Effect of acetazolamide on normoxic and hypoxic exercise in humans at sea level

Acetazolamide (A) is a potent inhibitor of carbonic anhydrase. It has been shown to be efficacious in preventing acute mountain sickness as well as decreasing the O₂ desaturation that occurs during sleep in individuals with chronic mountain sickness who live at altitude. Very little data, however, are available about its effect on exercise. We studied six healthy males in a double-blind cross-over design using acetazolamide and placebo (P) during normoxic and hypoxic (fractional inspired O₂ = 0.118) progressive work exercise to exhaustion on a bicycle ergometer. A metabolic acidosis was documented in all subjects on A (P < 0.045). Before exercise, subjects on A had 2.0 and 3.5 l/min increase in minute ventilation (V̇(E)) during normoxia (P = not significant) and hypoxia (P < 0.005), respectively, and a 2.2% increase in arterialized O₂ hemoglobin saturation (Sa(O₂)) during hypoxia. During normoxic and hypoxic exercise, V̇(E)/kpm and Sa(O₂)/kpm were significantly higher while the respiratory exchange ratio (R) was significantly lower on A. These effects were greater on hypoxia. During normoxia, maximal O₂ consumption (l/min) was lower on A [3.1 ± 0.4 (A) vs. 3.8 ± 0.2 (P), P < 0.025] and higher during hypoxia on A [2.6 ± 0.7 (A) vs. 2.4 ± 0.1 (P), P < 0.05]. The increase in exercise V̇(E) on A may result in an increased alveolar and subsequent arterial O₂ tension which may be important for exercise at altitude. Carbonic anhydrase inhibition may also affect CO₂ transport in the lung, which may explain the lower R.