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 less than 0.045). Before exercise, subjects on A had 2.0 and 3.5 l/min increase in minute ventilation (VE) during normoxia (P = not significant) and hypoxia (P less than 0.005), respectively, and a 2.2% increase in arterialized O2 hemoglobin saturation (SaO2) during hypoxia. During normoxic and hypoxic exercise, VE/kpm and SaO2/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 (1/min) was lower on A [3.1 +/- 0.4 (A) vs. 3.8 +/- 0.2 (P), P less than 0.025] and higher during hypoxia on A[2.6 +/- 0.7 (A) vs. 2.4 +/- 0.1 (P), P less than 0.05]. The increase in exercise VE 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.