Abstract
Background: Hypoxemia stimulates endothelin-1 (ET-1) secretion. The reduction in alveolar ventilation during sleep is considered sufficient to account for the hypoxemia observed in patients with respiratory diseases. Objective: The aim of this study was to evaluate the arterial ET-1 levels and their relationship with pulmonary hypertension in patients with interstitial lung disease (ILD) during sleep. Methods: We examined 38 patients with ILD using formal polysomnography (electroencephalogram, electrocardiogram, airflow, respiratory muscle movement, oximeter) to detect the presence of nocturnal, nonapneic, oxyhemoglobin desaturation. All patients desaturated below a baseline sleep saturation of 90% for 5 minutes or more, reaching a nadir saturation of at least 85%. Each patient had already undergone right heart catheterization with a Swan-Ganz catheter for measuring hemodynamic parameters. Sampling of arterial blood from a radial artery line for determination of blood gases and ET-1 values was performed simultaneously, after 5 minutes of the first desaturation. Results: At rest, arterial ET-1 levels were higher in ILD patients (1.73 ± 0.37 mgr/mL) than in controls (1.22 ± 0.15 mgr/mL) (p < 0.001). Also, the patients with pulmonary hypertension (Pa > 20 mm Hg) presented significantly higher arterial ET-1 levels (1.86 ± 0.32 mgr/mL) than those without pulmonary hypertension (1.31 ± 0.13 mgr/mL) (p < 0.001). Arterial ET-1 levels were significantly correlated with mean pulmonary arterial pressure (PAP) (r = 0.749, p < 0.001), and arterial oxygen partial pressure (PaO2) (r = 0.79, p < 0.001). At sleep, during desaturation, arterial ET-1 levels significantly increased in all patients (2.46 ± 0.13 mgr/mL) as compared with resting values (p < 0.001). Arterial ET-1 levels were significantly correlated with PAP (r = 0.657, p < 0.001) and PaO2 (r = 0.93, p < 0.001). Conclusions: According to our study, arterial ET-1 is markedly increased in ILD patients, especially in those with pulmonary hypertension.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Inoue A, Yanagisawa S, Kimura Y, et al. The human endothelin family; three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci USA 1989;86:2863–2867
Giaid A, Michel RP, Stewart DJ, SheppardM, Corria B, Hamid Q. Expression of endothelin-1 in lungs of patients with cryptogenic fibrosing alveolitis. Lancet 1993;341:1550–1554
Giaid A, Yanagisawa M, Langleben D, et al. Expression of endothelin-1 in lungs of patients with pulmonary hypertension. N Engl J Med 1993;328:1732–1739
Shirakami G, Nakap K, Saito Y, et al. Acute pulmonary alveolar hypoxia increases lung and plasma endothelin-1 levels in conscious rats. Life Sci 1991;48:969–976
Trask CH, Gree EM. Oximeter studies on patients with chronic obstructive emphysema, awake and during sleep. N Engl J Med 1962;266:639–642
Koo KW, Sax DS, Snider GL. Arterial blood gases and pH during sleep in chronic obstructive pulmonary disease. Am J Med 1975;58:663–670
Wynne JW, Block AJ, Hemenway I, HuntLA, Flick MR. Disordered breathing and oxygen desaturation during sleep in patients with chronic obstructive lung disease (COLD). Am J Med 1979;66:573–579
Trakada G, Marangos M, Spiropoulos K. Mechanisms of endothelin-1 elevation in chronic obstructive pulmonary disease patients with nocturnal oxyhemoglobin desaturation. Respiration 2001;68(2):134–139
Francis PW, Muller NL, Gurwitz D, Milligan DW, Levison H, BryanAC. Hemoglobin desaturation: its occurrence during sleep in patients with cystic fibrosis. Am J Dis Child 1980;134:734–740
