Effects of fenoterol on ventilatory response to hypercapnia and hypoxia in patients with chronic obstructive pulmonary disease.
BACKGROUND
It has previously been shown that fenoterol, a beta 2 adrenergic agonist, increases the ventilatory response to hypoxia (HVR) and hypercapnia (HCVR) in normal subjects. The effects of beta 2 adrenergic agonists on chemoreceptors in patients with chronic obstructive pulmonary disease (COPD) remain controversial. This study was designed to examine whether fenoterol increases the HVR and HCVR in patients with COPD.


METHODS
The HCVR was tested in 20 patients using a rebreathing method and the HVR was examined using a progressive isocapnic hypoxic method. The HCVR and HVR were assessed by calculating the slopes of plots of occlusion pressure (P0.1) and ventilation (VE) against end tidal carbon dioxide pressure (PETCO2) and arterial oxygen saturation (SaO2), respectively. Spirometric values, lung volumes, and respiratory muscle strength were also measured. The HCVR and HVR were examined after the oral administration of fenoterol (15 mg/day) or placebo for seven days.


RESULTS
Fenoterol treatment increased the forced expiratory volume in one second (FEV1) and inspiratory muscle strength. In the HCVR the slope of P0.1 versus PETCO2 was increased by fenoterol from 0.35 (0.23) to 0.43 (0.24) (p < 0.01). Moreover, the P0.1 at PETCO2 of 8 kPa was higher on fenoterol than on placebo (p < 0.05) and the VE was also greater (p < 0.01). In the HVR fenoterol treatment increased the P0.1 at 80% SaO2 from 0.90 (0.72) to 0.97 (0.55) kPa (p < 0.05) while the slopes of the response of P0.1 and VE were not changed.


CONCLUSIONS
Fenoterol increases the ventilatory response to hypercapnia in patients with COPD, presumably by stimulation of the central chemoreceptor. The hypoxic ventilatory response is only slightly affected by fenoterol.
Suzuki
S
S
First Department of Internal Medicine, Yokohama City University School of Medicine, Kanagawa, Japan.
Watanuki
Y
Y
Yoshiike
Y
Y
Okubo
T
T
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D002628:Chemoreceptor Cells / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005280:Fenoterol / Q000627:therapeutic use*; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012132:Respiratory Muscles / Q000187:drug effects* / Q000503:physiopathology; D013268:Stimulation, Chemical
D000318:Adrenergic beta-Agonists; D005280:Fenoterol