The influence of transpulmonary pressure on the diameter of small arterial blood vessels in the lung

MlCROVASCULAR

The

RESEARCH,

II,5766

(1976)

Influence of Transpulmonary of Small Arterial Blood

Pressure on the Diameter Vessels in the Lung

J. E. MALONEY, J. CANNATA, AND B. C. RITCHIE’ Baker Medical Research Institute,

Melbourne,

Australia

Received May 13, 1975

The diameters of pulmonary arterial blood vesselsof approximately 800-5000 flrn were measured in a double heart bypass preparation at known intravascular and transpulmonary pressures. Measurements were made from lateral radiographs of the lung on the deflation limb of the pressure volume curve at transpulmonary pressures of 30, 20, 10, and 0 cm H,O. Mean intravascular pressure decreased with decreasing transpulmonary pressure (TPP), while pulmonary vascular resistance showed no significant change. During deflation from a TPP of 30-O cm HLO, the smallest arteries (800 pm) increased their diameter by 40% and the larger arteries (1600-2000 pm) showed no change. No systematic changes in diameter occurred in vesselswith diameters ranging from 2000 to 5000 pm. In two lungs, changes in lengths were measured during deflation for vessels with diameters greater than 2000 pm. Vessel lengths decreased by an average of 38 and 23 % as TPP changed from 30 to 0 cm HZO. Thus it appears that lung deflation causes an increase in diameter of the smaller pulmonary blood vessels and no systematic change in diameter of the larger vessels. The length changes of the larger vessels, however, contribute to the decrease in pulmonary vascular volume with lung deflation.

While the mechanical properties of the airways during lung inflation have been investigated in some detail (Hughes et al., 1972), less is known of the changing dimensions of the blood vessels of the lung. With the exception of a recent series of experiments (Carroll et al., 1974; Benjamin et al., 1974), most considerations of the changing vascular geometry of the lung with lung inflation rest on the extrapolation from the studies on airways or the changes in pulmonary vascular resistance or blood volume with lung inflation (Macklin, 1946; Mead and Whittenberger, 1964; Permutt et al., 1961; Whittenberger et al., 1960). Because of the differences in structure between the airways and the intraparenchymal blood vessels of the lung, extrapolation from the behaviour of the airways may not be warranted. The present study was undertaken to analyze the influence of transpulmonary pressure on the dimensions of the small arterial blood vessels during lung deflation. The diameters of the vessels analyzed range from approximately 500 to 5000 pm. MATERIALS AND METHODS Preparation The basic details of the preparation and design have been previously described (Maloney et al., 1973). The nine sheep of bodyweight 13-24 kg used in this case were anaesthetized with 5 % thiopentone sodium (Tntraval) and 4 ml/kg of 1 % chloralose 1 Department of Medicine, The Alfred Hospital, Monash University, Melbourne, Australia, Copyright 0 1976 by Academic Press, Inc. All rights of reproduction in any form reserved. Printed in Great Britain

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solution. In each experiment, a tracheostomy was performed through which the sheep (in a supine position) were ventilated by a Harvard positive-pressure respirator. The animal was maintained with a tidal volume of 250-400 cm3 at a rate of 14 breaths/min and at a transpulmonary pressure (TPP) of 4.0-12.0 ) 1.0 (SEM) cm H,O measured with a water manometer. Flaxedil (gallamine triethiodide, 3 to 4 mg/kg) was administered periodically, and a carotid artery was cannulated for the measurement of systemic blood pressure. Following a midline thoracic incision and a sternal split, a double heart bypass preparation was set up as shown in Fig. 1. With the animal heparinized

FIG. I. A schematic diagram of the preparation. Blood drains from the superior and inferior vena cavae into a reservoir. It is then pumped through a heat exchanger and bubble trap into the pulmonary artery and to the lungs. Next the blood drains from the lungs via the left atrium into a reservoir, from where it is pumped through a heat exchanger and bubble trap into the aorta and the rest of the systemic circulation.

