Acetazolamide suppresses the prevalence of augmented breaths during exposure to hypoxia

Augmented breaths, or "sighs," commonly destabilize respiratory rhythm, precipitating apneas and variability in the depth and rate of breathing, which may then exacerbate sleep-disordered breathing in vulnerable individuals. We previously demonstrated that hypocapnia is a unique condition associated with a high prevalence of augmented breaths during exposure to hypoxia; the prevalence of augmented breaths during hypoxia can be returned to normal simply by the addition of CO(2) to the inspired air. We hypothesized that counteracting the effect of respiratory alkalosis during hypocapnic hypoxia by blocking carbonic anhydrase would yield a similar effect. We, therefore, investigated the effect of acetazolamide on the prevalence of augmented breaths in the resting breathing cycle in five awake, adult male rats. We found a 475% increase in the prevalence of augmented breaths in animals exposed to hypocapnic hypoxia compared with room air. Acetazolamide treatment (100 mg/kg i.p. bid) for 3 days resulted in a rapid and potent suppression of the generation of augmented breaths during hypoxia. Within 90 min of the first dose of acetazolamide, the prevalence of augmented breaths in hypoxia fell to levels that were no greater than those observed in room air. On cessation of treatment, exposure to hypocapnic hypoxia once again caused a large increase in the prevalence of augmented breaths. These results reveal a novel means by which acetazolamide acts to stabilize breathing and may help explain the beneficial effects of the drug on breathing stability at altitude and in patients with central forms of sleep-disordered breathing.