Effect of chlormadinone acetate on ventilatory control in patients with chronic obstructive pulmonary disease.
Twelve patients with chronic obstructive pulmonary disease (COPD) were studied to determine the effect of ventilatory stimulation with chlormadinone acetate (CMA), a potent synthetic progesterone, on chemical and neuromechanical respiratory controls and pulmonary gas exchange. Using a randomized, double-blind, cross-over trial, 1 wk of CMA therapy caused a significant reduction in arterial CO2 tension (Paco2) by 4.6 +/- 0.6 (SE) mmHg. This Paco2 fall was associated with increased minute ventilation (Vl), tidal volume (VT), and mean inspiratory flow (VT/Tl). During CMA administration, occlusion pressure response to CO2 with and without inspiratory flow-resistive loading increased significantly (p less than 0.01) over that during placebo administration, whereas ventilatory response to CO2 did not. In addition, normocapnic ventilatory and occlusion pressure response to hypoxia were significantly elevated (p less than 0.01) during CMA therapy. Furthermore, the degree of load compensation, which was assessed by the ratio of the loaded to unloaded slope in the occlusion pressure response to CO2, increased in all subjects after CMA administration. These results indicate that CMA augments not only the respiratory neuromuscular response to hypercapnia and hypoxia, but also flow-resistive load compensation in patients with COPD, and it may provide support for the use of CMA in patients who are able to decrease their Paco2 with this agent.
Tatsumi
K
K
Kimura
H
H
Kunitomo
F
F
Okita
S
S
Tojima
H
H
Yuguchi
Y
Y
Kuriyama
T
T
Watanabe
S
S
Honda
Y
Y
D001696:Biomechanical Phenomena; D002245:Carbon Dioxide / Q000494:pharmacology; D002715:Chlormadinone Acetate / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012119:Respiration / Q000187:drug effects*
D002715:Chlormadinone Acetate; D002245:Carbon Dioxide