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Distribution of Perfusion

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Abstract

Local driving pressures and resistances within the pulmonary vascular tree determine the distribution of perfusion in the lung. Unlike other organs, these local determinants are significantly influenced by regional hydrostatic and alveolar pressures. Those effects on blood flow distribution are further magnified by the large vertical height of the human lung and the relatively low intravascular pressures in the pulmonary circulation. While the distribution of perfusion is largely due to passive determinants such as vascular geometry and hydrostatic pressures, active mechanisms such as vasoconstriction induced by local hypoxia can also redistribute blood flow. This chapter reviews the determinants of regional lung perfusion with a focus on vascular tree geometry, vertical gradients induced by gravity, the interactions between vascular and surrounding alveolar pressures, and hypoxic pulmonary vasoconstriction. While each of these determinants of perfusion distribution can be examined in isolation, the distribution of blood flow is dynamically determined and each component interacts with the others so that a change in one region of the lung influences the distribution of blood flow in other lung regions. © 2011 American Physiological Society. Compr Physiol 1:245‐262, 2011.

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Figure 1. Figure 1.

Schematic of longitudinal resistances across arterial (RA), capillary (RC), and venous (RV) compartments in the lung. Flow (F) to a given lung region is determined by the relative longitudinal resistances through that region. The greatest flows will be to regions with relatively lower resistances.

Figure 2. Figure 2.

Resin cast of the human airway showing the dichotomous branching. In the left lung, the pulmonary arteries and veins are also shown in red and blue, respectively. Generously provided by Dr. Ewald Weibel, Institute of Anatomy, University of Berne, Berne, Switzerland.

Figure 3. Figure 3.

Dichotomous branching model. (Left) Basic transformation is the dichotomous branching of each terminal element. The asymmetric branching of the terminal branch divides flow into two fractions, γ and 1 − γ that are distributed to the daughter branches. Following a second iteration in which all terminal nodes branch again, blood flow is now distributed to four terminal branches.

With permission from Glenny and Robertson
Figure 4. Figure 4.

Frequency distribution of pulmonary blood flow in a laboratory animal. Note the rightward skew to the distribution consistent with a log‐normal distribution (fitted line).

Figure 5. Figure 5.

Frequency distributions of blood flow created with a dichotomous branching model similar to Figure . (Left) Flow distribution at the terminal branches after five generations (64 pieces). (Right) Flow distribution at the terminal branches after 10 generations (1024 pieces). Note the apparently greater heterogeneity revealed at the smaller piece size despite the flows being determined by the same branching asymmetry. This demonstrates that the scale dependence of flow heterogeneity measurements is a basic characteristic of all progressively branching distribution systems.

Figure 6. Figure 6.

(Left) Visual map of blood flow to ∼2‐cm3 lung pieces within a horizontal plane of a supine dog. Note the large heterogeneity of perfusion and the spatial organization with high‐flow regions near other high‐flow regions and low‐flow areas neighboring other low‐flow areas. (Right) Vascular tree with asymmetrical branching that leads to neighboring regions having similar flows.

Reproduced with permission from Glenny
Figure 7. Figure 7.

Correlation in blood flow between lung pieces as a function of distance between pieces. Neighboring regions (centers of regions separated by 1.2 cm) were highly correlated (r = 0.676). Correlation between regions decreased with distance, eventually becoming negatively correlated. Closed circles are significantly different from a correlation of r = 0.0.

Reproduced with permission from Glenny et al.
Figure 8. Figure 8.

Scanning electron micrograph of alveolar capillaries from a rat lung. The bar indicates 50 μm. B V indicates a large blood vessel.

Reproduced with permission from Guntheroth
Figure 9. Figure 9.

The temporal variability of pulmonary blood flow is spatially clustered. Lung pieces with similar temporal patterns are near each other. In addition, there are complementary patterns in which blood flow increases to one region at the expense of another region. These observations suggested that most of the variability in blood flow occurs at the level of lobar arteries .

Figure 10. Figure 10.

Per piece pulmonary perfusion distribution is relatively fixed with both decreasing cardiac output (tilt) and increasing cardiac output (exercise) during either exercise or decreased cardiac output (tilt) compared to resting blood flow.

Reprinted with permission from Parker et al.
Figure 11. Figure 11.

Initial studies used external scintillation counters on the chest wall to estimate regional blood flow and ventilation. (Left) These external counters averaged flow within isogravitational planes.

Adapted from Ball et al. . (Right) These studies revealed a vertical distribution of both ventilation and perfusion with increasing flows down the lung. Adapted from West
Figure 12. Figure 12.

