Comprehensive Physiology Wiley Online Library

Pulmonary Vascular Diseases

Full Article on Wiley Online Library



Abstract

Diseases of the pulmonary vasculature are a cause of increased pulmonary vascular resistance (PVR) in pulmonary embolism, chronic thromboembolic pulmonary hypertension (CTEPH), and pulmonary arterial hypertension or decreased PVR in pulmonary arteriovenous malformations on hereditary hemorrhagic telangiectasia, portal hypertension, or cavopulmonary anastomosis. All these conditions are associated with a decrease in both arterial Po2 and Pco2. Gas exchange in pulmonary vascular diseases with increased PVR is characterized by a shift of ventilation and perfusion to high ventilation‐perfusion ratios, a mild to moderate increase in perfusion to low ventilation‐perfusion ratios, and an increased physiologic dead space. Hypoxemia in these patients is essentially explained by altered ventilation‐perfusion matching amplified by a decreased mixed venous Po2 caused by a low cardiac output. Hypocapnia is accounted for by hyperventilation, which is essentially related to an increased chemosensitivity. A cardiac shunt on a patent foramen ovale may be a cause of severe hypoxemia in a proportion of patients with pulmonary hypertension and an increase in right atrial pressure. Gas exchange in pulmonary arteriovenous malformations is characterized by variable degree of pulmonary shunting and/or diffusion‐perfusion imbalance. Hypocapnia is caused by an increased ventilation in relation to an increased pulmonary blood flow with direct peripheral chemoreceptor stimulation by shunted mixed venous blood flow. © 2011 American Physiological Society. Compr Physiol 1:593‐619, 2011.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1.

Determination of the optimal ratio. Upper left: milliliters of alveolar ventilation (dotted line) or of blood flow (solid line) needed to exchange 1 ml of oxygen at each . The sum of + (long dashed line) passes through a minimum value for a < 1.0. Upper right: milliliters of alveolar ventilation (dotted line) or of blood flow (solid line) needed to exchange 1 ml of carbon dioxide at each . The sum of + (short dashed line) passes through a minimum value for a . Lower middle: when combining both lines for O2 and CO2 (solid line), the minimum is reached for a ≈ 1 corresponding to the optimal for which ventilation and perfusion are minimal to exchange 1 ml of O2 and 1 ml of CO2 (RER = 1.0).

Figure 2. Figure 2.

Distributions of Pao2 and Paco2 in disease 100 and 82 patients with pulmonary embolism, respectively, and no background cardiopulmonary susceptible to affect pulmonary gas exchange. Most values are decreased, with two thirds of Pao2 < 70 mmHg and 45% of Paco2 < 33 mmHg taken as lower limits of normal (shaded columns). From references 28,66,72,100,99,139,140,153,162,199.

Figure 3. Figure 3.

distributions before and after acute pulmonary embolization with autologous clots in dogs. Three patterns were observed: slightly broadened unimodal, hardly different from normal (left panel), broadly unimodal (middle panel), and bimodal with an additional high mode (right panel). Vd/Vt, inert gas dead space; Qs/Qt, inert gas shunt. From reference 40, © Copyright 1990 by the American Society of Anesthesiologists, Inc., with permission

Figure 4. Figure 4.

distributions before and after pulmonary embolization with 100‐ and 1000‐μm diameter glass beads, respectively, in dogs. Small 100‐μm beads embolization (left panels) was associated with a broad unimodal pattern, an increased inert gas shunt (Qs/Qt), and a decreased inert gas dead space (Vd/Vt). Large 1000‐μm beads embolization (right panels) was associated with a bimodal pattern, with a mode of ventilation and perfusion centered on lung units with low normal , and an additional mode, mainly of ventilation, centered on units with high , and an increased Vd/Vt. From reference 42, © Copyright 1990 by the American Physiological Society, with permission

Figure 5. Figure 5.

distributions in a patient with acute pulmonary embolism before and after thrombolytic therapy. Before treatment, the distribution showed a bimodal pattern. Arterial hypoxemia resulted mainly from a low cardiac output and a low o2. After treatment, cardiac output, Pao2, and o2 increased and distribution returned to normal excepted for the persistence of a slightly increased shunt. From reference 109, with permission

Figure 6. Figure 6.

Thin‐section computed tomography after induction of acute blood clot pulmonary embolism in a pig. Pulmonary embolism was associated with a mosaic pattern appearance. Dark areas are hypoperfused, ground‐glass appearing areas are hyperperfused courtesy of P. A. Gevenois.

Figure 7. Figure 7.

Computed tomographic angiographical view of pulmonary embolism showing a dilated pulmonary artery and incomplete obstruction by a clot (arrow) courtesy of P. A. Gevenois.

Figure 8. Figure 8.

Two‐compartment lung with blood flow () and ventilation () in three lung units, with ratios close to normal in the left panel (A), flow reduced by 56% in the low unit in the middle panel (B), and flow reduced by 83% in the high unit in the right panel (C). The changes in the ratios taking into account the flow diversion, the mixed Pao2, the arterial o2 saturation (Sao2), the venous admixture (va/t), the physiologic dead space (VDco2/Vt), and the mixed Pco2 are shown. Panel B mimics lower lobe emboli and panel C upper lobe emboli.

Figure 9. Figure 9.

Explanation of differential effects of embolus size on inert gas dead space (Vd/VtIG) in the presence of collateral ventilation. Diffusion of alveolar gas from perfused to unperfused alveoli through interalveolar Kohn's pores and interbronchiolar Martin's ducts is effective in reducing intraregional differences only for small size emboli. From reference 43, © Copyright 1993 by the American Physiological Society, with permission

Figure 10. Figure 10.

Quantification of the pulmonary and extrapulmonary contributors to Pao2 in patients with severe acute pulmonary embolism. Measured Pao2 was 63 mmHg. Correction of abnormal diffusion, shunt, Pvo2, and log SDQ, as a measure of the distribution of perfusion homogeneity, successively increased Pao2, with eventually a Pao2 of 128 mmHg higher than normal because of hyperventilation. From reference 139, with permission

Figure 11. Figure 11.

Left: computed tomographic scans of the lungs of patients with CTEPH showing eccentric thrombotic material within the pulmonary arteries (A) and a characteristic mosaic attenuation of the pulmonary parenchyma with the darker areas corresponding to the hypoperfused lung sections (B) Right: Preoperative (A) and postoperative (B) magnetic resonance imaging of a patient with CTEPH before (A) and after (B) pulmonary endarterectomy. The preoperative PVR was 768 dyne S/cm5 and the postoperative PVR was 196 dyne S/cm−5. From reference 68, with permission

Figure 12. Figure 12.

Distributions of Pao2 and Paco2 in 96 and 56 patients with CTEPH, respectively. Most values are decreased, with 65% of Pao2 < 70 mmHg and 33% of Paco2 < 33 mmHg taken as lower limits of normal (shaded columns). (P. Bresser, personal communication, in part reported in reference 182).

Figure 13. Figure 13.

Representative distribution in patients with CTEPH, showing moderate inhomogeneity of both ventilation and perfusion distributed to a widened mode, with shift to ventilation to higher . There was minimal shunting. Pulmonary endarterectomy improved the distribution of , markedly in patient 3 (Pt 3) and only slightly in Pt 4. From reference 85, with permission

Figure 14. Figure 14.

Distributions of Pao2 and Paco2 in 243 patients with idiopathic pulmonary arterial hypertension. Most values are decreased, with 51% of Pao2 < 70 mmHg and 45% of Paco2 < 33 mmHg taken as lower limits of normal (shaded columns). (O. Sitbon and G. Simonneau, personal communication).

