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Semin Respir Crit Care Med 2010; 31(3): 295-312
DOI: 10.1055/s-0030-1254070
© Thieme Medical Publishers

Right Heart Function in COPD

William MacNee1
  • 1Department of Respiratory and Environmental Medicine, University of Edinburgh, ELEGI Colt Laboratories, MRC Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh, Scotland, United Kingdom
Further Information

Publication History

Publication Date:
21 May 2010 (online)

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ABSTRACT

Pulmonary hypertension is a common complication in patients with severe hypoxic COPD, but the elevation in pulmonary arterial pressure (PAP) is usually relatively mild, although its presence indicates a poor prognosis. A minority of patients have severe pulmonary hypertension, whose prognosis is very poor with the development of right heart failure. Pulmonary hypertension in COPD is thought to result from hypoxic pulmonary vasoconstriction leading to structural remodeling of all layers of the pulmonary arterial walls.

The simple hypothesis that hypoxemia in patients with chronic lung disease results in pulmonary hypertension, which adversely affects right ventricular function and hence increases morbidity and decreases exercise tolerance, leading to the development of peripheral edema and increased mortality, is still somewhat controversial.

Whether therapeutic interventions that directly affect PAP or right ventricular function have a significant effect on long-term survival in patients with pulmonary hypertension secondary to hypoxic lung disease is still a matter of debate. Furthermore, whether such interventions will have an effect on symptoms or exercise tolerance remains unproven. Present therapies are limited to the correction of hypoxemia over the long term, which has been shown to have proven benefits on survival. Further studies are required of more specific pulmonary vasodilators or therapies to improve right ventricular function in these patients.

KEYWORDS

Chronic obstructive pulmonary disease - pulmonary circulation - pulmonary hypertension - cor pulmonale

