Resistance training and aerobic training improve muscle strength and aerobic capacity in chronic inflammatory demyelinating polyneuropathy

Introduction: We investigated the effects of aerobic and resistance exercise in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: Eighteen CIDP patients treated with subcutaneous immunoglobulin performed 12 weeks of aerobic exercise and 12 weeks of resistance exercise after a run‐in period of 12 weeks without exercise. Three times weekly the participants performed aerobic exercise on an ergometer bike or resistance exercise with unilateral training of knee and elbow flexion/extension. Primary outcomes were maximal oxygen consumption velocity (VO₂‐max) and maximal combined isokinetic muscle strength (cIKS) of knee and elbow flexion/extension. Results: VO₂‐max and muscle strength were unchanged during run‐in (?4.9% ± 10.3%, P = 0.80 and ?3.7% ± 10.1%, P = 0.17, respectively). Aerobic exercise increased VO₂‐max by 11.0% ± 14.7% (P = 0.02). Resistance exercise resulted in an increase of 13.8% ± 16.0% (P = 0.0004) in cIKS. Discussion: Aerobic exercise training and resistance exercise training improve fitness and strength in CIDP patients. Muscle Nerve 57 : 70–76, 2018     

Satellite cell pool expansion is affected by skeletal muscle characteristics

Introduction: We investigated changes in satellite cell (SC) pool size after an acute bout of strenuous exercise and evaluated the influence of baseline SC count and fiber type. Methods: Participants completed a downhill running (DHR) intervention (5 × 8 min, 2‐min rest; 80% VO _2max; ?10% gradient). Muscle biopsies were taken 7 days before VO _2max and 7–9 days after the DHR intervention. Delayed‐onset muscle soreness (DOMS) and creatine kinase activity (CK) were measured on days 1, 2, 7, and 9 post‐DHR. SCs were identified by Pax7 and laminin staining. Relative distribution of MHC isoforms was determined by electrophoresis. Results: DOMS and CK peaked on day 1 post‐DHR (P < 0.01). The SC pool increased (26%) after DHR (P = 0.005). SCs/total myonuclei after recovery correlated with baseline SCs (r = 0.979, P = 0.003) and VO _2max (r = 0.956, P = 0.011), whereas change in SC pool (Pax7⁺ cells/total myonuclei: recovery minus baseline) tended to correlate with percent MHC II (r = 0.848; P = 0.06). Conclusion: Interindividual physiological characteristics affect SC pool expansion after a single bout of DHR and are influenced by VO _2max. Muscle Nerve, 2013     

Vastus lateralis NA+‐K+‐ATpase activity,protein, and isoform distribution in chronic obstructive pulmonary disease

In this study we investigate the hypothesis that protein abundance, isoform distribution, and maximal catalytic activity of sodium–potassium–adenosine triphosphatase (Na⁺‐K⁺‐ATPase) would be altered in muscle of patients with moderate to severe chronic obstructive pulmonary disease (COPD). Tissue samples were obtained from the vastus lateralis of 10 patients with COPD (mean ± SE: age = 67 ± 2.9 years; FEV₁ = 39 ± 5.5%) and 10 healthy, matched controls (CON: age = 68 ± 2 years; FEV₁ = 114 ± 4.2%). The samples were assessed for maximal catalytic activity (V_max) of the enzyme using the K⁺‐stimulated 3‐O‐methylfluorescein‐phosphatase (3‐O‐MFPase) assay, enzyme abundance using the [³H]‐ouabain assay, and isoform content of both α (α₁, α₂, α₃) and β (β₁, β₂, β₃) using Western blot techniques. A 19.4% lower (P < 0.05) V_max was observed in COPD compared with CON (90.7 ± 6.7 vs. 73.1 ± 4.7 nmol · mg protein^?1 h^?1). No differences between groups were observed for pump concentration (259 ± 15 vs. 243 ± 17 pmol · g wet weight). For the isoforms, α₁ was decreased by 28% (P < 0.05), and α₂ was increased by 12% (P < 0.05) in COPD compared with CON. No differences between groups were observed for α₃ or for the β isoforms. We conclude that moderate COPD compromises V_max, which occurs in the absence of changes in pump abundance. The reduction in V_max could be due to a shift in isoform expression (α₁, α₂), alterations in intrinsic regulation, or to structural changes in the enzyme. The changes observed in the catalytic activity of the pump could have major effects on membrane excitability and fatigability, which are typically compromised in COPD. Muscle Nerve, 2009     

