Medroxyprogesterone improves nocturnal breathing in postmenopausal women with chronic obstructive pulmonary disease

BACKGROUND: Progestins as respiratory stimulants in chronic obstructive pulmonary disease (COPD) have been investigated in males and during wakefulness. However, sleep and gender may influence therapeutic responses. We investigated the effects of a 2-week medroxyprogesterone acetate (MPA) therapy on sleep and nocturnal breathing in postmenopausal women. METHODS: A single-blind placebo-controlled trial was performed in 15 postmenopausal women with moderate to severe COPD. A 12-week trial included 2-week treatment periods with placebo and MPA (60 mg/d/14 days). All patients underwent a polysomnography with monitoring of SaO(2 )and transcutaneous PCO(2 )(tcCO(2)) at baseline, with placebo, with medroxyprogesterone acetate (MPA 60 mg/d/14 days), and three and six weeks after cessation of MPA. RESULTS: Thirteen patients completed the trial. At baseline, the average ± SD of SaO(2 )mean was 90.6 ± 3.2 % and the median of SaO(2 )nadir 84.8 % (interquartile range, IQR 6.1). MPA improved them by 1.7 ± 1.6 %-units (95 % confidence interval (CI) 0.56, 2.8) and by 3.9 %-units (IQR 4.9; 95% CI 0.24, 10.2), respectively. The average of tcCO(2 )median was 6.0 ± 0.9 kPa and decreased with MPA by 0.9 ± 0.5 kPa (95% CI -1.3, -0.54). MPA improved SaO(2 )nadir and tcCO(2 )median also during REM sleep. Three weeks after cessation of MPA, the SaO(2 )mean remained 1.4 ± 1.8 %-units higher than at baseline, the difference being not significant (95% CI -0.03, 2.8). SaO(2 )nadir was 2.7 %-units (IQR 4.9; 95% CI 0.06, 18.7) higher than at baseline. Increases in SaO(2 )mean and SaO(2 )nadir during sleep with MPA were inversely associated with baseline SaO(2 )mean (r = -0.70, p = 0.032) and baseline SaO(2 )nadir (r = -0.77, p = 0.008), respectively. Treatment response in SaO(2 )mean, SaO(2 )nadir and tcCO(2 )levels did not associate with pack-years smoked, age, BMI, spirometric results or sleep variables. CONCLUSION: MPA-induced respiratory improvement in postmenopausal women seems to be consistent and prolonged. The improvement was greater in patients with lower baseline SaO(2 )values. Long-term studies in females are warranted

Effect of Dopamine on Carotid Chemoreceptor Activity in Newborn Kittens

In newborn kittens, intravenous bolus injections of dopamine may be inhibitory or excitatory to the carotid chemosensory activity. In order to further identify the role of dopaminergic mechanisms on the chemosensory activity in the kitten, 10 anesthetized, paralyzed and artificially ventilated kittens aged from 1 to 21 days were studied. The activity of a few chemoafferent fibers from one carotid sinus nerve was recorded at three levels of Fi&lt;sub&gt;O2&lt;/sub&gt; in N&lt;sub&gt;2&lt;/sub&gt;, 21,8 and 100%, before and during a continuous dopamine infusion at a dose of 10 μg/kg/min. The immediate effect of dopamine usually was a transient inhibition of carotid chemosensory discharge. After 2 min of infusion, the activity had consistently increased from 4.5 ± 0.8 to 8.8 ± 1.4 impulses/s (mean ± SEM, p &lt; 0.05) in normoxia. Dopamine also significantly increased the steady state chemosensory response to hypoxia from 24.6 ± 3.7 to 33.4 ± 5.3 impulses/s. Hence, continuous infusion of dopamine has a dual effect on carotid chemoreceptor activity: early inhibition followed by excitation. The excitatory effect enhances the response to hypoxia. These data suggest that the dual effect of dopamine on carotid chemosensory discharge may be related to dopamine concentration in the carotid body.</jats:p