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Pulmonary Hemodynamics and Fluid Exchange in the Lungs During Exercise

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Abstract

The sections in this article are:

1 Pressures and Flows in the Human Lung Circulation
1.1 Historical Notes
1.2 Human Data
1.3 Arterial, Intrathoracic, and Left Heart Pressures
1.4 Wedge and Pulmonary Arterial Pressures
1.5 Arteriovenous Pressure Gradient (Driving Pressure)
1.6 Exercise and Compliance in Large Pulmonary Arteries
2 Hemodynamics During Exercise in Animals
2.1 Sheep
2.2 Dogs
2.3 Horses
3 Lung Fluid Exchange
3.1 General Concepts
3.2 Factors that Oppose Edema Formation
3.3 Edema Safety Factors in Lung
3.4 Lung Microvascular Fluid Exchange
3.5 Fluid Drainage Patterns in Lung Tissue
3.6 Effects of Intra‐alveolar Edema on Gas Exchange
4 Fluid Exchange in Exercising Animal Models
5 Lung Fluid Exchange in Exercising Humans
5.1 Increases in Microvascular Pressures
5.2 Microvascular Stress Failure in Exercise
6 Conclusions
Figure 1. Figure 1.

A, Mean systemic arterial pressure vs. pulmonary flow during upright and supine cycle exercise for repeated measurements in 8 upright and 67 supine subjects. For all subjects pressure increased (r = 0.62) with increasing flow. B, Wedge pressure increased (r = 0.62) with increasing mean systemic arterial pressure during upright and supine cycle exercise for the same measurements as in A.

Figure 2. Figure 2.

Tracings from an exercising horse showing the large intrathoracic respiratory (esophageal) pressure. However, the mean pulmonary arterial pressure averaged over several respiratory cycles is approximately the same no matter whether the reference pressure is the atmosphere (B) or the esophageal pressure (D).

From Erickson et al. 16, permission
Figure 3. Figure 3.

Relation of left ventricular end‐diastolic pressure (LVEDP), y, to simultaneously measured wedge pressure, x, at rest and during exercise, supine and upright in ten healthy men. The two variables were closely related (y = 1.18x + 0.3; r > 0.9, P < 0.001). Identity is shown as a broken line.

Redrawn from Thadani and Parker 89
Figure 4. Figure 4.

Pulmonary wedge (A), mean pulmonary arterial (B), and pulmonary arterial minus wedge (C), pressures at rest and during cycle exercise vs. pulmonary blood flow in sitting (left panels) and supine subjects (right panels). Averaged slopes for the individual subjects were, sitting and supine, 0.8 and 0.3 for A, 1.0 and 1.0 for B, and 0.5 and 0.4 for C. Serial measurements (sitting) in subject # 6 (filled circles and unbroken line) and in subject # 9 (crosses and broken line) as taken from published reports (24, and the reviews 67,69) are indicated. Serial measurements in one supine subject is also indicated.

Figure 5. Figure 5.

Relationship of resting and exercising mean pulmonary arterial (x) to wedge (y) pressure for upright and supine normal men and women.

Figure 6. Figure 6.

Simultaneous average measurements during upright cycle exercise for men and women of left ventricular end‐diastolic volume index (LVEDV) (A), wedge pressure (B), and stroke volume index (C).

Redrawn from Sullivan, Cobb, and Higgen‐botham 81
Figure 7. Figure 7.

Measurements of stroke volume as related to wedge pressure showing the change from rest to exercise within 16 seated subjects. Although there tended to be a small increase in wedge pressure stroke volume with increasing wedge, the relationship was not significant.

Figure 8. Figure 8.

A, Pressure–diameter relationship for the dog with an intact (unbroken line) and an open (broken line) pericardium. [Redrawn from Glantz et al. 19.] B, Left atrial end‐diastolic pressure vs. a measure of left ventricular diameter with changes in intrathoracic volume in an unanesthetized resting pig showing progressive left ventricular dilation from 1 day to 8 days after pericardiectomy.

