Download Robb Glenny Division of Pulmonary and Critical Care Medicine

Point:Counterpoint
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24. 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.
25. Weibel ER. Fractal geometry: a design principle for living organisms.
Am J Physiol Lung Cell Mol Physiol 261: L361–L369, 1991.
26. West GB, Brown JH, Enquist BJ. The fourth dimension of life: fractal
geometry and allometric scaling of organisms. Science 284: 1677–1679, 1999.
27. West JB, Dollery CT. Distribution of blood flow and ventilation-perfusion ratio in the lung, measured with radioactive carbon dioxide. J Appl
Physiol 15: 405– 410, 1960.
28. 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.
Robb Glenny
Division of Pulmonary and Critical Care Medicine
University of Washington
e-mail: [email protected]
REBUTTAL FROM DRS. HUGHES AND WEST
J Appl Physiol • VOL
1. Anthonisen NR, Milic-Emili J. Distribution of pulmonary perfusion in
erect man. J Appl Physiol 21: 760 –766, 1966.
2. Dawson CA. Dynamics of blood flow and pressure-volume relationship. In:
The Lung: Scientific Foundations, edited by Crystal RG, West JB, et al.
Philadelphia: Lippincott-Raven, 1997, p. 1503–1522.
3. Glazier JB, Hughes JMB, Maloney JE, West JB. Measurements of
capillary dimensions and blood volume in rapidly frozen lungs. J Appl
Physiol 26: 65–76, 1969.
4. Glenny RW, Robertson HT. Fractal modelling of pulmonary blood flow
inhomogeneity. J Appl Physiol 70: 1024 –1030, 1991.
5. Glenny RW. Spatial correlation of regional pulmonary perfusion. J Appl
Physiol 72: 2378 –2386, 1992.
6. Hughes JMB, 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.
7. 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.
8. Warrell DA, Evans JW, Clarke RO, Kingaby JP, West JB. Pattern of
filling in the pulmonary vascular bed. J Appl Physiol 32: 346 –356, 1972.
9. West JB, Schneider AM, Mitchell MM. Recruitment in networks of
pulmonary capillaries. J Appl Physiol 39: 976 –984, 1975.
REBUTTAL FROM DR. GLENNY
Drs. Hughes and West (6) argue convincingly that a vertical
gradient of perfusion exists in human lungs. We agree completely and have never stated otherwise. The controversy,
however, is about whether gravity is the most important determinant of regional pulmonary blood flow. They reason that
gravity must be the single most important determinant of
regional perfusion because numerous prior studies have observed a gradient vertical. This logic parallels the argument
that the sun revolves around the earth because it is repeatedly
seen traversing from one horizon to the other. While the
observation is consistent with the hypothesis, it is not sufficient
proof. When it was discovered that the earth spins about its
axis, prior observations were not invalidated but rather reinterpreted. The realization that blood flow within horizontal
planes is present, well structured, and stable over time, suggests a reinterpretation of prior studies of pulmonary blood
flow distribution.
None of the studies cited in their Point (6) can determine if
gravity is the most important determinant of regional pulmonary blood flow. To settle this issue, high spatial resolution
measurements of perfusion must be obtained under varying
conditions of posture or gravity while tracking the same lung
regions across conditions. Although this kind of study is not
currently possible in humans, the requisite study has been
performed in baboons (2). The baboon is a biped that has
similar lung anatomy, muscularization of pulmonary vessels,
hydrostatic gradients, and pulmonary arterial pressures found
in humans and therefore meets the criteria set by Drs. Hughes
and West (4, 6). Baboons were studied in the upright, supine,
prone, and head-down postures. Blood flow to each lung region
was described by its vertical position in the lung and a
structural component that remained stable across changes in
posture. Vertical gradients of perfusion were observed in all
postures, corroborating prior observations in humans (5, 8).
Multiple stepwise linear regression was used to estimate the
relative importance of the gravitational and structural components of blood flow. As expected, gravity had its largest
influence in the upright posture. However, structure was more
than twice as important as gravity in determining regional
pulmonary blood flow (59 vs. 25%).