Initial three‐zone model of pulmonary perfusion popularized by John West .

Reproduced with permission from West et al.
Figure 13. Figure 13.

The relationships between Pa, Pv, and PA create regional differences in pulmonary perfusion. The zones have been traditionally vertically stacked on top of each other. However, recent observations that perfusion is heterogeneous within isogravitational planes demonstrates that zonal conditions may also vary within horizontal planes. The numbers of different zones within each plane likely shifts with increasing hydrostatic pressure down the lung from predominantly zones 1 and 2 at the top of the lung to all zone 3 conditions in the dependent lung regions.

Reproduced with permission from Glenny and Robertson
Figure 14. Figure 14.

Distribution of pulmonary blood flow with respect to height up the lung in the supine, prone, and upright postures. Blood flow was marked in each posture while imaging was performed in the supine posture for all measures so that the confounding effects of parenchymal redistribution were nullified.

Adapted with permission from Okada et al.
Figure 15. Figure 15.

The vertical gradient of blood flow in the lung is influenced by gravity. In this experiment, blood flow to nearly 1500 lung pieces was determined within the same animal during 2‐G supine, 0‐G supine, and 2‐G prone conditions. It is clear that gravity redistributes blood flow in the direction expected.

Figure 16. Figure 16.

Blood flow to nearly 1500 lung pieces within the same animal under 2‐G supine and 2‐G prone conditions. Note that despite the large difference in gravity and posture, high‐flow piece remain high flow and low‐flow piece remain low flow.

Figure 17. Figure 17.

Blood flow as a function of height up the lung in an upright primate. Data are from 1265 pieces of lung (2 cm3 in volume). (Left) Data averaged within horizontal planes to reproduce the spatial resolution available at the time the gravitational model was conceptualized. (Right) Same data but at a resolution that permits the heterogeneity of perfusion within isogravitational planes to be observed. At the lower spatial resolution, the data are remarkably similar to those of West and gravity appears to be a major determinant of perfusion (r2 = 0.64). However, at the higher resolution, gravity can account for at most 28% of the variability in perfusion.

Reproduced with permission from Fung and Sobin
Figure 18. Figure 18.

The hypoxic pulmonary vasoconstriction (HPV) response to global hypoxia varies within regions of the lung. In this study by Hlastala et al., lung pieces (∼2 cm3 in volume) were clustered into groups defined by changes in the blood flow to each piece with gradated hypoxia. The clusters are color coded and then represented in their spatial location above. Note that pieces with a similar HPV response are grouped together.

Adapted with permission from Hillier et al.


Figure 1.

Schematic of longitudinal resistances across arterial (RA), capillary (RC), and venous (RV) compartments in the lung. Flow (F) to a given lung region is determined by the relative longitudinal resistances through that region. The greatest flows will be to regions with relatively lower resistances.



Figure 2.

Resin cast of the human airway showing the dichotomous branching. In the left lung, the pulmonary arteries and veins are also shown in red and blue, respectively. Generously provided by Dr. Ewald Weibel, Institute of Anatomy, University of Berne, Berne, Switzerland.



Figure 3.

Dichotomous branching model. (Left) Basic transformation is the dichotomous branching of each terminal element. The asymmetric branching of the terminal branch divides flow into two fractions, γ and 1 − γ that are distributed to the daughter branches. Following a second iteration in which all terminal nodes branch again, blood flow is now distributed to four terminal branches.

With permission from Glenny and Robertson


Figure 4.

Frequency distribution of pulmonary blood flow in a laboratory animal. Note the rightward skew to the distribution consistent with a log‐normal distribution (fitted line).



Figure 5.

Frequency distributions of blood flow created with a dichotomous branching model similar to Figure . (Left) Flow distribution at the terminal branches after five generations (64 pieces). (Right) Flow distribution at the terminal branches after 10 generations (1024 pieces). Note the apparently greater heterogeneity revealed at the smaller piece size despite the flows being determined by the same branching asymmetry. This demonstrates that the scale dependence of flow heterogeneity measurements is a basic characteristic of all progressively branching distribution systems.



Figure 6.

(Left) Visual map of blood flow to ∼2‐cm3 lung pieces within a horizontal plane of a supine dog. Note the large heterogeneity of perfusion and the spatial organization with high‐flow regions near other high‐flow regions and low‐flow areas neighboring other low‐flow areas. (Right) Vascular tree with asymmetrical branching that leads to neighboring regions having similar flows.