TABLE 1”

PO2(mm I-k) Before radiographic series During radiographic series After radiographic series

120.8 f 35.7 85.1 k 12.7 90.2 f 25.0

PCO~

(mm

Hg)

31.7 + 0.5 32.4 f 1.2 36.5 f 5.0

PH

N

n

7.33 f 0.06 7.26 f 0.05 7.30 * 0.04

4 7 5

4 16 5

a Columns 2 and 3 show the mean f standard error of the mean (SEM) of the partial pressures of oxygen and carbon dioxide in arterial blood samples taken before, during, and after the radiographic series. The mean f SEM of corresponding pH units are shown in column 4. N = number of sheep; n = total number of blood samples.

(10,000 IU), carotid artery, left atrial, and pulmonary artery pressures were recorded by transducers (Statham P23Db), and flow was recorded with an electromagnetic flow probe 8 mm ID (E.M.I. 28, or Medical Electronics, Carolina). The two blood pumps (Model 3501 Portable Pump, Sarns Inc., Ann Arbor, Michigan) were calibrated prior to each experiment using saline, and the flow probe was calibrated after each experiment using the mixture of blood and perfusion fluid used during the experiment. Pressure transducer calibrations were checked at intervals throughout the experiment. The dead space of the perfusion circuit was 800 k 100 ml and was primed with blood and per-

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VESSEL DIAMETER

fusion fluid or perfusion fluid alone, the perfusion fluid being made up of a 1: 1: 1 mixture of Rheomacrodex in 10 ‘A dextrose: 10% dextrose:normal saline. Blood was drained from the superior and inferior vena cavae into a reservoir, then pumped via a heat exchanger and bubble trap to the lungs via the pulmonary artery catheter. The lungs were drained via the left atrium into a second reservoir, where the blood was then pumped via a heat exchanger and bubble trap to the aorta and into the rest of the systemic circulation. The partial pressure of oxygen and carbon dioxide in the arterial blood and pH were recorded before, during, and at the end of the radiographic series (Table 1). Experimental

Protocol

An anterior-posterior radiograph was first taken to determine the position of the injection catheter. It was found to be in the right branch of the pulmonary artery only in two cases, being in the left pulmonary artery in the remaining seven experiments. Once stable haemodynamic conditions were established, lateral radiographs were taken at transpulmonary pressures (TPP) of 30,20, 10, and 0 cm H,O with the appropriate lung nearest to the radiographic film. Blood flow is constant for each series of radiographs and intravascular pressure alters as a result of changes in TPP and/or pulmonary artery pressure at each lung volume. During this procedure to obtain accurate transpulmonary pressures the respirator was switched off, and a 2-litre Perspex syringe used to ventilate and hold the lung at the required TPP. Prior to each radiograph TABLE 2 A BRIEF PROTOCOL OF A TYPICAL EXPERIMENT REPEATING ONE LATERAL RADIOGRAPH -

Hours

Comment

1010 Induction with Pentothal 1115 Double heart bypass established 1203 A-P radiograph 1226 Radiograph ; TPP = 20 cm Hz0 1233 Radiograph; TPP = 26 cm Hz0 Reject

Hours

Comment

1246 Radiograph TPP = 10 cm Hz0 1249 Radiograph TPP = 0 cm Hz0 I 313 Radiograph TPP = 30 cm Hz0 (Repeat of radiograph at 1233 hr)

the lungs were taken through a constant repeated volume history of deflation and inflation between a TPP of 0 and 30 cm H,O. On obtaining the required TPP on the deflation limb of the pressure volume curve an impulse injection of approximately 15 ml of contrast material (Conray 480-Meglumine and sodium Iothalamate) was given manually with the radiograph being taken almost simultaneously. Radiographs were then developed automatically (Kodak X-Omat Processor), and after examination the procedure was repeated where the exposure was unsatisfactory. A sample protocol showing the time for each injection and a comment on the quality of the radiograph is given in Table 2 for one complete experiment. Measuring

