Mechanisms of endothelin-1 elevation in chronic obstructive pulmonary disease patients with nocturnal oxyhemoglobin desaturation

Background: Nonapneic, oxyhemoglobin desaturation associated with sleep has been described in patients with chronic obstructive pulmonary disease (COP D). Hypoxemia stimulates endothelin-1 (ET-1) secretion. Once released, ET-1 can act locally to elicit sustained pulmonary artery vasoconstriction, bro nchoconstriction and activation of alveolar macrophages. Objective: The aim of this study was to examine a possible correlation between ET-1 levels an d nocturnal, nonapneic, oxyhemoglobin desaturation during sleep, in patient s with COPD. Methods: We examined 48 COPD patients with formal polysomnogra phy (EEG, ECG, airflow, respiratory muscle movement, oximeter) to detect th e presence of nocturnal, nonapneic, oxyhemoglobin desaturation. Twelve of t hem were disqualified because of inadequate sleep or sleep apnea syndrome. Nineteen of them desaturated below a baseline sleep saturation of 90% for 5 min or more, reaching a nadir saturation of at least 85%. We collected art erial samples to measure ET-1 levels, after 5 min of the first period of de saturation, in each of the 19 patients. We also collected arterial samples in the morning, before the study, to measure baseline ET-1 levels in all pa tients. Results: Baseline arterial ET-1 levels during the day were very sig nificantly higher in 'desaturator' COPD patients (2.058 +/- 0.252 pg/ml) co mpared to 'non-desaturator' COPD patients (1.382 +/- 0.159 pg/ml; p < 0.001 ). Also in 'desaturator' COPD patients ET-1, levels during the night were s ignificantly higher (4.297 +/- 1.107 pg/ml) compared to those during the da y (p <less than or equal to> 0.001) and a significant negative correlation was observed between ET-1 levels and degree of desaturation (p < 0.0001, r = 0.9305). Conclusions: According to our study we can conclude that (1) ET- 1 levels are significantly higher in 'desaturator' COPD patients both durin g the day and during the night, and (2) ET-1 levels correlate negatively si gnificant with the degree of the oxyhemoglobin desaturation. These findings are consistent with the hypothesis that ET-1 plays a very important role i n the pathophysiological manifestations of COPD patients. Copyright (C) 200 1 S. Karger AG, Basel.