Scholars@Duke
Leonardo F Ferreira

Leonardo F Ferreira

Associate Professor in Orthopaedic Surgery
Orthopaedic Surgery, Physical Therapy
leonardo.ferreira@duke.edu
308 Research Dr, LSRC B330B, Durham, NC 27708

Selected Publications

Skeletal muscle knockout of NAD(P)H oxidase 2 delays the development of isotonic diaphragm fatigue in mice.

Journal Article Free Radic Biol Med · December 1, 2025 Mechanisms of skeletal muscle fatigue are commonly studied under isometric conditions, which exclude muscle shortening and limit physiological relevance. We developed a novel in vitro protocol to examine isotonic fatigue using afterload contractions that p ... Full text Link to item Cite

Relationship of red blood cell mass profiles and anemia type to outcomes and cardiopulmonary exercise performance in chronic heart failure.

Journal Article Am Heart J · October 2025 BACKGROUND: Blood volume analysis (BVA) allows direct measurement of red blood cell mass (RBCM) and differentiation of true and dilutional anemia in heart failure (HF). This study aimed to characterize the relationships of RBCM profiles and anemia types to ... Full text Link to item Cite

A 6-Minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models.

Journal Article JACC Basic Transl Sci · January 2025 In this study, we present a novel 6-minute limb function test that allows for the congruent assessment of muscular performance and hemodynamics in preclinical models of peripheral artery disease. Using several experimental conditions, the results demonstra ... Full text Link to item Cite

Respiratory pathology in the mdx/utrn -/- mouse: A murine model for Duchenne Muscular Dystrophy (DMD).

Journal Article PLoS One · 2025 Duchenne muscular dystrophy (DMD) is an X-linked devastating disease caused by a lack of dystrophin which results in progressive muscle weakness. As muscle weakness progresses, respiratory insufficiency and hypoventilation result in significant morbidity a ... Full text Link to item Cite

Intraoperative phrenic nerve stimulation to prevent diaphragm fiber weakness during thoracic surgery.

Journal Article PLoS One · 2025 Thoracic surgery rapidly induces weakness in human diaphragm fibers. The dysfunction is thought to arise from combined effects of the surgical procedures and inactivity. This project tested whether brief bouts of intraoperative hemidiaphragm stimulation wo ... Full text Link to item Cite

Nebulized and intravenous enzyme replacement therapy in mice with mucopolysaccharidosis type II.

Journal Article PLoS One · 2025 Mucopolysaccharidosis Type II is a hereditary lysosomal storage disease characterized by deficiency in the enzyme iduronate 2-sulfatase (IDS). IDS is critical in the breakdown of sulfated glycosaminoglycans and its deficiency leads to an accumulation of th ... Full text Link to item Cite

Pathogenic TNNI1 variants disrupt sarcomere contractility resulting in hypo- and hypercontractile muscle disease.

Journal Article Sci Transl Med · April 3, 2024 Troponin I (TnI) regulates thin filament activation and muscle contraction. Two isoforms, TnI-fast (TNNI2) and TnI-slow (TNNI1), are predominantly expressed in fast- and slow-twitch myofibers, respectively. TNNI2 variants are a rare cause of arthrogryposis ... Full text Link to item Cite

Activation of the Aryl Hydrocarbon Receptor in Muscle Exacerbates Ischemic Pathology in Chronic Kidney Disease.

Journal Article Circ Res · July 7, 2023 BACKGROUND: Chronic kidney disease (CKD) accelerates the development of atherosclerosis, decreases muscle function, and increases the risk of amputation or death in patients with peripheral artery disease (PAD). However, the mechanisms underlying this path ... Full text Link to item Cite

Chronic activation of the aryl hydrocarbon receptor in muscle exacerbates ischemic pathology in chronic kidney disease.

Journal Article bioRxiv · May 18, 2023 Chronic kidney disease (CKD) accelerates the development of atherosclerosis, decreases muscle function, and increases the risk of amputation or death in patients with peripheral artery disease (PAD). However, the cellular and physiological mechanisms under ... Full text Link to item Cite

Intraoperative Hemi-Diaphragm Electrical Stimulation Demonstrates Attenuated Mitochondrial Function without Change in Oxidative Stress in Cardiothoracic Surgery Patients.

Journal Article Antioxidants (Basel) · April 27, 2023 Mechanical ventilation during cardiothoracic surgery is life-saving but can lead to ventilator-induced diaphragm dysfunction (VIDD) and prolong ventilator weaning and hospital length of stay. Intraoperative phrenic nerve stimulation may preserve diaphragm ... Full text Link to item Cite

Skeletal muscle Nox4 knockout prevents and Nox2 knockout blunts loss of maximal diaphragm force in mice with heart failure with reduced ejection fraction.

