Effect of Acetazolamide on Pulmonary and Muscle Gas Exchange during Hypoxic Exercise

Acetazolamide (Acz) is used to prevent acute mountain sickness at altitude. We examined its effects on pulmonary and muscle gas exchange and acid base status during cycle exercise at 30, 50 & 90% VO 2max in acute hypoxia (FIO 2 = 0.125). In a double‐blind, randomized, cross‐over design, 6 healthy, trained men [normoxic VO 2max = 60 ml · kg−1 · min −1 ] exercised after Acz (3 doses of 250 mg, 8 h apart) or placebo (Con). One week later after the other drug (Con or Acz), this protocol was repeated. We measured cardiac output (Q T ), leg blood flow (LBF), and pulmonary (AaDO 2 ) and muscle gas exchange using blood gases and MIGET with arterial and femoral venous blood sampling. MIGET separated ventilation‐perfusion (V A /Q T ) mismatch from alveolar‐end‐capillary O 2 diffusion limitation. VO 2 and VCO 2 were lower with Acz ( P <0.05). Acz did not significantly affect Q T , LBF or muscle gas exchange. Acz led to lower arterial and venous blood [HCO3], pH and lactate levels ( P <0.05). As expected, V E was higher after Acz ( P <0.05), due to this significantly greater metabolic acidosis. Arterial PO 2 and saturation were higher and AaDO 2 lower after Acz ( P <0.05), while arterial PCO 2 and venous values (PvO 2 , SvO 2 and PvCO 2 ) were unaffected. AaDO 2 was smaller due to less V A /Q mismatch and less diffusion limitation. Thus, Acz improves arterial oxygenation during hypoxic exercise due to both hyperventilation and more efficient gas exchange, the latter possibly from less interstitial pulmonary fluid accumulation. Muscle gas exchange is however unaffected. Support NIH R01HL84281, AHA 0540002N