Stokes DC, McBride JT, Wall MA, Erba G, StriederDJ. Sleep hypoxemia in young adults with cystic fibrosis. Am J Dis Child 1980;134:741–743
Bye PT, Issa F, Berthon-Jones M, SullivanCE. Studies of oxygenation during sleep in patients with interstitial lung disease. Am Rev Respir Dis 1984;129:27–32
Perez-Padilla R, West P, Lertzman M, KrygerMH. Breathing during sleep in patients with interstitial lung disease. Am Rev Respir Dis 1985;132:224–229
Mezon BL, West P, Israels J, Kryger M. Sleep breathing abnormalities in kyphoscoliosis. Am Rev Respir Dis 1980;122:617–621
Guilleminault C, Motta J. Sleep apnea syndrome as a long-term sequela of poliomyelitis. In: Guilleminault C, Dement WC, eds. Sleep Apnea Syndromes. New York, NY: Alan R Liss; 1978:309–315
Douglas NJ, Calverley PM, Leggett RJ, Brash HM, Flenley DC, Brezinova V. Transient hypoxaemia during sleep in chronic bronchitis and emphysema. Lancet 1979;1:1–4
Boysen PG, Block JA, Wynne JW, Hunt LA, Flick MR. Nocturnal pulmonary hypertension in patients with obstructive pulmonary disease. Chest 1979;76:536–542
Fletcher EC, Levin DC. Cardiopulmonary haemodynamics during sleep in subjects with chronic obstructive pulmonary disease: the effect of short- and long-term oxygen. Chest 1984;85:6–14
Flenley DC. Clinical hypoxia: causes, consequences and correction. Lancet 1978;1:542–546
Block AJ, Boyson PG, Wynne JW. The origins of cor pulmonale, a hypothesis. Chest 1979;75:109–110
Rechtshaffen A, Kales A, eds. A Manual of Standarized Terminology, Techniques and Scoring Systems for Sleep Stages of Human Subjects Publication 204, Washington, DC: National Institutes of Health; 1968
Luscher TF. Endothelin [review]. J Cardiovasc Pharmacol 1991;18 (suppl 10):S15–S22
Hay DPW, Henry PJ, Goldie RG. Endothelin and the respiratory system. Trends Pharmacol Sci 1993;14:29–32
Trakada G, Tsourapis S, Marangos M, Spiropoulos K. Arterial and bronchoalveolar lavage fluid endothelin-1 concentration in asthma. Respir Med 2000;10:992–996
Langleben D, Demarchie M, Laporta D, et al. Endothelin-1 in acute lung injury and the adult distress syndrome. Am Rev Respir Dis 1993;148:1646–1650
Lippton HL, Hauth TA, Summer WR, Hyman AL. Endothelin produces pulmonary vasoconstriction and systemic vasodilation. J Appl Physiol 1989;66:1008–1012
Marhewitz BA, Kohan DE, Michael JR. Endothelin-1 synthesis, receptors and signal tranduction in alveolar epithelium: evidence for an autocrine role. Am J Physiol 1995;268:L192–L200
Komuro I, Kurihara H, Sugiyama T, Yoshizumi M, Tahaku F, Yazaki Y. Endothelin stimulates c-fos and c-myc expression and proliferation of vascular smooth muscle cells. FEBS Lett 1988;238:249–252
Trakada G, Spiropoulos K. Arterial endothelin-1 in interstitial lung disease patients with pulmonary hypertension. Monaldi Arch Chest Dis 2001;56:379–383
Bullow K. Respiration and wakefulness in man. Acta Physiol Scand 1963;59:1–110
Douglas NJ, White DP, Pickett CK, Weil JV, Zwillich CW. Respiration during sleep in normal man. Thorax 1982;37:840–844
Catterall JR, Douglas NJ, Carverley PM, et al. Transient hypoxemia during sleep in chronic obstructive pulmonary disease is not a sleep apnea syndrome. Am Rev Respir Dis 1983;128:24–29
Gould GA, Gugger M, Molloy J, Tsara V, ShapiroCM, Douglas NJ. Breathing pattern and eye movement density during REM sleep in humans. Am Rev Respir Dis 1988;138:870–874
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Trakada, G., Nikolaou, E., Pouli, A. et al. Endothelin-1 Levels in Interstitial Lung Disease Patients During Sleep. Sleep Breath 7, 111–118 (2003). https://doi.org/10.1007/s11325-003-0111-y
Issue Date:
DOI: https://doi.org/10.1007/s11325-003-0111-y