Redrawn from Hammond et al. 26
Figure 9. Figure 9.

A, Distribution in humans of the relationship of pulmonary artery minus wedge pressure to pulmonary blood flow during cycle exercise. A regression line was calculated for each of the 63 persons, and the distribution of the slopes is represented here. For the 47 supine persons, the regression included the resting measurement. B, Exercise slopes, (PA‐W)/Q as related to (W/Q) for the 16 subjects performing upright exercise. The statistically significant relationship (P < 0.05) suggests that those persons having large wedge pressure increments during exercise have smaller increments in the pulmonary pressure gradient from artery to vein.

Figure 10. Figure 10.

Pulmonary arterial minus wedge pressure (A) and (B) pulmonary vascular resistance (PVR) as related to oxygen uptake in upright (filled circles) compared to supine (open circles) subjects at rest and during cycle exercise as indicated.

Data are the mean values taken from the review in Reeves, Dempsey, and Grover 67
Figure 11. Figure 11.

The relation of segmental (RK) to total (RL) lung resistance as related to cumulative volume longitudinaly along the lung vasculature. Vertical lines mark the average end of the arterial volume (QA) and capillary volume (QC).

Adapted from Dawson et al. 14
Figure 12. Figure 12.

Relation of mean pulmonary arterial pressure to pulmonary blood flow for supine (unfilled circles) and upright (filled circles) subjects at rest and during exercise. For supine and upright posture respectively, the unbroken and broken lines represent a good fit to the data points assuming the coefficient of distensibility (α) is 1.35%/mm Hg pressure rise, and the resistance to flow at zero pressure (R0) is 1.54 mm Hg · min−1 · liter−1. The equation as derived by Linehan et al. 50 is shown in the text.

Figure 13. Figure 13.

Carbon monoxide pulmonary diffusion values at rest and during cycle exercise.

Unpublished Data provided by C. C. W. Hsia and R. L. Johnson
Figure 14. Figure 14.

Distribution of transit times for flow through a dog lung lobe when the flow was 400 ml/min (low), 800 ml/min (medium), and 1600 ml/min (high). The values of flow are approximately equivalent to cardiac outputs of 1.6, 3.2, and 6.4 liters/min, respectively, in the intact dog.

From Presson et al. 64, with permission
Figure 15. Figure 15.

Pulmonary pressure measurements for increasing pulmonary flow (Q PULM, expressed as percentage change from rest to exercise) in sheep (unfilled circles and broken line) and upright man (filled circles and unbroken line). From above downward are shown (A) left atrial (sheep) or wedge pressure (man), (B) mean pulmonary arterial pressure, and (C) pulmonary arterial minus left atrial pressure.

Human measurements are from Reeves et al. 40, and sheep measurements are redrawn from Newman et al. 58 and Kane et al. 41
Figure 16. Figure 16.

Measurements at rest (time 0) and during 3.5 min of treadmill exercise at a 10% grade and 4 mph in six young adult sheep. A, Pulmonary blood flow (Q PULM) using a main pulmonary arterial flow probe. B, Mean pressures from the pulmonary artery (PPA) wedge (PW), and left atrium (PLA). C, Resistances (pressure gradient/flow) from pulmonary artery to wedge and from wedge to left atrium.

Redrawn from Newman et al. 58
Figure 17. Figure 17.

Measurements in dogs. A, Drawing showing a 16 cm vertical distance, ventral to dorsal, for a lung in an adult, standing, facing leftward. B, Volume distribution in lung slices, 1 cm thick, from ventral (#1) to dorsal surface (#16) for each of three dogs. Note that most of the lung volume is dorsal. (The inflated lung was air dried prior to being sliced.) C, Estimated blood flow distribution for each lung slice in B. Note that for both rest and exercise, the distribution of blood flow resembles distribution of lung volume. (Flow determination was by microspheres injected intravenously in the living dog at rest and during one steady‐state exercise bout.) D, Ratio, for each lung slice, of exercise to resting blood flow. Note that for all slices in each dog, exercise flow was proportional to resting flow, where the constant of proportionality (slope) was the ratio of exercise to resting cardiac output for each dog.