Techniques

The radiographs were placed in an overhead projector, whereby the image was projected onto a sheet of white paper and magnified five to seven times. The pulmonary

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arterial tree was then traced out, together with referencewires which had been placed between the animal and the X-ray film in the vertical plane which passesthrough the midposition of the lung and parallel to the film. Errors in the absolute dimension due to different “source to object” distances range from 3 to 4% for vesselsgreater than 1250pm in diameter and greater than 10% for vesselsless than 1250pm in diameter. These values were determined experimentally by taking a series of radiographs of the referencemarkers which were shifted between7 and 13 cm (approximately the thickness of the lung) from the radiographic film, while the “focal spot to film” distancewasheld at 150 cm. TABLE

3

TYPICAL VALUES OF MAGNIFICATIONAND THE MEANS OF REPEATED MEASUREMENTS OF DIAMETERS ON THE MAGNIFIED PROJECTION OF A SINGLE RADIOGRAPHY

Wire diameters (‘m) 513 904 1250 1800 2800 4000 4750 9570.5

x f SEM (pm) 3600.0 5866.7 7683.3 10766.7 17170.0 24180.0 28750.0 56475.0

f f f + + + k +

31.6 169.6 42.2 185.6 33.9 43.6 35.4 193.1

Magnification 1.249 1.155 1.094 1.064 1.091 1.076 1.077 1.050

n Column 1 lists the diameters of each reference wire, and column 2 shows the values obtained when the radiograph was magnified 5.62 times. The values are the mean and SEM of approximately five repeated measurements of the diameter of each magnified wire. Column 3 shows the magnification of each wire as it appears on the radiograph. This was obtained by dividing the image size of the wire (i.e., the size on the radiograph) by its true size (Column 1).

The eight reference wires ranging in diameter from 513 to 9570 pm enabled the images of the vessels to be calibrated. The image of each wire was measured approximately five times along its length on each radiograph. The reproducibility of these measurementsis shown in Table 3 where wire size, final image dimension, and magnification is shown. The image of each vesselwas measured, and its true size was determined by dividing it by the appropriate magnification of the radiograph. projected

RESULTS The relationship of mean pulmonary arterial intravascular pressure and pulmonary vascular resistanceto transpulmonary pressure is drawn in Fig. 2. As transpulmonary pressure and lung volume decrease,mean intravascular arterial pressuredecreasesand vascular resistance remains unchanged. Means and standard errors of the mean are shown in Fig. 2. Within any one experiment, pulmonary blood flow was constant to

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61

40-

30MEAN INTRAVASCULAR PRESSURE (cmH20)

20 -

10 -

o-

L

I

20

-----f-l

VASCULAR RESISTANCE (CmH20)

‘0

(mI.min.-‘)

-

0t

I

10 20 0 TRANSPULMONARY PRESSURE [cmH201

30

FIG. 2. The top panel shows mean pulmonary intravascular arterial pressure (cm HZO) plotted against transpulmonary pressure (cm H,O). In the bottom panel, vascular resistance (cm HzO/(mI min-I)) shows no significant change as transpulmonary pressure is decreased. Mean valuesand SEM are shown.

within 3.7 f 1.3 % of the flow at a transpulmonary pressure of 30 cm Hz0 which was on the average 79.4 + 9.0 (ml/min)/kg. Where the lungs were in Zone 1I conditions (alveolar pressure greater than left atria1 pressure) the mean pulmonary arterial pressure was taken as the average of the alveolar and pulmonary artery pressures. This was the case at a transpulmonary pressure of 30 cm H,O. At other transpulmonary pressures the lungs were in Zone 111 (alveolar pressure less than left atria1 pressure) on 16 of 22 150-

140 2 L30L E a 0 120 iii (I) E.? 110 >

100 -

0

10 20 TRANSPULMONARY PRESSURE kmH20)

30

FIG. 3. The grouped results for vessels below 800 to 2000 pm in diameter. Vessel diameter is plotted along the ordinate as a percentage of the initial diameter of the vessels at a transpulmonary pressure of 30 cm HzO. The vessels increase in diameter as the lung is deflated, the smaller vessels showing the greater increase. Mean values and SEM are shown. 0, vessels -C800 pm; o, vessels between 8OC1200 pm; W, vessels between 12OC16OO~m; 0, vessels between 160&2000 brn.

