Medroxyprogesterone acetate with acetazolamide stimulates breathing in cats

Both medroxyprogesterone acetate (MPA) and acetazolamide (ACET) increase ve ntilation. Combined administration of these agents could result in an addit ional improvement of blood gases, for example in patients with chronic obst ructive pulmonary diseases. The aim of this study in anaesthetized female ( ovariohysterectomized: pre-treated with 17-beta-estradiol) cats was to comp are the effects on the CO2 response curve of MPA alone (4 mu g kg(-1), i.v. ) with those after MPA followed by ACET (4 mg kg(-1) i.v.). We performed dy namic end-tidal CO2 forcing and analysed the data with a two-compartment mo del comprising a fast peripheral and slow central compartment, characterize d by CO2 sensitivities (S-p and S-c, respectively) and a single offset (the apnoeic threshold B). MPA reduced S-p from 0.22 +/- 0.09 (mean +/- S.D.) t o 0.13 +/- 0.06 L min(-1) kPa (-1) (P < 0.01) and S, from 1.01 +/- 0.38 to 0.88 +/- 0.32 L min(-1) kPa(-1) (P < 0.01). B decreased from 4.02 +/- 0.27 to 3.64 +/- 0.42 kPa (P < 0.01). Subsequent administration of ACET reduced S-p and S-c further to 0.09 +/- 0.06 and to 0.70 +/- 0.39 L min(-1) kPa(-1) (P < 0.01), respectively. The apnoeic threshold decreased further to 2.46 +/- 1.50 kPa (P < 0.01). Because both treatments reduced ventilatory CO2 se nsitivity. we conclude that a simulating effect on ventilation is due to a decrease in the apnoeic threshold. Combined administration of MPA and ACET may lead to larger increases in ventilation than treatment with either drug s alone. (C) 2000 Elsevier Science B.V. All rights reserved.