Phrenic nerve involvement and respiratory muscle weakness in patients with Charcot‐Marie‐Tooth disease 1A

Diaphragm weakness in Charcot‐Marie‐Tooth disease 1A (CMT1A) is usually associated with severe disease manifestation. This study comprehensively investigated phrenic nerve conductivity, inspiratory and expiratory muscle function in ambulatory CMT1A patients. Nineteen adults with CMT1A (13 females, 47 ± 12 years) underwent spiromanometry, diaphragm ultrasound, and magnetic stimulation of the phrenic nerves and the lower thoracic nerve roots, with recording of diaphragm compound muscle action potentials (dCMAP, n = 15), transdiaphragmatic and gastric pressures (twPdi and twPgas, n = 12). Diaphragm motor evoked potentials (dMEP, n = 15) were recorded following cortical magnetic stimulation. Patients had not been selected for respiratory complaints. Disease severity was assessed using the CMT Neuropathy Scale version 2 (CMT‐NSv2). Healthy control subjects were matched for age, sex, and body mass index. The following parameters were significantly lower in CMT1A patients than in controls (all P < .05): forced vital capacity (91 ± 16 vs 110 ± 15% predicted), maximum inspiratory pressure (68 ± 22 vs 88 ± 29 cmH₂O), maximum expiratory pressure (91 ± 23 vs 123 ± 24 cmH₂O), and peak cough flow (377 ± 135 vs 492 ± 130 L/min). In CMT1A patients, dMEP and dCMAP were delayed. Patients vs controls showed lower diaphragm excursion (5 ± 2 vs 8 ± 2 cm), diaphragm thickening ratio (DTR, 1.9 [1.6‐2.2] vs 2.5 [2.1‐3.1]), and twPdi (8 ± 6 vs 19 ± 7 cmH₂O; all P < .05). DTR inversely correlated with the CMT‐NSv2 score (r = ?.59, P = .02). There was no group difference in twPgas following abdominal muscle stimulation. Ambulatory CMT1A patients may show phrenic nerve involvement and reduced respiratory muscle strength. Respiratory muscle weakness can be attributed to diaphragm dysfunction alone. It relates to neurological impairment and likely reflects a disease continuum.     

Ingestion of transient receptor potential channel agonists attenuates exercise‐induced muscle cramps

Introduction: Exercise‐associated muscle cramping (EAMC) is a poorly understood problem that is neuromuscular in origin. Ingestion of transient receptor potential (TRP) channel agonists has been efficacious in attenuating electrically induced muscle cramps. This study examines the effect of TRP agonist ingestion on voluntarily induced EAMC and motor function. Methods: Study 1: Thirty‐nine participants completed 2 trials after ingesting TRP agonist‐containing active treatment (A), or vehicle (V) control. Cramping in the triceps surae muscle was induced via voluntary isometric contraction. Study 2: After ingesting A or V, 31 participants performed kinematic and psychomotor tests of manual dexterity. Results: A increased precramp contraction duration (A, 36.9 ± 4.1 s; V, 27.8 ± 3.1 s), decreased cramp EMG area under the curve (A, 37.3 ± 7.7 %EMG_max·s; V, 77.2 ± 17.7 %EMG_max·s), increased contraction force to produce the cramp (A, 13.8 ± 1.8 kg; V, 9.9 ± 1.6 kg), and decreased postcramp soreness (A, 4.1 ± 0.3 arbitrary units (a.u.); V, 4.7 ± 0.3 a.u.). Kinematic and psychomotor tests were not affected. Discussion: TRP agonist ingestion attenuated EAMC characteristics without affecting motor function. Muscle Nerve 56 : 379–385, 2017     

Lack of caspase‐3 attenuates immobilization‐induced muscle atrophy and loss of tension generation along with mitigation of apoptosis and inflammation