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MALONEY, CANNATA

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occasions, and the mean pulmonary arterial pressure was taken as the average of the pressure between the pulmonary artery and left atrium. Similarly, in the calculation of pulmonary vascular resistance the pressure difference was either pulmonary artery pressure minus either alveolar pressure (Zone 11) or left atria1 pressure (Zone 111). In Table 1 the average changes in the partial pressures of oxygen and carbon dioxide and pH are shown. The variation in vessel diameter with transpulmonary pressure is shown in Fig. 3 for vessels below 800 ,um in initial diameter and in groups of 400 birn from 800 to 2000 pm. In each group, the initial diameter was taken as that diameter at a transpulmonary pressure of 30 cm H,O. The average number of vessels measured in each group up to 2000 pm was 23 1. As transpulmonary pressure (and thus lung volume) decreases from 110 ....

...........

.

. . . . ... ....

...

?-. 100 8 LT :

. .

p’

.........

.... ..........

*-

. . . ...

+

90 t

z

90L

t 0

I 10 20 TRANSPULMONARY PRESSURE (cmH20)

I 30

FIG. 4. The grouped results for vessels with diameters greater than 2000 pm is plotted. The vessel diameters are plotted along the ordinate and transpulmonary pressure along the abscissa for vessels with diameters from 2000 to 3600 pm in the upper panel, and 3600 humto approximately 5000 pm in the lower panel. Mean values and SEM are shown. Upper panel. 0, vessels 200%24OOpm; 0, 2400-28OO~m; n , 28W3200pm; 0, 3200-3600pm. Lower panel: 0, 360@-4OOO~m;0, 40005000 pm; I, >5000 pm.

30 cm H,O to 0 cm HzO, vascular diameter increases, the largest increase of 40% occurring in the smallest group of vessels below 800 ,um. The percentage increase in diameters as transpulmonary pressure decreases is reduced as initial vessel diameter becomes larger so that in the range 1600 to 2000 pm there is no significant (P > 0.05) increase in diameter between transpulmonary pressures of 0 and 30 cm H,O. All other points on this diagram are significantly different from their value at a TPP of 30 cm H,O (P < 0.05), with the exception of the point at a TPP of 20 cm Hz0 (1200-1600 pm). The percentage change in diameter with decreasing transpulmonary pressure is noted in six further groups of vessels combined from all animals in increments of 400 pm from 2000 to 5000 pm in Fig. 4. The final group is of intrapulmonary arterial blood vessels over 5000 pm in diameter. The average number of vessels whose behaviour was analysed in these groups was 30. Within each of these groups there is no monotonic change in diameter with variations in transpulmonary pressure and the average changes

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in diameter are small, being less than 6% on 21 out of 22 occasions, as indicated in Fig. 4. The change in length of vesselsover 2000 pm in initial diameter was studied in two lungs, the length measurementsbeing indicated by the change in the distance between IlO100 z : g

go80 70-

y/

: 50 ot

’ 0

20 10 TRANSPULMONARY PRESSUREkmHp)

, 30

110 a E z ‘: 3

100 90 80 70 I< OL

0

20 10 TRANSPULMONARY PRESSURE (cmH20)