Journal Article Free Radic Biol Med · January 2023 Patients with heart failure with reduced ejection fraction (HFrEF) experience diaphragm weakness that contributes to the primary disease symptoms of fatigue, dyspnea, and exercise intolerance. Weakness in the diaphragm is related to excessive production of ... Full text Link to item Cite

Cardiac and respiratory muscle responses to dietary N-acetylcysteine in rats consuming a high-saturated fat, high-sucrose diet.

Journal Article Exp Physiol · November 2022 NEW FINDINGS: What is the central question of this study? This study addresses whether a high-fat, high-sucrose diet causes cardiac and diaphragm muscle abnormalities in male rats and whether supplementation with the antioxidant N-acetylcysteine reverses d ... Full text Link to item Cite

Reversible Thiol Oxidation Increases Mitochondrial Electron Transport Complex Enzyme Activity but Not Respiration in Cardiomyocytes from Patients with End-Stage Heart Failure.

Journal Article Cells · July 25, 2022 Cardiomyocyte dysfunction in patients with end-stage heart failure with reduced ejection fraction (HFrEF) stems from mitochondrial dysfunction, which contributes to an energetic crisis. Mitochondrial dysfunction reportedly relates to increased markers of o ... Full text Link to item Cite

Nitric oxide and skeletal muscle contractile function.

Journal Article Nitric Oxide · May 1, 2022 Nitric oxide (NO) is complex modulator of skeletal muscle contractile function, capable of increasing or decreasing force and power output depending on multiple factors. This review explores the effects and potential mechanisms for modulation of skeletal m ... Full text Link to item Cite

Skeletal myopathy in a rat model of postmenopausal heart failure with preserved ejection fraction.

Journal Article J Appl Physiol (1985) · January 1, 2022 Heart failure with preserved ejection fraction (HFpEF) accounts for ∼50% of all patients with heart failure and frequently affects postmenopausal women. The HFpEF condition is phenotype-specific, with skeletal myopathy that is crucial for disease developme ... Full text Link to item Cite

Nox4 Knockout Does Not Prevent Diaphragm Atrophy, Contractile Dysfunction, or Mitochondrial Maladaptation in the Early Phase Post-Myocardial Infarction in Mice.

Journal Article Cell Physiol Biochem · August 20, 2021 BACKGROUND/AIMS: Diaphragm dysfunction with increased reactive oxygen species (ROS) occurs within 72 hrs post-myocardial infarction (MI) in mice and may contribute to loss of inspiratory maximal pressure and endurance in patients. METHODS: We used wild-typ ... Full text Link to item Cite

The impact of hindlimb disuse on sepsis-induced myopathy in mice.

Journal Article Physiol Rep · July 2021 Sepsis induces a myopathy characterized by loss of muscle mass and weakness. Septic patients undergo prolonged periods of limb muscle disuse due to bed rest. The contribution of limb muscle disuse to the myopathy phenotype remains poorly described. To char ... Full text Link to item Cite

RNA-sequencing reveals transcriptional signature of pathological remodeling in the diaphragm of rats after myocardial infarction.

Journal Article Gene · February 20, 2021 The diaphragm is the main inspiratory muscle, and the chronic phase post-myocardial infarction (MI) is characterized by diaphragm morphological, contractile, and metabolic abnormalities. However, the mechanisms of diaphragm weakness are not fully understoo ... Full text Link to item Cite

Impaired muscle mitochondrial energetics is associated with uremic metabolite accumulation in chronic kidney disease.

Journal Article JCI Insight · December 8, 2020 Chronic kidney disease (CKD) causes progressive skeletal myopathy involving atrophy, weakness, and fatigue. Mitochondria have been thought to contribute to skeletal myopathy; however, the molecular mechanisms underlying muscle metabolism changes in CKD are ... Full text Link to item Cite

Dietary nitrate supplementation increases diaphragm peak power in old mice.

Journal Article J Physiol · October 2020 KEY POINTS: Respiratory muscle function declines with ageing, contributing to breathing complications in the elderly. Here we report greater in vitro respiratory muscle contractile function in old mice receiving supplemental NaNO3 for 14 days compared with ... Full text Link to item Cite

Diaphragm weakness and proteomics (global and redox) modifications in heart failure with reduced ejection fraction in rats.

Journal Article J Mol Cell Cardiol · February 2020 Inspiratory dysfunction occurs in patients with heart failure with reduced ejection fraction (HFrEF) in a manner that depends on disease severity and by mechanisms that are not fully understood. In the current study, we tested whether HFrEF effects on diap ... Full text Link to item Cite

Chronic kidney disease exacerbates ischemic limb myopathy in mice via altered mitochondrial energetics.

