Effect of acetazolamide on pulmonary and muscle gas exchange during normoxic and hypoxic exercise

Abstract

Acetazolamide (ACZ) is used to prevent acute mountain sickness at altitude. Because it could affect O2 transport in several different and potentially conflicting ways, we examined its effects on pulmonary and muscle gas exchange and acid-base status during cycle exercise at approximately 30, 50 and 90% VO2max in normoxia (F(IO2) = 0.2093) and acute hypoxia (F(IO2) = 0.125). In a double-blind, order-balanced, crossover design, six healthy, trained men (normoxic VO2max= 59 ml kg(-1) min(-1)) exercised at both F(IO2) values after ACZ (3 doses of 250 mg, 8 h apart) and placebo. One week later this protocol was repeated using the other drug (placebo or ACZ). We measured cardiac output (QT), leg blood flow (LBF), and muscle and pulmonary gas exchange, the latter using the multiple inert gas elimination technique. ACZ did not significantly affect VO2, QT, LBF or muscle gas exchange. As expected, ACZ led to lower arterial and venous blood [HCO3-], pH and lactate levels (P < 0.05), and increased ventilation (P < 0.05). In both normoxia and hypoxia, ACZ resulted in higher arterial P(O2) and saturation and a lower alveolar-arterial P(O2) difference (AaD(O2)) due to both less VA/Q mismatch and less diffusion limitation (P < 0.05). In summary, ACZ improved arterial oxygenation during exercise, due to both greater ventilation and more efficient pulmonary gas exchange. However, muscle gas exchange was unaffected.

Figure 2

Indexes of pulmonary gas exchange during exercise Alveolar–arterial P_O2 difference measured [Aa$D_{{\text{O}}_2}$(m)] is shown at rest and during increasing exercise intensity (corresponding to ∼30, 50, and 90% of , respectively) in hypoxia (12.5% O₂) and normoxia. Inert gas data were not obtained during light exercise (i.e. 30% of ), and therefore measured minus predicted Aa$D_{{\text{O}}_2}$[Aa$D_{{\text{O}}_2}$(m–p)] and log standard deviation of the distribution of perfusion values are not shown at this level of exercise. Values are expressed as means ±s.e.m.†Significant main effect acetazolamide versus placebo, P < 0.05. ‡Significant main effect of exercise, P < 0.05. *Post hoc analysis identifying individual group differences between acetazolamide and placebo, P < 0.05.

Figure 1

AlveolarP_O2(P_aO2), arterialP_O2(P_aO2), arterial saturation (S_aO2), and arterialP_CO2(P_a,CO2) values during rest and during increasing exercise intensity (corresponding to ∼30, 50 and 90% of , respectively) in hypoxia (12.5% O₂) and normoxia Values are expressed as means ±s.e.m.†Significant main effect acetazolamide versus placebo, P < 0.05. ‡Significant main effect of exercise, P < 0.05. *Post hoc analysis identifying individual group differences between acetazolamide and placebo, P < 0.05.