30

FIG. 5. The average length for vessels above 2000 Drn in diameter is plotted along the ordinate as a percentage of the length at 30 cm Hz0 transpulmonary pressure, the segments measured being between two consecutive branch points. Transpulmonary pressure is plotted along the abscissa. As the lung is deflated from 30 to 0 cm HZ0 transpulmonary pressure, 15 arterial segments in one lung decreased their length by 38 % (top panel), and 20 segments in a second lung by 23 % (bottom panel).

consecutive branch points. Figure 5 reveals that the distance between branch points consistently decreasesas transpulmonary pressure decreases,by between 20 and 40 % approximately of their initial length. All points on this diagram are significantly different from their value at a TPP of 30 cm H,O (P < 0.05) with the exception of that at a TPP of 20 cm Hz0 (lower panel). DISCUSSION The results presented above indicate that the pulmonary arterial circulation behaves in a fashion which is contrary to the behaviour of the airways (Hughes et al., 1972), running in the same perivascular sheath, with variations in transpulmonary pressure. Vesselsup to 2000 pm in initial diameter appear to systematically increasetheir diameter with decreasesin transpulmonary pressure and lung volume, whereas vesselsbetween 2000 and 5000 ,um show no systematic variation with transpulmonary pressure. Airways from 1.17 to 0.1 cm in diameter change their length and, in many cases, their diameter in direct relation to the cube root of absolute lung volume (Hughes et al., 1972), and their behaviour appears to be independent of initial size. As indicated above, the pulmonary arterial vesselsbelow 2000 ilrn changetheir diameter in an inverse 3

64

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relationship to lung volume, the magnitude of the change depending on their initial size. Above 2000 pm there is no systematic change in vessel diameter with lung volume and transpulmonary pressure. These experiments demonstrate that caution must be applied in extrapolating from the mechanics of the intrapulmonary airways to the mechanics of the intrapulmonary blood vessels. If radial forces are transmitted to the vascular compartment through the perivascular space in the same manner as the airways (Hughes et al., 1972; Mead et al., 1970; Mead and Whittenberger, 1964; Permutt et al., 1961), and the perivascular pressure is magnified then these effects must be overcome by other forces operating on the vascular wall. While studies of the influence of lung inflation on the volume of the pulmonary arterial segment indicate an increasing blood volume with increasing lung inflation (Macklin, 1946; Howell et al., 1961; Permutt et al., 1961), evidence for the relative contribution of length and diameter changes rests largely on the earliest study in isolated cat lungs perfused with radio-opaque latex. Macklin concluded, “It thus, as far as it goes, lends support to the view that in ordinary breathing the arteries lengthen and widen, or if they do not widen, they at least maintain their caliber”. The evidence in the results reported above implies that lengthening is more important than widening in increasing arterial vascular volume in the lung. A recent study (Carroll et al., 1974) added support to this idea for vessels above 2000 pm in diameter though changes in individual vessel groups were not studied. Decreases in diameter were small, approximately 5 %. From these earlier studies on lung volume the vascular compartment of the lung was subdivided into a compressed or alveolar compartment and an extra-alveolar compartment (Mead and Whittenberger, 1964) whose volume expands on lung inflation. The anatomical division is difficult but it is presumed to lie in the region of vessels of 30 pm in diameter (Fowler et al., 1966). Lung expansion is presumed to compress the alveolar compartment, increasing its resistance, and expand the extra-alveolar compartment, decreasing its resistance. These changes are postulated to balance out and provide the constancy of vascular resistance indicated in the study of Whittenberger et al. (I 960) and reported abovein the results. From theevidence on the change of vascular diameters, “compression” or a decrease in diameter with increasing lung volume extends well beyond vessels of 30 pm and up to vessels of 2000 pm in diameter, and well within the extra-alveolar compartment as defined above. If these alterations take place in the resistance vessels of the “extra alveolar” compartment, then their diameters will not increase with lung expansion but will decrease, and the simple mechanism for the variation in extra-alveolar compartment vascular resistance would be no longer tenable. The explanation may then lie in subtle changes in vascular rheology with lung expansion. Studies of the elastic characteristics of the intrapulmonary arterial blood vessels at a constant transpulmonary pressure have been undertaken in the rabbit (Caro, 1965), the dog (Maloney et al., 1970), and the frog (Maloney and Castle, 1969). Results of the extensibility of the blood vessels in the rabbit and dog were similar, varying from 1.53.5 % increase in diameter per cm HZ0 increase in intravascular pressure for the rabbit, and from 2.0-3.8 %/cm H,O for the dog. The percentage increase in diameter per cm H,O increase in intravascular pressure was from 1.0-2.0 % cm H20-l for the smaller vessels of the frog lung. On the assumption that vessels change their diameter at approximately 2% per cm H,O increase in transmural pressure the smallest vessels which increase their diameter by 40 ‘A during deflation (Fig. 3), should increase their transmural

