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Pulmonary Circulation in Extreme Environments

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Abstract

The pulmonary circulation is subject to direct challenge from both altered pressure and altered gravity. To efficiently exchange gas, the pulmonary capillaries must be extremely thin‐walled and directly exposed to the alveolar space. Thus, alterations in ambient pressure are directly transmitted to the capillaries with the potential to alter pulmonary blood flow. To produce ventilation, the mammalian lung must expand and contract, and so it is a highly compliant structure. Thus, because the capillaries are contained in the alveolar walls, alterations in the apparent gravitational force deform the lung and directly affect pulmonary blood flow both through lung deformation and through changes in the hydrostatic pressure distribution in the lung. High gravitational forces are encountered in the aviation environment, while gravity is absent in spaceflight. Diving subjects the lung to large increases in ambient pressure, while large reductions in pressure occur, often associated with alterations in oxygen level and airway pressure, in aviation. This article reviews the effects of alterations in both gravity and ambient pressure on the pulmonary circulation. © 2011 American Physiological Society. Compr Physiol 1:319‐338, 2011.

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Figure 1. Figure 1.

The first demonstration that blood flow at the apex of the human lung was lower than at the base. A single breath of radioactive CO2 (C15O2) was inspired and the subsequent rate of removal measured using externally placed counters (A). The results (B) clearly demonstrated that there was a large difference in the clearance rate of the CO2, and this was taken as evidence for differences in pulmonary blood flow from apex to base of the lung. From , with permission.

Figure 2. Figure 2.

The three‐zone model of the effects of gravity on the vertical distribution of pulmonary blood flow in the upright human lung. In this model, both pulmonary arterial and pulmonary venous pressures are subject to a hydrostatic gradient in pressure, increasing down the lung. However, the pulmonary capillaries are also exposed to alveolar pressure, which has no corresponding gradient. Flow through the thin‐walled pulmonary capillaries depends on the relationship between these three pressures and this varies vertically in the lung. See text for details. From , with permission.

Figure 3. Figure 3.

The effect of +Gz acceleration on the vertical distribution of pulmonary blood flow in upright subjects. Note that as Gz is increased, a greater and greater proportion of the lung from the apex down becomes unperfused. From , with permission.

Figure 4. Figure 4.

Right‐to‐left shunt fractions in four subjects measured before, during, 1‐min following, and 5‐min following various accelerations as indicated measured using injected tritium (3H). Note that upon acceleration, a shunt is present but is essentially absent even 1 min after return to 1G. From , with permission.

Figure 5. Figure 5.

Distributions of perfusion (blood flow in ml/min/cm3) (A‐C), density (g/cm3) (D‐F), and density‐normalized perfusion (blood flow in ml/min/g) (G‐I) in six supine human subjects measured using MRI. The left column shows values on the x‐axis for individual voxels (approximate volumes of 0.07 cm3), with vertical height up the lung from posterior (bottom) to anterior (top). The superimposed white lines show the line of best fit and thus the apparent gravitational gradient. The center column plots the same data averaged into 1‐cm high horizontal (isogravitational) “slices” with the associated standard deviation. Note that in both presentations, the large amount of within‐plane variation (that is nongravitational variation) is apparent. The right column shows the same data, with the lung divided into upper (nondependent), middle, and lower (dependent) thirds based on vertical height. The perfusion data closely match the data in Figure 1; however, when the distortion of the lung due to gravity seen in the density data is accounted for (the Slinky effect), the density‐normalized perfusion shows a pattern consistent with the zone model (Fig. 2) and less overall gravitational effect. From , with permission.

Figure 6. Figure 6.

A Slinky spring provides a simplistic model of the effects of gravitational distortion on the apparent distribution of pulmonary blood flow. If blood flow is thought to occur within the coils of the spring, then gravitational distortion of the spring as seen in panel B (taken in +2G) makes for an apparent increase in dependent blood flow compared to the situation in the absence of gravity (panel A, taken in 0G). Correction for the deformation corrects this. Note, however, that this overly simplistic “Slinky” model does not include the important hydrostatic effects in the actual lung.

From , with permission, photographs taken by the author
Figure 7. Figure 7.

Cardiac output measured using soluble gas rebreathing during 17 days of 6° head‐down tilt (HDT) (A) and in spaceflights of 14 to 17 days duration (B). Compared to standing, there is an initial abrupt rise in cardiac output followed by a reduction for the following week. However, there is a subsequent increase in cardiac output due to an increase in heart rate in the face of a now stable stroke volume.

From , with permission
Figure 8. Figure 8.

