Editorial
The Volume of Blood in the Lungs
sible pulmonary circulation.7 Whether autonomic activity affects the distensibility characteristics is unsettled.8 9
Traditionally the lung is pictured as a blood
depot, operating to ensure an uninterrupted
supply of blood to the left ventricle during
acute disturbances in venous return, such as
those produced by breathing, change in posture, and exercise.2 Another accepted view is
that the lungs are at the mercy of the systemic
circulation, passively accommodating or yielding blood according to the dictates of systemic
vasomotor activity.8' Until recently, accurate
measurements of pulmonary blood volume, or
reliable indices of a change in pulmonary
blood volume, were unavailable to test these
concepts. But, during the last 2 years, two
new methods have become available.
The first of the new methods, applicable to
animals, is the use of chronically implanted
electromagnetic flow probes, one around a
pulmonary artery and another around a pulmonary vein; a change in pulmonary blood
volume at any instant is merely the difference
between inflow and outflow.2' 10 Since the
electromagnetic flow meter is still in its infancy, further comment will be confined to
the second method which uses the indicatordilution principle to measure the pulmonary
blood volume11 12 instead of "central blood
volume," a vague entity that includes not
only the volume of blood in the lungs but
also in the heart and in an indeterminate
portion of the systemic circulation.
For the measurement of the pulmonary
blood volume, systemic arterial dilution curves
are obtained after separate injections of the
test substance into the pulmonary artery and
left atrium; from this combination, the pulmonary blood volume is calculated by difference. It should be noted that the volume
calculated by the indicator-dilution technique
is a virtual rather than an anatomic- volume
since it only includes blood with which dye
has mixed and excludes stagnant and se-
the lungs are made by Nature as if for a
.....
storehouse of blood, so that it may constantly in
turns give forth blood to the heart, which, thence
driven into the whole body by continual circulation,
may impart life and motion to everything."-J.
YOUNG: Malpighi's "De Pulmonibus" [1661] Proc
Royal Soc Med 23:7, 1929.
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INTEREST in the pulmonary blood volume
apparently began with Malpighi who
noted that inflation displaced blood from the
lung of the frog.' Many such qualitative observations were made during subsequent years
but not until the turn of the present century,
and the advent of heart-lung preparations, did
quantitative measurements become possible.
In the 1920's, the development of the indicatordilution technique extended the prospect of
quantitative measurements to the intact animal
and man.
Reasons for the continuing interest in pulmonary blood volume have varied with the
times and with the investigators. At present,
four main lines of interest may be identified:
(1) the role of the lungs as a blood depot,
(2) the blood reservoir as the site of stretch
receptors, (3) the performance of the congested lung, and (4) the partition of the
pulmonary blood volume. All of these lines of
interest are apparent in the five papers that
have recently been published, or are about to
be published in Circulation.2
Blood Depot
The volume of blood in the lungs at
The Lungs
as a
any
instant depends on the balance between inflow
and outflow as determined by the respective
actions of the two ventricles and on the
distensibility characteristics of the pulmonary
vascular tree; variations in the ventilation, in
total blood volume, and in systemic vasomotor
activity exert considerable influences on the
regulation of the low-pressure, highly distenFrom the Department of Medicine, Columbia
University and Cardiorespiratory Laboratory, Presbyterian Hospital, New York, New York.
Circulation, Volume XXXIII, June 1966
835
836
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questered blood. It is true that the virtual
and anatomic volumes are probably similar
in the normal pulmonary circulation, but
there is no predicting how the volumes and
their meanings are affected either by drastic
experimental conditions or by clinical disorders of the heart and lungs.
Obviously, the combination of right and
left heart catheterization is too formidable
for regular clinical or investigative use. Also,
there is an inherent error in the calculation by
difference which is, at best, of the order of
10 to M5%.13 Nonetheless, this technique has
provided a standard of reference for less
direct methods, for example, external counting
after injection of a radioactive tracer, in which
the estimation of mean pulmonary transit
time is complicated by uncertainties concerning the exact vascular anatomy viewed
by the counter.14 In normal subjects, the
pulmonary blood volume is approximately 10%
of the total blood volume,11 12 a value almost
identical with that established long ago, by
direct measurement, in the heart-lung preparation of the dog.
The Blood Reservoir as the Site of
Stretch-Receptors
In recent years, stretch-receptors in the
intrathoracic portion of the circulation have
been postulated as devices for signaling the
degree of distention of the atria and venoatrial junctions and for reflexly modifying the
vasomotor behavior of the heart, the systemic
resistance vessels and the kidney.3 15. 16 At
present, it seems likely that either different or
adaptive mechanisms are operative during
acute experimental engorgement and during
chronic pulmonary congestion. To explore this
important problem further, reliable techniques are needed not only to measure total
pulmonary blood volume but also to partition
the intrathoracic blood volume for the sake of
determining the degree of distention of the
consecutive segments of the pulmonary circulation and of the individual cardiac chambers.
A preliminary step has been made in this
direction and will be considered subsequently.