LUNG

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pressure by 20 cm H20. Assuming that the mean intravascular pressure varies from 35 to 16 cm H,O during deflation, the constraint of the transmural pressure change requires perivascular pressureto becomemore negative by 39 cm H,O during deflation. There is no evidenceto suggestthis direction of movement in perivascular pressureand, indeed, the reverse is true (Permutt et al., 1961). An alternative proposition is that longitudinal extension of the arterial blood vesselsmarkedly increased their elastic modulus and that the opposite is true during deflation. The fact that lung expansion is able to compress the pulmonary vasculature was demonstrated in the liquid-filled foetal lung using radiography (Walker, 1973). In this study vesselsof diameter between 500 and 1500pm decreasedtheir diameter during lung inflation, and pulmonary vascular conductance was shown to fall over the same range. Vessels below 500 pm initially increased and then decreasedtheir diameters with lung inflation, which suggeststhat they did not play a major role in determining vascular conductance over this range of lung volumes. In all experiments in which contrast material is placed within the blood vesselsa problem arises becauseof its possible interaction with the vessel wall. In these experiments this effect has been minimized by randomizing the injections at various transpulmonary pressures and using minimal doses of contrast material compatible with reproducible radiographs. Furthermore, if it is assumedthat the major change which may be induced lies in the vascular smooth muscle, the greater effect would be expected in the muscular arteries of the pulmonary vasculature, i.e., those arteries below 1000pm diameter where circular smooth muscle fibres predominate (Harris and Heath, 1962). Hyperosmolar solutions appear to constrict the capacitance vesselsof the lung (Bar et al., 1971) and dilate the resistancevessels(Hauge and Bo, 1971).The changesnoted with lung volume would then be those superimposed on vesselswhose elastic characteristics have been influenced by the contrast material. This effect is thought to be minimal, as the time course of the influence of the changing osmolality is considerably longer than the milliseconds between injection and taking of the radiograph. In experiments on isolated lung lobes (Benjamin et al., 1974)it was demonstrated that vesselsaveraging 2000 and 5000 pm decreasedtheir diameters as TPP decreasedfrom 30 cm H,O. At a TPP of 0 cm H,O theseresults are consistent with two groups of vessels reported above, those greater than 5000 pm in sizeand those between2400and 2800 ,um (Student’s t test P < 0.05) (Fig. 4). The smaller subdivisions of diameter indicate a greater variability in response,and the conclusions are at variance with those reported in the above paper (Benjamin et al., 1974).The differencesin conclusion becomemore obvious in the smaller vessels,which are not available for observation with the air-filled technique of Benjamin et al. It is possible that the isolated, air-filled, tantalum-coated vasculature may behavedifferently from the intact perfused system,though in the latter preparation it may be argued that the interaction of the contrast material changesthe elastic characteristics of the blood vessels. As stated above, it is thought that this interaction is minimal. These studiesof the arterial segmentof the pulmonary blood vesselsdemonstrate that lung expansion causesa narrowing of the small pulmonary blood vesselswith no systematic influences on the diameters of the larger intrapulmonary vessels.During lung inflation the blood vessels lengthen considerably, possibly influencing their elastic characteristics to an extent which prevents the increase in diameter often postulated.

