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Gas Exchange Under Altered Gravitational Stress

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Abstract

Efficient gas exchange in the lung depends on the matching of ventilation and perfusion. However, the human lung is a readily deformable structure and as a result gravitational stresses generate gradients in both ventilation and perfusion. Nevertheless, the lung is capable of withstanding considerable change in the applied gravitational load before pulmonary gas exchange becomes impaired. The postural changes that are part of the everyday existence for most bipedal species are well tolerated, as is the removal of gravity (weightlessness). Increases in the applied gravitational load result only in a large impairment in pulmonary gas exchange above approximately three times that on the ground, at which point the matching of ventilation to perfusion is so impaired that efficient gas exchange is no longer possible. Much of the tolerance of the lung to alterations in gravitation stress comes from the fact that ventilation and perfusion are inextricably coupled. Deformations in the lung that alter ventilation necessarily alter perfusion, thus maintaining a degree of matching and minimizing the disruption in ventilation to perfusion ratio and thus gas exchange. © 2011 American Physiological Society. Compr Physiol 1:339‐355, 2011.

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Figure 1. Figure 1.

(A) The range of ventilation perfusion ratios in the lung. Both ventilation and perfusion are higher near the base of the upright lung, but the vertical variation in perfusion exceeds that in ventilation. As a consequence a/ is high near the uppermost (nondependent) part of the lung and low near the lowermost (dependent) part of the lung. From , with permission. (B) Typical values of the critical parameters of gas exchange in the uppermost (left) and lowermost (right) of nine imaginary isogravitational slices of an upright lung are shown. Note that because a/ is high in the nondependent lung, the resulting blood gases from that area more closely resemble inspired air while those from the dependent lung resemble mixed‐venous blood. From , with permission.

Figure 2. Figure 2.

Theoretical calculations of the surface pleural pressures in a lung with uniform soft‐tissue mechanics in the prone (A) and supine (B) postures. Note that the shape and dimensions of the chest wall and diaphragm position were held constant between postures in these calculations (i.e., the “container” for the lungs was unaltered), but despite that there is a very much grater gradient in pleural pressure (and as a consequence regional lung density) seen in the supine posture. From , with permission.

Figure 3. Figure 3.

The overall changes in pulmonary gas exchange in eight subjects measured upright (vertical shading), supine (horizontal shading), and in microgravity during spaceflight (open bars). Except for a slight increase in end‐tidal PCO2, likely as a result of environmental conditions (see text) gas exchange in sustained microgravity was unaltered compared to that seen standing on the ground in 1G. From , with permission. *P < 0.05 compared to upright 1G (vertical stripes). †P < 0.05 compared to supine 1G (horizontal stripes). Open bars: Microgravity.

Figure 4. Figure 4.

Cardiac output measured using soluble gas rebreathing during 17‐days of 6° head‐down tilt (HDT) (A) and in spaceflights of 14‐ to 17‐day 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. *P < 0.05 compared to control standing. #P < 0.05 compared to control supine. †P < 0.05 between standing and supine.

Figure 5. Figure 5.

(A) Peak o2 and incremental work load test during and after a 9‐day spaceflight with associated measures of heart rate (HR), stroke volume (SV), and cardiac output () [data from ]. Plasma volume measurements taken at that same time are from Alfrey et al. . Except for the day of return from spaceflight (R + 0), hemodynamic variable recover in parallel with plasma volume (PV). From , with permission. (B) Cardiac output as a function of o2 in six subjects before spaceflight (upright and supine) and in microgravity. The linear fits shown accounted for 95% of the variance in the measured data [data from ]. Note that in microgravity, the rise in cardiac output for a given increase in o2 was only 58% of that preflight. From , with permission.

Figure 6. Figure 6.

