Post-hypoxic Unstable Breathing in the C57BL/6J Mouse: Effects of Acetazolamide

Abstract

We examined whether acetazolamide (ACZ), a carbonic anhydrase inhibitor, would alter post-hypoxic ventilatory behavior and periodic breathing in the C57BL/6J (B6) mouse. Experiments were performed with unanaesthetized, awake adult male B6 mice (n = 5, 2.5 months old, 21.3 +/- 1.5 g, mean +/- SD) and ventilatory behavior was measured using a flow through body plethysmography. Mice were given an intraperitoneal injection of either vehicle or ACZ (40 mg/kg) and one hour later exposed to 1 min of 8% O2-balance N2 (poikilocapnic hypoxia) or 12%-O2, 3% CO2-balance N2 (non-poikilocapnic hypoxia) followed by rapid reoxygenation (100% O2) of 5 minutes. One minute after reoxygenation, ACZ-treated animals exhibited post-hypoxic frequency decline (p < 0.05), a lower coefficient of variability for frequency (p < 0.001) and no tendency towards periodic breathing (p < 0.05), as compared to vehicle-treated animals. ACZ improves unstable breathing in the B6 model of periodic breathing, despite producing post-hypoxic frequency decline. Our speculation is that periodic breathing occurs through pathways independent of the A5 pontine area.