Change in the components of the measurement of Dlco in spaceflight (A). Dlco rises immediately upon exposure to microgravity and remains elevated for the duration of the flight (data not shown). This is a result of increases in both Dm and Vc. In contrast, the upright to supine transition, which also causes an increase in Dlco is due only to an increase in Vc. Panel B provides a conceptual mechanism for these changes. Supine in 1G, there is distension of dependent capillaries but some nondependent capillaries remain de‐recruited, thus limiting the rise in Dm. In microgravity, the entire lung capillary bed is recruited causing parallel increases in Dm and Vc. Whether the lung is in zone 2 or zone 3, conditions in microgravity remains unknown.

From , with permission
Figure 9. Figure 9.

Hyperventilation‐breath‐hold measurement of the inequality of pulmonary perfusion in a subject in 1G (A), and the effects of postural and gravity changes (B). The subject hyperventilates reducing CO2 in all parts of the lung and then performs a breath‐hold at total lung capacity. During this time, CO2 evolves into the (uniformly sized) alveolar spaces at a rate dependent on local blood flow. During a subsequent slow exhalation to residual volume, the cardiogenic oscillations and terminal fall in CO2 following airway closure are indirect markers of the heterogeneity of pulmonary perfusion. In the supine posture, both the size of the oscillations and the height of the terminal fall are reduced to ∼60% of that seen standing (B). In microgravity, the terminal fall is absent despite other evidence showing the presence of airways closure. However, the cardiogenic oscillations persist. The results are consistent with the abolition of the top‐to‐bottom gradients in pulmonary blood flow in microgravity but with persisting smaller‐scale heterogeneity.

From , with permission
Figure 10. Figure 10.

The static pressures applying to the chest and abdominal wall of a relaxed subject sitting in air (A), immersed in water to the xiphoid process (B), and immersed to the neck (C). The broken lines in panels B and C indicate the original position of the chest and abdominal wall in panel A. The pressures indicted are the average from two subjects.

From , with permission
Figure 11. Figure 11.

Static lung loads (SLL) imposed on the pulmonary system in response to various immersion and submersion conditions. The static lung load is the pressure difference between the air source and the pressure at the chest centroid. In panel A, immersion to the neck provides a static lung load of approximately −20 cmH2O (equivalent to a negative end‐expiratory pressure of −20 cmH2O). Similarly, an upright SCUBA diver experiences an SLL of approximately −20 cmH2O because the pressure around the diving regulator is lower than around the chest (B). However, a change of posture to head‐down can rapidly reverse the SLL to a positive value (D).

From , with permission
Figure 12. Figure 12.

Vital capacity (VC) measured using tourniquets of dry, during head‐out immersion, and with varying degrees of arterial and venous occlusion. The results show that the reduction in VC seen with immersion is a result of translocation of blood into the thoracic cavity. Vals. Man.: Valsalva Maneuver.

From , with permission
Figure 13. Figure 13.

Measurement of intrabreath respiratory exchange ratio (intrabreath‐R) in a single subject, before and following ascent from a ∼300‐m saturation dive. Before the dive, the intrabreath‐R curve shows a normal pattern. After ascent, there is a steepening of the curve, indicating increased heterogeneity of in the lung. It is thought that the source of the mismatch is the consequence of venous gas emboli formed during decompression becoming trapped in the pulmonary circulation.

From , with permission
Figure 14. Figure 14.

Schematic of how pressure equilibrium is achieved in the lung during a deep breath‐hold dive, demonstrating the role of chest compression and blood translocation. At total lung capacity (TLC) before entering the water (A), vital capacity (VC) is the portion of TLC that can be used for pressure equilibration. The schematic manometer represents the fact that lung pressure exceeds air pressure at TLC (relaxed condition). Residual volume (RV) is the “noncollapsible” fraction of TLC. There is a modest intrathoracic blood volume (ITVB) in the heart and lungs and the majority of the blood is in the extrathoracic blood volume (ETBV). Early in descent (B), internal and ambient pressures are equilibrated by compression of the chest wall and some translocation of blood from the ETBV to the ITBV. At a greater depth (C), the limits of chest wall compression are reached but a large translocation of ETBV to ITBV maintains pressure equilibrium, further compressing the air in the lungs and maintaining pressure equilibrium. Further descent (D) reaches the limits of distensibility of the blood‐containing structures in the chest and so the pressure in the lungs becomes less than ambient. Further decent might lead to rupture of blood vessels in the lung.

From , with permission
Figure 15. Figure 15.

Changes in the distribution of (labeled ) and pulmonary blood flow (hyperventilation‐breath‐hold) (see Fig. 9 for details) in subjects before and ∼24 h after extravehicular activity (EVA, spacewalk) from the International Space Station. Note that all data were collected in microgravity. Any changes seen as a result of EVA were very small. For the purposes of comparison, the magnitude of the changes in same parameters seen going from the upright to supine postures in 1G are shown as the gray‐shaded bars behind the primary data. The data show that there is no significant disruption to matching or pulmonary blood flow distribution 24 h after EVA. COSC, cardiogenic oscillations.

