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Pulmonary Vascular Diseases

C. Mélot, R. Naeije

10.1002/cphy.c090014

Source: Volume 1, Issue 2, April 2011

Published online: April 2011

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.

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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.

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