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ACKNOWLEDGMENTS The authors wish to gratefully acknowledge the skilled technical assistance given by J. Dixon, C. Schwarze, W. Else, R. Smith, V. Brodecky, P. Carman, and I. Matheson. This study was supported by a grant from the National Health and Medical Research Council of Australia. REFERENCES Bo, G., HAUGE,A., ANDNICOLAYSEN,G. (1971). Hyperosmolarity and pulmonary vascular capacitance. Acta Physiol. Stand. 82,375-381.

CARO, C. G. (1965). Extensibility of blood vessels in isolated rabbit lungs. .Z.Physiol. 178, 193-210, 1965. CARROLL,F. E., WEISBROD,G., AND GREENSPAN, R. H. (1974). Radiographic measurements of volume changes of tantalum-labeled pulmonary arterial segments: A new approach to in viuo evaluation of pulmonary arterial dynamics. Znuest.Rudiol. 9, 425433. FOWLER,K. T., PAIN, M. C. F., AND WEST,J. B. (1966). Site of vascular resistance in the isolated lung. J. Physiol. 185,44P. HARRIS,P., ANDHEATH, D. (1962). In “The Human Pulmonary Circulation”, p. 62, Livingston, Edinburgh. HALJGE,A., AND BP),G. (1971). Blood Hyperosmolarity and pulmonary vascular resistance in the cat. Circ. Res. 28, 371-376. HOWELL,.I. B. L., PERMUTT,S., PROCTOR,D. F., AND RILEY, R. L. (1961). Effect of inflation of the lung on different parts of pulmonary vascular bed. J. Appl. Physiol. 16, 71-76. HUGHES,J. M. B., HOPPIN,F. G., AND MEAD, .I. (1972). Effect of lung inflation on bronchial length and diameter in excised lungs. J. Appl. Physiol. 32,25-35. MACKLIN, C. C. (1946). Evidences of increase in the capacity of the pulmonary arteries and veins of dogs, cats and rabbits, during inflation of the freshly excised lung. Rev. Cunad. Biol. 5, 199-232. MALONEY,J. E., ADAMSON,T. M., RITCHIE,B. C., AND WALKER,A. (1973). Distribution of pulmonary blood flow during controlled perfusion of the intact lung. Amt. J. Exp. Biol. Med. Sci. 51, 655-666. MALONEY,J. E., AND CASTLE,B. L. (1969). Pressure diameter relations of capillaries and small blood vessels in the frog lung. Respir. Physiol. 7, 150-162. MALONEY, J. E., ROOHOLAMINI,S., AND WEXLER,L. (1970). Pressure-diameter relations of small blood vessels in isolated dog lung. Microvasc. Res. 2, l-12. MEAD, J., TAKISHIMA,T., AND LEITH, D. (1970). Stress distribution in lungs: A model of pulmonary elasticity. J. Appl. Physiol. 28, 596-608. MEAD, J., AND WHITTENBERGER, J. L. (1964). Lung inflation and haemodynamics. In “Handbook of Physiology: Respiration”, Vol. 1, Section 3, pp. 477486. American Physiological Society, Washington, D.C. PERMUTT,S., HOWELL,J. B. L., PROCTOR,D. F., AND RILEY, R. L. (1961). Effect of lung inflation on static pressure volume characteristics of pulmonary vessels. J. Appl. Physiol. 16, 64-70. WALKER, A. (1973). Control of the pulmonary circulation in the foetal and newborn lamb. Ph.D. Thesis, Monash University, Melbourne, Australia. WHITTENBERGER, J. L., MCGREGOR,M., BERGLUND,E., ANDBORST,H. G. (1960). Influence of the state of inflation of the lung on pulmonary vascular resistance. J. Appl. Physiol. 15, 878-882.