From , with permission
Figure 16. Figure 16.

Effect of positive‐pressure breathing of 40 mmHg (54 cmH2O) with chest counterpressure. There is an immediate rise in central venous pressure matching the applied airway pressure reflecting the transmission of airway pressure to the vasculature. This stops venous return as evidenced by the rise in forearm volume. Peripheral venous pressure thus rises until venous return is reestablished.

From , with permission


Figure 1.

The first demonstration that blood flow at the apex of the human lung was lower than at the base. A single breath of radioactive CO2 (C15O2) was inspired and the subsequent rate of removal measured using externally placed counters (A). The results (B) clearly demonstrated that there was a large difference in the clearance rate of the CO2, and this was taken as evidence for differences in pulmonary blood flow from apex to base of the lung. From , with permission.



Figure 2.

The three‐zone model of the effects of gravity on the vertical distribution of pulmonary blood flow in the upright human lung. In this model, both pulmonary arterial and pulmonary venous pressures are subject to a hydrostatic gradient in pressure, increasing down the lung. However, the pulmonary capillaries are also exposed to alveolar pressure, which has no corresponding gradient. Flow through the thin‐walled pulmonary capillaries depends on the relationship between these three pressures and this varies vertically in the lung. See text for details. From , with permission.



Figure 3.

The effect of +Gz acceleration on the vertical distribution of pulmonary blood flow in upright subjects. Note that as Gz is increased, a greater and greater proportion of the lung from the apex down becomes unperfused. From , with permission.



Figure 4.

Right‐to‐left shunt fractions in four subjects measured before, during, 1‐min following, and 5‐min following various accelerations as indicated measured using injected tritium (3H). Note that upon acceleration, a shunt is present but is essentially absent even 1 min after return to 1G. From , with permission.



Figure 5.

Distributions of perfusion (blood flow in ml/min/cm3) (A‐C), density (g/cm3) (D‐F), and density‐normalized perfusion (blood flow in ml/min/g) (G‐I) in six supine human subjects measured using MRI. The left column shows values on the x‐axis for individual voxels (approximate volumes of 0.07 cm3), with vertical height up the lung from posterior (bottom) to anterior (top). The superimposed white lines show the line of best fit and thus the apparent gravitational gradient. The center column plots the same data averaged into 1‐cm high horizontal (isogravitational) “slices” with the associated standard deviation. Note that in both presentations, the large amount of within‐plane variation (that is nongravitational variation) is apparent. The right column shows the same data, with the lung divided into upper (nondependent), middle, and lower (dependent) thirds based on vertical height. The perfusion data closely match the data in Figure 1; however, when the distortion of the lung due to gravity seen in the density data is accounted for (the Slinky effect), the density‐normalized perfusion shows a pattern consistent with the zone model (Fig. 2) and less overall gravitational effect. From , with permission.



Figure 6.

A Slinky spring provides a simplistic model of the effects of gravitational distortion on the apparent distribution of pulmonary blood flow. If blood flow is thought to occur within the coils of the spring, then gravitational distortion of the spring as seen in panel B (taken in +2G) makes for an apparent increase in dependent blood flow compared to the situation in the absence of gravity (panel A, taken in 0G). Correction for the deformation corrects this. Note, however, that this overly simplistic “Slinky” model does not include the important hydrostatic effects in the actual lung.

From , with permission, photographs taken by the author


Figure 7.

Cardiac output measured using soluble gas rebreathing during 17 days of 6° head‐down tilt (HDT) (A) and in spaceflights of 14 to 17 days duration (B). Compared to standing, there is an initial abrupt rise in cardiac output followed by a reduction for the following week. However, there is a subsequent increase in cardiac output due to an increase in heart rate in the face of a now stable stroke volume.

From , with permission


Figure 8.

Change in the components of the measurement of Dlco in spaceflight (A). Dlco rises immediately upon exposure to microgravity and remains elevated for the duration of the flight (data not shown). This is a result of increases in both Dm and Vc. In contrast, the upright to supine transition, which also causes an increase in Dlco is due only to an increase in Vc. Panel B provides a conceptual mechanism for these changes. Supine in 1G, there is distension of dependent capillaries but some nondependent capillaries remain de‐recruited, thus limiting the rise in Dm. In microgravity, the entire lung capillary bed is recruited causing parallel increases in Dm and Vc. Whether the lung is in zone 2 or zone 3, conditions in microgravity remains unknown.

From , with permission


Figure 9.