Journal Article Sci Rep · October 29, 2019 Chronic kidney disease (CKD) substantially increases the severity of peripheral arterial disease (PAD) symptomology, however, the biological mechanisms remain unclear. The objective herein was to determine the impact of CKD on PAD pathology in mice. C57BL6 ... Full text Link to item Cite

Uremic metabolites impair skeletal muscle mitochondrial energetics through disruption of the electron transport system and matrix dehydrogenase activity.

Journal Article Am J Physiol Cell Physiol · October 1, 2019 Chronic kidney disease (CKD) leads to increased skeletal muscle fatigue, weakness, and atrophy. Previous work has implicated mitochondria within the skeletal muscle as a mediator of muscle dysfunction in CKD; however, the mechanisms underlying mitochondria ... Full text Link to item Cite

Mitochondrial respiration and H2O2 emission in saponin-permeabilized murine diaphragm fibers: optimization of fiber separation and comparison to limb muscle.

Journal Article Am J Physiol Cell Physiol · October 1, 2019 Diaphragm abnormalities in aging or chronic diseases include impaired mitochondrial respiration and H2O2 emission, which can be measured using saponin-permeabilized muscle fibers. Mouse diaphragm presents a challenge for isolation of fibers due to relative ... Full text Link to item Cite

Small-hairpin RNA and pharmacological targeting of neutral sphingomyelinase prevent diaphragm weakness in rats with heart failure and reduced ejection fraction.

Journal Article Am J Physiol Lung Cell Mol Physiol · April 1, 2019 Heart failure with reduced ejection fraction (HFREF) increases neutral sphingomyelinase (NSMase) activity and mitochondrial reactive oxygen species (ROS) emission and causes diaphragm weakness. We tested whether a systemic pharmacological NSMase inhibitor ... Full text Link to item Cite

Mitochondrial basis for sex-differences in metabolism and exercise performance.

Journal Article Am J Physiol Regul Integr Comp Physiol · June 1, 2018 Full text Link to item Cite

Advanced aging causes diaphragm functional abnormalities, global proteome remodeling, and loss of mitochondrial cysteine redox flexibility in mice.

Journal Article Exp Gerontol · March 2018 AIM: Inspiratory muscle (diaphragm) function declines with age, contributing to exercise intolerance and impaired airway clearance. Studies of diaphragm dysfunction in rodents have focused on moderate aging (~24months); thus, the impact of advanced age on ... Full text Link to item Cite

Osmolality Selectively Offsets the Impact of Hyperthermia on Mouse Skeletal Muscle in vitro.

Journal Article Front Physiol · 2018 Hyperthermia and dehydration can occur during exercise in hot environments. Nevertheless, whether elevations in extracellular osmolality contributes to the increased skeletal muscle tension, sarcolemmal injury, and oxidative stress reported in warm climate ... Full text Link to item Cite

Diaphragm abnormalities in heart failure and aging: mechanisms and integration of cardiovascular and respiratory pathophysiology.

Journal Article Heart Fail Rev · March 2017 Inspiratory function is essential for alveolar ventilation and expulsive behaviors that promote airway clearance (e.g., coughing and sneezing). Current evidence demonstrates that inspiratory dysfunction occurs during healthy aging and is accentuated by chr ... Full text Link to item Cite

An injectable capillary-like microstructured alginate hydrogel improves left ventricular function after myocardial infarction in rats.

Journal Article Int J Cardiol · October 1, 2016 BACKGROUND: A new post-myocardial infarction (MI) therapy is injection of high-water-content polymeric biomaterial gels (hydrogels) into damaged myocardium to modulate cardiac negative remodeling and preserve heart function. METHODS: We investigated the th ... Full text Link to item Cite

Regulation of NADPH oxidases in skeletal muscle.

Journal Article Free Radic Biol Med · September 2016 The only known function of NAD(P)H oxidases is to produce reactive oxygen species (ROS). Skeletal muscles express three isoforms of NAD(P)H oxidases (Nox1, Nox2, and Nox4) that have been identified as critical modulators of redox homeostasis. Nox2 acts as ... Full text Link to item Cite

Janus kinase inhibition prevents cancer- and myocardial infarction-mediated diaphragm muscle weakness in mice.

Journal Article Am J Physiol Regul Integr Comp Physiol · April 15, 2016 Respiratory dysfunction is prevalent in critically ill patients and can lead to adverse clinical outcomes, including respiratory failure and increased mortality. Respiratory muscles, which normally sustain respiration through inspiratory muscle contraction ... Full text Link to item Cite

Pharmacological targeting of mitochondrial reactive oxygen species counteracts diaphragm weakness in chronic heart failure.

Journal Article J Appl Physiol (1985) · April 1, 2016 Diaphragm muscle weakness in chronic heart failure (CHF) is caused by elevated oxidants and exacerbates breathing abnormalities, exercise intolerance, and dyspnea. However, the specific source of oxidants that cause diaphragm weakness is unknown. We examin ... Full text Link to item Cite

Diaphragm Abnormalities in Patients with End-Stage Heart Failure: NADPH Oxidase Upregulation and Protein Oxidation.