EDITORIAL
The Congested Lung
It has long been known that the lungs are
stiffened by either acute or chronic engorgement.17 It has also been appreciated that the
diminished compliance of the engorged lung
somehow helps to set the breathing pattern
and is somehow involved in the genesis of
dyspnea. In patients with chronic pulmonary
congestion, the distinction between changes in
compliance attributable solely to expansion of
the pulmonary blood volume and to anatomic
sequelae of chronic pulmonary engorgement
has not been easy to accomplish either by
studies of the mechanies of breathing or by
determinations of "central blood volume."
But, in general, anatomic changes do seem to
reduce further the low compliance effected by
pulmonary engorgement and to lead to obliteration of dependent parts of the pulmonary
vascular tree. One consequence of the anatomic restriction and the reduced compliance
in chronic pulmonary congestion may be a
normal pulmonary blood volume despite high
pulmonary vascular pressures.6
It is difficult to generalize from chronic to
acute congestion: In states of chronic circulatory congestion with normal hearts, the lungs
seem to share in the expanded total blood
volume;18 on the other hand, in the acute expansion of the total blood volume by infusion,
the lungs appear to be spared and the expanded blood volume is accommodated largely in
systemic veins.8
Partition of the Pulmonary Blood Volume
Interpretations of the behavior of the pulmonary circulation on the basis of pressureflow measurements have been handicapped
by lack of simultaneous measurements of
pressure-volume. This is true not only for the
entire pulmonary circulation but also for the
behavior of the consecutive pulmonary vascular segments.
The first step in establishing the volume of
a pulmonary vascular segment was made by
Roughton,19 in 1945, when he used an equation to calculate the volume of pulmonary
capillary blood exposed to alveolar gas (V,).
The ingredients of the equation were: (1) inCirculation. Volume XXXIII,
June
1966
EDITORIAL
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vitro measurements of the rate of reaction of
carbon monoxide with suspensions of human
erythrocytes at normal and at high oxygen
tensions, (2) in-vivo measurements of the
rate of uptake of carbon monoxide at high
oxygen tensions, and (3) several reasonable
physiological assumptions. He concluded that
V, was approximately 60 ml at rest and 95 ml
during heavy work.19
Subsequently, Roughton and Forster20 provided another ingenious equation which made
possible the determination of V, by fractionating the total diffusing capacity of the
lungs as though it were composed of two
components, the diffusing capacity of the
alveolar-capillary membrane (Dm,) and the
volume of blood in the pulmonary capillaries
(½V). Obviously, this approach is an important
conceptual advance.4' But, in practice, especially when applied to patients with heart
or lung disease, the V, is subject to considerable uncertainty: its determination includes
all of the opportunities for technical error
that are involved in determining the total
diffusing capacity of the lungs for carbon
monoxide; the reaction rate of carbon monoxide and hemoglobin has been measured
only under certain limited conditions; different modifications of the method for measuring
the diffusing capacity introduce new errors;
the DI, and V, are highly sensitive to slight
technical errors; the separation of the total
diffusing capacity into Dt,, and V, based on
the kinetics of combination of carbon monoxide with intracellular hemoglobin is somewhat unreliable. These considerations suggest
that V, probably has no sharp anatomic
boundaries; that even in normals, this virtual
volume may vary with the experimental condition and method; that it is most meaningful
when compared under identical conditions in
the same subject; and that V, is most difficult
to measure reliably and to interpret meaningfully in those diseases which affect the
determination of the diffusing capacity of the
lungs.2'
A second step in partitioning the pulmonary
blood volume in vivo has recently been proposed by Feisal and associates.22 It involves
Circulation, Volume XXXIII, June 1966
837
the combination of indicator-dilution and
ether-plethysmographic techniques in dogs to
determine the pulmonary arterial blood volume. By this fresh approach the pulmonary
arterial blood volume is approximately 20 to
25% of the total pulmonary blood volume.
Although this value is somewhat lower than
expected on the basis of observations on the
isolated lung,13 and this discrepancy remains
to be resolved, this approach represents a
needed beginning in the partitioning of the
pulmonary blood volume in intact animals.
It is clear from the above, that the pulmonary blood volume has been, and continues
to be, a subject of lively interest from many
different points of view. For a long while the
intensity of this interest tended to obscure
the approximate nature of the methods used
for its measurement. Recently, more accurate
measurements of the total pulmonary blood
volume became available and the partitioning
of the pulmonary blood volume in vivo became an attainable objective. It seems likely
that the next few years will see fresh techniques and further clarifications of the physiological and pathophysiological roles of the
pulmonary blood volume.
ALFRED P. FISHMAN, M.D.
References
1. YOUNG, J.: Malpighi "De pulmonibus." Proc
Roy Soc Med 23: 1, 1929.
2. COMROE, J. H., JR.: Main functions of the
pulmonary circulation. Circulation 33: 146,
1966.
3. SHEPHERD, J. T.: Role of the veins in the
circulation. Circulation 33: 484, 1966.