Reproduced with permission from Glenny


Figure 7.

Correlation in blood flow between lung pieces as a function of distance between pieces. Neighboring regions (centers of regions separated by 1.2 cm) were highly correlated (r = 0.676). Correlation between regions decreased with distance, eventually becoming negatively correlated. Closed circles are significantly different from a correlation of r = 0.0.

Reproduced with permission from Glenny et al.


Figure 8.

Scanning electron micrograph of alveolar capillaries from a rat lung. The bar indicates 50 μm. B V indicates a large blood vessel.

Reproduced with permission from Guntheroth


Figure 9.

The temporal variability of pulmonary blood flow is spatially clustered. Lung pieces with similar temporal patterns are near each other. In addition, there are complementary patterns in which blood flow increases to one region at the expense of another region. These observations suggested that most of the variability in blood flow occurs at the level of lobar arteries .



Figure 10.

Per piece pulmonary perfusion distribution is relatively fixed with both decreasing cardiac output (tilt) and increasing cardiac output (exercise) during either exercise or decreased cardiac output (tilt) compared to resting blood flow.

Reprinted with permission from Parker et al.


Figure 11.

Initial studies used external scintillation counters on the chest wall to estimate regional blood flow and ventilation. (Left) These external counters averaged flow within isogravitational planes.

Adapted from Ball et al. . (Right) These studies revealed a vertical distribution of both ventilation and perfusion with increasing flows down the lung. Adapted from West


Figure 12.

Initial three‐zone model of pulmonary perfusion popularized by John West .

Reproduced with permission from West et al.


Figure 13.

The relationships between Pa, Pv, and PA create regional differences in pulmonary perfusion. The zones have been traditionally vertically stacked on top of each other. However, recent observations that perfusion is heterogeneous within isogravitational planes demonstrates that zonal conditions may also vary within horizontal planes. The numbers of different zones within each plane likely shifts with increasing hydrostatic pressure down the lung from predominantly zones 1 and 2 at the top of the lung to all zone 3 conditions in the dependent lung regions.

Reproduced with permission from Glenny and Robertson


Figure 14.

Distribution of pulmonary blood flow with respect to height up the lung in the supine, prone, and upright postures. Blood flow was marked in each posture while imaging was performed in the supine posture for all measures so that the confounding effects of parenchymal redistribution were nullified.

Adapted with permission from Okada et al.


Figure 15.

The vertical gradient of blood flow in the lung is influenced by gravity. In this experiment, blood flow to nearly 1500 lung pieces was determined within the same animal during 2‐G supine, 0‐G supine, and 2‐G prone conditions. It is clear that gravity redistributes blood flow in the direction expected.



Figure 16.

Blood flow to nearly 1500 lung pieces within the same animal under 2‐G supine and 2‐G prone conditions. Note that despite the large difference in gravity and posture, high‐flow piece remain high flow and low‐flow piece remain low flow.



Figure 17.

Blood flow as a function of height up the lung in an upright primate. Data are from 1265 pieces of lung (2 cm3 in volume). (Left) Data averaged within horizontal planes to reproduce the spatial resolution available at the time the gravitational model was conceptualized. (Right) Same data but at a resolution that permits the heterogeneity of perfusion within isogravitational planes to be observed. At the lower spatial resolution, the data are remarkably similar to those of West and gravity appears to be a major determinant of perfusion (r2 = 0.64). However, at the higher resolution, gravity can account for at most 28% of the variability in perfusion.

Reproduced with permission from Fung and Sobin


Figure 18.

The hypoxic pulmonary vasoconstriction (HPV) response to global hypoxia varies within regions of the lung. In this study by Hlastala et al., lung pieces (∼2 cm3 in volume) were clustered into groups defined by changes in the blood flow to each piece with gradated hypoxia. The clusters are color coded and then represented in their spatial location above. Note that pieces with a similar HPV response are grouped together.