Journal Article Front Physiol · 2016 Patients with heart failure (HF) have diaphragm abnormalities that contribute to disease morbidity and mortality. Studies in animals suggest that reactive oxygen species (ROS) cause diaphragm abnormalities in HF. However, the effects of HF on ROS sources, ... Full text Link to item Cite

NAD(P)H oxidase subunit p47phox is elevated, and p47phox knockout prevents diaphragm contractile dysfunction in heart failure.

Journal Article Am J Physiol Lung Cell Mol Physiol · September 1, 2015 Patients with chronic heart failure (CHF) have dyspnea and exercise intolerance, which are caused in part by diaphragm abnormalities. Oxidants impair diaphragm contractile function, and CHF increases diaphragm oxidants. However, the specific source of oxid ... Full text Link to item Cite

Chronic heart failure alters orexin and melanin concentrating hormone but not corticotrophin releasing hormone-related gene expression in the brain of male Lewis rats.

Journal Article Neuropeptides · August 2015 OBJECTIVE: The aim of this study was to investigate the effect of chronic heart failure (HF; 16 weeks post left coronary artery ligation) on the brain's orexin (ORX) and related neuropeptide systems. METHODS: Indicators of cardiac function, including the p ... Full text Link to item Cite

Diaphragm dysfunction caused by sphingomyelinase requires the p47(phox) subunit of NADPH oxidase.

Journal Article Respir Physiol Neurobiol · January 1, 2015 Sphingomyelinase (SMase) activity is elevated in inflammatory states and may contribute to muscle weakness in these conditions. Exogenous SMase depresses muscle force in an oxidant-dependent manner. However, the pathway stimulated by SMase that leads to mu ... Full text Link to item Cite

Genome-wide identification of FoxO-dependent gene networks in skeletal muscle during C26 cancer cachexia.

Journal Article BMC Cancer · December 24, 2014 BACKGROUND: Evidence from cachectic cancer patients and animal models of cancer cachexia supports the involvement of Forkhead box O (FoxO) transcription factors in driving cancer-induced skeletal muscle wasting. However, the genome-wide gene networks and a ... Full text Link to item Cite

Diaphragm dysfunction in heart failure is accompanied by increases in neutral sphingomyelinase activity and ceramide content.

Journal Article Eur J Heart Fail · May 2014 AIMS: Chronic heart failure (CHF) causes inspiratory (diaphragm) muscle weakness and fatigue that contributes to dyspnoea and limited physical capacity in patients. However, the mechanisms that lead to diaphragm dysfunction in CHF remain poorly understood. ... Full text Link to item Cite

HDAC1 activates FoxO and is both sufficient and required for skeletal muscle atrophy.

Journal Article J Cell Sci · April 1, 2014 The Forkhead box O (FoxO) transcription factors are activated, and necessary for the muscle atrophy, in several pathophysiological conditions, including muscle disuse and cancer cachexia. However, the mechanisms that lead to FoxO activation are not well de ... Full text Link to item Cite

Mechanical properties of respiratory muscles.

Journal Article Compr Physiol · October 2013 Striated respiratory muscles are necessary for lung ventilation and to maintain the patency of the upper airway. The basic structural and functional properties of respiratory muscles are similar to those of other striated muscles (both skeletal and cardiac ... Full text Link to item Cite

Diaphragm and ventilatory dysfunction during cancer cachexia.

Journal Article FASEB J · July 2013 Cancer cachexia is characterized by a continuous loss of locomotor skeletal muscle mass, which causes profound muscle weakness. If this atrophy and weakness also occurs in diaphragm muscle, it could lead to respiratory failure, which is a major cause of de ... Full text Link to item Cite

Cancer cachexia decreases specific force and accelerates fatigue in limb muscle.

Journal Article Biochem Biophys Res Commun · June 7, 2013 Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachex ... Full text Link to item Cite

Loss of the inducible Hsp70 delays the inflammatory response to skeletal muscle injury and severely impairs muscle regeneration.

Journal Article PLoS One · 2013 Skeletal muscle regeneration following injury is a highly coordinated process that involves transient muscle inflammation, removal of necrotic cellular debris and subsequent replacement of damaged myofibers through secondary myogenesis. However, the molecu ... Full text Link to item Cite

Diaphragm atrophy and contractile dysfunction in a murine model of pulmonary hypertension.

Journal Article PLoS One · 2013 Pulmonary hypertension (PH) causes loss of body weight and inspiratory (diaphragm) muscle dysfunction. A model of PH induced by drug (monocrotaline, MCT) has been extensively used in mice to examine the etiology of PH. However, it is unclear if PH induced ... Full text Link to item Cite

A degradable, bioactive, gelatinized alginate hydrogel to improve stem cell/growth factor delivery and facilitate healing after myocardial infarction.