Introduction: Immobilization by casting induces disuse muscle atrophy (DMA). Methods: Using wild type (WT) and caspase‐3 knockout (KO) mice, we evaluated the effect of caspase‐3 on muscle mass, apoptosis, and inflammation during DMA. Results: Caspase‐3 deficiency significantly attenuated muscle mass decrease [gastrocnemius: 28 ± 1% in KO vs. 41 ± 3% in WT; soleus: 47 ± 2% in KO vs. 56 ± 2% in WT; (P < 0.05)] and gastrocnemius twitch tension decrease (23 ± 4% in KO vs. 36 ± 3% in WT, P < 0.05) at day 14 in immobilized vs. contralateral hindlimb. Lack of caspase‐3 decreased immobilization‐induced increased apoptotic myonuclei (3.2‐fold) and macrophage infiltration (2.2‐fold) in soleus muscle and attenuated increased monocyte chemoattractant protein‐1 mRNA expression (2‐fold in KO vs. 18‐fold in WT) in gastrocnemius. Conclusions: Caspase‐3 plays a key role in DMA and associated decreased tension, presumably by acting on the apoptosis and inflammation pathways. Muscle Nerve 47: 711–721, 2013     

Estimation of skeletal muscle energy metabolism in Machado‐Joseph disease using 31P‐MR spectroscopy

The aim of this study was to determine if muscle energy metabolism, as measured by ³¹P‐magnetic resonance spectroscopy (MRS), is a metabolic marker for the efficacy of treatment of Machado‐Joseph disease (MJD). We obtained ³¹P‐MRS in the calf muscle of 8 male patients with MJD and 11 healthy men before, during, and after a 4 minute plantar flexion exercise in a supine position. The data showed that there was a significant difference between the groups in terms of the PCr/(Pi + PCr) ratio at rest (P = 0.03) and the maximum rate of mitochondrial ATP production (V_max) (P < 0.01). In addition, V_max was inversely correlated with the scale for the assessment and rating of ataxia score (r = ?0.34, P = 0.04). The MJD group also showed a reduction in V_max over the course of 2 years (P < 0.05). These data suggest that this noninvasive measurement of muscle energy metabolism may represent a surrogate marker for MJD. © 2010 Movement Disorder Society     

LAMA2‐related myopathy: Frequency among congenital and limb‐girdle muscular dystrophies

Introduction: Muscular dystrophy caused by LAMA2‐gene mutations is an autosomal recessive disease typically presenting as a severe, early‐onset congenital muscular dystrophy (CMD). However, milder cases with a limb‐girdle type muscular dystrophy (LGMD) have been described. Methods: In this study, we assessed the frequency and phenotypic spectrum of LAMA2‐related muscular dystrophy in CMD (n = 18) and LGMD2 (n = 128) cohorts identified in the last 15 years in eastern Denmark. The medical history, brain‐MRI, muscle pathology, muscle laminin‐α2 expression, and genetic analyses were assessed. Results: Molecular genetics revealed 2 pathogenic LAMA2 mutations in 5 of 18 CMD and 3 of 128 LGMD patients, corresponding to a LAMA2‐mutation frequency of 28% in the CMD and 2.3% in the LGMD cohorts, respectively. Conclusions: This study demonstrates a wide clinical spectrum of LAMA2‐related muscular dystrophy and its prevalence in an LGMD2 cohort, which indicates that LAMA2 muscular dystrophy should be included in the LGMD2 nomenclature. Muscle Nerve 52: 547–553, 2015     

Impairment of muscle mitochondrial oxidative metabolism in McArdle's disease

Impairment of muscle glycogenolysis in McArdle's disease (myophosphorylase deficiency) leads to exercise intolerance and exercise-induced myalgia. The pathophysiology of these symptoms is not entirely clear. We used phosphorus magnetic resonance spectroscopy to measure muscle phosphate metabolite concentrations and intracellular pH during brief ischemic exercise and in the period of aerobic metabolic recovery after exercise, with special attention to cytoplasmic adenosine 5′-diphosphate (ADP). In 5 patients with McArdle's disease, calculated muscle intracellular ADP concentrations at the beginning of recovery were higher than in normal control subjects (70–425 mmol/L, control mean: 73 ± 40 mmol/L, P < 0.05). The half-time for intracellular ADP recovery after exercise, an index of maximal mitochondrial oxidative phosphorylation, was 0.16 ± 0.07 in normal controls and was independent of metabolic state or intracellular pH. ADP recoveries were abnormally slow in all patients with McArdle's disease (range: 0.32–0.83 min, mean = 0.2 min, P < 0.0001). These results are indicative of a limitation in the rate of oxidative phosphorylation in muscle of patients with McArdle's disease, most likely due to impaired substrate delivery to mitochondria. This impairment of mitochondrial function may contribute to the exercise-related symptoms in McArdle's disease. © 1996 John Wiley & Sons, Inc.     