Figure 15. Figure 15.

distributions before and after the administration of nifedipine in a 61‐year‐old woman with idiopathic pulmonary arterial hypertension. Before nifedipine administration, the distribution showed a bimodal pattern with an additional low mode and an increased shunt (s/t). Arterial hypoxemia resulted from an elevated shunt, partially due to a right‐to‐left atrial shunt demonstrated by contrast echocardiography, and a low o2. After nifedipine administration, Pao2 increased as a result of the reduction in shunt and an increase in o2, in relation to increased cardiac output and decreased right ventricular afterload. Increase in Vd/Vt was explained by a decrease in tidal volume. From reference 112, © Copyright 1983 by the American College of Chest Physicians, with permission

Figure 16. Figure 16.

Typical telangiectasias in a patient with hereditary hemorrhagic telangiectasias. The chest radiography shows two pulmonary arteriovenous malformations (PAVMs) in the right lung (arrows). The right pulmonary angiogram of the same patient shows multiple PAVMs of variable size (arrows). M‐mode contrast‐enhanced echocardiography shows a delayed (4‐6 beats) microbubble opacification of left heart chambers. From reference 144, with permission

Figure 17. Figure 17.

Distributions of Pao2 and Paco2 in 110 patients with PAVM on hereditary hemorrhagic telangiectasia. Most values are decreased, with 44% of Pao2 < 70 mmHg and 39% of Paco2 < 33 mmHg taken as lower limits of normal (shaded columns) (V. Cottin, personal communication).

Figure 18. Figure 18.

Measured and calculated arterial Po2 (Pao2) 10 patients with liver cirrhosis. Columns show the mean actual value, and the effects of normalization procedures performed using the mathematical model of the multiple inert gas elimination technique. Thus, Pao2 decreases after normalizing circulating hemoglobin (Hb) and P50, increases after normalizing shunt and ventilation/perfusion () imbalance, and increases even further after adding measured increases in ventilation (Ve) and P50. From reference 110.



Figure 1.

Determination of the optimal ratio. Upper left: milliliters of alveolar ventilation (dotted line) or of blood flow (solid line) needed to exchange 1 ml of oxygen at each . The sum of + (long dashed line) passes through a minimum value for a < 1.0. Upper right: milliliters of alveolar ventilation (dotted line) or of blood flow (solid line) needed to exchange 1 ml of carbon dioxide at each . The sum of + (short dashed line) passes through a minimum value for a . Lower middle: when combining both lines for O2 and CO2 (solid line), the minimum is reached for a ≈ 1 corresponding to the optimal for which ventilation and perfusion are minimal to exchange 1 ml of O2 and 1 ml of CO2 (RER = 1.0).



Figure 2.

Distributions of Pao2 and Paco2 in disease 100 and 82 patients with pulmonary embolism, respectively, and no background cardiopulmonary susceptible to affect pulmonary gas exchange. Most values are decreased, with two thirds of Pao2 < 70 mmHg and 45% of Paco2 < 33 mmHg taken as lower limits of normal (shaded columns). From references 28,66,72,100,99,139,140,153,162,199.



Figure 3.

distributions before and after acute pulmonary embolization with autologous clots in dogs. Three patterns were observed: slightly broadened unimodal, hardly different from normal (left panel), broadly unimodal (middle panel), and bimodal with an additional high mode (right panel). Vd/Vt, inert gas dead space; Qs/Qt, inert gas shunt. From reference 40, © Copyright 1990 by the American Society of Anesthesiologists, Inc., with permission



Figure 4.

distributions before and after pulmonary embolization with 100‐ and 1000‐μm diameter glass beads, respectively, in dogs. Small 100‐μm beads embolization (left panels) was associated with a broad unimodal pattern, an increased inert gas shunt (Qs/Qt), and a decreased inert gas dead space (Vd/Vt). Large 1000‐μm beads embolization (right panels) was associated with a bimodal pattern, with a mode of ventilation and perfusion centered on lung units with low normal , and an additional mode, mainly of ventilation, centered on units with high , and an increased Vd/Vt. From reference 42, © Copyright 1990 by the American Physiological Society, with permission



Figure 5.

distributions in a patient with acute pulmonary embolism before and after thrombolytic therapy. Before treatment, the distribution showed a bimodal pattern. Arterial hypoxemia resulted mainly from a low cardiac output and a low o2. After treatment, cardiac output, Pao2, and o2 increased and distribution returned to normal excepted for the persistence of a slightly increased shunt. From reference 109, with permission



Figure 6.

Thin‐section computed tomography after induction of acute blood clot pulmonary embolism in a pig. Pulmonary embolism was associated with a mosaic pattern appearance. Dark areas are hypoperfused, ground‐glass appearing areas are hyperperfused courtesy of P. A. Gevenois.



Figure 7.

Computed tomographic angiographical view of pulmonary embolism showing a dilated pulmonary artery and incomplete obstruction by a clot (arrow) courtesy of P. A. Gevenois.



Figure 8.

Two‐compartment lung with blood flow () and ventilation () in three lung units, with ratios close to normal in the left panel (A), flow reduced by 56% in the low unit in the middle panel (B), and flow reduced by 83% in the high unit in the right panel (C). The changes in the ratios taking into account the flow diversion, the mixed Pao2, the arterial o2 saturation (Sao2), the venous admixture (va/t), the physiologic dead space (VDco2/Vt), and the mixed Pco2 are shown. Panel B mimics lower lobe emboli and panel C upper lobe emboli.



Figure 9.

Explanation of differential effects of embolus size on inert gas dead space (Vd/VtIG) in the presence of collateral ventilation. Diffusion of alveolar gas from perfused to unperfused alveoli through interalveolar Kohn's pores and interbronchiolar Martin's ducts is effective in reducing intraregional differences only for small size emboli. From reference 43, © Copyright 1993 by the American Physiological Society, with permission



Figure 10.

Quantification of the pulmonary and extrapulmonary contributors to Pao2 in patients with severe acute pulmonary embolism. Measured Pao2 was 63 mmHg. Correction of abnormal diffusion, shunt, Pvo2, and log SDQ, as a measure of the distribution of perfusion homogeneity, successively increased Pao2, with eventually a Pao2 of 128 mmHg higher than normal because of hyperventilation. From reference 139, with permission



Figure 11.

Left: computed tomographic scans of the lungs of patients with CTEPH showing eccentric thrombotic material within the pulmonary arteries (A) and a characteristic mosaic attenuation of the pulmonary parenchyma with the darker areas corresponding to the hypoperfused lung sections (B) Right: Preoperative (A) and postoperative (B) magnetic resonance imaging of a patient with CTEPH before (A) and after (B) pulmonary endarterectomy. The preoperative PVR was 768 dyne S/cm5 and the postoperative PVR was 196 dyne S/cm−5. From reference 68, with permission



Figure 12.

Distributions of Pao2 and Paco2 in 96 and 56 patients with CTEPH, respectively. Most values are decreased, with 65% of Pao2 < 70 mmHg and 33% of Paco2 < 33 mmHg taken as lower limits of normal (shaded columns). (P. Bresser, personal communication, in part reported in reference 182).



Figure 13.

Representative distribution in patients with CTEPH, showing moderate inhomogeneity of both ventilation and perfusion distributed to a widened mode, with shift to ventilation to higher . There was minimal shunting. Pulmonary endarterectomy improved the distribution of , markedly in patient 3 (Pt 3) and only slightly in Pt 4. From reference 85, with permission



Figure 14.

Distributions of Pao2 and Paco2 in 243 patients with idiopathic pulmonary arterial hypertension. Most values are decreased, with 51% of Pao2 < 70 mmHg and 45% of Paco2 < 33 mmHg taken as lower limits of normal (shaded columns). (O. Sitbon and G. Simonneau, personal communication).



Figure 15.

distributions before and after the administration of nifedipine in a 61‐year‐old woman with idiopathic pulmonary arterial hypertension. Before nifedipine administration, the distribution showed a bimodal pattern with an additional low mode and an increased shunt (s/t). Arterial hypoxemia resulted from an elevated shunt, partially due to a right‐to‐left atrial shunt demonstrated by contrast echocardiography, and a low o2. After nifedipine administration, Pao2 increased as a result of the reduction in shunt and an increase in o2, in relation to increased cardiac output and decreased right ventricular afterload. Increase in Vd/Vt was explained by a decrease in tidal volume. From reference 112, © Copyright 1983 by the American College of Chest Physicians, with permission



Figure 16.