Journal Article Med Hypotheses · November 2012 Despite remarkable effectiveness of reperfusion and drug therapies to reduce morbidity and mortality following myocardial infarction (MI), many patients have debilitating symptoms and impaired left ventricular (LV) function highlighting the need for improv ... Full text Link to item Cite

Sphingomyelinase depresses force and calcium sensitivity of the contractile apparatus in mouse diaphragm muscle fibers.

Journal Article J Appl Physiol (1985) · May 2012 Diseases that result in muscle weakness, e.g., heart failure, are characterized by elevated sphingomyelinase (SMase) activity. In intact muscle, SMase increases oxidants that contribute to diminished muscle force. However, the source of oxidants, specific ... Full text Link to item Cite

Kinetics of muscle deoxygenation and microvascular PO(2) during contractions in rat: comparison of optical spectroscopy and phosphorescence-quenching techniques.

Journal Article J Appl Physiol (1985) · January 2012 The overarching presumption with near-infrared spectroscopy measurement of muscle deoxygenation is that the signal reflects predominantly the intramuscular microcirculatory compartment rather than intramyocyte myoglobin (Mb). To test this hypothesis, we co ... Full text Link to item Cite

Methodological validation of the dynamic heterogeneity of muscle deoxygenation within the quadriceps during cycle exercise.

Journal Article Am J Physiol Regul Integr Comp Physiol · August 2011 The conventional continuous wave near-infrared spectroscopy (CW-NIRS) has enabled identification of regional differences in muscle deoxygenation following onset of exercise. However, assumptions of constant optical factors (e.g., path length) used to conve ... Full text Link to item Cite

Effectiveness of sulfur-containing antioxidants in delaying skeletal muscle fatigue.

Journal Article Med Sci Sports Exerc · June 2011 UNLABELLED: Reactions involving thiol biochemistry seem to play a crucial role in skeletal muscle fatigue. N-acetylcysteine amide (NACA) and L-ergothioneine (ERGO) are thiol-based antioxidants available for human use that have not been evaluated for effect ... Full text Link to item Cite

N-acetylcysteine in handgrip exercise: plasma thiols and adverse reactions.

Journal Article Int J Sport Nutr Exerc Metab · April 2011 UNLABELLED: N-acetylcysteine (NAC) is a thiol donor with antioxidant properties that has potential use as an ergogenic aid. However, NAC is associated with adverse reactions that limit its use in humans. PURPOSE: The authors evaluated NAC efficacy as a thi ... Full text Link to item Cite

TNF/TNFR1 signaling mediates doxorubicin-induced diaphragm weakness.

Journal Article Am J Physiol Lung Cell Mol Physiol · February 2011 Doxorubicin, a common chemotherapeutic agent, causes respiratory muscle weakness in both patients and rodents. Tumor necrosis factor-α (TNF), a proinflammatory cytokine that depresses diaphragm force, is elevated following doxorubicin chemotherapy. TNF-ind ... Full text Link to item Cite

Treatment with a corticotrophin releasing factor 2 receptor agonist modulates skeletal muscle mass and force production in aged and chronically ill animals.

Journal Article BMC Musculoskelet Disord · January 14, 2011 BACKGROUND: Muscle weakness is associated with a variety of chronic disorders such as emphysema (EMP) and congestive heart failure (CHF) as well as aging. Therapies to treat muscle weakness associated with chronic disease or aging are lacking. Corticotroph ... Full text Link to item Cite

Progressive chronic heart failure slows the recovery of microvascular O2 pressures after contractions in the rat spinotrapezius muscle.

Journal Article Am J Physiol Heart Circ Physiol · December 2010 Chronic heart failure (CHF) induces muscle fiber-type specific alterations in skeletal muscle O(2) delivery and utilization during metabolic transitions. As a result, the recovery of microvascular Po(2) (Pmv(O(2))) is prolonged in slow-twitch skeletal musc ... Full text Link to item Cite

Nitric oxide bioavailability modulates the dynamics of microvascular oxygen exchange during recovery from contractions.

Journal Article Acta Physiol (Oxf) · October 2010 AIM: lowered microvascular PO(2) (PO(2) mv) during the exercise off-transient likely impairs muscle metabolic recovery and limits the capacity to perform repetitive tasks. The current investigation explored the impact of altered nitric oxide (NO) bioavaila ... Full text Link to item Cite

Sphingomyelinase stimulates oxidant signaling to weaken skeletal muscle and promote fatigue.