REFERENCES

  • 1 Fishman A P. State of the art: chronic cor pulmonale.  Am Rev Respir Dis. 1976;  114 775-794
    PubMedGoogle Scholar
  • 2 Bishop J M. Cardiovascular complications of chronic bronchitis and emphysema.  Med Clin North Am. 1973;  57 771-780
    PubMedGoogle Scholar
  • 3 MacNee W. Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease. Part two.  Am J Respir Crit Care Med. 1994;  150 1158-1168
    PubMedGoogle Scholar
  • 4 Weitzenblum E, Hirth C, Roeslin N, Vandevenne A, Oudet P. Pulmonary hemodynamic changes during the acute respiratory insufficiency of chronic bronchopneumopathies [in French].  Respiration. 1971;  28 539-554
    CrossrefPubMedGoogle Scholar
  • 5 Williams B T, Nicholl J P. Prevalence of hypoxaemic chronic obstructive lung disease with reference to long-term oxygen therapy.  Lancet. 1985;  2 369-372
    PubMedGoogle Scholar
  • 6 World Health Organisation . Chronic cor pulmonale: a report of an expert committee.  World Health Organ Tech Rep Ser. 1961;  213 35
    PubMedGoogle Scholar
  • 7 Niederman M S, Matthay R A. Cardiovascular function in secondary pulmonary hypertension.  Heart Lung. 1986;  15 341-351
    PubMedGoogle Scholar
  • 8 Weitzenblum E, Chaoat A, Canuet M. Pulmonary hypertension in chronic obstructive pulmonary disease. In: Voelkel NF, MacNee W Chronic Obstructive Lung Diseases. 2nd ed. Hamilton, ON; BC Dekker 2008: 299-316
    PubMedGoogle Scholar
  • 9 Fishman A P. Clinical classification of pulmonary hypertension.  Clin Chest Med. 2001;  22 385-391, vii
    CrossrefPubMedGoogle Scholar
  • 10 Kessler R, Faller M, Weitzenblum E et al.. “Natural history” of pulmonary hypertension in a series of 131 patients with chronic obstructive lung disease.  Am J Respir Crit Care Med. 2001;  164 219-224
    CrossrefPubMedGoogle Scholar
  • 11 Naeije R, Torbicki A. More on the noninvasive diagnosis of pulmonary hypertension: Doppler echocardiography revisited.  Eur Respir J. 1995;  8 1445-1449
    PubMedGoogle Scholar
  • 12 Naeije R, MacNee W. Pulmonary circulation. In: Calverley P, MacNee W, Pride P, Rennard S Chronic Obstructive Pulmonary Disease. 2nd ed. London; Arnold Health Sciences 2003: 228-242
    PubMedGoogle Scholar
  • 13 Eddahibi S, Chaouat A, Morrell N et al.. Polymorphism of the serotonin transporter gene and pulmonary hypertension in chronic obstructive pulmonary disease.  Circulation. 2003;  108 1839-1844
    CrossrefPubMedGoogle Scholar
  • 14 Scharf S M, Iqbal M, Keller C, Criner G, Lee S, Fessler H E. National Emphysema Treatment Trial (NETT) Group . Hemodynamic characterization of patients with severe emphysema.  Am J Respir Crit Care Med. 2002;  166 314-322
    CrossrefPubMedGoogle Scholar
  • 15 Croxton T L, Weinmann G G, Senior R M, Wise R A, Crapo J D, Buist A S. Clinical research in chronic obstructive pulmonary disease: needs and opportunities.  Am J Respir Crit Care Med. 2003;  167 1142-1149
    CrossrefPubMedGoogle Scholar
  • 16 Thabut G, Dauriat G, Stern J B et al.. Pulmonary hemodynamics in advanced COPD candidates for lung volume reduction surgery or lung transplantation.  Chest. 2005;  127 1531-1536
    CrossrefPubMedGoogle Scholar
  • 17 Arcasoy S M, Christie J D, Ferrari V A et al.. Echocardiographic assessment of pulmonary hypertension in patients with advanced lung disease.  Am J Respir Crit Care Med. 2003;  167 735-740
    CrossrefPubMedGoogle Scholar
  • 18 Higham M A, Dawson D, Joshi J, Nihoyannopoulos P, Morrell N W. Utility of echocardiography in assessment of pulmonary hypertension secondary to COPD.  Eur Respir J. 2001;  17 350-355
    CrossrefPubMedGoogle Scholar
  • 19 Wilkinson M, Langhorne C A, Heath D, Barer G R, Howard P. A pathophysiological study of 10 cases of hypoxic cor pulmonale.  Q J Med. 1988;  66 65-85
    PubMedGoogle Scholar
