The skeletal muscle metaboreflex: a novel driver of ventilation, dyspnoea and pulmonary haemodynamics during exercise in pulmonary arterial hypertension

Impairment of exercise capacity, predominately limited symptomatically by dyspnoea [1], affects most patients with pulmonary arterial hypertension (PAH) despite current therapies [2] with significant implication for patients, adversely impairing health-related quality of life [3] and clinical prognosis [4]. However, the underpinning physiologic mechanisms behind dyspnoea and exercise limitation remain incompletely understood. Skeletal muscle metabolic and microcirculatory deficits are present in PAH [2] and likely lead to earlier and more pronounced accumulation of metabolites during exercise. We hypothesised that this would augment the activation of group III/IV afferents responsive to metabolites present in exercising limb muscles ( i.e. , muscle metaboreflex), and provide a novel driver for hyperventilation [5], pulmonary arterial pressure [6] and sensations of dyspnoea [7] in PAH. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.