Journal Article Am J Physiol Cell Physiol · September 2010 Sphingomyelinase (SMase) hydrolyzes membrane sphingomyelin into ceramide, which increases oxidants in nonmuscle cells. Serum SMase activity is elevated in sepsis and heart failure, conditions where muscle oxidants are increased, maximal muscle force is dim ... Full text Link to item Cite

Kinetics analysis of muscle arterial-venous O(2) difference profile during exercise.

Journal Article Respir Physiol Neurobiol · August 31, 2010 Muscle vascular dysfunction, a hallmark of chronic diseases such as heart failure and diabetes, impairs the matching of blood flow (Q(m)) to O(2) utilization (V(O(2m))) following exercise onset. One recently described consequence of this behavior is that a ... Full text Link to item Cite

Bronchodilators accelerate the dynamics of muscle O2 delivery and utilisation during exercise in COPD.

Journal Article Thorax · July 2010 BACKGROUND: Expiratory flow limitation and lung hyperinflation promote cardiocirculatory perturbations that might impair O(2) delivery to locomotor muscles in patients with chronic obstructive pulmonary disease (COPD). The hypothesis that decreases in lung ... Full text Link to item Cite

Aging impacts microvascular oxygen pressures during recovery from contractions in rat skeletal muscle.

Journal Article Respir Physiol Neurobiol · December 31, 2009 Aging-induced alterations in peripheral circulatory control during contractions reduce the microvascular partial pressure of O(2) (P(O)(2)mv; which reflects the dynamic balance in the O(2) delivery-to-O(2) uptake ratio), resulting in exaggerated intramuscu ... Full text Link to item Cite

Doxorubicin acts through tumor necrosis factor receptor subtype 1 to cause dysfunction of murine skeletal muscle.

Journal Article J Appl Physiol (1985) · December 2009 Cancer patients receiving doxorubicin chemotherapy experience both muscle weakness and fatigue. One postulated mediator of the muscle dysfunction is an increase in tumor necrosis factor-alpha (TNF), a proinflammatory cytokine that mediates limb muscle cont ... Full text Link to item Cite

Recovery dynamics of skeletal muscle oxygen uptake during the exercise off-transient.

Journal Article Respir Physiol Neurobiol · September 30, 2009 UNLABELLED: The time course of muscle .V(O2) recovery from contractions (i.e., muscle .V(O2) off-kinetics), measured directly at the site of O(2) exchange, i.e., in the microcirculation, is unknown. Whereas biochemical models based upon creatine kinase flu ... Full text Link to item Cite

The effects of antioxidants on microvascular oxygenation and blood flow in skeletal muscle of young rats.

Journal Article Exp Physiol · September 2009 Alterations of skeletal muscle redox state via antioxidant supplementation have the potential to impact contractile function and vascular smooth muscle tone. The effects of antioxidants on the regulation of muscle O(2) delivery-O(2) utilization (Q(O(2)m/V( ... Full text Link to item Cite

Effects of prior heavy exercise on heterogeneity of muscle deoxygenation kinetics during subsequent heavy exercise.

Journal Article Am J Physiol Regul Integr Comp Physiol · September 2009 We investigated the effects of prior heavy exercise on the spatial heterogeneity of muscle deoxygenation kinetics and the relationship to the pulmonary O(2) uptake (pVO(2)) kinetics during subsequent heavy exercise. Seven healthy men completed two 6-min bo ... Full text Link to item Cite

L-2-Oxothiazolidine-4-carboxylate reverses glutathione oxidation and delays fatigue of skeletal muscle in vitro.

Journal Article J Appl Physiol (1985) · July 2009 Fatiguing exercise promotes oxidation of intracellular thiols, notably glutathione. Interventions that oppose or reverse thiol oxidation can inhibit fatigue. The reduced cysteine donor l-2-oxothiazolidine-4-carboxylate (OTC) supports glutathione synthesis ... Full text Link to item Cite

Reply to Quaresima and Ferrari

Journal Article Journal of Applied Physiology · July 1, 2009 Full text Cite

Heliox improves oxygen delivery and utilization during dynamic exercise in patients with chronic obstructive pulmonary disease.

Journal Article Am J Respir Crit Care Med · June 1, 2009 RATIONALE: Normoxic heliox (mixture of 79% He and 21% O(2)) may enhance exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). It remains to be determined whether part of these beneficial effects could be ascribed to increased O( ... Full text Link to item Cite

The effects of aging on capillary hemodynamics in contracting rat spinotrapezius muscle.

Journal Article Microvasc Res · March 2009 Advancing age alters the structural and functional determinants of convective and diffusive muscle oxygen (O(2)) flux. However, capillary red blood cell (RBC) hemodynamics have not been investigated during contractions in muscles of old animals. Therefore, ... Full text Link to item Cite

Effects of antioxidants on contracting spinotrapezius muscle microvascular oxygenation and blood flow in aged rats.

