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.