Effects of acetazolamide on cerebrovascular function and breathing stability at 5050 m

Abstract

One of the many actions of the carbonic anhydrase inhibitor, acetazolamide (ACZ), is to accelerate acclimatisation and reduce periodic breathing during sleep. The mechanism(s) by which ACZ may improve breathing stability, especially at high altitude, remain unclear. We tested the hypothesis that acute i.v. ACZ would enhance cerebrovascular reactivity to CO 2 at altitude, and thereby lower ventilatory drive and improve breathing stability during wakefulness. We measured arterial blood gases, minute ventilation and middle cerebral artery blood flow velocity (MCAv) before and 30 min following ACZ administration (i.v. 10 mg kg -1) in 12 healthy participants at sea level and following partial acclimatisation to altitude (5050 m). Measures were made at rest and during changes in end-tidal and (isocapnic hypoxia). At sea level, ACZ increased resting MCAv and its reactivity to both hypocapnia and hypercapnia (P < 0.05), and lowered resting, arterial O 2 saturation and arterial (P < 0.05); arterial was unaltered (P > 0.05). At altitude, ACZ also increased resting MCAv and its reactivity to both hypocapnia and hypercapnia (resting MCAv and hypocapnia reactivity to a greater extent than at sea level). Moreover, ACZ at altitude elevated and again lowered resting and (P < 0.05). Although the sensitivity to hypercapnia or isocapnic hypoxia was unaltered following ACZ at both sea level and altitude (P > 0.05), breathing stability at altitude was improved (e.g. lower incidence of ventilatory oscillations and variability of tidal volume; P < 0.05). Our data indicate that i.v. ACZ elevates cerebrovascular reactivity and improves breathing stability at altitude, independent of changes in peripheral or central chemoreflex sensitivities. We speculate that -mediated elevations in cerebral perfusion and an enhanced cerebrovascular reactivity may partly account for the improved breathing stability following ACZ at high altitude. © 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society.