Hyperventilation‐breath‐hold measurement of the inequality of pulmonary perfusion in a subject in 1G (A), and the effects of postural and gravity changes (B). The subject hyperventilates reducing CO2 in all parts of the lung and then performs a breath‐hold at total lung capacity. During this time, CO2 evolves into the (uniformly sized) alveolar spaces at a rate dependent on local blood flow. During a subsequent slow exhalation to residual volume, the cardiogenic oscillations and terminal fall in CO2 following airway closure are indirect markers of the heterogeneity of pulmonary perfusion. In the supine posture, both the size of the oscillations and the height of the terminal fall are reduced to ∼60% of that seen standing (B). In microgravity, the terminal fall is absent despite other evidence showing the presence of airways closure. However, the cardiogenic oscillations persist. The results are consistent with the abolition of the top‐to‐bottom gradients in pulmonary blood flow in microgravity but with persisting smaller‐scale heterogeneity.

From , with permission


Figure 10.

The static pressures applying to the chest and abdominal wall of a relaxed subject sitting in air (A), immersed in water to the xiphoid process (B), and immersed to the neck (C). The broken lines in panels B and C indicate the original position of the chest and abdominal wall in panel A. The pressures indicted are the average from two subjects.

From , with permission


Figure 11.

Static lung loads (SLL) imposed on the pulmonary system in response to various immersion and submersion conditions. The static lung load is the pressure difference between the air source and the pressure at the chest centroid. In panel A, immersion to the neck provides a static lung load of approximately −20 cmH2O (equivalent to a negative end‐expiratory pressure of −20 cmH2O). Similarly, an upright SCUBA diver experiences an SLL of approximately −20 cmH2O because the pressure around the diving regulator is lower than around the chest (B). However, a change of posture to head‐down can rapidly reverse the SLL to a positive value (D).

From , with permission


Figure 12.

Vital capacity (VC) measured using tourniquets of dry, during head‐out immersion, and with varying degrees of arterial and venous occlusion. The results show that the reduction in VC seen with immersion is a result of translocation of blood into the thoracic cavity. Vals. Man.: Valsalva Maneuver.

From , with permission


Figure 13.

Measurement of intrabreath respiratory exchange ratio (intrabreath‐R) in a single subject, before and following ascent from a ∼300‐m saturation dive. Before the dive, the intrabreath‐R curve shows a normal pattern. After ascent, there is a steepening of the curve, indicating increased heterogeneity of in the lung. It is thought that the source of the mismatch is the consequence of venous gas emboli formed during decompression becoming trapped in the pulmonary circulation.

From , with permission


Figure 14.

Schematic of how pressure equilibrium is achieved in the lung during a deep breath‐hold dive, demonstrating the role of chest compression and blood translocation. At total lung capacity (TLC) before entering the water (A), vital capacity (VC) is the portion of TLC that can be used for pressure equilibration. The schematic manometer represents the fact that lung pressure exceeds air pressure at TLC (relaxed condition). Residual volume (RV) is the “noncollapsible” fraction of TLC. There is a modest intrathoracic blood volume (ITVB) in the heart and lungs and the majority of the blood is in the extrathoracic blood volume (ETBV). Early in descent (B), internal and ambient pressures are equilibrated by compression of the chest wall and some translocation of blood from the ETBV to the ITBV. At a greater depth (C), the limits of chest wall compression are reached but a large translocation of ETBV to ITBV maintains pressure equilibrium, further compressing the air in the lungs and maintaining pressure equilibrium. Further descent (D) reaches the limits of distensibility of the blood‐containing structures in the chest and so the pressure in the lungs becomes less than ambient. Further decent might lead to rupture of blood vessels in the lung.

From , with permission


Figure 15.

Changes in the distribution of (labeled ) and pulmonary blood flow (hyperventilation‐breath‐hold) (see Fig. 9 for details) in subjects before and ∼24 h after extravehicular activity (EVA, spacewalk) from the International Space Station. Note that all data were collected in microgravity. Any changes seen as a result of EVA were very small. For the purposes of comparison, the magnitude of the changes in same parameters seen going from the upright to supine postures in 1G are shown as the gray‐shaded bars behind the primary data. The data show that there is no significant disruption to matching or pulmonary blood flow distribution 24 h after EVA. COSC, cardiogenic oscillations.

From , with permission


Figure 16.

Effect of positive‐pressure breathing of 40 mmHg (54 cmH2O) with chest counterpressure. There is an immediate rise in central venous pressure matching the applied airway pressure reflecting the transmission of airway pressure to the vasculature. This stops venous return as evidenced by the rise in forearm volume. Peripheral venous pressure thus rises until venous return is reestablished.

From , with permission
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G. Kim Prisk. Pulmonary Circulation in Extreme Environments. Compr Physiol 2011, 1: 319-338. doi: 10.1002/cphy.c090006