Difference in the Effects of Acetazolamide and Ammonium Chloride Acidosis on Ventilatbry Responses to CO₂ and Hypoxia in Humans

Abstract

The effects of acetazolamide, a potent carbonic anhydrase inhibitor, and ammonium chloride (NH₄Cl) on arterial blood gas tension, resting ventilation, and ventilatory responses to CO₂ (HCVR) and hypoxia (HVR) were studied in healthy male subjects. Both drugs induced chronic metabolic acidosis with the reduction in plasma bicarbonate by a mean of 7.0±2.0 (S.D.) mM after acetazolamide and by 5.6±1.8mM after NH₄Cl. The ratio in the decrement of Pa_CO2 to that of plasma bicarbonate (ΔPa_CO2/Δ[HCO₃^-]) was 1.51 in the former and 0.98 in the latter. Both drugs increased inspiratory minute ventilation (VI) predominantly due to increased tidal volume (VT) with acetazolamide and to increased respiratory frequency (f) with NH₄Cl. In HCVR, the increments in CO₂-ventilation slope and in ventilation at PET_CO2 60mmHg after drug administration were 0.77±0.51l•min^-1•mmHg^-1 and 20.0±11.2l/min with acetazolamide and 0.59±0.40l•min^-1•mmHg^-1 and 8.0±2.8l/min with NH₄Cl, respectively. On the other hand, HVR both in terms of ΔVI/ΔSa_O2 slope and of ventilation at Sa_O2 75% significantly increased after NH₄Cl but not after acetazolamide administration. Thus, augmented VT and HCVR in the acetazolamide group and increased f and HVR in the NH₄Cl group suggested that the central chemosensitive mechanism in the former and the peripheral chemosensitive mechanism in the latter may predominantly be responsible for the elevated ventilatory activities.