Pulmonary artery pressure limits exercise capacity at high altitude

• Published in: The European respiratory journal Vol. 36; no. 5; pp. 1049 - 1055
• Main Authors: Naeije, R., Huez, S., Lamotte, M., Retailleau, K., Neupane, S., Abramowicz, D., Faoro, V.
• Format: Journal Article
• Language: English
• Published: Leeds Maney 01.11.2010
• Subjects: Acute Disease; Adult; Altitude; Biological and medical sciences; Blood Pressure - physiology; Chronic Disease; Endothelin A Receptor Antagonists; Exercise - physiology; Female; Humans; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - physiopathology; Hypoxia - physiopathology; Isoxazoles - administration & dosage; Kidney - drug effects; Kidney - physiology; Male; Medical sciences; Middle Aged; Oxygen Consumption - physiology; Pneumology; Pulmonary Artery - drug effects; Pulmonary Artery - physiology; Pulmonary Gas Exchange - drug effects; Pulmonary Gas Exchange - physiology; Thiophenes - administration & dosage; Vascular Resistance - drug effects; Vascular Resistance - physiology; Young Adult; Physical exercise; High altitude; Oxygen; Renal function; Lung; maximal oxygen uptake; Sitaxentan; Pulmonary artery; Uptake; Vascular resistance; Capacity; Hypoxia; Blood pressure; Limit; pulmonary vascular resistance; Pneumology
• ISSN: 0903-1936; 1399-3003; 1399-3003
• DOI: 10.1183/09031936.00024410

Altitude exposure is associated with decreased exercise capacity and increased pulmonary vascular resistance (PVR). Echocardiographic measurements of pulmonary haemodynamics and a cardiopulmonary exercise test were performed in 13 healthy subjects at sea level, in normoxia and during acute hypoxic breathing (1 h, 12% oxygen in nitrogen), and in 22 healthy subjects after acclimatisation to an altitude of 5,050 m. The measurements were obtained after randomisation, double-blinded to the intake of placebo or the endothelin A receptor blocker sitaxsentan (100 mg·day −1 for 7 days). Blood and urine were sampled for renal function measurements. Normobaric as well as hypobaric hypoxia increased PVR and decreased maximum workload and oxygen uptake ( V ′ O 2 ,max ). Sitaxsentan decreased PVR in acute and chronic hypoxia (both p<0.001), and partly restored V ′ O 2 ,max , by 30 % in acute hypoxia (p<0.001) and 10% in chronic hypoxia (p<0.05). Sitaxsentan-induced changes in PVR and V ′ O 2 ,max were correlated (p = 0.01). Hypoxia decreased glomerular filtration rate and free water clearance, and increased fractional sodium excretion. These indices of renal function were unaffected by sitaxsentan intake. Selective endothelin A receptor blockade with sitaxsentan improves mild pulmonary hypertension and restores exercise capacity without adverse effects on renal function in hypoxic normal subjects.