Endogenous opiates and the control of breathing in normal subjects and patients with chronic airflow obstruction

Abstract

To investigate the role of endorphins in central respiratory control, the effect of naloxone, a specific opiate antagonist, on resting ventilation and ventilatory control was investigated in a randomised double-blind, placebo-controlled study of normal subjects and patients with chronic airways obstruction and mild hypercapnia due to longstanding chronic bronchitis. In 13 normal subjects the ventilatory response to hypercapnia increased after an intravenous injection of naloxone (0- 1 mg/kg), ventilation (VE) at a Pco2 of 8- 5 kPa increasing from 55 6 ± SEM 6- 2 to 75- 9 ± 8- 2 1 min-' (p < 0 001) and the AVE/APCo2 slope increasing from 28- 6 ± 4 4 to 34- 2 ± 4- 2 1 min-' kPa-' (p < 0 05). There was no significant change after placebo (saline) injection. Naloxone had no effect on resting ventilation or on the ventilatory response to hypoxia in normal subjects. In all six patients naloxone significantly (p < 0 02) increased mouth occlusion pressure (Po0,) responses to hypercapnia. Although there was no change in resting respiratory frequency or tidal volume patients showed a significant (p < 0 01) decrease in inspiratory timing (Ti/Ttot) and increase in mean inspiratory flow (VT/Ti) after naloxone. These results indicate that endorphins have a modulatory role in the central respiratory response to hypercapnia in both normal subjects and patients with airways obstruction. In addition, they have an inhibitory effect on the control of tidal breathing in patients with chronic bronchitis.