(A) Ventilatory heterogeneity persists in microgravity. Tracing of an exhaled argon bolus inspired at residual volume in microgravity. Note that the markers of heterogeneity typically ascribed to gravitational influences on the lung, cardiogenic oscillations (COSC) and a terminal rise (following airways closure) are still present in microgravity. From , with permission. (B) Ventilatory heterogeneity persists in microgravity. Cumulative data from seven subjects showing persisting COSC and a terminal rise (phase IV height) in microgravity (vertical shading: standing in 1G; horizontal shading: supine in 1G; open bars: microgravity). From , with permission. *P < 0.05 compared with standing.

Figure 7. Figure 7.

(A) Perfusion heterogeneity persists in microgravity. Composite plot of typical hyperventilation‐breathhold tracings from four subjects standing in 1G (left column), supine in 1G (middle column), and in microgravity (right column). In microgravity, cardiogenic oscillations persist at a size comparable to the supine, but the terminal fall in CO2 is absent despite persisting airways closure (Fig. ). From , with permission. (B) Perfusion heterogeneity persists in microgravity. Composite results from the same four subjects as shown in panel A. Note that the supine posture results in a more uniform distribution of perfusion consistent with the reduced vertical height of the lung in that posture. The results are consistent with the abolition of top‐to‐bottom gradients in pulmonary perfusion but persisting nongravitational heterogeneity. From , with permission. *Different from standing (P < 0.05).

Figure 8. Figure 8.

Heterogeneity in a/ is largely unchanged in microgravity. Indirect measurements of the heterogeneity of ventilation‐perfusion ratio standing in 1G (vertical shading), supine in 1G (horizontal shading), and in microgravity (open bars). Over the majority of the expiration (phase III), there was no significant difference in the degree of heterogeneity of a/ between standing in 1G and in microgravity, despite large reductions in the underlying heterogeneity of both ventilation (Fig. ) and perfusion (Fig. ). Following the onset of airways closure, the heterogeneity of a/ was somewhat reduced in microgravity. The results imply a gravitationally imposed matching of ventilation and perfusion. From , with permission. *P < 0.05 compared to standing in 1G. †P < 0.05 compared to supine in 1G.

Figure 9. Figure 9.

Distributions of perfusion (blood flow in ml/min/cm3) (A‐C), density (g/cm3) (panels D‐F), and density‐normalized perfusion (blood flow in ml/min/g) (panels 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 on the basis of vertical height. The perfusion data closely match the data in Figure ; 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. ) and less overall gravitational effect. From , with permission. *Significantly different from middle and dependent region. # Significantly different from dependent and non‐dependent region. † Significantly different from non‐dependent and middle region, all P < 0.05.

Figure 10. Figure 10.

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 (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 11. Figure 11.

(A) Effect of acceleration on the vertical distributions of ventilation in supine humans subjected to +Gx acceleration (“eyeballs in”). In the ventilation studies, the distribution of the first 1.2 liters of gas inspired from residual volume (RV) is shown (upper panel), followed by the distribution of the subsequent 1 liter of gas. Note that there is evidence for airway closure (no ventilation) at both +3Gx and +5Gx for gas inspired at RV but that complete airway closure is seen only at +5Gx at higher lung volumes. Note also that ventilation remains intact in the nondependent regions of the lung. From , with permission. (B) Effect of acceleration on the vertical distributions of perfusion in supine humans subjected to +Gx acceleration (“eyeballs in”). Perfusion shows a different pattern to ventilation (Fig. A), with a significant reduction in nondependent regions of the lung at +5Gx. As a consequence of the different patterns of change, ventilation‐perfusion matching is significantly disrupted by acceleration. From , with permission. Ant., anterior; Post., posterior.

Figure 12. Figure 12.

SPECT images from human lungs marked with radiolabeled, macroaggregated albumen when the subjects were in the posture (supine/prone) and G‐levels (1Gx, 3Gx) indicated. Following injection of the tracer, subjects were subsequently imaged in the same posture in 1G. For the studies in which labeling occurred at 1G, there was a higher blood flow in dependent lung regions (red colors). However, when labeling occurred at 3G, blood flow was greatly attenuated in the most dependent lung regions, likely as a result of large parts of the dependent lung being in zone 4 conditions. When the lung was returned to 1G, this lung reexpanded and appears as regions of low perfusion. From , with permission.