Typical telangiectasias in a patient with hereditary hemorrhagic telangiectasias. The chest radiography shows two pulmonary arteriovenous malformations (PAVMs) in the right lung (arrows). The right pulmonary angiogram of the same patient shows multiple PAVMs of variable size (arrows). M‐mode contrast‐enhanced echocardiography shows a delayed (4‐6 beats) microbubble opacification of left heart chambers. From reference 144, with permission



Figure 17.

Distributions of Pao2 and Paco2 in 110 patients with PAVM on hereditary hemorrhagic telangiectasia. Most values are decreased, with 44% of Pao2 < 70 mmHg and 39% of Paco2 < 33 mmHg taken as lower limits of normal (shaded columns) (V. Cottin, personal communication).



Figure 18.

Measured and calculated arterial Po2 (Pao2) 10 patients with liver cirrhosis. Columns show the mean actual value, and the effects of normalization procedures performed using the mathematical model of the multiple inert gas elimination technique. Thus, Pao2 decreases after normalizing circulating hemoglobin (Hb) and P50, increases after normalizing shunt and ventilation/perfusion () imbalance, and increases even further after adding measured increases in ventilation (Ve) and P50. From reference 110.

 1. Abenhaim L, Moride Y, Brenot F, Rich S, Benichou J, Kurz X, Higenbottam T, Oakley C, Wouters E, Aubier M, Simonneau G, Bégaud B. Appetite‐suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group. New Engl J Med 335: 609–616, 1996.
 2. Allgood RJ, Wolfe WG, Ebert PA, Sabiston DC. Effects of carbon dioxide on bronchoconstriction after pulmonary artery occlusion. Am J Physiol 214: 772–775, 1968.
 3. Altemeier WA, Robertson HT, McKenney S, Glenny BW. Pulmonary embolization causes hypoxemia by redistributing regional blood flow without changing ventilation. J Appl Physiol 85: 2337–2343, 1998.
 4. Andrivet P, Lofaso F, Carette MF, Allegrini J, Adnot S. Haemodynamics and gas exchange before and after coil embolization of pulmonary arteriovenous malformations. Eur Respir J 8: 1228–1230, 1995.
 5. Bageant WE, Rapee LA. The treatment of pulmonary embolism by stellate block. Anesthesiology 8: 500–505, 1947.
 6. Barbera JA, Roger N, Roca J, Ravira I, Higenbottam TW, Rodriguez‐Roisin R. Worsening of pulmonary gas exchange with nitric oxide inhalation in chronic obstructive pulmonary disease. Lancet 347: 436–440, 1996.
 7. Bates ER, Crevey BJ, Remington Sprague F, Pitt B. Oral hydralazine therapy for acute pulmonary embolism and low output state. Arch Intern Med 141: 1537–1538, 1981.
 8. Bauer M, Wilkens H, Langer F, Schneider SO, Lausberg H, Schafers HJ. Selective upregulation of endothelin B receptor gene expression in severe pulmonary hypertension. Circulation 105: 1034–1036, 2002.
 9. Böttiger BW, Motsch J, Dörsam J, Mieck U, Gries A, Weiman J, Martin E. Inhaled nitric oxide selectively decreases pulmonary artery pressure and pulmonary vascular resistance following acute massive microembolism in piglets. Chest 110: 296–298, 1996.
 10. Brimioulle S, Lejeune P, Naeije R. Effects of hypoxic pulmonary vasoconstriction on gas exchange. J Appl Physiol 81: 1535–1543, 1996.
 11. Brown JW, Ruzmetov M, Palaniswamy V, Rodefeld MD, Turrentine MW. Pulmonary arteriovenous malformations in children after the Kawashima operation. Ann Thorac Surg 80: 1592–1596, 2005.
 12. Calvin JE, Dervin G. Intravenous ibuprofen blocks the hypoxemia of pulmonary glass bead embolism in the dog. Crit Care Med 16: 852–856, 1988.
 13. Carlens E, Hanson HE, Nordenstrom BEW. Temporary unilateral occlusion of the pulmonary artery; new method of determining separate lung function and of radiologic examination. J Thorac Surg 22: 527–536, 1951.
 14. Castaing Y, Manier G. Hemodynamic disturbances and V·A/Q· matching in hypoxemic cirrhotic patients. Chest 96: 1064–1069, 1989.
 15. Chaouat A, Naeije R, Weitzenblum E. Pulmonary hypertension in COPD. Eur Respir J 32: 1372–1385, 2008.
 16. Cheney FW, Pavlin J, Ferens J, Allen D. Effect of microembolism on arteriovenous shunt flow. J Thorac Cardiovasc Surg 76: 473–478, 1978.
 17. Cherniack V, Hodson WH, Greenfield LJ. Effects of chronic pulmonary artery ligation on pulmonary mechanics and surfactant. J Appl Physiol 21: 1315–1320, 1966.
 18. Chilvers ER, Whyte MK, Jackson JE, Allison DJ, Hughes JM. Effect of percutaneous transcatheter embolization on pulmonary function, right‐to‐left shunt, and arterial oxygenation in patients with pulmonary arteriovenous malformations. Am Rev Respir Dis 142: 420–425, 1990.
 19. Chua TP, Ponikowski P, Harrington D, Anker SD, Webb‐Peploe K, Clark AL, Poole‐Wilson PA, Coats AJ. Clinical correlates and prognostic significance of the ventilatory response to exercise in chronic heart failure. J Am Coll Cardiol 29: 1585–90, 1997.
 20. Ciarka A, Vachiery JL, Houssiere A, Gujic M, Stoupel E, Velez‐Roa S, Naeije R, van de Borne P. Atrial septostomy decreases sympathetic overactivity in pulmonary arterial hypertension. Chest 131: 1831–1837, 2007.
 21. Cloutier A, Ash JM, Smallhorn JF, Williams WG, Trusler GA, Rowe RD, Rabinovitch M. Abnormal distribution of pulmonary blood flow after the Glenn shunt or Fontan procedure: Risk of development of arteriovenous fistulae. Circulation 72: 471– 479, 1985.
 22. Corsico AG, D'Armini AM, Cerveri I, Klersy C, Ansaldo E, Niniano R, Gatto E, Monterosso C, Morsolini M, Nicolardi S, Tramontin C, Pozzi E, Viganò M. Long‐term outcome after pulmonary endarterectomy. Am J Respir Crit Care Med 178: 419–424, 2008.
 23. Cottin V, Chinet T, Lavolé A, Corre R, Marchand E, Reynaud‐Gaubert M, Plauchu H, Cordier JF. Pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: A series of 126 patients. Medicine 86: 1–17, 2007.
 24. Cottin V, Plauchu H, Bayle JY, Barthelet M, Revel D, Cordier JF. Pulmonary arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia. Am J Respir Crit Care Med 169: 994–1000, 2004.
 25. Crawford ABH, Regnis J, Lals L, Donnelly P, Engel LA, Young IH. Pulmonary vascular dilatation and diffusion‐dependent impairment of gas exchange in liver cirrhosis. Eur Respir J 8: 2015–2021, 1995.
 26. Crevey BJ, Dantzker DR, Bower JS, Popat KD, Walker SD. Hemodynamic and gas exchange effects of intravenous diltiazem in patients with pulmonary hypertension. Am J Cardiol 49: 578–583, 1982.
 27. D'Alonzo GE, Bower JS, Dantzker DR. Differentiation of patients with primary and thromboembolic pulmonary hypertension. Chest 84: 457–461, 1984.
 28. D'Alonzo GE, Bower JS, DeHart P, Dantzker DR. The mechanisms of abnormal gas exchange in acute massive pulmonary embolism. Am Rev Respir Dis 128: 170–172, 1983.