Violence in a Finnish forensic psychiatric hospital

Background: Patients with schizophrenia have a high risk of cardiovascular disease (CVD). High aerobic intensity training (HIT) improve peak oxygen uptake (VO_2peak), net mechanical efficiency of walking and risk factors for CVD but has not been investigated in patients with schizophrenia. Aims: To investigate effects from HIT on VO_2peak, net mechanical efficiency of walking and risk factors for CVD in patients with schizophrenia. Methods: 25 inpatients (F20–29, ICD-10) were allocated to either HIT or playing computer games (CG), 3 days per week for 8 weeks. HIT consisted of 4 × 4-min intervals with 3-min break periods, at 85–95% and 70% of peak heart rate, respectively. Results: 12 and seven patients completed HIT and CG, respectively. The baseline VO_2peak in both groups combined (n = 19) was 36.8 ± 8.2 ml/kg/min and 3.12 ± 0.55 l/min. The HIT group improved VO_2peak by 12% from 3.17 ± 0.59 to 3.56 ± 0.68 l/min (P < 0.001), more than the CG group (P = 0.014). Net mechanical efficiency of walking improved by 12% in the HIT group from 19.8 ± 3.0% to 22.2 ± 4.5% (P = 0.005), more than the CG group (P = 0.031). The psychiatric symptoms, expressed as the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS), did not improve in either group. Conclusions: VO_2peak and net mechanical efficiency of walking improved significantly by 8 weeks of HIT. HIT should be included in rehabilitation in order to improve physical capacity and contribute risk reduction of CVD.     

Prophylactic stretching does not reduce cramp susceptibility

Introduction: Some clinicians advocate stretching to prevent muscle cramps. It is unknown whether static or proprioceptive neuromuscular facilitation (PNF) stretching increases cramp threshold frequency (TF_c), a quantitative measure of cramp susceptibility. Methods: Fifteen individuals completed this randomized, counterbalanced, cross‐over study. We measured passive hallux range of motion (ROM) and then performed 3 minutes of either static stretching, PNF stretching (hold–relax—with agonist contraction), or no stretching. ROM was reassessed and TF_c was measured. Results: PNF stretching increased hallux extension (pre‐PNF 81 ± 11°, post‐PNF 90 ± 10°; P < 0.05) but not hallux flexion (pre‐PNF 40 ± 7°, post‐PNF 40 ± 7°; P > 0.05). Static stretching increased hallux extension (pre‐static 80 ± 11°, post‐static 88 ± 9°; P < 0.05) but not hallux flexion (pre‐static 38 ± 9°, post‐static 39 ± 8°; P > 0.05). No ROM changes occurred with no stretching (P > 0.05). TF_c was unaffected by stretching (no stretching 18 ± 7 Hz , PNF 16 ± 4 Hz , static 16 ± 5 Hz ; P = 0.37). Discussion: Static and PNF stretching increased hallux extension, but neither increased TF_c. Acute stretching may not prevent muscle cramping. Muscle Nerve 57 : 473–477, 2018     

Increased 5‐HT2A receptors in the temporal cortex of parkinsonian patients with visual hallucinations

Well‐formed visual hallucinations (VH) are common in patients with Parkinson's disease (PD). The pathophysiology of VH in PD is unknown but may involve structures mediating visual processing such as the inferior temporal cortex. Serotonergic type 2A (5‐HT_2A) receptors have been linked to many psychiatric disorders, including psychosis. We hypothesized that enhanced 5‐HT_2A receptor levels may be involved in VH in PD. Autoradiographic binding using [³H]‐ketanserin and spiperone, to define 5‐HT_2A receptors, was performed in 6 PD patients with VH, 6 PD patients without VH, and 5 healthy, age‐matched controls. The cerebral regions studied included the orbitofrontal cortex, inferolateral temporal cortex, motor cortex, striatum, and substantia nigra. There was a significant (45.6%) increase in the levels of [³H]‐ketanserin binding in the inferolateral temporal cortex of PD patients with VH when compared with PD patients without VH (54.3 ± 5.2 fmol/mg vs. 37.3 ± 4.3 fmol/mg, P = 0.039). Additionally, there was a significant increase in the levels of 5‐HT_2A receptors in the motor cortex of all PD patients taken as a group when compared with controls (57.8 ± 5.7 fmol/mg vs. 41.2 ± 2.6 fmol/mg, P = 0.0297). These results suggest that enhanced 5‐HT_2A‐mediated neurotransmission in the inferolateral temporal cortex, a critical structure in visual processing, might be associated with the development of VH in PD. Our results provide new insights into the pathophysiology of VH in PD and provide an anatomical basis to explain why compounds with 5‐HT_2A antagonist activity are effective at alleviating this debilitating complication. © 2010 Movement Disorder Society     