Data, unpublished, were provided by W. W. Wagner
Figure 18. Figure 18.

Pressure–flow relationships for the horse at rest and during exercise showing the mean pulmonary arterial pressure (PPA), estimated capillary pressure (Est Cap), and wedge pressure (PW). Shown are composite mean and individual values from references 16, 33, 46, 52, 62, 90, 93 and W. W. Wagner, personal communication. Where flow data were not available, they were estimated from heart rate.

Figure 19. Figure 19.

Schematic representation of the Starling forces operating between pulmonary capillaries and the interstitium. Note that the alveolar surface tension is exactly opposed by the sub‐atmospheric interstitial fluid pressure (‐5) and the lymphatic filling pressure (PIF ‐ PLYM) [‐5 ‐(‐6)] is positive, which promotes the filling of lymphatic vessels. (Redrawn from Guyton, Textbook of Medical Physiology, 7th edition, Saunders, 1986.)

Figure 20. Figure 20.

Effect of capillary pressure on lung edema when only capillary pressure is increased (pressure), plasma proteins are decreased (πP↓,), and endothelial damage (damage).

Redrawn from Newman et al. 56
Figure 21. Figure 21.

Effect of elevating capillary pressure on arterial oxygen tension (Pao2 dashed line) and extravascular lung water (solid line). At the left arrow, capillary pressure was increased by volume expansion. Mechanical ventilation (CMV) at 8 cm PEEP was applied at the right arrow. Note the dramatic improvement of (Pao2 when mechanical ventilation (CMV) with PEEP was applied. (Modified from Noble, W. H.: Pulmonary oedema: a review. Can. Anesth. Soc J. 27: 286–302, 1981.)

Figure 22. Figure 22.

Microvascular pressure and lymph flow as a function of time during either exercise or passive left atrial hypertension from four sheep under conditions shown in Figure 22. Estimated microvascular pressure was approximately 15 cm H2O during exercise and 17 cm H2O during left atrial hypertension.

Reproduced with permission of A. Holmgren 33
Figure 23. Figure 23.

A, Pulmonary arterial pressure; B, wedge pressure; C, vascular resistance; and D, cardiac output as a function of exercise intensity in upright cycling men at sea level 24,69 and from the Operation Everest II data base.

Figure 24. Figure 24.

Histological slide provided by P. D. Wagner from pig lungs after exercise (print shows 850 × 600 μm area). Only slight perivascular cuffing was present and no intra‐alveolar edema.



Figure 1.

A, Mean systemic arterial pressure vs. pulmonary flow during upright and supine cycle exercise for repeated measurements in 8 upright and 67 supine subjects. For all subjects pressure increased (r = 0.62) with increasing flow. B, Wedge pressure increased (r = 0.62) with increasing mean systemic arterial pressure during upright and supine cycle exercise for the same measurements as in A.



Figure 2.

Tracings from an exercising horse showing the large intrathoracic respiratory (esophageal) pressure. However, the mean pulmonary arterial pressure averaged over several respiratory cycles is approximately the same no matter whether the reference pressure is the atmosphere (B) or the esophageal pressure (D).

From Erickson et al. 16, permission


Figure 3.

Relation of left ventricular end‐diastolic pressure (LVEDP), y, to simultaneously measured wedge pressure, x, at rest and during exercise, supine and upright in ten healthy men. The two variables were closely related (y = 1.18x + 0.3; r > 0.9, P < 0.001). Identity is shown as a broken line.

Redrawn from Thadani and Parker 89


Figure 4.

Pulmonary wedge (A), mean pulmonary arterial (B), and pulmonary arterial minus wedge (C), pressures at rest and during cycle exercise vs. pulmonary blood flow in sitting (left panels) and supine subjects (right panels). Averaged slopes for the individual subjects were, sitting and supine, 0.8 and 0.3 for A, 1.0 and 1.0 for B, and 0.5 and 0.4 for C. Serial measurements (sitting) in subject # 6 (filled circles and unbroken line) and in subject # 9 (crosses and broken line) as taken from published reports (24, and the reviews 67,69) are indicated. Serial measurements in one supine subject is also indicated.