 29. D'Alonzo GE, Dantzker DR. Gas exchange alterations following pulmonary embolism. Clin Chest Med 5: 411–419, 1984.
 30. D'Alonzo GE, Gianotti L, Dantzker DR. Noninvasive assessment of hemodynamic improvement during chronic vasodilator therapy in obliterative pulmonary hypertension. Am Rev Respir Dis 133: 380–384, 1986.
 31. D'Alonzo GE, Pohil RL, DuRee SL, Dantzker DR. Comparison of progressive exercise performance of normal subjects and patients with primary pulmonary hypertension. Chest 92: 57–62, 1987.
 32. Dantzker DR. The influence of cardiovascular function on gas exchange. Clin Chest Med 4: 149–159, 1983.
 33. Dantzker DR, Bower JS. Mechanisms of gas exchange abnormality in patients with chronic obliterative pulmonary vascular disease. J Clin Invest 64: 1050–1055, 1979.
 34. Dantzker DR, Bower JS. Partial reversibility of chronic pulmonary hypertension caused by pulmonary thromboembolic disease. Am Rev Respir Dis 124: 129–131, 1981.
 35. Dantzker DR, Bower JS. Pulmonary vascular tone improves V·A/Q· matching in obliterative pulmonary hypertension. J Appl Physiol 51: 607–613, 1981.
 36. Dantzker DR, D'Alonzo GE, Bower JS, Popat K, Crevey BJ. Pulmonary gas exchange during exercise in patients with chronic obliterative pulmonary hypertension. Am Rev Respir Dis 130: 412–416, 1984.
 37. Dantzker DR, Wagner PD, Tornabene VW, Alazraki NP, West JB. Gas exchange after pulmonary thromboembolization in dogs. Circ Res 42: 92–103, 1978.
 38. Davis HH II, Schwartz DJ, Lefrak SS, Susman N, Schainker BA. Alveolar‐capillary oxygen disequilibrium in hepatic cirrhosis. Chest 73: 507–511, 1978
 39. Deboeck G, Niset G, Lamotte M, Vachiéry JL, Naeije R. Cardiopulmonary exercise testing in pulmonary arterial hypertension and in congestive heart failure: What are the differences? Eur Respir J 23: 747–751, 2004.
 40. Delcroix M, Mélot C, Lejeune P, Leeman M, Naeije R. Effects of vasodilators on gas exchange in acute canine embolic pulmonary hypertension. Anesthesiology 72: 77–84, 1990.
 41. Delcroix M, Mélot C, Lejeune P, Leeman M, Naeije R. Cyclooxygenase inhibition aggravates pulmonary hypertension and deteriorates gas exchange in canine pulmonary embolism. Am Rev Respir Dis 145: 806–810, 1992.
 42. Delcroix M, Mélot C, Vachiéry JL, Lejeune P, Leeman M, Vanderhoeft P, Naeije R. Effects of embolus size on hemodynamics and gas exchange in canine embolic pulmonary hypertension. J Appl Physiol 69: 2254–2261, 1990.
 43. Delcroix M, Mélot C, Vanderhoeft P, Naeije R. Embolus size affects gas exchange in canine autologous blood clot pulmonary embolism. J Appl Physiol 74: 1140–1148, 1993.
 44. Delcroix M, Mélot C, Vermeulen F, Naeije R. Hypoxic pulmonary vasoconstriction and gas exchange in acute canine pulmonary embolism. J Appl Physiol 80: 1240–1248, 1996.
 45. Dewachter L, Adnot S, Fadel E, Humbert M, Maitre B, Barlier‐Mur AM, Simonneau G, Hamon M, Naeije R, Eddahibi S. Angiopoietin/Tie2 pathway influences smooth muscle hyperplasia in idiopathic pulmonary hypertension. Am J Respir Crit Care Med 174: 1025–33, 2006.
 46. Dias‐Junior CA, Viera TF, Moreno H Jr, Evora PR, Tanus‐Santos JE. Sildenafil selectively inhibits acute pulmonary embolism‐induced pulmonary hypertension. Pulm Pharmacol Ther 18: 181–186, 2005.
 47. Du L, Sullivan CC, Chu D, Cho AJ, Kido M, Wolf PL, Yuan JX, Deutsch R, Jamieson SW, Thisteltwaite P. Signaling molecules in nonfamilial pulmonary hypertension. N Engl J Med 348: 500–509, 2003.
 48. Ducas J, Duval D, Dasilva H, Boiteau P, Prewitt RM. Treatment of canine pulmonary hypertension: Effects of norepinephrine and isoproterenol on pulmonary vascular pressure‐flow characteristics. Circulation 75: 235–242, 1987.
 49. Ducas J, Light RB, Girgling L, Shick U, Prewitt RM. Pulmonary vascular effects of hydralazine in a canine preparation of thromboembolism. Circulation 73: 1050–1057, 1986.
 50. Dutton JA, Jackson JE, Hughes JM, Whyte MK, Peters AM. Pulmonary arteriovenous malformations: Results with coil embolization in 53 patients. Am J Roentgenol 165: 1119–1125, 1995.
 51. Edell ES, Cortese DA, Krowka MJ, Rehder K. Severe hypoxemia and liver disease. Am Rev Respir Dis 142: 1631–1635, 1989.
 52. Edelman NH, Lahiri S, Braudo L, Cherniack NS, Fishman AP. Blunted ventilatory response to hypoxia in cyanotic congenital heart disease. N Engl J Med 282: 405–411, 1970.
 53. Faughnan ME, Granton JT, Young LH. The pulmonary vascular complications of hereditary haemorrhagic telangiectasia. Eur Respir J 33: 1186–1194, 2009.
 54. Faxon HH, Flynn JH, Anderson RM. Stellate block as an adjunct to the treatment of pulmonary embolism. N Engl J Med 244: 586–590, 1951.
 55. Fedullo PF, Auger WR, Kerr KM, Rubin LJ. Chronic thromboembolic pulmonary hypertension. N Engl J Med 345: 1465–1472, 2001.
 56. Folkow B, Pappenheimer JR. Components of the respiratory dead space and their variation with pressure breathing and with bronchoactive drugs. J Appl Physiol 8: 102–110, 1955.
 57. Freed DH, Thomson BM, Tsui SSL, Dunning JJ, Sheares KK, Pepke‐Zaba J, Jenkins DP. Functional and haemodynamic outcome 1 year after pulmonary thromboendarterectomy. Eur J Cardio Thorac Surg 34: 525–530, 2008.
 58. Gazetopoulos N, Davies H, Oliver C, Deuchar D. Ventilation and hemodynamics in heart disease. Br Heart J 28: 1–15, 1966.
 59. Gazetopoulos N, Salonikides N, Davies H. Cardiopulmonary function in patients with pulmonary hypertension. Br Heart J 36: 19–28, 1974.
 60. Genovesi MG, Tierney DF, Taplin GV, Eisenberg H. An intravenous radionuclide method to evaluate hypoxemia caused by abnormal alveolar vessels. Am Rev Respir Dis 114: 59–65, 1976.
 61. Glenny RW, Bernard S, Brinckley M. Validation of fluorescent labeled microspheres for measurement of regional perfusion. J Appl Physiol 74: 2585–2597, 1993.
 62. Grant BJB, Davies EE, Jones HA, Hughes JMB. Local regulation of pulmonary blood flow and ventilation‐perfusion ratios in the coatimundi. J Appl Physiol 40: 216–228, 1976.
 63. Haldane JBS. Respiration. New Haven, CT: Yale University Press, 1922, p. 137.
 64. Hales M. Multiple small arteriovenous fistulae of the lungs. Am J Pathol 32: 927–943, 1956
 65. Hattle L, Rokseth R. The arterial to end‐expiratory carbon dioxide tension gradient in acute pulmonary embolism and other cardiopulmonary diseases. Chest 66: 352–357, 1974.
 66. Hervé P, Petitpretz P, Simonneau G, Salmeron S, Laine JF, Duroux P. The mechanisms of abnormal gas exchange in acute massive pulmonary embolism. Am Rev Respir Dis 128: 1101, 1983.
