Patients with idiopathic pulmonary fibrosis (IPF) usually develop hypoxemia and pulmonary hypertension when exercising. To what extent endothelium-derived vasodilating agents modify these changes is unknown. The study was aimed to investigate in patients with IPF whether exercise induces changes in plasma levels of endotlelium-derived signalling mediators, and to asses the acute effects of inhaled nitric oxide (NO) on pulmonary hemodynamics and gas exchange, at rest and during exercise. We evaluated 7 patients with IPF (6 men/1 woman; 57±11 years; forced vital capacity, 60±13% predicted; CO diffusing capacity, 52±10% predicted). Levels of endothelin, prostaglandin-F1α (PGF1α), thromboxane-B2 and nitrates were measured at rest and during submaximal exercise. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion (VA/Q) relationships, were assessed breathing ambient air and 40 ppm of NO, both at rest and during submaximal exercise. The concentration of thromboxane-B2 increased during exercise (p=0.046), whereas levels of other mediators did not change. The change in PGF1α correlated with that of mean pulmonary artery pressure (mPAP) (r=0.94; p<0.005). Inhaled NO reduced mPAP at rest (-4.6±2.1 mmHg) and during exercise (-11.7±7.1 mmHg) (p=0.001 and p=0.004, respectively), without altering arterial oxygenation or VA/Q distributions in any of the study conditions. Alveolar-to-capillary oxygen diffusion limitation, which accounted for the decrease of PaO2 during exercise, was not modified by NO administration. We conclude that in IPF some endothelium-derived signalling molecules may modulate the development of pulmonary hypertension during exercise, and that the administration of inhaled NO exerts beneficial effects on pulmonary hemodynamics without disturbing pulmonary gas exchange.
- pulmonary hemodynamics
- gas exchange
- ventilation-perfusion relationships
- pulmonary circulation
- vasodilator agents
- Copyright © 2010, Journal of Applied Physiology