  • 20 Magee F, Wright J L, Wiggs B R, Paré P D, Hogg J C. Pulmonary vascular structure and function in chronic obstructive pulmonary disease.  Thorax. 1988;  43 183-189
    CrossrefPubMedGoogle Scholar
  • 21 Santos S, Peinado V I, Ramírez J et al.. Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD.  Eur Respir J. 2002;  19 632-638
    CrossrefPubMedGoogle Scholar
  • 22 Hale K A, Niewoehner D E, Cosio M G. Morphologic changes in the muscular pulmonary arteries: relationship to cigarette smoking, airway disease, and emphysema.  Am Rev Respir Dis. 1980;  122 273-278
    PubMedGoogle Scholar
  • 23 Wright J L, Lawson L, Paré P D et al.. The structure and function of the pulmonary vasculature in mild chronic obstructive pulmonary disease: the effect of oxygen and exercise.  Am Rev Respir Dis. 1983;  128 702-707
    PubMedGoogle Scholar
  • 24 Peinado V I, Barberá J A, Abate P et al.. Inflammatory reaction in pulmonary muscular arteries of patients with mild chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 1999;  159(5 Pt 1) 1605-1611
    CrossrefPubMedGoogle Scholar
  • 25 MacNee W. Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease. Part One.  Am J Respir Crit Care Med. 1994;  150 833-852
    CrossrefPubMedGoogle Scholar
  • 26 Archer S, Michelakis E. The mechanism(s) of hypoxic pulmonary vasoconstriction: potassium channels, redox O(2) sensors, and controversies.  News Physiol Sci. 2002;  17 131-137
    PubMedGoogle Scholar
  • 27 Dinh-Xuan A T, Higenbottam T W, Clelland C A et al.. Impairment of endothelium-dependent pulmonary-artery relaxation in chronic obstructive lung disease.  N Engl J Med. 1991;  324 1539-1547
    CrossrefPubMedGoogle Scholar
  • 28 Giaid A, Yanagisawa M, Langleben D et al.. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension.  N Engl J Med. 1993;  328 1732-1739
    CrossrefPubMedGoogle Scholar
  • 29 Clini E, Cremona G, Campana M et al.. Production of endogenous nitric oxide in chronic obstructive pulmonary disease and patients with cor pulmonale: correlates with echo-Doppler assessment.  Am J Respir Crit Care Med. 2000;  162(2 Pt 1) 446-450
    PubMedGoogle Scholar
  • 30 Lee D J, Taraseviciene-Stewart L, Keith R et al.. The expression of prostacyclin synthase is decreased in the small pulmonary arteries from patients with emphysema.  Chest. 2005;  128(6 Suppl) 575S
    PubMedGoogle Scholar
  • 31 Santos S, Peinado V I, Ramirez J et al.. Enhanced expression of vascular endothelial growth factor in pulmonary arteries of smokers and patients with moderate chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2003;  167 1250-1256
    CrossrefPubMedGoogle Scholar
  • 32 Grover R F. Chronic hypoxic pulmonary hypertension. In: Fishman A The Pulmonary Circulation: Normal and Abnormal. Philadelphia; University of Pennsylvania Press 1990: 283-299
    PubMedGoogle Scholar
  • 33 Ashutosh K, Mead G, Dunsky M. Early effects of oxygen administration and prognosis in chronic obstructive pulmonary disease and cor pulmonale.  Am Rev Respir Dis. 1983;  127 399-404
    PubMedGoogle Scholar
  • 34 Weitzenblum E, Schrijen F, Mohan-Kumar T, Colas des Francs V, Lockhart A. Variability of the pulmonary vascular response to acute hypoxia in chronic bronchitis.  Chest. 1988;  94 772-778
    CrossrefPubMedGoogle Scholar
  • 35 Voelkel N F. Hypoxic pulmonary vasoconstriction and hypertension. In: Peacock AJ Pulmonary Circulation. Glasgow; Chapman and Hall 1996: 71-85
    PubMedGoogle Scholar
  • 36 Weir E K, López-Barneo J, Buckler K J, Archer S L. Acute oxygen-sensing mechanisms.  N Engl J Med. 2005;  353 2042-2055
    CrossrefPubMedGoogle Scholar
  • 37 Sweeney M, Yuan J XJ. Hypoxic pulmonary vasoconstriction: role of voltage-gated potassium channels.  Respir Res. 2000;  1 40-48
    CrossrefPubMedGoogle Scholar
  • 38 Nana-Sinkam S P, Lee J D, Sotto-Santiago S et al.. Prostacyclin prevents pulmonary endothelial cell apoptosis induced by cigarette smoke.  Am J Respir Crit Care Med. 2007;  175 676-685
