Acetazolamide protects against posthypoxic unstable breathing in the C57BL/6J mouse.
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% O(2)-balance N(2) (poikilocapnic hypoxia) or 12% O(2)-3% CO(2)-balance N(2) (isocapnic hypoxia) followed by rapid reoxygenation (100% O(2)). Hypercapnic response (8% CO(2)-balance O(2)) 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.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. mountain@pastel.ocn.ne.jp
Motoo
M
Yamauchi
Jesse
J
Dostal
Kingman P
KP
Strohl
D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D006935:Hypercapnia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010507:Periodicity; D010993:Plethysmography, Whole Body; D012123:Pulmonary Ventilation / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*; D012120:Respiration Disorders / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide