The effect of acetazolamide on hypercapnic and eucapnic/poikilocapnic hypoxic ventilatory responses in normal...

We have studied the effect of acetazolamide 500 mg bd for three days on ventilatory response to CO2 (HCVR) and hypoxia under both isocapnic and poikilocapnic conditions (isocapnic and poikilocapnic HVR) in five normal subjects. Although acetazolamide reduced calculated arterial pH (7.41 [SEM] 0.01 to 7.37 [SEM] 0.01: p less than 0.01) there was no significant change in either isocapnic HVR (with PetCO2 held at the post-drug resting level) or poikilocapnic HVR in terms of slope and ventilation at SaO2 = 80%. HCVR slope rose slightly (+1.82 [SEM] 0.43 to +2.2 [SEM] 0.29 l/min/mmHg: NS) and there was a significant increase in ventilation at Pet-CO2 = 50 mmHg (9.42 [SEM] 3.3 to 31.4 [SEM] 6.31/min: p less than 0.01). These findings are consistent with the claim that acetazolamide stimulates central chemoreceptors and inhibits peripheral chemoreceptors. Increased sensitivity to CO2 would reverse the suppressive effect of respiratory alkalosis on hypoxic ventilatory drive following rapid ascent to high altitude, and this probably accounts for the efficacy of acetazolamide in the prophylaxis of acute mountain sickness. However, inhibition of peripheral chemoreceptors may also result in symptomatic benefit by reducing sleep disturbance due to periodic breathing.