    CrossrefPubMedGoogle Scholar
  • 39 Oswald-Mammosser M, Apprill M, Bachez P, Ehrhart M, Weitzenblum E. Pulmonary hemodynamics in chronic obstructive pulmonary disease of the emphysematous type.  Respiration. 1991;  58 304-310
    CrossrefPubMedGoogle Scholar
  • 40 Tschernko E M, Wisser W, Wanke T et al.. Changes in ventilatory mechanics and diaphragmatic function after lung volume reduction surgery in patients with COPD.  Thorax. 1997;  52 545-550
    CrossrefPubMedGoogle Scholar
  • 41 Hemple V, Cornfield D N, Huang J, Schultz P I, Weir E K, Archer S L. Nitric oxide. In: Peacock AJ Pulmonary Circulation. Glasgow; Chapman and Hall 1996: 100-114
    PubMedGoogle Scholar
  • 42 Naeije R. Should pulmonary hypertension be treated in chronic obstructive pulmonary disease?. In: Weir EK, Archer SL, Reeves JT The Diagnosis and Treatment of Pulmonary Hypertension. New York; Futura 1992: 209-239
    PubMedGoogle Scholar
  • 43 Chaouat A, Bugnet A S, Kadaoui N et al.. Severe pulmonary hypertension and chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 2005;  172 189-194
    CrossrefPubMedGoogle Scholar
  • 44 Biernacki W, Flenley D C, Muir A L, MacNee W. Pulmonary hypertension and right ventricular function in patients with COPD.  Chest. 1988;  94 1169-1175
    CrossrefPubMedGoogle Scholar
  • 45 Stevens D, Sharma K, Szidon P, Rich S, McLaughlin V, Kesten S. Severe pulmonary hypertension associated with COPD.  Ann Transplant. 2000;  5 8-12
    PubMedGoogle Scholar
  • 46 Abraham A S, Cole R B, Green I D, Hedworth-Whitty R B, Clarke S W, Bishop J M. Factors contributing to the reversible pulmonary hypertension of patients with acute respiratory failure studies by serial observations during recovery.  Circ Res. 1969;  24 51-60
    CrossrefPubMedGoogle Scholar
  • 47 Weitzenblum E, Apprill M, Oswald M, Chaouat A, Imbs J L. Pulmonary hemodynamics in patients with chronic obstructive pulmonary disease before and during an episode of peripheral edema.  Chest. 1994;  105 1377-1382
    CrossrefPubMedGoogle Scholar
  • 48 Weitzenblum E, Chaouat A. Severe pulmonary hypertension in COPD. Is it a distinct disease?.  Chest. 2005;  127 1480-1482
    CrossrefPubMedGoogle Scholar
  • 49 Raeside D A, Brown A, Patel K R, Welsh D, Peacock A J. Ambulatory pulmonary artery pressure monitoring during sleep and exercise in normal individuals and patients with COPD.  Thorax. 2002;  57 1050-1053
    CrossrefPubMedGoogle Scholar
  • 50 Hudgel D W, Martin R J, Capehart M, Johnson B, Hill P. Contribution of hypoventilation to sleep oxygen desaturation in chronic obstructive pulmonary disease.  J Appl Physiol. 1983;  55 669-677
    PubMedGoogle Scholar
  • 51 Fletcher E C, Gray B A, Levin D C. Nonapneic mechanisms of arterial oxygen desaturation during rapid-eye-movement sleep.  J Appl Physiol. 1983;  54 632-639
    PubMedGoogle Scholar
  • 52 Catterall J R, Douglas N J, Calverley 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
    PubMedGoogle Scholar
  • 53 Coccagna G, Lugaresi E. Arterial blood gases and pulmonary and systemic arterial pressure during sleep in chronic obstructive pulmonary disease.  Sleep. 1978;  1 117-124
    PubMedGoogle Scholar
  • 54 Boysen P G, Block A J, Wynne J W, Hunt L A, Flick M R. Nocturnal pulmonary hypertension in patients with chronic obstructive pulmonary disease.  Chest. 1979;  76 536-542
    CrossrefPubMedGoogle Scholar
  • 55 Weitzenblum E, Muzet A, Ehrhart M, Ehrhart J, Sautegeau A, Weber L. Nocturnal changes in blood gases and pulmonary arterial pressure in chronic bronchitis patients with respiratory insufficiency (author's transl) [in French].  Nouv Presse Med. 1982;  11 1119-1122
    PubMedGoogle Scholar
  • 56 Fletcher E C, Levin D C. Cardiopulmonary hemodynamics during sleep in subjects with chronic obstructive pulmonary disease: the effect of short- and long-term oxygen.  Chest. 1984;  85 6-14
