Pulmonary artery pressure limits exercise capacity at high altitude

Area of Science:

• Physiology
• Pharmacology

Background:

• Altitude exposure leads to decreased exercise capacity and increased pulmonary vascular resistance (PVR).
• Hypoxia, whether acute or chronic, significantly impacts cardiopulmonary function.

Purpose of the Study:

• To investigate the effects of sitaxsentan, an endothelin A receptor blocker, on pulmonary haemodynamics and exercise capacity during acute and chronic hypoxia.
• To assess the impact of sitaxsentan on renal function in hypoxic conditions.

Main Methods:

• Echocardiographic measurements and cardiopulmonary exercise tests were conducted in healthy subjects under normoxic, acute hypoxic, and chronic hypoxic conditions (5,050 m).
• Subjects received either a placebo or sitaxsentan (100 mg/day for 7 days) in a randomized, double-blind manner.
• Blood and urine samples were analyzed for renal function parameters.

Main Results:

• Both normobaric and hypobaric hypoxia increased PVR and decreased maximum workload and oxygen uptake (V'(O(2),max)).
• Sitaxsentan significantly decreased PVR in both acute and chronic hypoxia (p<0.001) and partially restored V'(O(2),max) (30% in acute, 10% in chronic hypoxia).
• Sitaxsentan did not affect hypoxia-induced changes in glomerular filtration rate, free water clearance, or fractional sodium excretion.

Conclusions:

• Selective endothelin A receptor blockade with sitaxsentan effectively improves mild pulmonary hypertension and exercise capacity in healthy individuals exposed to hypoxia.
• Sitaxsentan demonstrates a favorable safety profile concerning renal function in hypoxic states.