Figure 5.

Relationship of resting and exercising mean pulmonary arterial (x) to wedge (y) pressure for upright and supine normal men and women.



Figure 6.

Simultaneous average measurements during upright cycle exercise for men and women of left ventricular end‐diastolic volume index (LVEDV) (A), wedge pressure (B), and stroke volume index (C).

Redrawn from Sullivan, Cobb, and Higgen‐botham 81


Figure 7.

Measurements of stroke volume as related to wedge pressure showing the change from rest to exercise within 16 seated subjects. Although there tended to be a small increase in wedge pressure stroke volume with increasing wedge, the relationship was not significant.



Figure 8.

A, Pressure–diameter relationship for the dog with an intact (unbroken line) and an open (broken line) pericardium. [Redrawn from Glantz et al. 19.] B, Left atrial end‐diastolic pressure vs. a measure of left ventricular diameter with changes in intrathoracic volume in an unanesthetized resting pig showing progressive left ventricular dilation from 1 day to 8 days after pericardiectomy.

Redrawn from Hammond et al. 26


Figure 9.

A, Distribution in humans of the relationship of pulmonary artery minus wedge pressure to pulmonary blood flow during cycle exercise. A regression line was calculated for each of the 63 persons, and the distribution of the slopes is represented here. For the 47 supine persons, the regression included the resting measurement. B, Exercise slopes, (PA‐W)/Q as related to (W/Q) for the 16 subjects performing upright exercise. The statistically significant relationship (P < 0.05) suggests that those persons having large wedge pressure increments during exercise have smaller increments in the pulmonary pressure gradient from artery to vein.



Figure 10.

Pulmonary arterial minus wedge pressure (A) and (B) pulmonary vascular resistance (PVR) as related to oxygen uptake in upright (filled circles) compared to supine (open circles) subjects at rest and during cycle exercise as indicated.

Data are the mean values taken from the review in Reeves, Dempsey, and Grover 67


Figure 11.

The relation of segmental (RK) to total (RL) lung resistance as related to cumulative volume longitudinaly along the lung vasculature. Vertical lines mark the average end of the arterial volume (QA) and capillary volume (QC).

Adapted from Dawson et al. 14


Figure 12.

Relation of mean pulmonary arterial pressure to pulmonary blood flow for supine (unfilled circles) and upright (filled circles) subjects at rest and during exercise. For supine and upright posture respectively, the unbroken and broken lines represent a good fit to the data points assuming the coefficient of distensibility (α) is 1.35%/mm Hg pressure rise, and the resistance to flow at zero pressure (R0) is 1.54 mm Hg · min−1 · liter−1. The equation as derived by Linehan et al. 50 is shown in the text.



Figure 13.

Carbon monoxide pulmonary diffusion values at rest and during cycle exercise.

Unpublished Data provided by C. C. W. Hsia and R. L. Johnson


Figure 14.

Distribution of transit times for flow through a dog lung lobe when the flow was 400 ml/min (low), 800 ml/min (medium), and 1600 ml/min (high). The values of flow are approximately equivalent to cardiac outputs of 1.6, 3.2, and 6.4 liters/min, respectively, in the intact dog.

From Presson et al. 64, with permission


Figure 15.

Pulmonary pressure measurements for increasing pulmonary flow (Q PULM, expressed as percentage change from rest to exercise) in sheep (unfilled circles and broken line) and upright man (filled circles and unbroken line). From above downward are shown (A) left atrial (sheep) or wedge pressure (man), (B) mean pulmonary arterial pressure, and (C) pulmonary arterial minus left atrial pressure.

Human measurements are from Reeves et al. 40, and sheep measurements are redrawn from Newman et al. 58 and Kane et al. 41


Figure 16.