 67. Hirose T, Yasutake T, Tarabeih A, Stein M. Location of airway constriction following acute experimental pulmonary thromboembolism. J Appl Physiol 34: 431–437, 1973.
 68. Hoeper MM, Mayer E, Simonneau G, Rubin LJ. Chronic thromboembolic pulmonary hypertension. Circulation 113: 2011–2020, 2006.
 69. Hoeper MM, Pletz H, Welte T. Prognostic values of blood gas analyses in patients with idiopathic pulmonary arterial hypertension. Eur Respir J 29: 944–50, 2007.
 70. Hopkins S, Olfert IM, Wagner PD. Counterpoint: Exercise‐induced intrapulmonary shunting is imaginary. J Appl Physiol 107: 993–994, 2009.
 71. Huet Y, Brun‐Buisson C, Lemaire F, Teisseire B, Lhoste F, Rapin M. Cardiopulmonary effects of ketanseine infusion in human pulmonary embolism. Am Rev Respir Dis 135: 114–117, 1987.
 72. Huet Y, Lemaire F, Brun‐Buisson C, Knaus W, Teisseire B, Payen D, Mathieu D. Hypoxemia in acute pulmonary embolism. Chest 88: 829–836, 1985.
 73. Huseby JS, Culver BH, Butler J. Pulmonary arteriovenous fistulas: Increase in shunt at high lung volume. Am Rev Respir Dis 115: 229–232, 1977.
 74. Huval WV, Mathieson MA, Stemp LI, Dunham BM, Jones AG, Shepro D, Hechtman HB. Therapeutic benefits of 5‐hydroxytryptamine inhibition following pulmonary embolism. Ann Surg 197: 220–225, 1983.
 75. Hyland JW, Smith GT, McGuire LB, Harrison DC, Haynes FW, Dexter L. Effect of selective embolization of various size pulmonary arteries in dogs. Am J Physiol 204: 619–625, 1963.
 76. Ingram RH Jr. effects of airway versus arterial CO2 changes on lung mechanics in dogs. J Appl Physiol 38: 603–607, 1975.
 77. Iwase T, Nagaya N, Ando M, Satoh T, Sakamaki F, Kyotani S, Takaki H, Goto Y, Ohkita Y, Uematsu M, Nakanishi N, Miyatake K. Acute and chronic effects of surgical thromboendarterectomy on exercise capacity and ventilatory efficiency in patients with chronic thromboembolic pulmonary hypertension. Heart 86: 188–192, 2001.
 78. Jaïs X, D'Armini AM, Jansa P, Torbicki A, Delcroix M, Ghofrani HA, Hoeper MM, Lang IM, Mayer E, Pepke‐Zaba J, Perchenet L, Morganti A, Simonneau G, Rubin LJ. Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension: J Am Coll Cardiol 52: 2127–2134, 2008.
 79. Janicki JS, Weber KT, Likoff MJ, Fishman AP. Exercise testing to evaluate patients with pulmonary vascular disease. Am Rev Respir Dis 129 (Suppl): S92–S95, 1984.
 80. Johnson A, Malik AB. Effects of different‐size microemboli on lung fluid and protein exchange. J Appl Physiol 51: 461–464, 1981.
 81. Johnson RL Jr. Gas exchange efficiency in congestive heart failure. II. Circulation 103: 916–918, 2001.
 82. Jones NL, Goodwin JF. Respiratory function in pulmonary thromboembolic disorders. BMJ I: 1089–1093, 1965.
 83. Julian DG, Travis DM, Robin Ed, Crump C. Effect of pulmonary artery occlusion upon end‐tidal CO2 tension. J Appl Physiol 15: 87–91, 1960.
 84. Kapitan KS, Buchbinder M, Wagner PD, Moser KM. Mechanisms of hypoxemia in chronic thromboembolic pulmonary hypertension. Am Rev Respir Dis 139: 1149–1154, 1989.
 85. Kapitan KS, Clausen JL, Moser KM. Gas exchange in chronic thromboembolism after pulmonary endarterectomy. Chest 98: 14–19, 1990.
 86. Katz S, Horres AD. Medullary respiratory neuron responses to pulmonary emboli and pneumothorax. J Appl Physiol 33: 390–395, 1972.
 87. Kennedy TC, Knudson RJ. Exercise‐aggravated hypoxemia and orthodeoxia in cirrhosis. Chest 72: 305–309, 1977.
 88. Kerbaul F, Gariboldi V, Giorgi R, Mekkaoui C, Guieu R, Fesler P, Gouin F, Brimioulle S, Collart F. Effects of levosimendan on acute pulmonary embolism‐induced right ventricular failure. Crit Care Med 35: 1948–1954, 2007.
 89. Kim H, Yung GL, Marsh JJ, Konopka RG, Pedersen CA, Chiles PG, Morris TA, Channick RN. Endothelin mediates pulmonary vascular remodeling in a canine model of chronic thromboembolic pulmonary hypertension. Eur Respir J 15: 640–648, 2000.
 90. Kimura H, Okada O, Tanabe N, Tanaka Y, Terai M, Takiguchi Y, Masuda M, Nakajima N, Hiroshima K, Inadera H, Matsushima K, Kuriyama T. Plasma monocyte chemoattractant protein‐1 and pulmonary vascular resistance in chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med 164: 319–324, 2001.
 91. Kleber FX, Vietzke G, Wernecke KD, Bauer U, Opitz C, Wensel R, Sperfeld A, Glaser S. Impairment of ventilatory efficiency in heart failure: prognostic impact. Circulation 101: 2803–9, 2000.
 92. Lee JH, Chun YG, Lee IC, Tuder RM, Hong SB, Shim TS, Lim CM, Koh Y, Kim WS, Kim DS, Kim WD, Lee SD. Pathogenic role of endothelin 1 in hemodynamic dysfunction in experimental acute pulmonary embolism. Am J Respir Crit Care Med 164: 1282–1287, 2001.
 93. Levy SE, Simmons DH. Redistribution of alveolar ventilation following pulmonary thromboembolism in the dog. J Appl Physiol 36: 60–68, 1974.
 94. Levy SE, Stein M, Totten RS, Bruderman I, Wessler S, Robin ED. Ventilation‐perfusion abnormalities in experimental pulmonary embolism. J Clin Invest 44: 1699–1707, 1965.
 95. Lindner J, Jansa P, Kunstyr J, Mayer E, Blaha J, Palecek T, Aschermann M, Grus T, Ambroz D, Tosovský J, Vitkova I. Implementation of a new programme for the surgical treatment of CTEPH in the Czech Republic—pulmonary endarterectomy. J Thorac Cardiovasc Surg 54: 528–531, 2006.
 96. Lippmann M, Fein A. Pulmonary embolism in the patient with chronic obstructive pulmonary disease. Chest 79: 39–42, 1981.
 97. Lovering AT, Eldridge MW, Stickland MK. Counterpoint: Exercise‐induced intrapulmonary shunting is real. J Appl Physiol 107: 994–997, 2009.
 98. Malik AB, Van Der Zee H. Mechanism of pulmonary edema induced by microembolization in dogs. Circ Res 42: 72–79, 1978.
 99. Manier G, Castaing Y. Influence of cardiac output on oxygen exchange in acute pulmonary embolism. Am Rev Respir Dis 145: 130–136, 1992.
 100. Manier G, Castaing Y, Guénard H. Determinants of hypoxemia during the acute phase of pulmonary embolism in humans. Am Rev Respir Dis 132: 332–338, 1985.
 101. Marshall BE, Marshall C. A model for hypoxic constriction of the pulmonary circulation. J Appl Physiol 64: 68–77, 1988.
 102. Matsuda H, Ogino H, Minatoya K, Sasaki H, Nakanishi N, Kyotani S, Kobayashi J, Yagihara T, Kitamura S. Long‐term recovery of exercise ability after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Ann Thorac Surg 82: 1338–13343, 2006.
 103. McFaul RC, Tajik AJ, Mair DD, Danielson GK, Seward JB. Development of pulmonary arteriovenous shunt after superior vena cava‐right pulmonary artery (Glenn) anastomosis. Circulation 55: 212–216, 1977.
 104. McGinn S, White PD. Acute cor pulmonale resulting from pulmonary embolism. JAMA 104: 1473–1480, 1935.