Figure 13. Figure 13.

(A) Acceleration‐induced ventilation‐perfusion inequality and the consequences on pulmonary gas exchange. The calculated relative ventilation‐perfusion ratio from the data in Figure (absolute a/ cannot be determined from these studies) at +1Gx and +5Gx. At +1Gx, there was the expected vertical distribution of a/, with higher values being observed in the nondependent lung regions. At +5Gx, the gradient in a/ is very much steeper, with much of the nondependent lung having values above 2.0, and with much of the dependent lung having values below 0.5 (outside the range in which gas exchange remains reasonably efficient), and with much of the dependent lung having a a/ of zero. Ant., anterior; Post., posterior. From , with permission. (B) Acceleration‐induced ventilation‐perfusion inequality and the consequences on pulmonary gas exchange. Measured arterial oxygen saturations from a large number of studies in which subjects were exposed to the indicated accelerations for periods of 50 s to 6 min. Note that as acceleration increases, arterial oxygen saturation generally falls, indicating worsening gas exchange. From , with permission.

Figure 14. Figure 14.

Oxygen uptake measured before, during, and after a period of +2Gz acceleration. The diagonal line represents the slope that would be measured if o2 were zero. During the period of 1G, o2 is constant but then falls during the period of acceleration, as indicated by a lower slope of the tracing. Following return to 1G, there is a short period of increased o2 thought to be recovery for the oxygen debt incurred during the period of acceleration, followed by a return to baseline conditions. From , with permission.

Figure 15. Figure 15.

(A) Effects of +3Gz acceleration on hemodynamic parameters in exercising subjects. Acceleration caused a reduction in stroke volume (SV) (likely because of impaired venous return) at all exercise levels, which was only partially compensated for by an increased heart rate (HR) [data from ], figure from , with permission]. (B) Effects of +3Gz acceleration on ventilatory parameters in exercising subjects. Minute ventilation was increased by acceleration, while alveolar ventilation remained unchanged, indicating an increase in alveolar dead space. Gas exchange was significantly impaired by acceleration, partly through the development of shunt [data from , figure from , with permission].

Figure 16. Figure 16.

Oxygen requirements of exercising muscles is increased by acceleration during leg exercise. Net o2 (defined as the exercise‐resting values) plotted as a function of external power output. The best fit lines for three values of acceleration are plotted showing a steady increase in o2 required to generate a given power output as acceleration is increased, likely due to the extra work required to lift the legs at higher G levels.

From , with permission


Figure 1.

(A) The range of ventilation perfusion ratios in the lung. Both ventilation and perfusion are higher near the base of the upright lung, but the vertical variation in perfusion exceeds that in ventilation. As a consequence a/ is high near the uppermost (nondependent) part of the lung and low near the lowermost (dependent) part of the lung. From , with permission. (B) Typical values of the critical parameters of gas exchange in the uppermost (left) and lowermost (right) of nine imaginary isogravitational slices of an upright lung are shown. Note that because a/ is high in the nondependent lung, the resulting blood gases from that area more closely resemble inspired air while those from the dependent lung resemble mixed‐venous blood. From , with permission.



Figure 2.

Theoretical calculations of the surface pleural pressures in a lung with uniform soft‐tissue mechanics in the prone (A) and supine (B) postures. Note that the shape and dimensions of the chest wall and diaphragm position were held constant between postures in these calculations (i.e., the “container” for the lungs was unaltered), but despite that there is a very much grater gradient in pleural pressure (and as a consequence regional lung density) seen in the supine posture. From , with permission.



Figure 3.

The overall changes in pulmonary gas exchange in eight subjects measured upright (vertical shading), supine (horizontal shading), and in microgravity during spaceflight (open bars). Except for a slight increase in end‐tidal PCO2, likely as a result of environmental conditions (see text) gas exchange in sustained microgravity was unaltered compared to that seen standing on the ground in 1G. From , with permission. *P < 0.05 compared to upright 1G (vertical stripes). †P < 0.05 compared to supine 1G (horizontal stripes). Open bars: Microgravity.