Journal Article J Appl Physiol (1985) · December 2008 Aged rats exhibit a decreased muscle microvascular O(2) partial pressure (Pmv(O(2))) at rest and during contractions compared with young rats. Age-related reductions in nitric oxide bioavailability due, in part, to elevated reactive O(2) species, constrain ... Full text Link to item Cite

Matching of blood flow to metabolic rate during recovery from moderate exercise in humans.

Journal Article Exp Physiol · October 2008 It is unclear whether measurement of limb or conduit artery blood flow during recovery from exercise provides an accurate representation of flow to the muscle capillaries where gas exchange occurs. To investigate this, we: (a) examined the kinetic response ... Full text Link to item Cite

Kinetics of muscle deoxygenation are accelerated at the onset of heavy-intensity exercise in patients with COPD: relationship to central cardiovascular dynamics.

Journal Article J Appl Physiol (1985) · May 2008 Patients with chronic obstructive pulmonary disease (COPD) have slowed pulmonary O(2) uptake (Vo(2)(p)) kinetics during exercise, which may stem from inadequate muscle O(2) delivery. However, it is currently unknown how COPD impacts the dynamic relationshi ... Full text Link to item Cite

Muscle-derived ROS and thiol regulation in muscle fatigue.

Journal Article J Appl Physiol (1985) · March 2008 Muscles produce oxidants, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), from a variety of intracellular sources. Oxidants are detectable in muscle at low levels during rest and at higher levels during contractions. RNS depres ... Full text Link to item Cite

Muscle microvascular hemoglobin concentration and oxygenation within the contraction-relaxation cycle.

Journal Article Respir Physiol Neurobiol · February 1, 2008 Inability to directly measure microvascular oxygen distribution and extraction in striated muscle during a contraction/relaxation cycle limits our understanding of oxygen transport to and utilization by contracting muscle. We examined muscle microvascular ... Full text Link to item Cite

Dynamics of noninvasively estimated microvascular O2 extraction during ramp exercise.

Journal Article J Appl Physiol (1985) · December 2007 Utilization of near-infrared spectroscopy (NIRS) in clinical exercise testing to detect microvascular abnormalities requires characterization of the responses in healthy individuals and theoretical foundation for data interpretation. We examined the profil ... Full text Link to item Cite

Spatial heterogeneity of quadriceps muscle deoxygenation kinetics during cycle exercise.

Journal Article J Appl Physiol (1985) · December 2007 To test the hypothesis that, during exercise, substantial heterogeneity of muscle hemoglobin and myoglobin deoxygenation [deoxy(Hb + Mb)] dynamics exists and to determine whether such heterogeneity is associated with the speed of pulmonary O(2) uptake (pVo ... Full text Link to item Cite

The final frontier: oxygen flux into muscle at exercise onset.

Journal Article Exerc Sport Sci Rev · October 2007 In humans at exercise onset, intramuscular phosphocreatine decreases immediately, whereas muscle oxygen (O2) uptake seems to rise after a delay of up to 15 s which is inconsistent with models of metabolic control. Novel microcirculatory investigations reve ... Full text Link to item Cite

Oxygen exchange in muscle of young and old rats: muscle-vascular-pulmonary coupling.

Conference Exp Physiol · March 2007 Sustained performance of muscular exercise is contingent upon increasing muscle O(2) delivery (Qo2; the product of blood flow and arterial O(2) content, i.e. Q X Cao2) and utilization (Vo2m ) rapidly at exercise onset and sustaining necessary conductive an ... Full text Link to item Cite

Effects of assuming constant optical scattering on measurements of muscle oxygenation by near-infrared spectroscopy during exercise.

Journal Article J Appl Physiol (1985) · January 2007 The aim of this study was to examine the effects of assuming constant reduced scattering coefficient (mu'(s)) on the muscle oxygenation response to incremental exercise and its recovery kinetics. Fifteen subjects (age: 24 +/- 5 yr) underwent incremental cy ... Full text Link to item Cite

Downhill treadmill running trains the rat spinotrapezius muscle.

Journal Article J Appl Physiol (1985) · January 2007 There are currently no models of exercise that recruit and train muscles, such as the rat spinotrapezius, that are suitable for transmission intravital microscopic investigation of the microcirculation. Recent experimental evidence supports the concept tha ... Full text Link to item Cite

Blood flow and O2 extraction as a function of O2 uptake in muscles composed of different fiber types.

Journal Article Respir Physiol Neurobiol · October 27, 2006 We examined how the greater vasodilatory capacity of slow--(ST) versus fast-twitch (FT) muscles impacts the relationship between blood flow (Q ) and O2 uptake (VO2) and, consequently, the O2 extraction (a-vO2 diff.)-to-VO2 relationship. Q was measured with ... Full text Link to item Cite

Muscle microvascular oxygenation in chronic heart failure: role of nitric oxide availability.

