Mechanisms of Endothelin-1 Elevation in Chronic Obstructive Pulmonary Disease Patients with Nocturnal Oxyhemoglobin Desaturation

Abstract

Background: Nonapneic, oxyhemoglobin desaturation associated with sleep has been described in patients with chronic obstructive pulmonary disease (COPD). Hypoxemia stimulates endothelin-1 (ET-1) secretion. Once released, ET-1 can act locally to elicit sustained pulmonary artery vasoconstriction, bronchoconstriction and activation of alveolar macrophages. Objective: The aim of this study was to examine a possible correlation between ET-1 levels and nocturnal, nonapneic, oxyhemoglobin desaturation during sleep, in patients with COPD. Methods: We examined 48 COPD patients with formal polysomnography (EEG, ECG, airflow, respiratory muscle movement, oximeter) to detect the presence of nocturnal, nonapneic, oxyhemoglobin desaturation. Twelve of them 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 arterial samples to measure ET-1 levels, after 5 min of the first period of desaturation, 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 patients. Results: Baseline arterial ET-1 levels during the day were very significantly higher in ‘desaturator’ COPD patients (2.058 ± 0.252 pg/ml) compared 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 significantly higher (4.297 ± 1.107 pg/ml) compared to those during the day (p ≤ 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 during the day and during the night, and (2) ET-1 levels correlate negatively significant with the degree of the oxyhemoglobin desaturation. These findings are consistent with the hypothesis that ET-1 plays a very important role in the pathophysiological manifestations of COPD patients.

Mediators of Chronic Obstructive Pulmonary Disease

“…Plasma ET-1 concentrations are also elevated in COPD patients, particularly in patients who develop nocturnal hypoxemia during the night (Trakada et al, 2001;Spiropoulos et al, 2003) and in patients with hypoxemia (Faller et al, 1998), but it is not correlated with secondary pulmonary hypertension (Bacakoglu et al, 2003). This may reflect the release of ET-1 by hypoxemia, suggesting that the release of ET-1 may contribute to pulmonary vasoconstriction and pulmonary hypertension in COPD patients.…”

Evaluation of Arterial Endothelin-1 Levels, before and during a Sleep Study, in Patients with Bronchial Asthma and Chronic Obstructive Pulmonary Disease

“…In COPD patients in remission PaO 2 varies during the day and night [31]. Interestingly, hypoxaemia has been shown to induce airway ET-1 production, which suggests that ET-1 may play an important role in the physiopathology of stable COPD.…”

Variability in pulmonary function following rapid altitude ascent to the Amundsen–Scott South Pole station

“…Endothelin-1, a potent pulmonary vasoconstrictor peptide that also augments microvascular permeability (Chalmers et al 1997;Goldie and Fernandes 2000;Nally et al 1994;Springall et al 1991;Trakada et al 2001), was measured by a quantitative two-site chemiluminescent immunoassay (R & D Systems, Minneapolis, MN). Plasma catecholamines, which induce bronchodilation and interstitial fluid clearance (Mazzeo et al 1994;Milic-Emili et al 2001;Sartori et al 2002), were measured by reversed phase HPLC with electrochemical detection after extraction with activated alumina.…”