Figure 4.

Cardiac output measured using soluble gas rebreathing during 17‐days of 6° head‐down tilt (HDT) (A) and in spaceflights of 14‐ to 17‐day 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. *P < 0.05 compared to control standing. #P < 0.05 compared to control supine. †P < 0.05 between standing and supine.



Figure 5.

(A) Peak o2 and incremental work load test during and after a 9‐day spaceflight with associated measures of heart rate (HR), stroke volume (SV), and cardiac output () [data from ]. Plasma volume measurements taken at that same time are from Alfrey et al. . Except for the day of return from spaceflight (R + 0), hemodynamic variable recover in parallel with plasma volume (PV). From , with permission. (B) Cardiac output as a function of o2 in six subjects before spaceflight (upright and supine) and in microgravity. The linear fits shown accounted for 95% of the variance in the measured data [data from ]. Note that in microgravity, the rise in cardiac output for a given increase in o2 was only 58% of that preflight. From , with permission.



Figure 6.

(A) Ventilatory heterogeneity persists in microgravity. Tracing of an exhaled argon bolus inspired at residual volume in microgravity. Note that the markers of heterogeneity typically ascribed to gravitational influences on the lung, cardiogenic oscillations (COSC) and a terminal rise (following airways closure) are still present in microgravity. From , with permission. (B) Ventilatory heterogeneity persists in microgravity. Cumulative data from seven subjects showing persisting COSC and a terminal rise (phase IV height) in microgravity (vertical shading: standing in 1G; horizontal shading: supine in 1G; open bars: microgravity). From , with permission. *P < 0.05 compared with standing.



Figure 7.

(A) Perfusion heterogeneity persists in microgravity. Composite plot of typical hyperventilation‐breathhold tracings from four subjects standing in 1G (left column), supine in 1G (middle column), and in microgravity (right column). In microgravity, cardiogenic oscillations persist at a size comparable to the supine, but the terminal fall in CO2 is absent despite persisting airways closure (Fig. ). From , with permission. (B) Perfusion heterogeneity persists in microgravity. Composite results from the same four subjects as shown in panel A. Note that the supine posture results in a more uniform distribution of perfusion consistent with the reduced vertical height of the lung in that posture. The results are consistent with the abolition of top‐to‐bottom gradients in pulmonary perfusion but persisting nongravitational heterogeneity. From , with permission. *Different from standing (P < 0.05).



Figure 8.

Heterogeneity in a/ is largely unchanged in microgravity. Indirect measurements of the heterogeneity of ventilation‐perfusion ratio standing in 1G (vertical shading), supine in 1G (horizontal shading), and in microgravity (open bars). Over the majority of the expiration (phase III), there was no significant difference in the degree of heterogeneity of a/ between standing in 1G and in microgravity, despite large reductions in the underlying heterogeneity of both ventilation (Fig. ) and perfusion (Fig. ). Following the onset of airways closure, the heterogeneity of a/ was somewhat reduced in microgravity. The results imply a gravitationally imposed matching of ventilation and perfusion. From , with permission. *P < 0.05 compared to standing in 1G. †P < 0.05 compared to supine in 1G.



Figure 9.

Distributions of perfusion (blood flow in ml/min/cm3) (A‐C), density (g/cm3) (panels D‐F), and density‐normalized perfusion (blood flow in ml/min/g) (panels 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 on the basis of vertical height. The perfusion data closely match the data in Figure ; 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. ) and less overall gravitational effect. From , with permission. *Significantly different from middle and dependent region. # Significantly different from dependent and non‐dependent region. † Significantly different from non‐dependent and middle region, all P < 0.05.



Figure 10.

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 (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 11.