Prevention of muscle disuse atrophy by MG132 proteasome inhibitor

Introduction: Our goal was to determine whether in vivo administration of the proteasome inhibitor MG132 can prevent muscle atrophy caused by hindlimb unloading (HU). Methods: Twenty‐seven NMRI mice were assigned to a weight‐bearing control, a 6‐day HU, or a HU+MG132 (1 mg/kg/48 h) treatment group. Results: Gastrocnemius wasting was significantly less in HU+MG132 mice (?6.7 ± 2.0%) compared with HU animals (?12.6 ± 1.1%, P = 0.011). HU was also associated with an increased expression of MuRF‐1 (P = 0.006), MAFbx (P = 0.001), and USP28 (P = 0.027) mRNA, whereas Nedd4, E3α, USP19, and UBP45 mRNA did not change significantly. Increases in MuRF‐1, MAFbx, and USP28 mRNA were largely repressed after MG132 administration. β5 proteasome activity tended to increase in HU (+16.7 ± 6.1%, P = 0.086). Neither β1 and β2 proteasome activities nor ubiquitin‐conjugated proteins were changed by HU. Conclusions: Our results indicate that in vivo administration of MG132 partially prevents muscle atrophy associated with disuse and highlight an unexpected regulation of MG132 proteasome inhibitor on ubiquitin‐ligases. Muscle Nerve, 2011     

Episodes of exercise-induced dark urine and myalgia in LGMD 2I

Lindberg C, Sixt C, Oldfors A. Episodes of exercise‐induced dark urine and myalgia in LGMD 2I.
Acta Neurol Scand: 2012: 125: 285–287.
© 2011 John Wiley & Sons A/S. Background – Mutations in the fukutin‐related protein gene FKRP (MIM *606596) cause a form of congenital muscular dystrophy (MDC1C) and also limb girdle muscular dystrophy type 2I (LGMD2I). Exercise‐induced myoglobinuria, frequently occurring in metabolic myopathies, has been described in Becker muscular dystrophy and in a few cases of LGMD. Objectives – To describe that episodes with myoglobinuria, often associated with exercise‐induced myalgia, may be common and a presenting symptom in patients with LGMD2I. Methods – Data on episodes of suspected myoglobinuria and myalgia were collected from the patient records on 14 patients with a diagnosis of LGMDI. Results – Five LGMD2I patients reported recurrent episodes of dark urine and myalgia after exercise, and in three of them, this was the only symptom for several years. Conclusions – We conclude that episodes compatible with exercise‐induced myoglobinuria may be frequent in LGMD2I.     

Goodbye to neuromuscular images

The limb‐girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous, autosomal inherited muscular dystrophies with a childhood to adult onset, manifesting with hip‐ and shoulder‐girdle muscle weakness. When the term LGMD was first conceptualized in 1954, it was thought to be a single entity. Currently, there are 8 autosomal dominant (LGMD1A–1H) and 26 autosomal recessive (LGMD2A–2Z) variants according to the Online Mendelian Inheritance in Man database. In addition, there are other genetically identified muscular dystrophies with an LGMD phenotype not yet classified as LGMD. This highlights the entanglement of LGMDs, which represents an area in continuous expansion. Herein we aim to simplify the complexity of LGMDs by subgrouping them on the basis of the underlying defective protein and impaired function. Muscle Nerve 58 : 167–177, 2018     

Cardiac pathology exceeds skeletal muscle pathology in two cases of limb‐girdle muscular dystrophy type 2I

Limb‐girdle muscular dystrophy type 2I (LGMD‐2I) is caused by mutations in the fukutin‐related protein gene (FKRP) that lead to abnormal glycosylation of α‐dystroglycan in skeletal muscle. Heart involvement in LGMD‐2I is common, but little is known about a underlying cardiac pathology. Herein we describe two patients with LGMD‐2I (homozygous FKRP mutation c.826C>A, p.Leu276Ile) who developed severe congestive heart failure that required cardiac transplantation. The dystrophic pathology and impairment of α‐dystroglycan glycosylation were severe in the heart but mild in skeletal muscle, underscoring the lack of correlation between cardiac and skeletal muscle involvement in some LGMD‐2I patients. Muscle Nerve, 2009     

How to Score the Peak Oxygen Consumption Obtained Through Cardiopulmonary Exercise Test in Individuals after Stroke?