 105. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J, Harrington RA, Anderson JL, Bates ER, Bridges CR, Eisenberg MJ, Ferrari VA, Grines CL, Hlatky MA, Jacobs AK, Kaul S, Lichtenberg RC, Lindner JR, Moliterno DJ, Mukherjee D, Pohost GM, Rosenson RS, Schofield RS, Shubrooks SJ, Stein JH, Tracy CM, Weitz HH, Wesley DJ. ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension. A report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association. Circulation 119: 2250–94, 2009.
 106. Mélot C. Relationships between gas exchange and the pulmonary circulation. Ph.D. thesis, Free University of Brussels, Brussels, Belgium, 1989.
 107. Mélot C, Delcroix M, Closset J, Vanderhoeft P, Lejeune P, Leeman M, Naeije R. Starling resistor versus distensible vessel models for embolic pulmonary hypertension. Am J Physiol 267: H817–H827, 1995.
 108. Mélot C, Hallemans R, Mols P, Lejeune P, Naeije R. Deleterious effects of nifedipine on pulmonary gas exchange in chronic obstructive pulmonary disease. Am Rev Respir Dis 130: 612–616, 1984.
 109. Mélot C, Naeije R. Pulmonary vascular disease. In: Roca J, Rodriguez‐Roisin R, Wagner PD, editors. Pulmonary and Peripheral Gas Exchange in Health and Disease. Series “Lung Biology in Health and Disease” edited by Claude Lenfant, Volume 148, New York: Marcel Dekker, 2000, p. 285–302.
 110. Mélot C, Naeije R, Dechamps P, Hallemans R, Lejeune P. Pulmonary and extrapulmonary contributors to hypoxemia in liver cirrhosis. Am Rev Respir Dis 139: 632–640, 1989.
 111. Mélot C, Naeije R, Mols P, Hallemans R, Lejeune P, Jaspar N. Pulmonary vascular tone improves gas exchange in the adult respiratory distress syndrome. Am Rev Respir Dis 136: 1232–1236, 1987.
 112. Mélot C, Naeije R, Mols P, Vandenbossche JL, Denolin H. Effects of nifedipine on ventilation/perfusion matching in primary pulmonary hypertension. Chest 83: 203–207, 1983.
 113. Meyer FJ, Ewert R, Hoeper MM, Olschewski H, Behr J, Winkler J, Wilkens H, Breuer C, Kübler W, Borst MM, for The German Pph Study Group. Peripheral airway obstruction in primary pulmonary hypertension. Thorax 57: 473–476, 2002.
 114. Meyer FJ, Lossnitzer D, Kristen AV, Schoene AM, Kübler W, Katus HA, MM Borst. Respiratory muscle dysfunction in idiopathic pulmonary arterial hypertension. Eur Respir J 25: 125–130, 2005.
 115. Moore RL, Humphreys GH, Cochran HW. The effects of sudden occlusion of either primary pulmonary artery on cardiac output and pulmonary expansion. J Thorac Cardiovasc Surg 3: 573–589, 1934.
 116. Moser KM, Bloor CM. Pulmonary vascular lesions occurring in patients with chronic major vessel thromboembolic pulmonary hypertension. Chest 103: 685–692, 1993.
 117. Moser KM, Metersky ML, Auger WR, Fedullo PF. Resolution of vascular steal after pulmonary thromboendarterectomy. Chest 104: 1441–1444, 1993.
 118. Nadel JA, Gold WM, Burgess JH. Early diagnosis of pulmonary vascular obstruction. Am J Med 44: 16–25, 1968.
 119. Naeije R. Hepatopulmonary syndrome and portopulmonary hypertension. Swiss Med Wkly 133: 163–169, 2003.
 120. Naeije R. Breathing more with weaker respiratory muscles in pulmonary arterial hypertension. Eur Respir J 25: 6–8, 2005.
 121. Naeije R, Faoro V. Pathophysiological insight into shunted bubbles. J Appl Physiol 107: 999–1000, 2009.
 122. Naeije R, van de Borne P. Clinical relevance of autonomic nervous system disturbances in pulmonary arterial hypertension. Eur Respir J 34: 792–794, 2009
 123. Niden AH, Aviado DM. Effects of pulmonary embolism on the pulmonary circulation with special reference to arteriovenous shunts in the lung. Cir Res 4: 67–73, 1956.
 124. Olman MA, Auger WR, Fedullo PF, Moser KM. Pulmonary vascular steal in chronic thromboembolic pulmonary hypertension. Chest 98: 1430–1434, 1990.
 125. Olschewski H, Simonneau G, Galié N, Higenbottam T, Naeije R, Rubin LJ, Nikkho S, Speich R, Hoeper M, Behr J, Winkler J, Seeger W, for the AIR Study Group. Inhaled iloprost is an effective treatment for severe pulmonary hypertension. double‐blind, placebo‐controlled, multicenter study A. N Engl J Med 347: 322–329, 2002.
 126. Overton DT, Bocka JJ. The alveolar‐arterial gradient in patients with documented pulmonary embolism. Arch Int Med 148: 1617–1619, 1988.
 127. Pennington DW, Gold WM, Gordon RL, Steiger D, Ring EJ, Golden JA. Treatment of pulmonary arteriovenous malformations by therapeutic embolization. Am Rev Respir Dis 145: 1047–1051, 1992.
 128. Ponikowski P, Francis DP, Piepoli MF, Davies LC, Chua TP, Davos CH, Florea V, Banasiak W, Poole‐Wilson PA, Coats AJ, Amker SD. Enhanced ventilatory response to exercise in patients with chronic heart failure and preserved exercise tolerance: Marker of abnormal cardiorespiratory reflex control and predictor of poor prognosis. Circulation 103: 967–72, 2001.
 129. Reesink HJ, Van Der Plas MN, Verhey NE, van Steenwijk RP, Kloek JJ, Bresser P. Six‐minute walk distance as parameter of functional outcome after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. J Thorac Cardiovasc Surg 133: 510–516, 2007.
 130. Rich S, Dantzker DR, Ayres SM, Bergofsky EH, Brundage B, Detre K, Fishman AP, Goldring R, Groves B, Koerner S, Levy P, Reid L, Vreim C, Williams G. Primary pulmonary hypertension. A national prospective study. Ann Intern Med 107: 216–223, 1987.
 131. Riedel M, Stanek V, Widimsky J. Spirometry and gas exchange in chronic pulmonary thromboembolism. Bull Eur Physiopathol Respir 17: 209–221, 1981.
 132. Riedel M, Stanek V, Widimsky J, Prerovsky I. Long‐term follow‐up of patients with thromboembolism. Chest 81: 151–158, 1982.
 133. Robertson HT, Glenny RW, Stanford D, McInnes LM, Luchtel DL, Govert D. High resolution maps of regional ventilation utilizing inhaled fluorescent microspheres. J Appl Physiol 82: 943–953, 1997.
 134. Robin ED, Forkner CE, Bromberg PA, Croteau JR, Crump CH. Alveolar gas exchange in clinical pulmonary embolism. N Engl J Med 262: 283–287, 1960.
 135. Robin ED, Julian DG, Travis DM, Crump CH. A physiologic approach to the diagnosis of acute pulmonary embolism. N Engl J Med 260: 586–591, 1959.
 136. Robin ED, Laman D, Horn BR, Theodore J. Platypnea related to orthodeoxia caused by true vascular shunts. N Engl J Med 294: 941–943, 1976.
 137. Rodríguez‐Roisin R, Krowka MJ. Hepatopulmonary syndrome—a liver‐induced lung vascular disorder. N Engl J Med 358: 2378–2387, 2008.
 138. Rodriguez‐Roisin R, Roca J, Agusti AGN, Mastai R, Wagner PD, Bosch J. Gas exchange and pulmonary vascular reactivity in patients with liver cirrhosis. Am Rev Respir Dis 135: 1085–1092, 1987.