(A) Effect of acceleration on the vertical distributions of ventilation in supine humans subjected to +Gx acceleration (“eyeballs in”). In the ventilation studies, the distribution of the first 1.2 liters of gas inspired from residual volume (RV) is shown (upper panel), followed by the distribution of the subsequent 1 liter of gas. Note that there is evidence for airway closure (no ventilation) at both +3Gx and +5Gx for gas inspired at RV but that complete airway closure is seen only at +5Gx at higher lung volumes. Note also that ventilation remains intact in the nondependent regions of the lung. From , with permission. (B) Effect of acceleration on the vertical distributions of perfusion in supine humans subjected to +Gx acceleration (“eyeballs in”). Perfusion shows a different pattern to ventilation (Fig. A), with a significant reduction in nondependent regions of the lung at +5Gx. As a consequence of the different patterns of change, ventilation‐perfusion matching is significantly disrupted by acceleration. From , with permission. Ant., anterior; Post., posterior.



Figure 12.

SPECT images from human lungs marked with radiolabeled, macroaggregated albumen when the subjects were in the posture (supine/prone) and G‐levels (1Gx, 3Gx) indicated. Following injection of the tracer, subjects were subsequently imaged in the same posture in 1G. For the studies in which labeling occurred at 1G, there was a higher blood flow in dependent lung regions (red colors). However, when labeling occurred at 3G, blood flow was greatly attenuated in the most dependent lung regions, likely as a result of large parts of the dependent lung being in zone 4 conditions. When the lung was returned to 1G, this lung reexpanded and appears as regions of low perfusion. From , with permission.



Figure 13.

(A) Acceleration‐induced ventilation‐perfusion inequality and the consequences on pulmonary gas exchange. The calculated relative ventilation‐perfusion ratio from the data in Figure (absolute a/ cannot be determined from these studies) at +1Gx and +5Gx. At +1Gx, there was the expected vertical distribution of a/, with higher values being observed in the nondependent lung regions. At +5Gx, the gradient in a/ is very much steeper, with much of the nondependent lung having values above 2.0, and with much of the dependent lung having values below 0.5 (outside the range in which gas exchange remains reasonably efficient), and with much of the dependent lung having a a/ of zero. Ant., anterior; Post., posterior. From , with permission. (B) Acceleration‐induced ventilation‐perfusion inequality and the consequences on pulmonary gas exchange. Measured arterial oxygen saturations from a large number of studies in which subjects were exposed to the indicated accelerations for periods of 50 s to 6 min. Note that as acceleration increases, arterial oxygen saturation generally falls, indicating worsening gas exchange. From , with permission.



Figure 14.

Oxygen uptake measured before, during, and after a period of +2Gz acceleration. The diagonal line represents the slope that would be measured if o2 were zero. During the period of 1G, o2 is constant but then falls during the period of acceleration, as indicated by a lower slope of the tracing. Following return to 1G, there is a short period of increased o2 thought to be recovery for the oxygen debt incurred during the period of acceleration, followed by a return to baseline conditions. From , with permission.



Figure 15.

(A) Effects of +3Gz acceleration on hemodynamic parameters in exercising subjects. Acceleration caused a reduction in stroke volume (SV) (likely because of impaired venous return) at all exercise levels, which was only partially compensated for by an increased heart rate (HR) [data from ], figure from , with permission]. (B) Effects of +3Gz acceleration on ventilatory parameters in exercising subjects. Minute ventilation was increased by acceleration, while alveolar ventilation remained unchanged, indicating an increase in alveolar dead space. Gas exchange was significantly impaired by acceleration, partly through the development of shunt [data from , figure from , with permission].



Figure 16.

Oxygen requirements of exercising muscles is increased by acceleration during leg exercise. Net o2 (defined as the exercise‐resting values) plotted as a function of external power output. The best fit lines for three values of acceleration are plotted showing a steady increase in o2 required to generate a given power output as acceleration is increased, likely due to the extra work required to lift the legs at higher G levels.

From , with permission
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G. Kim Prisk. Gas Exchange Under Altered Gravitational Stress. Compr Physiol 2011, 1: 339-355. doi: 10.1002/cphy.c090007