title: Effect of low-dose acetazolamide on the ventilatory CO2 response during hypoxia in the anaesthetized cat.
abstract: Acetazolamide, a carbonic anhydrase inhibitor, is used in patients with chronic obstructive pulmonary diseases and central sleep apnoea syndrome and in the prevention and treatment of the symptoms of acute mountain sickness. In these patients, the drug increases minute ventilation (V'E), resulting in an improvement in arterial oxygen saturation. However, the mechanism by which it stimulates ventilation is still under debate. Since hypoxaemia is a frequently observed phenomenon in these patients, the effect of 4 mg x kg(-1) acetazolamide (i.v.) on the ventilatory response to hypercapnia during hypoxaemia (arterial oxygen tension (Pa,O2)=6.8+/-0.8 kPa, mean+/-SD) was investigated in seven anaesthetized cats. The dynamic end-tidal forcing (DEF) technique was used, enabling the relative contributions of the peripheral and central chemoreflex loops to the ventilatory response to a step change in end-tidal carbon dioxide tension, (PET,CO2) to be separated. Acetazolamide reduced the CO2 sensitivities of the peripheral (Sp) and central (Sc) chemoreflex loops from 0.22+/-0.08 to 0.11+/-0.03 L x min(-1) x kPa(-1) (mean+/-SD) (p<0.01) and from 0.74+/-0.32 to 0.40+/-0.10 L x min(-1) x kPa(-1) (p<0.01), respectively. The apnoeic threshold B (x-intercept of the ventilatory CO2 response curve) decreased from 2.88+/-0.97 to 0.95+/-0.92 kPa (p<0.01). The net result was a stimulation of ventilation at PET,CO2 <5 kPa. The effect of acetazolamide is possibly due to a direct effect on the peripheral chemoreceptors as well as to an effect on the cerebral blood flow regulation. Possible clinical implications of these results are discussed.
authors.affiliation: Dept of Physiology, University of Leiden, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Wagenaar
authors.forename: L
authors.initials: L
authors.lastname: Teppema
authors.forename: A
authors.initials: A
authors.lastname: Berkenbosch
authors.forename: C
authors.initials: C
authors.lastname: Olievier
authors.forename: H
authors.initials: H
authors.lastname: Folgering
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D002245:Carbon Dioxide / Q000502:physiology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002415:Cats; D002628:Chemoreceptor Cells; D000860:Hypoxia / Q000503:physiopathology*; D012123:Pulmonary Ventilation / Q000187:drug effects*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D002245:Carbon Dioxide; D000086:Acetazolamide