Adapted with permission from Hillier et al.
References
 1. Agostoni E, Piiper J. Capillary pressure and distribution of vascular resistance in isolated lung. Am J Physiol 202: 1033‐1036, 1962.
 2. Altemeier WA, Robertson HT, Glenny RW. Pulmonary gas‐exchange analysis by using simultaneous deposition of aerosolized and injected microspheres. J Appl Physiol 85: 2344‐2351, 1998.
 3. Amis TC, Heather JD, Hughes JM, Jones HA, Rhodes CG. Regional distribution of pulmonary ventilation and perfusion in the conscious dog [proceedings]. J Physiol 295: 40P, 1979.
 4. Arai TJ, Henderson AC, Dubowitz DJ, Levin DL, Friedman PJ, Buxton RB, Prisk GK, Hopkins SR. Hypoxic pulmonary vasoconstriction does not contribute to pulmonary blood flow heterogeneity in normoxia in normal supine humans. J Appl Physiol 10(4): 1057‐1064, 2009.
 5. Arborelius M Jr, Lilja B, Zauner CW. The relative effect of hypoxia and gravity on pulmonary blood flow. Respiration 31: 369‐380, 1974.
 6. Ball WC Jr, Stewart PB, Newsham LG, Bates DV. Regional pulmonary function studied with xenon 133. J Clin Invest 41: 519‐531, 1962.
 7. Banister J, Torrance RW. The effects of the tracheal pressure upon flow: Pressure relations in the vascular bed of isolated lungs. Q J Exp Physiol Cogn Med Sci 45: 352‐367, 1960.
 8. Baumgartner WA Jr, Jaryszak EM, Peterson AJ, Presson RG Jr, Wagner WW Jr. Heterogeneous capillary recruitment among adjoining alveoli. J Appl Physiol 95: 469‐476, 2003.
 9. Beck KC, Rehder K. Differences in regional vascular conductances in isolated dog lungs. J Appl Physiol 61: 530‐538, 1986.
 10. Bernard SL, Glenny RW, Erickson HH, Fedde MR, Polissar N, Basaraba RJ, Hlastala MP. Minimal redistribution of pulmonary blood flow with exercise in racehorses. J Appl Physiol 81: 1062‐1070, 1996.
 11. Bhattacharya J, Staub NC. Direct measurement of microvascular pressures in the isolated perfused dog lung. Science 210: 327‐328, 1980.
 12. Brody JS, Stemmler EJ, DuBois AB. Longitudinal distribution of vascular resistance in the pulmonary arteries, capillaries, and veins. J Clin Invest 47: 783‐799, 1968.
 13. Bryan AC, Bentivoglio LG, Beerel F, Macleish H, Zidulka A, Bates DV. Factors affecting regional distribution of ventilation and perfusion in the lung. J Appl Physiol 19: 395‐402, 1964.
 14. Burrowes KS, Hunter PJ, Tawhai MH. Anatomically based finite element models of the human pulmonary arterial and venous trees including supernumerary vessels. J Appl Physiol 99: 731‐738, 2005.
 15. Burrowes KS, Hunter PJ, Tawhai MH. Evaluation of the effect of postural and gravitational variations on the distribution of pulmonary blood flow via an image‐based computational model. Conf Proc IEEE Eng Med Biol Soc 6: 6138‐6140, 2005.
 16. Burrowes KS, Hunter PJ, Tawhai MH. Investigation of the relative effects of vascular branching structure and gravity on pulmonary arterial blood flow heterogeneity via an image‐based computational model. Acad Radiol 12: 1464‐1474, 2005.
 17. Burrowes KS, Tawhai MH. Computational predictions of pulmonary blood flow gradients: Gravity versus structure. Respir Physiol Neurobiol 154: 515‐523, 2006.
 18. Caruthers SD, Harris TR. Effects of pulmonary blood flow on the fractal nature of flow heterogeneity in sheep lungs. J Appl Physiol 77: 1474‐1479, 1994.
 19. Dirken NMJ, Heemstra H. Alveloar oxygen tension and lung circulation. Q J Exp Physiol 34: 193‐210, 1948.
 20. Dock W. Apical localization of phthisis; its significance in treatment by prolonged rest in bed. Am Rev Tuberc 53: 297‐305, 1946.
 21. Elliot FM, Reid L. Some new facts about the pulmonary artery and its branching pattern. Clin Radiol 16: 193‐198, 1965.
 22. Frostell C, Fratacci MD, Wain JC, Jones R, Zapol WM. Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction. Circulation 83: 2038‐2047, 1991.