Journal Article Acta Physiol (Oxf) · September 2006 AIM: To test the hypothesis that diminished vascular nitric oxide availability might explain the inability of individuals with chronic heart failure (CHF) to maintain the microvascular PO(2)'s (PO(2mv) proportional, variant O(2) delivery-to-uptake ratio) s ... Full text Link to item Cite

Human femoral artery and estimated muscle capillary blood flow kinetics following the onset of exercise.

Journal Article Exp Physiol · July 2006 The purpose of this study was to compare the kinetics of estimated capillary blood flow (Qcap) to those of femoral artery blood flow (QFA) and estimated muscle oxygen uptake (VO2m). Nine healthy subjects performed a series of transitions from rest to moder ... Full text Link to item Cite

Temporal profile of rat skeletal muscle capillary haemodynamics during recovery from contractions.

Journal Article J Physiol · June 15, 2006 In skeletal muscle capillaries, red blood cell (RBC) flux (F(RBC)), velocity (V(RBC)) and haematocrit (Hct(CAP)) are key determinants of microvascular O2 exchange. However, the mechanisms leading to the changes in F(RBC), V(RBC) and Hct(CAP) during muscle ... Full text Link to item Cite

Effects of pedal frequency on estimated muscle microvascular O2 extraction.

Journal Article Eur J Appl Physiol · March 2006 An increase in muscle contraction frequency could limit muscle blood flow QM compromising the matching of QM and muscle oxygen uptake VO2M. This study examined the effects of pedal cadence on skeletal muscle oxygenation at low, moderate and peak exercise. ... Full text Link to item Cite

Effects of arterial hypotension on microvascular oxygen exchange in contracting skeletal muscle.

Journal Article J Appl Physiol (1985) · March 2006 In healthy animals under normotensive conditions (N), contracting skeletal muscle perfusion is regulated to maintain microvascular O2 pressures (PmvO2) at levels commensurate with O2 demands. Hypovolemic hypotension (H) impairs muscle contractile function; ... Full text Link to item Cite

Frequency-domain characteristics and filtering of blood flow following the onset of exercise: implications for kinetics analysis.

Journal Article J Appl Physiol (1985) · March 2006 We examined the validity and usefulness of a low-pass filter (LPFILTER) to reduce point-to-point variability and enhance parameter estimation of the kinetics of blood flow (BF). Computer simulations were used to determine the power spectrum of simulated re ... Full text Link to item Cite

Effects of altered nitric oxide availability on rat muscle microvascular oxygenation during contractions.

Journal Article Acta Physiol (Oxf) · March 2006 AIM: To explore the role of nitric oxide (NO) in controlling microvascular O2 pressure (P(O2)mv) at rest and during contractions (1 Hz). We hypothesized that at the onset of contractions sodium nitroprusside (SNP) would raise P(O2)mv and slow the kinetics ... Full text Link to item Cite

Kinetics of estimated human muscle capillary blood flow during recovery from exercise.

Journal Article Exp Physiol · September 2005 The kinetic characteristics of muscle capillary blood flow (Qcap) during recovery from exercise are controversial (e.g. one versus two phases). Furthermore, it is not clear how the overall Qcap kinetics are temporally associated with muscle oxygen uptake ( ... Full text Link to item Cite

Kinetics of restoration of arteriolar tone after exercise.

Journal Article J Appl Physiol (1985) · August 2005 Full text Link to item Cite

Muscle blood flow-O2 uptake interaction and their relation to on-exercise dynamics of O2 exchange.

Journal Article Respir Physiol Neurobiol · May 12, 2005 A computer model was developed to provide a theoretical framework for interpreting the dynamics of muscle capillary O(2) exchange in health and disease. We examined the effects of different muscle oxygen uptake (V O(2m)) and CvO(2) profiles on muscle blood ... Full text Link to item Cite

Dynamics of skeletal muscle oxygenation during sequential bouts of moderate exercise.

Journal Article Exp Physiol · May 2005 In rat muscle, faster dynamics of microvascular P(O2) (approximately blood flow (Q(m) to O2 uptake (V(O2) ratio) after prior contractions that did not alter blood [lactate] have been considered to be a consequence of faster V(O2) kinetics. However, in huma ... Full text Link to item Cite

Muscle capillary blood flow kinetics estimated from pulmonary O2 uptake and near-infrared spectroscopy.

Journal Article J Appl Physiol (1985) · May 2005 The near-infrared spectroscopy (NIRS) signal (deoxyhemoglobin concentration; [HHb]) reflects the dynamic balance between muscle capillary blood flow (Q(cap)) and muscle O(2) uptake (Vo(2)(m)) in the microcirculation. The purposes of the present study were ... Full text Link to item Cite