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Acetazolamide protects against posthypoxic unstable breathing in the C57BL/6J mouse

¹Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Case Western Reserve University, and ²Louis Stokes Department of Veterans Affairs Medical Center, Cleveland, Ohio

Submitted 14 November 2006 ; accepted in final form 30 July 2007

Acetazolamide (Acz), a carbonic anhydrase inhibitor, is used to manage periodic breathing associated with altitude and with heart failure. We examined whether Acz would alter posthypoxic ventilatory behavior in the C57BL/6J (B6) mouse model of recurrent central apnea. Experiments were performed with unanesthetized, awake adult male B6 mice (n = 9), ventilatory behavior was measured using flow-through whole body plethysmography. Mice were given an intraperitoneal injection of either vehicle or Acz (40 mg/kg), and 1 h later they were exposed to 1 min of 8% O₂-balance N₂ (poikilocapnic hypoxia) or 12% O₂-3% CO₂-balance N₂ (isocapnic hypoxia) followed by rapid reoxygenation (100% O₂). Hypercapnic response (8% CO₂-balance O₂) was examined in six mice. With Acz, ventilation, including respiratory frequency, tidal volume, and minute ventilation, in room air was significantly higher and hyperoxic hypercapnic ventilatory responsiveness was generally lower compared with vehicle. Poikilocapnic and isocapnic hypoxic ventilatory responsiveness were similar among treatments. One minute after reoxygenation, animals given Acz exhibited posthypoxic frequency decline, a lower coefficient of variability for frequency, and no tendency toward periodic breathing, compared with vehicle treatment. We conclude that Acz improves unstable breathing in the B6 model, without altering hypoxic response or producing short-term potentiation, but with some blunting of hypercapnic responsiveness.

ventilation; periodic breathing; carbonic anhydrase inhibitor

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