ObjectivesTo compare five distinct methods to score the peak of oxygen consumption (VO2peak) obtained through the cardiopulmonary exercise testing (CPET) in individuals after stroke.Materials and methodsThe VO_2peak was obtained through the CPET with five methods: method-1: the highest value of the test; method-2: the highest value of the last 30 seconds at peak exercise; method-3: the mean of the last 30 seconds at peak exercise; method-4: the mean of the last 20 seconds at peak exercise; method-5: the highest value averaged of the 3 last blocks of 10 seconds at peak exercise. The coefficient of variance (CV) and the mean differences with 95% confidence interval (CI) between the scoring methods were calculated. A post-hoc test (Tukey HSD) was performed to calculate the adjusted 95%CI.ResultsFifty-nine individuals were included (54±12 years, 56±60 months after stroke). The CV of the methods 1-to-5 were, respectively: 27.91%, 25.77%, 23.38%, 23.83%, and 23.33%. There was no difference between method-1 and method-2 (95%CI: -1.10 to 4.69) and between methods 3 to 5: method-3 and method-4 (95%CI: -2.97 to 2.82); method-3 and method-5 (95%CI: -3.57 to 2.22); method-4 and method-5 (95%CI: -3.49 to 2.30). However, method-1 and -2 provided VO_2peak values different from that of methods 3-to-5.ConclusionsThe scoring method of obtaining the VO_2peak has an influence on its magnitude. Since methods 3-to-5 showed lower CV and provided similar values, they should be used to calculate the VO_2peak obtained through the CPET in individuals after stroke.     

Effects of exercise and muscle type on BDNF,NT‐4/5, and TrKB expression in skeletal muscle

Muscle‐derived neurotrophins are thought to contribute to the adaptation of skeletal muscle to exercise, but the effects of brief exercise interventions on BDNF, NT‐4/5, and trkB are not understood. RNA was extracted for RT‐PCR from soleus and medial gastrocnemius of Sprague‐Dawley rats exercised on a treadmill at speeds up to 20 m/min at 5% incline for 5 or 10 days. BDNF expression was elevated in soleus following 5 days (184%, P < 0.001) but not 10 days of exercise. NT‐4/5 and trkB were not affected at either time‐point. BDNF mRNA was significantly higher in soleus at rest when compared with medial gastrocnemius (193%, P < 0.05). No significant effects of muscle type were detected for NT‐4/5 and trkB. Our results indicate differential control of BDNF expression between soleus and medial gastrocnemius following 5 days of exercise. BDNF may be a protein with an uncharacterized contribution to the acute adaptation of skeletal muscle to exercise, whereas NT‐4/5 shows no response. Muscle Nerve, 2009     

Sympathetic nerve activity restrains reflex vasodilatation in heart failure

Background Blunted reflex muscle vasodilatory response during exercise in heart failure (HF) patients may be secondary to augmented vasoconstriction. We tested the hypothesis that the exaggerated sympathetic nerve activity restrains the reflex muscle vasodilatation during exercise in HF patients. Methods We studied the reflex vasodilatory response (plethysmography) during 3 min static handgrip exercise at 30% maximal voluntary contraction in 10 advanced HF patients (45 ± 3year, NYHA Functional Class III/IV) and 10 age-matched normal controls (NC, 40 ± 3year, P = 0.23) during intra-arterial infusion of: (1) saline control; and (2) alpha-adrenergic blocker (phentolamine). Results Baseline forearm vascular conductance (FVC) was lower in HF patients than in NC (2.07 ± 0.2 vs. 4.26 ± 0.6 units, respectively; P = 0.002). FVC responses during exercise increased significantly in NC, but not in HF patients (delta changes: 1.05 ± 0.4 vs. 0.05 ± 0.2 units, respectively). Phentolamine significantly increased resting FVC in HF patients (from 2.07 ± 0.2 to 5.74 ± 0.7 units, P = 0.00004) and restored reflex vasodilatory responses during exercise (delta changes: from 0.05 ± 0.2 to 1.82 ± 0.9 units) eliminating the difference in FVC between both groups. Conclusions The blunted reflex muscle vasodilatory response during exercise in advanced HF patients is, at least in part, due to the increase in sympathetic nerve activity.