 23. Frostell CG, Blomqvist H, Hedenstierna G, Lundberg J, Zapol WM. Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation. Anesthesiology 78: 427‐435, 1993.
 24. Fung YC, Sobin SS. Elasticity of the pulmonary alveolar sheet. Circ Res 30: 451‐469, 1972.
 25. Fung YC, Sobin SS. Theory of sheet flow in lung alveoli. J Appl Physiol 26: 472‐488, 1969.
 26. Glazier JB, DeNardo GL. Pulmonary function studied with the xenon‐133 scanning technique. Normal values and a postural study. Am Rev Respir Dis 94: 188‐194, 1966.
 27. Glazier JB, Hughes JM, Maloney JE, West JB. Measurements of capillary dimensions and blood volume in rapidly frozen lungs. J Appl Physiol 26: 65‐76, 1969.
 28. Glenny R. Counterpoint: Gravity is not the major factor determining the distribution of blood flow in the healthy human lung. J Appl Physiol 104: 1533‐1535; discussion 1535‐1536, 2008.
 29. Glenny R, Bernard S, Neradilek B, Polissar N. Quantifying the genetic influence on mammalian vascular tree structure. Proc Natl Acad Sci U S A 104: 6858‐6863, 2007.
 30. Glenny RW. Spatial correlation of regional pulmonary perfusion. J Appl Physiol 72: 2378‐2386, 1992.
 31. Glenny RW. Determinants of regional ventilation and blood flow in the lung. Intensive Care Med 35: 1833‐1842, 2009.
 32. Glenny RW, Bernard S, Robertson HT, Hlastala MP. Gravity is an important but secondary determinant of regional pulmonary blood flow in upright primates. J Appl Physiol 86: 623‐632, 1999.
 33. Glenny RW, Bernard SL, Luchtel DL, Neradilek B, Polissar NL. The spatial‐temporal redistribution of pulmonary blood flow with postnatal growth. J Appl Physiol 102: 1281‐1288, 2007.
 34. Glenny RW, Bernard SL, Robertson HT. Pulmonary blood flow remains fractal down to the level of gas exchange. J Appl Physiol 89: 742‐748, 2000.
 35. Glenny RW, Lamm WJ, Bernard SL, An D, Chornuk M, Pool SL, Wagner WW Jr, Hlastala MP, Robertson HT. Selected contribution: Redistribution of pulmonary perfusion during weightlessness and increased gravity. J Appl Physiol 89: 1239‐1248, 2000.
 36. Glenny RW, McKinney S, Robertson HT. Spatial pattern of pulmonary blood flow distribution is stable over days. J Appl Physiol 82: 902‐907, 1997.
 37. Glenny RW, Polissar NL, McKinney S, Robertson HT. Temporal heterogeneity of regional pulmonary perfusion is spatially clustered. J Appl Physiol 79: 986‐1001, 1995.
 38. Glenny RW, Robertson HT. Fractal properties of pulmonary blood flow: Characterization of spatial heterogeneity. J Appl Physiol 69: 532‐545, 1990.
 39. Glenny RW, Robertson HT. Fractal modeling of pulmonary blood flow heterogeneity. J Appl Physiol 70: 1024‐1030, 1991.
 40. Glenny RW, Robertson HT. A computer simulation of pulmonary perfusion in three dimensions. J Appl Physiol 79: 357‐369, 1995.
 41. Glenny RW, Robertson HT. Regional differences in the lung: A changing perspective on blood flow distribution. In: Hlastala MP, Robertson HT, editors. Complexity in Structure and Function of the Lung. New York: Marcel Dekker, 1998, p. 461‐481.
 42. Glenny RW, Robertson HT, Hlastala MP. Vasomotor tone does not affect perfusion heterogeneity and gas exchange in normal primate lungs during normoxia. J Appl Physiol 89: 2263‐2267, 2000.
 43. Glenny RW, Robertson HT, Yamashiro S, Bassingthwaighte JB. Applications of fractal analysis to physiology. J Appl Physiol 70: 2351‐2367, 1991.
 44. Godbey PS, Graham JA, Presson RG Jr, Wagner WW Jr, Lloyd TC Jr. Effect of capillary pressure and lung distension on capillary recruitment. J Appl Physiol 79: 1142‐1147, 1995.
 45. Greenleaf JF, Ritman EL, Sass DJ, Wood EH. Spatial distribution of pulmonary blood flow in dogs in left decubitus position. Am J Physiol 227: 230‐244, 1974.