 139. Santolicandro A, Prediletto R, Fornai E, Formichi B, Begliomini E, Gianello‐Netto A, Giuntini C. Mechanisms of hypoxemia and hypocapnia in pulmonary embolism. Am J Respir Crit Care Med 152: 336–347, 1995.
 140. Sasahara AA, Stein M, Simon M, Littmann D. Pulmonary angiography in the diagnosis of pulmonary embolism. N Engl J Med 270: 1075–1081, 1964.
 141. Schenk P, Fuhrman V, Madl C, Funk G, Lehr S, Kandel O, Muller C. Hepatopulmonary syndrome: Prevalence and predictive value of various cut offs for arterial oxygenation and their clinical consequences. Gut 51: 853–859, 2002.
 142. Severinghaus JW, Swenson EW, Finley TN, Lategola MT, Williams J. Unilateral hypoventilation produced in dogs by occluding one pulmonary artery. J Appl Physiol 16: 53–60, 1961.
 143. Sharma GVRK, McIntyre KM, Sharma S, Sasahara AA. Clinical and hemodynamic correlates in pulmonary embolism. Clin Chest Med 5: 421–437, 1984.
 144. Shovlin C, Letarte M. Hereditary haemorrhagic telangiectasia and pulmonary arterio‐venous malformations: Issues in clinical management and review of pathogenic mechanisms. Thorax 54: 714–729, 1999.
 145. Sietsema KE, Cooper DM, Perloff JK, Child JS, Rosove MH, Wasserman K, Whipp BJ. Control of ventilation during exercise in patients with central venous‐to‐systemic shunts. J Appl Physiol 64: 234–242, 1988.
 146. Simon BA, Tsuzaki K, Venegas JG. Changes in regional lung mechanics and ventilation distribution after unilateral pulmonary artery occlusion. J Appl Physiol 82: 882–891, 1997.
 147. Skoro‐Sajer N, Hack N, Saduchi‐Kolici R, Bonderman D, Jakowitsch J, Klepetko W, Kneussl M, Fedullo P, Lang I. Pulmonary vascular reactivity and prognosis in patients with chronic thromboembolic pulmonary hypertension. Circulation 119: 298–305, 2009.
 148. Smulders YM. Pathophysiology and treatment of haemodynamic instability in acute pulmonary embolism: The pivotal role of pulmonary vasoconstriction. Cardiovasc Res 48: 23–33, 2000.
 149. Sofia M, Faraone S, Alifano M, Micco A, Albisinni R, Manisalco M, Di Minno G. Endothelin abnormalities in patients with pulmonary embolism. Chest 111: 544–549, 1997.
 150. Sorenson SC, Severinghaus JV. Respiratory insensitivity to acute hypoxia persisting after correction of tetralogy of Fallot. J Appl Physiol 25: 221–223, 1968.
 151. Souza‐Silva AR, Dias‐Junior CA, Uzuelli JA, Moreno H Jr, Evora PR, Tanus‐Santos JE. Hemodynamic effects of combined sildenafil and l‐arginine during acute pulmonary embolism‐induced pulmonary hypertension. Eur J Pharmacol 525: 126–131, 2005.
 152. Srivastava D, Preminger T, Lock JE, Mandell V, Keane JF, Mayer JE Jr, Kozakewich H, Spevak PJ. Hepatic venous blood and the development of pulmonary arteriovenous malformations in congenital heart disease. Circulation 92: 1217–1222, 1995.
 153. Stanek V, Riedel M, Widimsky J. Hemodynamic monitoring in acute pulmonary embolism. Bull Eur Physiopathol Respir 14: 561–572, 1978.
 154. Stein M, Forkner CE Jr, Robin ED, Wessler S. Gas exchange after autologous thromboembolism in dogs. J Appl Physiol 16: 488–492, 1961.
 155. Stein PD, Goldhaber SZ, Henry JW. Alveolar‐arterial oxygen gradient in the diagnosis of acute pulmonary embolism. Chest 107: 139–143, 1995.
 156. Stein PD, Henry JW. Prevalence of acute pulmonary embolism in central and subsegmental pulmonary arteries and relation to probability interpretation of ventilation/perfusion lung scans. Chest 111: 246–1248, 1997.
 157. Stein PD, Terrin ML, Hales CA, Palevsky HI, Saltzman HA, Thompson BT, Weg JG. Clinical, laboratory, Roentgenographic and electrocardiographic findings in patients with acute pulmonary embolism and no pre‐existing cardiac or pulmonary disease. Chest 100: 598–603, 1991.
 158. Sun XG, Hansen JE, Oudiz RJ, Wasserman K. Exercise pathophysiology in patients with primary pulmonary hypertension. Circulation 104: 429–35, 2001.
 159. Sun XG, Hansen JE, Oudiz RJ, Wasserman K. Gas exchange detection of exercise‐induced right‐to‐left shunt in patients with primary pulmonary hypertension. Circulation 105: 54–60, 2002.
 160. Suntharalingam J, Treacy CM, Doughty NJ, Goldsmith K, Soon E, Toshner MR, Sheares KK, Hughes R, Morrell NW, Pepke‐Zaba J. Long‐term use of sildenafil in inoperable chronic thromboembolic pulmonary hypertension. Chest 134: 229–236, 2008.
 161. Swenson EW, Finley TN, Guzman SV. Unilateral hypoventilation in man during temporary occlusion of one pulmonary artery. J Clin Invest 40: 828–835, 1961.
 162. Szucs MM, Brooks HL, Grossman W, Banas JS, Meister SG, Dexter L, Dalen JE. Diagnostic sensitivity of laboratory findings in acute pulmonary embolism. Ann Intern Med 74: 161–166, 1971.
 163. Tanabe N, Okada O, Nakagawa Y, Masuda M, Kato K, Nakajima N, Kuriyama T. The efficacy of thromboendarterectomy on long‐term gas exchange. Eur Respir J 10: 2066–2072, 1997.
 164. Tanus‐Santos JE, Gordo WM, Udelsmann A, Cittadino MH, Moreno H Jr. Nonselective endothelin receptor antagonism attenuates hemodynamic changes after massive pulmonary embolism in dogs. Chest 118: 175–179, 2000.
 165. Tapson VF, Witty LA. Massive pulmonary embolism: Diagnostic and therapeutic strategies. Clin Chest Med 16: 329–340, 1995.
 166. Terry PB, White RI, Barth KH, Kaufman SL, Mitchell SE. Pulmonary arteriovenous malformations. observations and results of therapeutic balloon embolization Physiologic. N Engl J Med 308: 1197–1200, 1983.
 167. Theodore J, Robin ED, Morris AJ, Burke CM, Jamieson SW, Van Kessel A, Stinson EB, Shumway NE. Augmented ventilatory response to exercise in pulmonary hypertension. Chest 89: 39–44, 1986.
 168. Thoma P, Rondelet B, Mélot C, Tack D, Naeije R, Gevenois PA. Acute pulmonary embolism: Relationships between ground‐glass opacification at thin‐section CT and hemodynamics in pigs. Radiology 250: 721–729, 2009.
 169. Thomas D, Stein M, Tanabe G, Rege V, Wessler S. Mechanism of bronchoconstriction produced by thromboemboli in dogs. Am J Physiol 206: 1207–1212, 1964.
 170. Thompson JA, Millen JE, Glauser FL, Hess ML. Role of 5‐HT2 receptor inhibition in pulmonary embolization. Circ Shock 20: 299–309, 1986.
 171. Thomson AJ, Drummond GR, Waring WS, Webb DJ, Maxwell SRJ. Effects of short‐term isocapnic hyperoxia and hypoxia on cardiovascular function. J Appl Physiol 101: 809–816, 2006.
 172. Thorens JB, Junod AF. Hypoxaemia and liver cirrhosis: A new argument in favour of a “diffusion‐perfusion defect”. Eur Respir J 5: 754–756, 1992.
