title: Low-dose acetazolamide reduces the hypoxic ventilatory response in the anesthetized cat.
abstract: Low intravenous dose acetazolamide causes a decrease in steady-state CO(2) sensitivity of both the peripheral and central chemoreflex loops. The effect, however, on the steady-state hypoxic response is unknown. In the present study, we measured the effect of 4 mg x kg(-1) acetazolamide (i.v.) on the isocapnic steady-state hypoxic response in anesthetized cats. Before and after acetazolamide administration, the eucapnic steady-state hypoxic response in these animals was measured by varying inspiratory P(O2) levels to achieve steady-state Pa(O2) levels between hyperoxia Pa(O2) approximately 55 kPa, approximately 412 mmHg) and hypoxia (Pa(O2) approximately 7 kPa, approximately 53 mmHg). The hypoxic ventilatory response was described by the exponential function V(I) = G exp (-DP(o2) + A with an overall hypoxic sensitivity G, a shape parameter D and ventilation during hyperoxia A. Acetazolamide significantly reduced G from 3.057 +/- 1.616 to 1.573 +/- 0.8361 min(-1) (mean +/- S D). Parameter A increased from 0.903 +/- 0.257 to 1.193 +/- 0.321 min(-1), while D remained unchanged. The decrease in overall hypoxic sensitivity by acetazolamide is probably mediated by an inhibitory effect on the carotid bodies and may have clinical significance in the treatment of sleep apneas, particularly those cases that are associated with an increased ventilatory sensitivity to oxygen and/or carbon dioxide.
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, PO Box 9604, 2300 RC Leiden, The Netherlands. l.j.s.m.teppema@lumc.nl
authors.forename: Luc J
authors.initials: LJ
authors.lastname: Teppema
authors.forename: Albert
authors.initials: A
authors.lastname: Dahan
mesh_terms: D000086:Acetazolamide / Q000008:administration & dosage*; D000758:Anesthesia; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D010100:Oxygen / Q000097:blood; D012123:Pulmonary Ventilation / Q000187:drug effects*; D015656:Respiratory Mechanics / Q000187:drug effects*; D013990:Tidal Volume / Q000187:drug effects
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D002245:Carbon Dioxide; D000086:Acetazolamide; D010100:Oxygen