 46. Guntheroth WG, Luchtel DL, Kawabori I. Pulmonary microcirculation: Tubules rather than sheet and post. J Appl Physiol 53: 510‐515, 1982.
 47. Guntheroth WG, Luchtel DL, Kawabori I. Functional implications of the pulmonary microcirculation. An update. Chest 101: 1131‐1134, 1992.
 48. Gupte SA, Wolin MS. Oxidant and redox signaling in vascular oxygen sensing: Implications for systemic and pulmonary hypertension. Antioxid Redox Signal 10: 1137‐1152, 2008.
 49. Hanaoka M, Tanaka M, Ge RL, Droma Y, Ito A, Miyahara T, Koizumi T, Fujimoto K, Fujii T, Kobayashi T, Kubo K. Hypoxia‐induced pulmonary blood redistribution in subjects with a history of high‐altitude pulmonary edema. Circulation 101: 1418‐1422, 2000.
 50. Hedenstierna G. Pulmonary perfusion during anesthesia and mechanical ventilation. Minerva Anestesiol 71: 319‐324, 2005.
 51. Hillier SC, Godbey PS, Hanger CC, Graham JA, Presson RG Jr, Okada O, Linehan JH, Dawson CA, Wagner WW Jr. Direct measurement of pulmonary microvascular distensibility. J Appl Physiol 75: 2106‐2111, 1993.
 52. Hillier SC, Graham JA, Hanger CC, Godbey PS, Glenny RW, Wagner WW Jr. Hypoxic vasoconstriction in pulmonary arterioles and venules. J Appl Physiol 82: 1084‐1090, 1997.
 53. Hlastala MP, Bernard SL, Erickson HH, Fedde MR, Gaughan EM, McMurphy R, Emery MJ, Polissar N, Glenny RW. Pulmonary blood flow distribution in standing horses is not dominated by gravity. J Appl Physiol 81: 1051‐1061, 1996.
 54. Hlastala MP, Lamm WJ, Karp A, Polissar NL, Starr IR, Glenny RW. Spatial distribution of hypoxic pulmonary vasoconstriction in the supine pig. J Appl Physiol 96: 1589‐1599, 2004.
 55. Hogan BL, Grindley J, Bellusci S, Dunn NR, Emoto H, Itoh N. Branching morphogenesis of the lung: New models for a classical problem. Cold Spring Harb Symp Quant Biol 62: 249‐256, 1997.
 56. Hopkins SR, Henderson AC, Levin DL, Yamada K, Arai T, Buxton RB, Prisk GK. Vertical gradients in regional lung density and perfusion in the supine human lung: The Slinky effect. J Appl Physiol 103: 240‐248, 2007.
 57. Hughes JM, Glazier JB, Maloney JE, West JB. Effect of extra‐alveolar vessels on distribution of blood flow in the dog lung. J Appl Physiol 25: 701‐712, 1968.
 58. Hughes JM, Glazier JB, Maloney JE, West JB. Effect of lung volume on the distribution of pulmonary blood flow in man. Respir Physiol 4: 58‐72, 1968.
 59. Hughes M, West JB. Point: Gravity is the major factor determining the distribution of blood flow in the human lung. J Appl Physiol 104: 1531‐1533, 2008.
 60. Jones AT, Hansell DM, Evans TW. Pulmonary perfusion in supine and prone positions: An electron‐beam computed tomography study. J Appl Physiol 90: 1342‐1348, 2001.
 61. Krenz GS, Dawson CA. Vessel distensibility and flow distribution in vascular trees. J Math Biol 44: 360‐374, 2002.
 62. Kuebler WM, Ying X, Bhattacharya J. Pressure‐induced endothelial Ca(2+) oscillations in lung capillaries. Am J Physiol Lung Cell Mol Physiol 282: L917‐L923, 2002.
 63. Kuwahira I, Moue Y, Urano T, Kamiya U, Iwamoto T, Ishii M, Clancy RL, Gonzalez NC. Redistribution of pulmonary blood flow during hypoxic exercise. Int J Sports Med 22: 393‐399, 2001.
 64. Lamm WJ, Starr IR, Neradilek B, Polissar NL, Glenny RW, and Hlastala MP. Hypoxic pulmonary vasoconstriction is heterogeneously distributed in the prone dog. Respir Physiol Neurobiol 144: 281‐294, 2004.
 65. Lefevre J. Teleonomical optimization of a fractal model of the pulmonary arterial bed. J Theor Biol 102: 225‐248, 1983.
 66. Lundberg JO, Lundberg JM, Settergren G, Alving K, Weitzberg E. Nitric oxide, produced in the upper airways, may act in an “aerocrine” fashion to enhance pulmonary oxygen uptake in humans. Acta Physiol Scand 155: 467‐468, 1995.
 67. Mandelbrot BB. The Fractal Geometry of Nature. San Francisco, CA: Freeman, 1983.