4. KRUMHOLZ, R. A., BRASHEAR, R. E., DALY,
W. J., AND Ross, J. C.: Physiological alterations in the pulmonary capillary bed at rest
and during exercise: The effect of body position and trimethaphan camphorsulfonate. Circulation 33: 872, 1966.
5. MCCREDIE, R. M.: The pulmonary capillary bed
in various forms of pulmonary hypertension.
Circulation 33: 854, 1966.
6. SCHREINER, B. F., JR., MURPHY, G. W., AND
Yu, P. N.: The pulmonary blood volume in
congestive heart failure. Circulation. In press.
7. BONDURANT, S., HICKAM, J. B., AND ISLEY, J. K.:
Pulmonary and circulatory effects of acute
pulmonary vascular engorgement in normal
subjects. J Clin Invest 36: 59, 1957.
EDITORIAL
838
8. DE FREITAS, F. M., FARACO, E. Z., DE AZEVEDO,
D. F., ZADUCHLIVER, J., AND LEWIN, I.:
Behavior of normal pulmonary circulation
16.
during changes of total blood volume in man.
J Clin Invest 44: 366, 1965.
9. FEELEY, J. WV., LEE, T. D., AND MILNOR, W. R.:
Active and passive components of pulmonary
vascular response to vasoactive drugs in the
dog. Amer J Physiol 205: 1193, 1963.
10. MORKIN, E., COLLINS, J. A., GOLDMAN, H. S.,
AND FISHMAN, A. P.: Pattern of blood flow in
the pulmonary veins. J Appl Physiol 20: 1118,
1965.
11. DOCK, D. S., KRAUS, W. L., McGuIRE, L. B.,
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19.
HYLAND, J. W., HAYNES, F. W., AND DEXTER,
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L.: The pulmonary blood volume in man. J
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MILNOR, W. R., JOSE, A. D., AND MCGAFF, C. J.:
Pulmonary vascular volume, resistance and
compliance in man. Circulation 22: 130, 1960.
FISHMAN, A. P.: Dynamics of the pulmonary
circulation. In: Handbook of Physiology. Section 2: Circulation, vol. 2, edited by W. F.
Hamilton and P. Dow. Washington, D. C.,
American Physiological Society, 1963, p. 1667.
GIUNTINI, C., LEWIS, M. L., SALES Luis, A.,
AND HARVEY, R. M.: Study of the pulmonary
blood volume in man by quantitative radiography. J Clin Invest 42: 1589, 1963.
LEDSOME, J. R., AND LINDEN, R. J.: Reflex
increase in heart rate from distension of the
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pulmonary vein-atrial junctions. j Physiol
170: 456, 1964.
GAUER, 0. H., AND HENRY, J. P.: Circulatory
basis of fluid volume control. Physiol Rev
43: 423, 1963.
TURINO, G. M., AND FISHMAN, A. P.: The
congested lung. J Chronic Dis 9: 510, 1959.
EICHNA, L. W., FARBER, S. J., BERGER, A. R.,
RADER, B., SMITH, WV. WV., AND ALBERT, R E.:
Non-cardiac circulatory congestion simulating
congestive heart failure. Trans Ass Amer Physicians 67: 72, 1954.
ROUGHTON, F. J. W.: Average time spent by
blood in the human lung capillary and its
relation to the rates of CO uptake and
elimination in man. Amer J Physiol 143: 621,
1945.
FORSTER, R. E.: Diffusion of gases. In: Handbook of Physiology. Section 3: Respiration,
vol. 1, edited by W. 0. Fenn and H. Rahn.
WVashington, D. C., American Physiological
Society, 1964, p 839.
BATES, D. V., VARVIS, C. J., DONEVAN, R. E.,
AND CHRISTIE, R. V.: Variations in the pulmonary capillary blood volume and membrane
diffusion component in health and disease. J
Clin Invest 39: 1401, 1960.
FEISAL, K. A., SONI, J., AND DuBoIs, A. B.:
Pulmonary arterial circulation time, pulmonary arterial blood volume, and the ratio of gas
to tissue volume in the lungs of dogs. J Clin
Invest 41: 390, 1962.
.4.
Because Bacon and others advocated that the experimental method could best be
promoted by the corporate action of natural philosophers, frequent informal and sometimes secret meetings of men of science were held between 1600 and 1650 in various
centers of Europe. These assemblies (sometimes referred to as the "invisible college")
were soon to lead to the founding of many great scientific academies and societies. The
results of the experiments and discussions, and the other events of philosophical and
political importance in the early meetings, were frequently recorded. Copies of the
records were then sent as letters to friends engaged in similar activities in other centers. Communication in all countries at that time was facilitated by Latin, the international language of the learned. But the vernacular was also coming into use by natural
philosophers.-J. R. PORTER: The Scientific Journal-300th Anniversary. Bact Rev
28: 211, 1964.
Circulation, Volume XXXIII, June 1966
The Volume of Blood in the Lungs
ALFRED P. FISHMAN
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Circulation. 1966;33:835-838
doi: 10.1161/01.CIR.33.6.835
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
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