    CrossrefPubMedGoogle Scholar
  • 57 Weitzenblum E, Loiseau A, Hirth C, Mirhom R, Rasaholinjanahary J. Course of pulmonary hemodynamics in patients with chronic obstructive pulmonary disease.  Chest. 1979;  75 656-662
    CrossrefPubMedGoogle Scholar
  • 58 Weitzenblum E, Sautegeau A, Ehrhart M, Mammosser M, Hirth C, Roegel E. Long-term course of pulmonary arterial pressure in chronic obstructive pulmonary disease.  Am Rev Respir Dis. 1984;  130 993-998
    PubMedGoogle Scholar
  • 59 Report of the Medical Research Council Working Party . Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema.  Lancet. 1981;  1 681-686
    PubMedGoogle Scholar
  • 60 Timms R M, Khaja F U, Williams G W. Hemodynamic response to oxygen therapy in chronic obstructive pulmonary disease.  Ann Intern Med. 1985;  102 29-36
    CrossrefPubMedGoogle Scholar
  • 61 Weitzenblum E, Sautegeau A, Ehrhart M, Mammosser M, Pelletier A. Long-term oxygen therapy can reverse the progression of pulmonary hypertension in patients with chronic obstructive pulmonary disease.  Am Rev Respir Dis. 1985;  131 493-498
    PubMedGoogle Scholar
  • 62 Weitzenblum E, Hirth C, Ducolone A, Mirhom R, Rasaholinjanahary J, Ehrhart M. Prognostic value of pulmonary artery pressure in chronic obstructive pulmonary disease.  Thorax. 1981;  36 752-758
    CrossrefPubMedGoogle Scholar
  • 63 France A J, Prescott R J, Biernacki W, Muir A L, MacNee W. Does right ventricular function predict survival in patients with chronic obstructive lung disease?.  Thorax. 1988;  43 621-626
    CrossrefPubMedGoogle Scholar
  • 64 Skwarski K, MacNee W, Wraith P K, Sliwinski P, Zielinski J. Predictors of survival in patients with chronic obstructive pulmonary disease treated with long-term oxygen therapy.  Chest. 1991;  100 1522-1527
    CrossrefPubMedGoogle Scholar
  • 65 Khaja F, Parker J O. Right and left ventricular performance in chronic obstructive lung disease.  Am Heart J. 1971;  82 319-327
    CrossrefPubMedGoogle Scholar
  • 66 Brent B N, Berger H J, Matthay R A, Mahler D, Pytlik L, Zaret B L. Physiologic correlates of right ventricular ejection fraction in chronic obstructive pulmonary disease: a combined radionuclide and hemodynamic study.  Am J Cardiol. 1982;  50 255-262
    CrossrefPubMedGoogle Scholar
  • 67 Burghuber O C, Bergmann H. Right-ventricular contractility in chronic obstructive pulmonary disease: a combined radionuclide and hemodynamic study.  Respiration. 1988;  53 1-12
    CrossrefPubMedGoogle Scholar
  • 68 Mols P, Huynh C H, Dechamps P, Naeije N, Guillaume M, Ham H. Prediction of pulmonary arterial pressure in chronic obstructive pulmonary disease by radionuclide ventriculography.  Chest. 1989;  96 1280-1284
    CrossrefPubMedGoogle Scholar
  • 69 MacNee W, Skwarski K M. Right heart failure in cor pulmonale. In: Crawford MH, DiMarco JP, Paulus WJ Cardiology. London, UK; Mosby 2004: 1017-1026
    PubMedGoogle Scholar
  • 70 MacNee W, Skwarski K M. Right heart failure in cor pulmonale. In: Crawford MH, DiMarco JP, Paulus WJ Cardiology. London, UK; Mosby 2004: 1017-1026
    PubMedGoogle Scholar
  • 71 MacNee W, Wathen C G, Hannan W J, Flenley D C, Muir A L. Effects of pirbuterol and sodium nitroprusside on pulmonary haemodynamics in hypoxic cor pulmonale.  Br Med J (Clin Res Ed). 1983;  287 1169-1172
    CrossrefPubMedGoogle Scholar
  • 72 Burghuber O C. Right ventricular contractility is preserved and preload increased in patients with chronic obstructive pulmonary disease and pulmonary artery hypertension. In: Jezek V, Morpurgo M, Tramarin R Current Topics in Rehabilitation: Right Ventricular Hypertrophy and Function in Chronic Lung Disease. Berlin; Springer-Verlag 1992: 135-141
    PubMedGoogle Scholar