 68. Martin C, Cline F, Marshall H. Lobar alveolar gas concentrations: Effect of body position. J Clin Invest 32: 617‐621, 1953.
 69. Melsom MN, Flatebo T, Kramer‐Johansen J, Aulie A, Sjaastad OV, Iversen PO, Nicolaysen G. Both gravity and non‐gravity dependent factors determine regional blood flow within the goat lung. Acta Physiol Scand 153: 343‐353, 1995.
 70. Melsom MN, Flatebo T, Sjaastad OV, Aulie A, Nicolaysen G. Minor redistribution of ventilation and perfusion within the lung during exercise in sheep. Acta Physiol Scand 165: 283‐292, 1999.
 71. Metzger RJ, Krasnow MA. Genetic control of branching morphogenesis. Science 284: 1635‐1639, 1999.
 72. Michels DB, West JB. Distribution of pulmonary ventilation and perfusion during short periods of weightlessness. J Appl Physiol 45: 987‐998, 1978.
 73. Montmerle S, Sundblad P, Linnarsson D. Residual heterogeneity of intra‐ and interregional pulmonary perfusion in short‐term microgravity. J Appl Physiol 98: 2268‐2277, 2005.
 74. Moudgil R, Michelakis ED, Archer SL. Hypoxic pulmonary vasoconstriction. J Appl Physiol 98: 390‐403, 2005.
 75. Neumann PH, Kivlen CM, Johnson A, Minnear FL, Malik AB. Effect of alveolar hypoxia on regional pulmonary perfusion. J Appl Physiol 56: 338‐342, 1984.
 76. Okada O, Presson RG Jr, Godbey PS, Capen RL, Wagner WW Jr. Temporal capillary perfusion patterns in single alveolar walls of intact dogs. J Appl Physiol 76: 380‐386, 1994.
 77. Okada O, Presson RG Jr, Kirk KR, Godbey PS, Capen RL, and Wagner WW Jr. Capillary perfusion patterns in single alveolar walls. J Appl Physiol 72: 1838‐1844, 1992.
 78. Oyamada Y, Mori M, Kuwahira I, Aoki T, Suzuki Y, Suzuki K, Miyata A, Nishio K, Sato N, Naoki K, Kudo H, Ohta Y, Yamaguchi K. Effects of active vasoconstriction and total flow on perfusion distribution in the rabbit lung. Am J Physiol 273: R1465‐R1473, 1997.
 79. Parker JC, Ardell JL, Hamm CR, Barman SA, Coker PJ. Regional pulmonary blood flow during rest, tilt, and exercise in unanesthetized dogs. J Appl Physiol 78: 838‐846, 1995.
 80. Parker JC, Cave CB, Ardell JL, Hamm CR, Williams SG. Vascular tree structure affects lung blood flow heterogeneity simulated in three dimensions. J Appl Physiol 83: 1370‐1382, 1997.
 81. Permutt S, Bromberger‐Barnea B, Bane HN. Alveolar pressure, pulmonary venous pressure, and the vascular waterfall. Med Thorac 19: 239‐260, 1962.
 82. Petersson J, Rohdin M, Sanchez‐Crespo A, Nyren S, Jacobsson H, Larsson SA, Lindahl SG, Linnarsson D, Neradilek B, Polissar NL, Glenny RW, Mure M. Posture primarily affects lung tissue distribution with minor effect on blood flow and ventilation. Respir Physiol Neurobiol 156: 293‐303, 2007.
 83. Petersson J, Rohdin M, Sanchez‐Crespo A, Nyren S, Jacobsson H, Larsson SA, Lindahl SG, Linnarsson D, Neradilek B, Polissar NL, Glenny RW, Mure M. Regional lung blood flow and ventilation in upright humans studied with quantitative SPECT. Respir Physiol Neurobiol 166: 54‐60, 2009.
 84. Prisk GK, Yamada K, Henderson AC, Arai TJ, Levin DL, Buxton RB, Hopkins SR. Pulmonary perfusion in the prone and supine postures in the normal human lung. J Appl Physiol 103: 883‐894, 2007.
 85. Qian H, Bassingthwaighte JB. A class of flow bifurcation models with lognormal distribution and fractal dispersion. J Theor Biol 205: 261‐268, 2000.
 86. Raj JU, Bland RD, Lai‐Fook SJ. Microvascular pressures measured by micropipettes in isolated edematous rabbit lungs. J Appl Physiol 60: 539‐545, 1986.
 87. Raj JU, Chen P. Microvascular pressures measured by micropuncture in isolated perfused lamb lungs. J Appl Physiol 61: 2194‐2201, 1986.
 88. Raj JU, Chen P, Navazo L. Micropuncture measurement of lung microvascular pressure profile in 3‐ to 4‐week‐old rabbits. Pediatr Res 20: 1107‐1111, 1986.