Measurements at rest (time 0) and during 3.5 min of treadmill exercise at a 10% grade and 4 mph in six young adult sheep. A, Pulmonary blood flow (Q PULM) using a main pulmonary arterial flow probe. B, Mean pressures from the pulmonary artery (PPA) wedge (PW), and left atrium (PLA). C, Resistances (pressure gradient/flow) from pulmonary artery to wedge and from wedge to left atrium.

Redrawn from Newman et al. 58


Figure 17.

Measurements in dogs. A, Drawing showing a 16 cm vertical distance, ventral to dorsal, for a lung in an adult, standing, facing leftward. B, Volume distribution in lung slices, 1 cm thick, from ventral (#1) to dorsal surface (#16) for each of three dogs. Note that most of the lung volume is dorsal. (The inflated lung was air dried prior to being sliced.) C, Estimated blood flow distribution for each lung slice in B. Note that for both rest and exercise, the distribution of blood flow resembles distribution of lung volume. (Flow determination was by microspheres injected intravenously in the living dog at rest and during one steady‐state exercise bout.) D, Ratio, for each lung slice, of exercise to resting blood flow. Note that for all slices in each dog, exercise flow was proportional to resting flow, where the constant of proportionality (slope) was the ratio of exercise to resting cardiac output for each dog.

Data, unpublished, were provided by W. W. Wagner


Figure 18.

Pressure–flow relationships for the horse at rest and during exercise showing the mean pulmonary arterial pressure (PPA), estimated capillary pressure (Est Cap), and wedge pressure (PW). Shown are composite mean and individual values from references 16, 33, 46, 52, 62, 90, 93 and W. W. Wagner, personal communication. Where flow data were not available, they were estimated from heart rate.



Figure 19.

Schematic representation of the Starling forces operating between pulmonary capillaries and the interstitium. Note that the alveolar surface tension is exactly opposed by the sub‐atmospheric interstitial fluid pressure (‐5) and the lymphatic filling pressure (PIF ‐ PLYM) [‐5 ‐(‐6)] is positive, which promotes the filling of lymphatic vessels. (Redrawn from Guyton, Textbook of Medical Physiology, 7th edition, Saunders, 1986.)



Figure 20.

Effect of capillary pressure on lung edema when only capillary pressure is increased (pressure), plasma proteins are decreased (πP↓,), and endothelial damage (damage).

Redrawn from Newman et al. 56


Figure 21.

Effect of elevating capillary pressure on arterial oxygen tension (Pao2 dashed line) and extravascular lung water (solid line). At the left arrow, capillary pressure was increased by volume expansion. Mechanical ventilation (CMV) at 8 cm PEEP was applied at the right arrow. Note the dramatic improvement of (Pao2 when mechanical ventilation (CMV) with PEEP was applied. (Modified from Noble, W. H.: Pulmonary oedema: a review. Can. Anesth. Soc J. 27: 286–302, 1981.)



Figure 22.

Microvascular pressure and lymph flow as a function of time during either exercise or passive left atrial hypertension from four sheep under conditions shown in Figure 22. Estimated microvascular pressure was approximately 15 cm H2O during exercise and 17 cm H2O during left atrial hypertension.

Reproduced with permission of A. Holmgren 33


Figure 23.

A, Pulmonary arterial pressure; B, wedge pressure; C, vascular resistance; and D, cardiac output as a function of exercise intensity in upright cycling men at sea level 24,69 and from the Operation Everest II data base.



Figure 24.

Histological slide provided by P. D. Wagner from pig lungs after exercise (print shows 850 × 600 μm area). Only slight perivascular cuffing was present and no intra‐alveolar edema.

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John T. Reeves, Aubrey E. Taylor. Pulmonary Hemodynamics and Fluid Exchange in the Lungs During Exercise. Compr Physiol 2011, Supplement 29: Handbook of Physiology, Exercise: Regulation and Integration of Multiple Systems: 585-613. First published in print 1996. doi: 10.1002/cphy.cp120113