Dexamethasone But Not Tadalafil Improves Exercise Capacity in Adults Prone to High-Altitude Pulmonary Edema

Abstract

Corticosteroids, but not phosphodiesterase-5 inhibition, partially prevented the limitation of exercise capacity in subjects with intense hypoxic pulmonary vasoconstriction at high altitude.

Pulmonary artery pressure limits exercise capacity at high altitude

“…Arterial oxygenation was unchanged at rest or during exercise. This argues against an improvement in pulmonary gas exchange, as was observed with the administrations of sildenafil [4,5,7] or dexamethasone [6]. Maximum ventilation and ventilatory equivalents for CO 2 were unchanged.…”

“…The mechanisms of decreased exercise capacity associated with hypoxic exposure in healthy subjects are complex, with cardiovascular disturbances and more obvious decreases in arterial O 2 content accounting for decreased O 2 delivery to exercising muscles [1][2][3]. Recent observations of improved exercise capacity in hypoxia by pharmacologic interventions to decrease PVR, such as sildenafil [4,5,7], dexamethasone [6], and bosentan [8], have raised the possibility of the participation of increased right ventricular afterload to limit O 2 delivery to the tissues. This interpretation is supported by significant inverse correlations between changes in V9O 2 ,max and systolic Ppa, and better preservation of right ventricular function with unchanged TAPSE and Tei index after sitaxsentan intake in the present study.…”

“…An additional factor might be a limitation in right ventricular flow output secondary to hypoxic pulmonary hypertension. An improvement in maximal workload and maximal oxygen uptake (V9O 2 ,max) together with a decrease in pulmonary artery pressure (Ppa) has indeed been reported after the intake of sildenafil in hypoxic healthy volunteers [4,5]. More recently, there has been report of decreased Ppa and improved V9O 2 ,max in subjects susceptible to high-altitude pulmonary oedema taking dexamethasone before altitude exposure [6].…”

“…More recently, there has been report of decreased Ppa and improved V9O 2 ,max in subjects susceptible to high-altitude pulmonary oedema taking dexamethasone before altitude exposure [6]. However, improved exercise capacity in these studies could not unequivocally be ascribed to associated inhibition of hypoxic pulmonary vasoconstriction because of additional effects, including a variable improvement in arterial O 2 content [4][5][6][7].…”

Update on Pulmonary Hypertension 2009

“…This notion was supported by studies showing that phosphodiesterase 5 inhibition could improve exercise ability at high altitudes (21,22). Fischler and colleagues have now evaluated the impact of either dexamethasone, tadalafil, or placebo on exercise capacity in subjects prone to develop HAPE (23). Twenty-three subjects with a previous history of HAPE were randomized to dexamethasone at 8 mg twice a day, tadalafil at 10 mg twice a day, or placebo (double-blinded), starting the day before ascent to an altitude of 4,559 m. Dexamethasone improved maximum oxygen uptake and oxygen kinetics and reduced the ventilatory equivalent for CO 2 .…”