 89. Raj JU, Kaapa P, Anderson J. Effect of pulsatile flow on microvascular resistance in adult rabbit lungs. J Appl Physiol 72: 73‐81, 1992.
 90. Raj JU, Kaapa P, Hillyard R, Anderson J. Pulmonary vascular pressure profile in adult ferrets: Measurements in vivo and in isolated lungs. Acta Physiol Scand 142: 41‐48, 1991.
 91. Reed JH Jr, Wood EH. Effect of body position on vertical distribution of pulmonary blood flow. J Appl Physiol 28: 303‐311, 1970.
 92. Sanchez Crespo A, Hallberg J, Lundberg JO, Lindahl SG, Jacobsson H, Weitzberg E, Nyren S. Nasal nitric oxide and regulation of human pulmonary blood flow in the upright position. J Appl Physiol 108: 181‐188, 2010.
 93. Sobin SS, Tremer HM, Fung YC. Morphometric basis of the sheet‐flow concept of the pulmonary alveolar microcirculation in the cat. Circ Res 26: 397‐414, 1970.
 94. Staub NC, Schultz EL. Pulmonary capillary length in dogs, cat and rabbit. Respir Physiol 5: 371‐378, 1968.
 95. Stickland MK, Welsh RC, Haykowsky MJ, Petersen SR, Anderson WD, Taylor DA, Bouffard M, Jones RL. Intra‐pulmonary shunt and pulmonary gas exchange during exercise in humans. J Physiol 561: 321‐329, 2004.
 96. Stone H, Warren B, Wagner H. The distribution of pulmonary blood flow in human subjects during zero‐G. AGARD Conf Proc 2: 129‐148, 1965.
 97. Sylvester JT, Harabin AL, Peake MD, Frank RS. Vasodilator and constrictor responses to hypoxia in isolated pig lungs. J Appl Physiol 49: 820‐825, 1980.
 98. Tawhai MH, Burrowes KS, Hoffman EA. Computational models of structure‐function relationships in the pulmonary circulation and their validation. Exp Physiol 91: 285‐293, 2006.
 99. Van Beek JH, Roger SA, Bassingthwaighte JB. Regional myocardial flow heterogeneity explained with fractal networks. Am J Physiol 257: H1670‐H1680, 1989.
 100. von Euler US, Liljestrand G. Observations on the pulmonary arterial blood pressure in the cat. Acta Physiol Scand 12: 301‐320, 1946.
 101. Wagner WW Jr. Pulmonary microcirculatory observations in vivo under physiological conditions. J Appl Physiol 26: 375‐377, 1969.
 102. Wagner WW Jr, Todoran TM, Tanabe N, Wagner TM, Tanner JA, Glenny RW, Presson RG Jr. Pulmonary capillary perfusion: Intra‐alveolar fractal patterns and interalveolar independence. J Appl Physiol 86: 825‐831, 1999.
 103. Ward JP. Point: Hypoxic pulmonary vasoconstriction is mediated by increased production of reactive oxygen species. J Appl Physiol 101: 993‐995; discussion 999, 2006.
 104. Wearn JT, Ernstene AC, Bromer AW, Barr JS, German WJ, Zschiesche LJ. The normal behavior of the pulmonary blood vessels with observations on the intermittence of the flow of blood in the arterioles and capillaries. Am J Physiol 109: 236‐256, 1934.
 105. Weibel ER. Morphometry of the Human Lung. New York: Academic Press, 1963.
 106. Weibel ER, Gomez DM. Architecture of the human lung. Use of quantitative methods establishes fundamental relations between size and number of lung structures. Science 137: 577‐585, 1962.
 107. West GB, Brown JH, Enquist BJ. The fourth dimension of life: Fractal geometry and allometric scaling of organisms. Science 284: 1677‐1679, 1999.
 108. West JB. Regional differences in gas exchange in the lung of erect man. J Appl Physiol 17: 893‐898, 1962.
 109. West JB, Dollery CT, Naimark A. Distribution of blood flow in isolated lung: Relation to vascular and alveolar pressures. J Appl Physiol 19: 713‐724, 1964.
 110. Zhuang FY, Yen MR, Fung YC, Sobin SS. How many pulmonary alveoli are supplied by a single arteriole and drained by a single venule? Microvasc Res 29: 18‐31, 1985.

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Robb Glenny, H. Thomas Robertson. Distribution of Perfusion. Compr Physiol 2011, 1: 245-262. doi: 10.1002/cphy.c100012