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J Appl Physiol 104: 1531-1533, 2008. First published November 15, 2007; doi:10.1152/japplphysiol.01092.2007
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POINT-COUNTERPOINT

Point:Counterpoint: Gravity is/is not the major factor determining the distribution of blood flow in the human lung

Michael Hughes1 and John B. West2

1National Heart and Lung Institutes-Imperial College
Respiratory Medicine
London, United Kingdom
e-mail: mike.hughes{at}imperial.ac.uk2University of California
San Diego School of Medicine
La Jolla, California
e-mail: jwest{at}ucsd.edu

POINT: GRAVITY IS THE MAJOR FACTOR DETERMINING THE DISTRIBUTION OF BLOOD FLOW IN THE HUMAN LUNG

In 1944 the first recordings of pulmonary artery pressure (Ppa) in normal humans were published (6a). Dock (7), a Brooklyn physician, foresaw that in the upright position, with such a low Ppa, the upper quarter of the lung would be relatively ischemic in most people. He linked this notion to the apical (cranial) location of tuberculous lesions in humans in contrast to its caudal and dorsal distribution in quadrupeds and bats (8). Dock in 1947 did not consider a gradient of increasing blood flow below the bloodless apical regions; in 1960, West and Dollery (25) found a systematic increase in blood flow per unit volume from apex to base in the erect lung with a tenfold increase from top to bottom (Fig. 1). Apical blood flow increases at the onset of exercise and decreases when exercise stops (14), in keeping with the known increases and decreases in pulmonary artery pressure—further confirmation of Dock's reasoning.


Figure 1
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  		Fig. 1. Distribution of blood flow in the upright lung in 16 normal subjects, following single inhalation of radioactive CO2 (C15O2): mean and SD of clearance rates. Blood flow decreases systematically from lung base to apex along the axis of gravity. Redrawn from West (26)

 
Postural changes.   Subsequently, with a variety of radiotracers and detection systems and also contrast enhanced computed tomography [electron-beam CT or EBCT (16)], a vertical gradient of blood flow from upper to lower regions has been found in other postures [prone and/or supine (1, 5, 16–20), right and left lateral decubitus (1, 17, 20), supine anesthetized (23)] in keeping with a gravitationally determined gradient. Despite widely different methodologies and techniques such as 1) single breath hold at TLC (17) or at midlung volumes (17, 18) or steady-state tidal breathing (1, 5, 20), 2) front and back detector pairs (17) or gamma cameras (1) or single photon emission tomography (SPECT; Refs. 19, 20, 23) or positron emission tomography (PET; Refs. 5, 18) or EBCT (16), 3) inert gas radiotracers (1, 5, 17–20) or radiolabel led albumin macroaggregates (MAA; Refs. 19, 23), the data in humans have been remarkably consistent. Interestingly, no vertical gradient was found in the dependent lung in lateral decubitus (1), where the lower lung is relatively compressed by the mediastinum above, in keeping with earlier studies (2, 15) showing loss of the vertical gradient in the erect position at low lung volumes. SPECT is the one technique that has at times been out of line. Hakim et al. (13) found in supine humans that, in any given sagittal slice, blood flow diminished from the center in a concentric fashion without a recognizable gravity gradient. This finding has not been confirmed. Another SPECT study (19) found no vertical blood flow gradient in the prone posture, but four other studies, using EBCT (16), PET (5, 18), and SPECT (20), disagree. Finally, a recent SPECT study (21) suggested that flow tracer distribution is determined by the posture during imaging, not the posture during the flow measurement, with a dorsal predominance of flow in prone (but imaged supine) identical to that in supine. The authors' postulate that vertical redistribution of tissue occurred when posture changed and that flow predominance seen in dorsal regions in both supine and prone was caused by a greater number of alveoli and blood vessels per unit volume dorsally rather than by gravity. However, the reconstruction algorithms are of such complexity that verification of these findings is needed using a different approach.

Changes in gravity.   Acceleration of erect subjects [increasing the head to foot gravity vector (Gz) 3- or 4-fold] in a centrifuge increased in a systematic fashion the unperfused region [~zone 1 where alveolar pressure (Palv) exceeds Ppa] at the apex of the lung in line with a fall in pulmonary artery pressure (9); at the same time the gradient of increasing blood flow from apex to base became steeper (6, 9). No topographic measurements have been made in micro- or zero gravity (~weightlessness) but cardiogenic oscillations in CO2, an indirect index of uneven blood flow, were reduced to 60% during and after exposure to microgravity in the Spacelab Life Sciences-1 Mission (22).

Gravity and the microvasculature.   In addition to topographic differences between regions of lung 1–5 cm apart or 0.6–6 cm3 in volume, gravity has an important role to play in terms of capillary recruitment and distension. The generally accepted zone I, II, III model is based on measurements of blood flow distribution in isolated perfused lungs and on the relationships between pulmonary artery, Palv, and venous (Pv) pressures (27). The driving pressure ({Delta}P) for flow in zone II is the Ppa–Palv difference (Palv is >Pv), and clearly {Delta}P increases by 1 cmH2O/cm vertical distance down zone II. But why does blood flow increase down zone III, right to the bottom of the lung at high lung volumes (2, 15), or in decubitus postures, when {Delta}P (~Ppa – Pv) is constant down this zone? The reason is that mean microvascular pressure [~(Ppa + Pv)/2] increases by 1 cmH2O/cm vertical distance leading to recruitment of septal vessels and distension of those already open, thus reducing microvascular resistance and increasing flow (10). This mechanism also contributes to the increase of flow with distance down zone II.

Human vs. animal lungs.   Those who question the importance of gravity in determining flow distribution in the human lung refer extensively to experiments in animal lungs (12). Although such experiments assist our understanding of mechanisms, biped humans differ from quadrupeds, particularly in the topography of pulmonary blood flow and in the muscularization of pulmonary vessels, just as the distribution of tuberculous lesions differs (8), which invalidate the comparison. The most important factor potentiating the effect of gravity on blood flow distribution is the level of Ppa in relation to the height of the lung, as Dock (7) pointed out. When PVR is low, most of the central Ppa will be "seen" by the microvasculature and vascular conductance will be dominated by the zone I-III relationships, which are very gravity dependent. In the erect posture, the height of the human lung is large in relation to the low PVR and Ppa. On the other hand, with a high PVR and muscularized pulmonary arteries and arterioles, or when the operating lung volume is low, the effects of gravity may be obscured.

Gravity vs. non-gravity effects.   We do not maintain that gravity is the only factor. It is clear that heterogeneity of blood flow increases as the scale of the enquiry narrows (3)—the "what is the length of the coastline?" effect. As the fraction of vascular resistance upstream of the microvasculature increases, so subtle differences in arterial branching ratios may influence flow distribution. As the Seattle group pointed out (11), a daughter:daughter branching ratio of 1.1:1 means a flow variation of (1.1)4, i.e., 1.46:1. With the advent of reasonably accurate reconstructions for small regions of interest (ROIs) using PET or EBCT, sufficient ROIs can be mapped in human lungs for regressions of local blood flow vs. vertical distance to be calculated. On this basis, gravity contributes in the supine lung 24% (18), 34% (16), or 61% (5) to the overall variance of blood flow. Although these are crude estimates, they support our thesis that gravity is the single most important factor in determining blood flow distribution in a large low vascular resistance organ such as the human lung.

REFERENCES

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Point:Counterpoint: Gravity is/is not the major factor determining the distribution of blood flow in the human lung.
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J Appl Physiol, May 1, 2008; 104(5): 1540 - 1540.
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