Impaired Skeletal Muscle Oxygenation and Exercise Tolerance in Pulmonary Hypertension.

Background: Limb muscle dysfunction is documented in pulmonary arterial hypertension (PAH), but little is known regarding muscle oxygen (O2) supply and its possible effects on exercise tolerance in PAH.

Methods: Ten patients with PAH and 10 matched controls underwent progressive maximal cardiopulmonary exercise test, voluntary and nonvolitional dominant quadriceps muscle strength measures, and nondominant quadriceps biopsy to assess maximal oxygen uptake, muscle function, and lower limb fiber type and capillarity, respectively. Both groups then performed normoxic and hyperoxic submaximal intensity exercise protocol at the same absolute workload during which muscle O2 supply was assessed by measuring changes in myoglobin-deoxyhemoglobin level (Δ[Mb-HHb]) and tissue oxygenation index in the dominant quadriceps using near-infrared spectroscopy.

Alternatives to the six-minute walk test in pulmonary arterial hypertension.

Introduction: The physiological response during the endurance shuttle walk test (ESWT), the cycle endurance test (CET) and the incremental shuttle walk test (ISWT) remains unknown in PAH. We tested the hypothesis that endurance tests induce a near-maximal physiological demand comparable to incremental tests. We also hypothesized that differences in respiratory response during exercise would be related to the characteristics of the exercise tests.

Impaired angiogenesis and peripheral muscle microcirculation loss contribute to exercise intolerance in pulmonary arterial hypertension.

Rationale: Pulmonary arterial hypertension (PAH) is characterized by significant exercise intolerance, which is multifactorial and involves skeletal muscle alterations. There is growing evidence that microRNAs (miRs) are involved in PAH pathogenesis.

Objectives: We hypothesized that miR-126, an endothelial-specific, proangiogenic miR, is down-regulated in the peripheral muscles of patients with PAH, which would account for skeletal muscle microcirculation loss and exercise intolerance.

Tolerance and physiological correlates of neuromuscular electrical stimulation in COPD: a pilot study.

Rationale: Neuromuscular electrical stimulation (NMES) of the lower limbs is an emerging training strategy in patients with COPD. The efficacy of this technique is related to the intensity of the stimulation that is applied during the training sessions. However, little is known about tolerance to stimulation current intensity and physiological factors that could determine it.

Pathogenesis of hyperinflation in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable lung disease characterized by airflow limitation that is not fully reversible. In a significant proportion of patients with COPD, reduced lung elastic recoil combined with expiratory flow limitation leads to lung hyperinflation during the course of the disease. Development of hyperinflation during the course of COPD is insidious.

Repeatability and responsiveness of exercise tests in pulmonary arterial hypertension.

Exercise tolerance in pulmonary arterial hypertension (PAH) is most commonly assessed by the 6-min walk test (6MWT). Whether endurance exercise tests are more responsive than the 6MWT remains unknown. 20 stable PAH patients (mean±sd age 53±15 years and mean pulmonary arterial pressure 44±16 mmHg) already on PAH monotherapy completed the 6MWT, the endurance shuttle walk test (ESWT) and the cycle endurance test (CET) before and after the addition of sildenafil citrate 20 mg three times daily or placebo for 28 days in a randomised double-blind crossover setting.

Effect of bisoprolol on respiratory function and exercise capacity in chronic obstructive pulmonary disease.

Cardioselective β blockers are considered to have little impact on lung function at rest in patients with chronic obstructive pulmonary disease (COPD). However, their effects on dynamic hyperinflation, an important mechanism contributing to symptoms and exercise tolerance in patients with COPD, have not been evaluated. Twenty-seven patients with moderate to severe COPD (forced expiratory volume in 1 second 52 ± 13% predicted) completed pulmonary function tests, echocardiography, maximal exercise tests, and cycle endurance tests at baseline.

Functional and muscular effects of neuromuscular electrical stimulation in patients with severe COPD: a randomized clinical trial.

Background: The mechanisms through which neuromuscular electrical stimulation (NMES) training may improve limb muscle function and exercise tolerance in COPD are poorly understood. We investigated the functional and muscular effects of NMES in advanced COPD.

Methods: Twenty of 22 patients with COPD were randomly assigned to NMES (n = 12) or sham (n = 8) training in a double-blind controlled study.

Assessment of daily life physical activities in pulmonary arterial hypertension.

Background: In pulmonary arterial hypertension (PAH), the six-minute walk test (6MWT) is believed to be representative of patient's daily life physical activities (DL(PA)). Whether DL(PA) are decreased in PAH and whether the 6MWT is representative of patient's DL(PA) remain unknown.

Methods: 15 patients with idiopathic PAH (IPAH) and 10 patients with PAH associated with limited systemic sclerosis (PAH-SSc) were matched with 15 healthy control subjects and 10 patients with limited systemic sclerosis without PAH.

Signal transducers and activators of transcription-3/pim1 axis plays a critical role in the pathogenesis of human pulmonary arterial hypertension.

Background: Pulmonary artery hypertension (PAH) is a proliferative disorder associated with enhanced pulmonary artery smooth muscle cell proliferation and suppressed apoptosis. The sustainability of this phenotype required the activation of a prosurvival transcription factor like signal transducers and activators of transcription-3 (STAT3) and nuclear factor of activated T cell (NFAT). Because these factors are implicated in several physiological processes, their inhibition in PAH patients could be associated with detrimental effects.

Effects of a rehabilitation program on skeletal muscle function in idiopathic pulmonary arterial hypertension.

Introduction: A majority of patients with idiopathic pulmonary arterial hypertension (IPAH) display persistent exercise intolerance despite current therapies. Whether a rehabilitation program elicits favorable changes in muscle function which would partly explain improvements in exercise tolerance of IPAH patients remains unknown. We performed this study to assess the effect of a 12-week rehabilitation program on skeletal muscle characteristics and exercise tolerance in patients with IPAH.

Peripheral muscle dysfunction in idiopathic pulmonary arterial hypertension.

Background: A majority of patients with idiopathic pulmonary arterial hypertension (IPAH) display persistent exercise intolerance despite new specific therapies. Whether patients with IPAH exhibit peripheral muscle dysfunction that may contribute to this limitation remains unknown. The hypothesis that the muscles of patients with IPAH are weaker and display morphological changes compared with those of control subjects and that those changes partly correlate with their exercise capacity was tested.

Impact of preinduced quadriceps fatigue on exercise response in chronic obstructive pulmonary disease and healthy subjects.

Exercise intolerance in chronic obstructive pulmonary disease (COPD) results from a complex interaction between central (ventilatory) and peripheral (limb muscles) components of exercise limitation. The purpose of this study was to evaluate the influence of quadriceps muscle fatigue on exercise tolerance and ventilatory response during constant-workrate cycling exercise testing (CWT) in patients with COPD and healthy subjects. Fifteen patients with COPD and nine age-matched healthy subjects performed, 7 days apart, two CWTs up to exhaustion at 80% of their predetermined maximal work capacity.