  • 73 Anand I S, Chandrashekhar Y, Ferrari R et al.. Pathogenesis of congestive state in chronic obstructive pulmonary disease: studies of body water and sodium, renal function, hemodynamics, and plasma hormones during edema and after recovery.  Circulation. 1992;  86 12-21
    PubMedGoogle Scholar
  • 74 MacNee W, Wathen C G, Flenley D C, Muir A D. The effects of controlled oxygen therapy on ventricular function in patients with stable and decompensated cor pulmonale.  Am Rev Respir Dis. 1988;  137 1289-1295
    PubMedGoogle Scholar
  • 75 Vandenbergh E, Clement J, Van de Woestijne K P. Course and prognosis of patients with advanced chronic obstructive pulmonary disease: evaluation by means of functional indices.  Am J Med. 1973;  55 736-746
    CrossrefPubMedGoogle Scholar
  • 76 Baudouin S V, Bott J, Ward A, Deane C, Moxham J. Short term effect of oxygen on renal haemodynamics in patients with hypoxaemic chronic obstructive airways disease.  Thorax. 1992;  47 550-554
    CrossrefPubMedGoogle Scholar
  • 77 Farber M O, Weinberger M H, Robertson G L, Fineberg N S, Manfredi F. Hormonal abnormalities affecting sodium and water balance in acute respiratory failure due to chronic obstructive lung disease.  Chest. 1984;  85 49-54
    CrossrefPubMedGoogle Scholar
  • 78 MacNee W, Skwarski K. The pathogenesis of peripheral edema in chronic obstructive pulmonary disease.  Clin Pulmon Med. 1997;  4 309-315
    PubMedGoogle Scholar
  • 79 Skwarski K, Lee M, Turnbull L, MacNee W. Atrial natriuretic peptide in stable and decompensated chronic obstructive pulmonary disease.  Thorax. 1993;  48 730-735
    CrossrefPubMedGoogle Scholar
  • 80 Skwarski K M, Morrison D, Barratt A, Lee M, MacNee W. Effects of hypoxia on renal hormonal balance in normal subjects and in patients with COPD.  Respir Med. 1998;  92 1331-1336
    CrossrefPubMedGoogle Scholar
  • 81 Matthay R A, Schwarz M I, Ellis Jr J H et al.. Pulmonary artery hypertension in chronic obstructive pulmonary disease: determination by chest radiography.  Invest Radiol. 1981;  16 95-100
    CrossrefPubMedGoogle Scholar
  • 82 Oswald-Mammosser M, Oswald T, Nyankiye E, Dickele M C, Grange D, Weitzenblum E. Non-invasive diagnosis of pulmonary hypertension in chronic obstructive pulmonary disease. Comparison of ECG, radiological measurements, echocardiography and myocardial scintigraphy.  Eur J Respir Dis. 1987;  71 419-429
    PubMedGoogle Scholar
  • 83 Incalzi R A, Fuso L, De Rosa M et al.. Electrocardiographic signs of chronic cor pulmonale: a negative prognostic finding in chronic obstructive pulmonary disease.  Circulation. 1999;  99 1600-1605
    PubMedGoogle Scholar
  • 84 Marchandise B, De Bruyne B, Delaunois L, Kremer R. Noninvasive prediction of pulmonary hypertension in chronic obstructive pulmonary disease by Doppler echocardiography.  Chest. 1987;  91 361-365
    CrossrefPubMedGoogle Scholar
  • 85 Cacho A, Prakash R, Sarma R, Kaushik V S. Usefulness of two-dimensional echocardiography in diagnosing right ventricular hypertrophy.  Chest. 1983;  84 154-157
    CrossrefPubMedGoogle Scholar
  • 86 Himelman R B, Struve S N, Brown J K, Namnum P, Schiller N B. Improved recognition of cor pulmonale in patients with severe chronic obstructive pulmonary disease.  Am J Med. 1988;  84 891-898
    CrossrefPubMedGoogle Scholar
  • 87 Miguéres M, Escamilla R, Coca F, Didier A, Krempf M. Pulsed Doppler echocardiography in the diagnosis of pulmonary hypertension in COPD.  Chest. 1990;  98 280-285
    CrossrefPubMedGoogle Scholar
  • 88 Yock P G, Popp R L. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation.  Circulation. 1984;  70 657-662
    CrossrefPubMedGoogle Scholar
  • 89 Chan K L, Currie P J, Seward J B, Hagler D J, Mair D D, Tajik A J. Comparison of three Doppler ultrasound methods in the prediction of pulmonary artery pressure.  J Am Coll Cardiol. 1987;  9 549-554
    CrossrefPubMedGoogle Scholar
