Download PDF
Sleep Breath 2003; 07(3): 111-118
DOI: 10.1055/s-2003-43072
ORIGINAL ARTICLE

Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Endothelin-1 Levels in Interstitial Lung Disease Patients During Sleep

Georgia Trakada1 , Eugenia Nikolaou2 , Athanasia Pouli3 , Maria Tsiamita1 , Kostas Spiropoulos1
  • 1University of Patras Medical School, Division of Pulmonology, Laboratory of Sleep, Patras, Greece
  • 2Laboratory of Immunology, Onashion Cardiosurgery Hospital, Athens, Greece
  • 3Department of Hematological Diseases, Agios Sabas Hospital, Athens, Greece
Further Information

Publication History

Publication Date:
21 October 2003 (online)

    Permissions and Reprints

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.

KEYWORDS

Interstitial lung disease - sleep - endothelin-1 (ET-1) - hypoxemia

REFERENCES

  • 1 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
    PubMedSearch in Google Scholar
  • 2 Giaid A, Michel R P, Stewart D J, Sheppard M, Corria B, Hamid Q. Expression of endothelin-1 in lungs of patients with cryptogenic fibrosing alveolitis.  Lancet . 1993;  341 1550-1554
    CrossrefPubMedSearch in Google Scholar
  • 3 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
    CrossrefPubMedSearch in Google Scholar
  • 4 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
    CrossrefPubMedSearch in Google Scholar
  • 5 Trask C H, Gree E M. Oximeter studies on patients with chronic obstructive emphysema, awake and during sleep.  N Engl J Med . 1962;  266 639-642
    PubMedSearch in Google Scholar
  • 6 Koo K W, Sax D S, Snider G L. Arterial blood gases and pH during sleep in chronic obstructive pulmonary disease.  Am J Med . 1975;  58 663-670
    CrossrefPubMedSearch in Google Scholar
  • 7 Wynne J W, Block A J, Hemenway I, Hunt L A, Flick M R. Disordered breathing and oxygen desaturation during sleep in patients with chronic obstructive lung disease (COLD).  Am J Med . 1979;  66 573-579
    CrossrefPubMedSearch in Google Scholar
  • 8 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
    CrossrefPubMedSearch in Google Scholar
  • 9 Francis P W, Muller N L, Gurwitz D, Milligan D W, Levison H, Bryan A C. Hemoglobin desaturation: its occurrence during sleep in patients with cystic fibrosis.  Am J Dis Child . 1980;  134 734-740
    PubMedSearch in Google Scholar
  • 10 Stokes D C, McBride J T, Wall M A, Erba G, Strieder D J. Sleep hypoxemia in young adults with cystic fibrosis.  Am J Dis Child . 1980;  134 741-743
    PubMedSearch in Google Scholar
  • 11 Bye P T, Issa F, Berthon-Jones M, Sullivan C E. Studies of oxygenation during sleep in patients with interstitial lung disease.  Am Rev Respir Dis . 1984;  129 27-32
    PubMedSearch in Google Scholar
  • 12 Perez-Padilla R, West P, Lertzman M, Kryger M H. Breathing during sleep in patients with interstitial lung disease.  Am Rev Respir Dis . 1985;  132 224-229
    PubMedSearch in Google Scholar
  • 13 Mezon B L, West P, Israels J, Kryger M. Sleep breathing abnormalities in kyphoscoliosis.  Am Rev Respir Dis . 1980;  122 617-621
    PubMedSearch in Google Scholar
  • 14 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
    Search in Google Scholar
  • 15 Douglas N J, Calverley P M, Leggett R J, Brash H M, Flenley D C, Brezinova V. Transient hypoxaemia during sleep in chronic bronchitis and emphysema.  Lancet . 1979;  1 1-4
    PubMedSearch in Google Scholar
  • 16 Boysen P G, Block J A, Wynne J W, Hunt L A, Flick M R. Nocturnal pulmonary hypertension in patients with obstructive pulmonary disease.  Chest . 1979;  76 536-542
    CrossrefPubMedSearch in Google Scholar
  • 17 Fletcher E C, Levin D C. Cardiopulmonary haemodynamics during sleep in subjects with chronic obstructive pulmonary disease: the effect of short- and long-term oxygen.  Chest . 1984;  85 6-14
    CrossrefPubMedSearch in Google Scholar
  • 18 Flenley D C. Clinical hypoxia: causes, consequences and correction.  Lancet . 1978;  1 542-546
    PubMedSearch in Google Scholar
  • 19 Block A J, Boyson P G, Wynne J W. The origins of cor pulmonale, a hypothesis.  Chest . 1979;  75 109-110
    PubMedSearch in Google Scholar
  • 20 Rechtshaffen A, Kales A. A Manual of Standarized Terminology, Techniques and Scoring Systems for Sleep Stages of Human Subjects Publication 204. Washington, DC: National Institutes of Health 1968
    Search in Google Scholar
  • 21 Luscher T F. Endothelin [review].  J Cardiovasc Pharmacol . 1991;  18 (suppl 10) S15-S22
    PubMedSearch in Google Scholar
  • 22 Hay D PW, Henry P J, Goldie R G. Endothelin and the respiratory system.  Trends Pharmacol Sci . 1993;  14 29-32
    PubMedSearch in Google Scholar
  • 23 Trakada G, Tsourapis S, Marangos M, Spiropoulos K. Arterial and bronchoalveolar lavage fluid endothelin-1 concentration in asthma.  Respir Med . 2000;  10 992-996
    PubMedSearch in Google Scholar
  • 24 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
    PubMedSearch in Google Scholar
  • 25 Lippton H L, Hauth T A, Summer W R, Hyman A L. Endothelin produces pulmonary vasoconstriction and systemic vasodilation.  J Appl Physiol . 1989;  66 1008-1012
    PubMedSearch in Google Scholar
  • 26 Marhewitz B A, Kohan D E, Michael J R. Endothelin-1 synthesis, receptors and signal tranduction in alveolar epithelium: evidence for an autocrine role.  Am J Physiol . 1995;  268 L192-L200
    PubMedSearch in Google Scholar
  • 27 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
    CrossrefPubMedSearch in Google Scholar
  • 28 Trakada G, Spiropoulos K. Arterial endothelin-1 in interstitial lung disease patients with pulmonary hypertension.  Monaldi Arch Chest Dis . 2001;  56 379-383
    PubMedSearch in Google Scholar
  • 29 Bullow K. Respiration and wakefulness in man.  Acta Physiol Scand . 1963;  59 1-110
    PubMedSearch in Google Scholar
  • 30 Douglas N J, White D P, Pickett C K, Weil J V, Zwillich C W. Respiration during sleep in normal man.  Thorax . 1982;  37 840-844
    CrossrefPubMedSearch in Google Scholar
  • 31 Catterall J R, Douglas N J, Carverley P M. 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
    PubMedSearch in Google Scholar
  • 32 Gould G A, Gugger M, Molloy J, Tsara V, Shapiro C M, Douglas N J. Breathing pattern and eye movement density during REM sleep in humans.  Am Rev Respir Dis . 1988;  138 870-874
    PubMedSearch in Google Scholar