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The areas of agreement in this debate are twofold: 1) mean
pulmonary blood flow per horizontal slice [per unit volume or,
more accurately, per unit density or “alveolus” (1,6)] increases
in the gravity direction, independent (for the most part) of
postural orientation, 2) there is considerable inhomogeneity of
blood flow within a slice of minimal vertical height. Heterogeneity, whether random or ordered, is inevitable as the spatial
resolution increases, just as the length of the shoreline increases indefinitely as the sample size gets smaller. Suffice to
say that there are two extremes, 1) a well-expanded, vasodilated lung with low PVR and a mean Ppa level below the top
of the lung, and 2) a low volume vasoconstricted lung with
high PVR and a Ppa level greater than the lung’s vertical
height. The effects of gravity will be prominent in the former
and largely obscured in the latter.
The core of the debate is about the mechanisms responsible
for pulmonary blood flow heterogeneity. There has been acceptance (for more than 40 yr) that mean pulmonary blood flow
per horizontal slice is influenced by the relations between Ppa,
Palv, and Pv (zones I, II, and III) (7), provided the lung is well
expanded and PVR is normal. But what determines heterogeneity at the same horizontal level? Between acini, or larger
domains, the Seattle group maintains that the architecture of
the vascular tree (presumably, arterial) determines local vascular resistance and blood flow by, for example, uneven diameters of the two daughter vessels at a bifurcation. Glenny (5)
maintains that this is not random, but forms part of the fractal
design of the lung (4). Against this hypothesis is 1) the arterial
system contributes only 40% to total PVR (2), and 2) the
compliance of the arterial tree means diameters are not fixed,
but respond to changes of smooth muscle tone or intra- or
extravascular pressures (themselves influenced by gravity from
distortion of the lung by its own weight and by other intrathoracic structures).
Distal to the arterial tree, at the alveolar septal level, recruitment and distension of vessels occurs (3), independent of
arteriolar domains (8), as input pressure increases and exceeds
critical opening pressure (9); in the lung periphery, input
pressures are a function of vertical height and gravity. So, in
subtle ways, gravity may interact with compliant vascular
structures to influence local PVR within as well as between
horizontal lung slices.
REFERENCES
Point:Counterpoint
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The perspective that the geometry of the vascular tree is
more important than gravity in determining regional blood flow
requires that other concepts of the gravitational model be
reconsidered. While the zones of the lung must exist due to
physical laws, they do not need to be vertically stacked in the
lung (3). The fractal model predicts that all three zones can
exist within the same horizontal plane. The concept that the
shared effects of gravity cause matching of regional ventilation
and perfusion, however, cannot explain efficient gas exchange
in the face of large heterogeneities of ventilation (1) and
perfusion within isogravitational planes or during sustained
microgravity (7).
REFERENCES
1. Altemeier WA, McKinney S, Glenny RW. Fractal nature of regional
ventilation distribution. J Appl Physiol 88: 1551–1557, 2000.
2. 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.
3. Glenny RW, Robertson HT. Regional differences in the lung. In:
Complexity in Structure and Function of the Lung, edited by
Hlastala MP and Robertson HT. New York: Marcel Dekker, 1998, p.
461– 481.
4. Hughes JM. Pulmonary blood flow distribution in exercising and in resting
horses. J Appl Physiol 81: 1049 –1050, 1996.
5. 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.
6. Hughes JM, West JB. Counterpoint: Gravity is not the major factor
determining the distribution of blood flow in the healthy human lung. J Appl
Physiol; doi:10.1152/japplphysiol.01092.2007a.
7. Prisk GK, Guy HJ, Elliott AR, West JB. Inhomogeneity of pulmonary
perfusion during sustained microgravity on SLS-1. J Appl Physiol 76:
1730 –1738, 1994.
8. West JB, Dollery CT. Distribution of blood flow and ventilation-perfusion
ratio in the lung, measured with radioactive carbon dioxide. J Appl Physiol
15: 405– 410, 1960.
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