  • 90 Tramarin R, Torbicki A, Marchandise B, Laaban J P, Morpurgo M. Doppler echocardiographic evaluation of pulmonary artery pressure in chronic obstructive pulmonary disease: a European multicentre study. Working Group on Noninvasive Evaluation of Pulmonary Artery Pressure. European Office of the World Health Organization, Copenhagen.  Eur Heart J. 1991;  12 103-111
    PubMedGoogle Scholar
  • 91 Torbicki A, Skwarski K, Hawrylkiewicz I, Pasierski T, Miskiewicz Z, Zielinski J. Attempts at measuring pulmonary arterial pressure by means of Doppler echocardiography in patients with chronic lung disease.  Eur Respir J. 1989;  2 856-860
    PubMedGoogle Scholar
  • 92 Laaban J P, Diebold B, Zelinski R, Lafay M, Raffoul H, Rochemaure J. Noninvasive estimation of systolic pulmonary artery pressure using Doppler echocardiography in patients with chronic obstructive pulmonary disease.  Chest. 1989;  96 1258-1262
    CrossrefPubMedGoogle Scholar
  • 93 McGoon M, Gutterman D, Steen V American College of Chest Physicians et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines.  Chest. 2004;  126(1, Suppl) 14S-34S
    CrossrefPubMedGoogle Scholar
  • 94 Turnbull L W, Ridgway J P, Biernacki W et al.. Assessment of the right ventricle by magnetic resonance imaging in chronic obstructive lung disease.  Thorax. 1990;  45 597-601
    CrossrefPubMedGoogle Scholar
  • 95 Saito H, Dambara T, Aiba M, Suzuki T, Kira S. Evaluation of cor pulmonale on a modified short-axis section of the heart by magnetic resonance imaging.  Am Rev Respir Dis. 1992;  146 1576-1581
    PubMedGoogle Scholar
  • 96 Krüger S, Haage P, Hoffmann R et al.. Diagnosis of pulmonary arterial hypertension and pulmonary embolism with magnetic resonance angiography.  Chest. 2001;  120 1556-1561
    CrossrefPubMedGoogle Scholar
  • 97 Saito H, Dambara T, Aiba M, Suzuki T, Kira S. Evaluation of cor pulmonale on a modified short-axis section of the heart by magnetic resonance imaging.  Am Rev Respir Dis. 1992;  146 1576-1581
    PubMedGoogle Scholar
  • 98 Yamamoto K, Burnett Jr J C, Jougasaki M et al.. Superiority of brain natriuretic peptide as a hormonal marker of ventricular systolic and diastolic dysfunction and ventricular hypertrophy.  Hypertension. 1996;  28 988-994
    PubMedGoogle Scholar
  • 99 Leuchte H H, Baumgartner R A, Nounou M E et al.. Brain natriuretic peptide is a prognostic parameter in chronic lung disease.  Am J Respir Crit Care Med. 2006;  173 744-750
    CrossrefPubMedGoogle Scholar
  • 100 Bozkanat E, Tozkoparan E, Baysan O, Deniz O, Ciftci F, Yokusoglu M. The significance of elevated brain natriuretic peptide levels in chronic obstructive pulmonary disease.  J Int Med Res. 2005;  33 537-544
    PubMedGoogle Scholar
  • 101 Barberà J A, Peinado V I, Santos S. Pulmonary hypertension in chronic obstructive pulmonary disease.  Eur Respir J. 2003;  21 892-905
    CrossrefPubMedGoogle Scholar
  • 102 Adnot S, Defouilloy C, Brun-Buisson C, Abrouk F, Piquet J, Lemaire F. Hemodynamic effects of urapidil in patients with pulmonary hypertension: a comparative study with hydralazine.  Am Rev Respir Dis. 1987;  135 288-293
    PubMedGoogle Scholar
  • 103 Saadjian A, Philip-Joët F, Hot B et al.. Effects of nicardipine on pulmonary and systemic vascular reactivity to oxygen in patients with pulmonary hypertension secondary to chronic obstructive lung disease.  J Cardiovasc Pharmacol. 1991;  17 731-737
    CrossrefPubMedGoogle Scholar
  • 104 Saadjian A Y, Philip-Joet F F, Vestri R, Arnaud A G. Long-term treatment of chronic obstructive lung disease by nifedipine: an 18-month haemodynamic study.  Eur Respir J. 1988;  1 716-720
    PubMedGoogle Scholar
  • 105 Adnot S, Kouyoumdjian C, Defouilloy C et al.. Hemodynamic and gas exchange responses to infusion of acetylcholine and inhalation of nitric oxide in patients with chronic obstructive lung disease and pulmonary hypertension.  Am Rev Respir Dis. 1993;  148 310-316
