerates on reoxygenation, 2) lipid peroxidation impacts on functional membrane integrity during the reperfusion phase only, and 3) membrane injury accompanying ischemia and reperfusion may occur through fundamentally different mechanisms, of which only the latter is iron dependent.

Animals↗

PubMed2001

46,XX gonadal dysgenesis, short stature, and recurrent metabolic acidosis in two sisters.

Gonadal (ovarian) dysgenesis in 46,XX individuals is genetically heterogeneous. We report on two sisters who, in addition to primary ovarian failure, have marked short stature and recurrent episodes of dehydration with metabolic acidosis. Studies performed during one of these episodes suggested mitochondrial dysfunction; however, results of biochemical analysis of electron transport chain activity in skeletal muscle and mitochondrial DNA studies were normal. We discuss the phenotype in relation to previously described conditions of 46,XX gonadal dysgenesis. We suggest this constellation of findings represents a new syndrome.

Acidosis↗