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Bronchodilators accelerate the dynamics of muscle O2 delivery and utilisation during exercise in COPD
  1. Danilo C Berton1,
  2. Priscila B Barbosa1,
  3. Luciana S Takara1,
  4. Gaspar R Chiappa1,
  5. Ana Cristina B Siqueira1,
  6. Daniela M Bravo1,
  7. Leonardo F Ferreira2,
  8. J Alberto Neder1
  1. 1Pulmonary Function and Clinical Exercise Physiology Unit (SEFICE), Division of Respiratory Diseases, Department of Medicine, Federal University of Sao Paulo (UNIFESP), São Paulo, Brazil
  2. 2Department of Physiology, University of Kentucky, Lexington, Kentucky, USA
  1. Correspondence to Professor J A Neder, Pulmonary Function and Clinical Exercise Physiology Unit (SEFICE), Respiratory Division, Department of Medicine, Federal University of São Paulo (UNIFESP), Rua Professor Francisco de Castro 54, Vila Clementino, São Paulo CEP: 04020-050, Brazil; albneder{at}


Background Expiratory flow limitation and lung hyperinflation promote cardiocirculatory perturbations that might impair O2 delivery to locomotor muscles in patients with chronic obstructive pulmonary disease (COPD). The hypothesis that decreases in lung hyperinflation after the inhalation of bronchodilators would improve skeletal muscle oxygenation during exercise was tested.

Methods Twelve non- or mildly hypoxaemic males (forced expiratory volume in 1 s (FEV1)=38.5±12.9% predicted; Pao2>60 mm Hg) underwent constant work rate cycle ergometer exercise tests (70–80% peak) to the limit of tolerance (Tlim) after inhaled bronchodilators (salbutamol plus ipratropium) or placebo. Muscle (de)oxygenation (∼fractional O2 extraction) was determined in the vastus lateralis by changes (Δ) in the deoxyhaemoglobin/myoglobin signal ([HHb]) from near-infrared spectroscopy, and cardiac output (QT) was monitored by impedance cardiography.

Results Bronchodilators reduced lung hyperinflation and increased Tlim compared with placebo (454±131 s vs 321±140 s, respectively; p<0.05). On-exercise kinetics of QT and pulmonary O2 uptake (V˙o2) were accelerated with active treatment; Δ[HHb] dynamics, however, were delayed by ∼78% and the signal amplitude diminished by ∼21% (p<0.01). Consequently, the ratio between V˙o2 and Δ[HHb] dynamics decreased, suggesting improved microvascular O2 delivery (τ-V˙o2/MRT-Δ[HHb]=4.48±1.57 s vs 2.08±1.15 s, p<0.05). Of note, reductions in lung hyperinflation were related to faster QT kinetics and larger decrements in τ-V˙o2/MRT-Δ[HHb] (p<0.01).

Conclusions Decreases in operating lung volumes after the inhalation of bronchodilators are associated with faster ‘central’ cardiovascular adjustments to high-intensity exercise with beneficial consequences on muscle oxygenation in patients with moderate to severe COPD.

  • Bronchodilator
  • chronic obstructive pulmonary disease
  • exercise tolerance
  • oxygen consumption
  • respiratory mechanics
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  • Funding DCB was suppported by a Doctoral Research Fellowship from Coordenadoria de Aperfeiçoamento do Pessoal de Nível Superior (CAPES), Brazil. GRC was suppported by a Postdoctoral Research Fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil. JAN is an Investigator of the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil. The study was supported by a Research Grant from FAPESP, Brazil.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Institutional Medical Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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