    PubMedGoogle Scholar
  • 106 Katayama Y, Higenbottam T W, Diaz de Atauri M J et al.. Inhaled nitric oxide and arterial oxygen tension in patients with chronic obstructive pulmonary disease and severe pulmonary hypertension.  Thorax. 1997;  52 120-124
    CrossrefPubMedGoogle Scholar
  • 107 Roger N, Barberà J A, Roca J, Rovira I, Gómez F P, Rodriguez-Roisin R. Nitric oxide inhalation during exercise in chronic obstructive pulmonary disease.  Am J Respir Crit Care Med. 1997;  156(3 Pt 1) 800-806
    PubMedGoogle Scholar
  • 108 Vonbank K, Ziesche R, Higenbottam T W et al.. Controlled prospective randomised trial on the effects on pulmonary haemodynamics of the ambulatory long term use of nitric oxide and oxygen in patients with severe COPD.  Thorax. 2003;  58 289-293
    CrossrefPubMedGoogle Scholar
  • 109 Archer S L, Huang J M, Hampl V, Nelson D P, Shultz P J, Weir E K. Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase.  Proc Natl Acad Sci U S A. 1994;  91 7583-7587
    CrossrefPubMedGoogle Scholar
  • 110 Alp S, Skrygan M, Schmidt W E, Bastian A. Sildenafil improves hemodynamic parameters in COPD—an investigation of six patients.  Pulm Pharmacol Ther. 2006;  19 386-390
    CrossrefPubMedGoogle Scholar
  • 111 Rietema H, Holverda S, Bogaard H J et al.. Sildenafil treatment in COPD does not affect stroke volume or exercise capacity.  Eur Respir J. 2008;  31 759-764
    CrossrefPubMedGoogle Scholar
  • 112 Blanco I, Gimeno E, Munoz P A et al.. Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension.  Am J Respir Crit Care Med. 2010;  181 270-278
    CrossrefPubMedGoogle Scholar
  • 113 Nocturnal Oxygen Therapy Trial Group . Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial.  Ann Intern Med. 1980;  93 391-398
    PubMedGoogle Scholar
  • 114 Zieliński J, Tobiasz M, Hawryłkiewicz I, Sliwiński P, Pałasiewicz G. Effects of long-term oxygen therapy on pulmonary hemodynamics in COPD patients: a 6-year prospective study.  Chest. 1998;  113 65-70
    CrossrefPubMedGoogle Scholar
  • 115 Chaouat A, Weitzenblum E, Kessler R et al.. A randomized trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease patients.  Eur Respir J. 1999;  14 1002-1008
    CrossrefPubMedGoogle Scholar
  • 116 Fletcher E C, Luckett R A, Goodnight-White S, Miller C C, Qian W, Costarangos-Galarza C. A double-blind trial of nocturnal supplemental oxygen for sleep desaturation in patients with chronic obstructive pulmonary disease and a daytime PaO2 above 60 mm Hg.  Am Rev Respir Dis. 1992;  145 1070-1076
    CrossrefPubMedGoogle Scholar
  • 117 Deem S, Swenson E R, Alberts M K, Hedges R G, Bishop M J. Red-blood-cell augmentation of hypoxic pulmonary vasoconstriction: hematocrit dependence and the importance of nitric oxide.  Am J Respir Crit Care Med. 1998;  157(4 Pt 1) 1181-1186
    PubMedGoogle Scholar
  • 118 Azarov I, Huang K T, Basu S, Gladwin M T, Hogg N, Kim-Shapiro D B. Nitric oxide scavenging by red blood cells as a function of hematocrit and oxygenation.  J Biol Chem. 2005;  280 39024-39032
    CrossrefPubMedGoogle Scholar
  • 119 Borst M M, Leschke M, König U, Worth H. Repetitive hemodilution in chronic obstructive pulmonary disease and pulmonary hypertension: effects on pulmonary hemodynamics, gas exchange, and exercise capacity.  Respiration. 1999;  66 225-232
    CrossrefPubMedGoogle Scholar
  • 120 Turino G M, Goldring R M, Heineman M D. Water, electrolytes and acid based relationships in chronic cor pulmonale.  Prog Cardiovasc Dis. 1970;  12 467-483
    CrossrefPubMedGoogle Scholar

William MacNeeM.B. Ch.B. M.D. 

ELEGI Colt Laboratories, University of Edinburgh, MRC Centre for Inflammation Research

The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, UK

Email: w.macnee@ed.ac.uk

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