 173. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy‐Jardin M, Bassand JP, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck‐Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Zamorano JL, Andreotti F, Ascherman M, Athanassopoulos G, De Sutter J, Fitzmaurice D, Forster T, Heras M, Jondeau G, Kjeldsen K, Knuuti J, Lang I, Lenzen M, Lopez‐Sendon J, Nihoyannopoulos P, Perez Isla L, Schwehr U, Torraca L, Vachiery JL, Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology. Guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 29: 2276–2315, 2008.
 174. Tsang JY, Lamm WJE, Starr IR, Hlastala MP. Spatial pattern of ventilation‐perfusion mismatch following acute pulmonary thromboembolism in pigs. J Appl Physiol 98: 1862–1868, 2005.
 175. Tsang JYC, Frazer D, Hlastala MP. Ventilation heterogeneity does not change following pulmonary microembolism. J Appl Physiol 88: 705–712, 2000.
 176. Tsang JYC, Lamm WJE, Neradilek B, Polissar NL, Hlastala MP. Endothelin receptor blockade does not improve hypoxemia following acute pulmonary thromboembolism. J Appl Physiol 102: 762–771, 2007.
 177. Tulleken JE, Zijlstra J, Evers K, Van Der Werf TS. Oxygen desaturation after treatment with inhaled nitric oxide for obstructive shock due to massive pulmonary embolism. Chest 112: 296–297, 1997.
 178. Ueki J, Hughes JM, Peters AM, Bellingan GJ, Mohammed MA, Dutton J, Ussov W, Knight D, Glass D. Oxygen and 99mTc‐MAA shunt estimations in patients with pulmonary arteriovenous malformations: Effects of changes in posture and lung volume. Thorax 49: 327–331, 1994
 179. Ulrich S, Fischler M, Speich R, Popov V, Maggiorini M. Chronic thromboembolic and pulmonary arterial hypertension share vasoactive properties. Chest 130: 841–846, 2006.
 180. Utsunomiya T, Krausz MM, Levine L, Shepro D, Hechtman HB. Thromboxane mediation of cardiopulmonary effects of embolism. J Clin Invest 70: 361–368, 1982.
 181. Van de Borne P, Oren R, Anderson EA, Mark AL, Somers VK. Tonic chemoreflex activation does not contribute to elevated muscle sympathetic nerve activity in heart failure. Circulation 94: 1325–8, 1996.
 182. van de Plas MN, Reesink HJ, Roos CM, van Steenwijk RP, Kloek JJ, Bogaard HJ, Sterk P, Bresser P. Pulmonary endarterectomy improves dyspnea by the relief of dead space ventilation. Ann Thorac Surg 89 (2): 347–352, 2010.
 183. Velez Roa S, Ciarka A, Najem B, Vachiery JL, Naeije R, Van de Borne P. Increased sympathetic nerve activity in primary pulmonary hypertension. Circulation 110: 1308–1312, 2004.
 184. Vidal Melo M, Scott Harris R, Layfield D, Musch G, Venegas JG. Changes in regional ventilation after autologous blood clot pulmonary embolism. Anesthesiology 97: 671–681, 2002.
 185. Voswinckel R, Reichenberger F, Enke B, Kreckel A, Krick S, Gall H, Schermuly RT, Grimminger F, Rubin LJ, Olschewski H, Seeger W, Ghofrani HA. Acute effects of the combination of sildenafil and inhaled treprostinil on haemodynamics and gas exchange in pulmonary hypertension. Pulm Pharmacol Ther 21: 824–832, 2008.
 186. Wagner PD. Impairment of gas exchange in liver cirrhosis. Eur Respir J 8: 1993–1995, 1995.
 187. Wagner PD. The multiple inert gas elimination technique (MIGET). Intensive Care Med 34: 994–1001, 2008.
 188. Wasserman K, Whipp BJ, Castagna K. Cardiodynamic hyperpnea secondary to cardiac output increase. J Appl Physiol 36: 4–464, 1974.
 189. Wasserman K, Zhang YY, Gitt A, Belardinelli R, Koike A, Lubarsky L, Agostoni PG. Lung function and exercise gas exchange in chronic heart failure. Circulation 96: 2221–7, 1997.
 190. Weber KT, Kinasewitz GT, Janicki JS, Fishman AP. Oxygen utilization and ventilation during exercise in patients with chronic heart failure. Circulation 65: 1213–1223, 1982.
 191. Wensel R, Jilek C, Dörr M, Francis DP, Stadler H, Lange T, Blumberg F, Opitz C, Pfeifer M, Ewert R. Impaired cardiac autonomic control relates to disease severity in pulmonary hypertension. Eur Respir J 34: 895–901, 2009.
 192. Wensel R, Opitz CF, Anker SD, Winkler J, Höffken G, Kleber FX, Sharma R, Hummel M, Hetzer R, Ewert R. Assessment of survival in patients with primary pulmonary hypertension. Importance of cardiopulmonary exercise testing. Circulation 106: 319–324, 2002.
 193. Wessel HU, Kezdi PK, Cugell DW. Respiratory and cardiovascular function in patients with severe pulmonary hypertension. Circulation 29: 825–832, 1964.
 194. West JB. Effects of ventilation‐perfusion inequality on over‐all gas exchange studied in computer models of the lung. Respir Physiol 7: 88–110, 1969.
 195. West JB, Mathieu‐Costello O. Stress failure of pulmonary capillaries: Role in lung and heart disease. Lancet 340: 762–767, 1992.
 196. Whyte MK, Hughes JM, Peters AM, Ussov W, Patel S, Burroughs AK. Analysis of intrapulmonary right to left shunt in the hepatopulmonary syndrome. J Hepatol 29: 85–93, 1998.
 197. Whyte MK, Peters AM, Hughes JMB, Henderson BL, Bellinghan BJ, Jackson JE, Chilvers ER. Quantification of right to left shunt at rest and during exercise in patients with pulmonary arteriovenous malformations. Thorax 47: 790–796, 1992.
 198. Whyte MKB, Hughes JMB, Jackson JE, Peters AM, Hempleman SC, Moore DP, Jones HA. Cardiopulmonary response to exercise in patients with intrapulmonary shunts. J Appl Physiol 75: 321–328, 1993.
 199. Wilson JE, Pierce KA, Johnson RL, Winga ER, Harrell WR, Curry JC, Mullins CB. Hypoxemia in pulmonary embolism, a clinical study. J Clin Invest 50: 481–491, 1971.
 200. Wolfe MW, Saad RM, Spence TH. Hemodynamic effects of amrinone in a canine model of massive pulmonary embolism. Chest 102: 274–278, 1992.
 201. Yasunobu Y, Oudiz RJ, Sun XG, Hansen JE, Wasserman K. End‐tidal Pco2 abnormality and exercise limitation in patients with primary pulmonary hypertension. Chest 127: 1637–1646, 2005.
 202. Young I, Mazzone RW, Wagner PD. Identification of functional lung unit in the dog by graded vascular embolization. J Appl Physiol 49: 132–141, 1980.
 203. Zoia MC, D'Armini AM, Beccaria M, Corsico A, Fulgoni P, Klersy C, Piovella F, Viganò M, Cerveri I; Pavia Thromboendarterectomy Group. Mid term effects of pulmonary thromboendarterectomy on clinical and cardiopulmonary function status. Thorax 57: 608–612, 2002.
 204. Zwissler B, Welte M, Habler O, Kleen M, Messmer K. Effects of inhaled prostacyclin as compared with inhaled nitric oxide in a canine model of pulmonary microembolism and oleic acid edema. J Thorac Cardiovasc Anesth 9: 634–640, 1995.
Further Reading

Related Articles:

Pulmonary Vascular Disease

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

C. Mélot, R. Naeije. Pulmonary Vascular Diseases. Compr Physiol 2011, 1: 593-619. doi: 10.1002/cphy.c090014