Longitudinal distribution of vascular resistancein the pulmonary arteries, capillaries, and veins

Jerome S. Brody, … , Edward J. Stemmler, Arthur B. DuBois

J Clin Invest. 1968;47(4):783-799. https://doi.org/10.1172/JCI105773.

A new method has been described for measuring the pressure and resistance to blood flowin the pulmonary arteries, capillaries, and veins. Studies were performed in dog isolatedlung lobes perfused at constant flow with blood from a donor dog. Pulmonary artery andvein volume and total lobar blood volume were measured by the ether plethysmograph anddyedilution techniques. The longitudinal distribution of vascular resistance was determinedby analyzing the decrease in perfusion pressure caused by a bolus of low viscosity liquidintroduced into the vascular inflow of the lobe.

The pulmonary arteries were responsible for 46% of total lobar vascular resistance,whereas the pulmonary capillaries and veins accounted for 34 and 20% of total lobarvascular resistance respectively. Vascular resistance was 322 dynes ·sec·cm-5/ml of vesselin the lobar pulmonary arteries, 112 dynes·sec·cm-5/ml in the pulmonary capillaries, and 115dynes·sec·cm-5/ml in the lobar pulmonary veins. Peak vascular resistivity (resistance permilliliter of volume) was in an area 2 ml proximal to the capillary bed, but resistivity was highthroughout the pulmonary arterial tree. The pulmonary arteries accounted for approximately50% of vascular resistance upstream from the sluice point when alveolar pressureexceeded venous pressure.

The method described provides the first measurements of pulmonary capillary pressure.Mid-capillary pressure averaged 13.3 cm H2O, pulmonary artery pressure averaged 20.4 cmH2O, and […]

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Longitudinal Distribution of Vascular Resistance

in the Pulmonary Arteries, Capillaries, and Veins

JEROMES. BRODY, EDWARDJ. STEMMLER,and ARTHu B. DuBois

From the Department of Physiology, Division of Graduate Medicine, Universityof Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

A B S T R A C T A new method has been describedfor measuring the pressure and resistance to bloodflow in the pulmonary arteries, capillaries, andveins. Studies were performed in dog isolatedlung lobes perfused at constant flow with bloodfrom a donor dog. Pulmonary artery and veinvolume and total lobar blood volume were mea-sured by the ether plethysmograph and dye-dilution techniques. The longitudinal distributionof vascular resistance was determined by analyzingthe decrease in perfusion pressure caused by abolus of low viscosity liquid introduced into thevascular inflow of the lobe.

The pulmonary arteries were responsible for46% of total lobar vascular resistance, whereasthe pulmonary capillaries and veins accounted for34 and 20% of total lobar vascular resistancerespectively. Vascular resistance was 322 dynes

* sec* cm-5/ml of vessel in the lobar pulmonaryarteries, 112 dynes sec.cm-5/ml in the pulmonarycapillaries, and 115 dynes- sec* cm5/ml in thelobar pulmonary veins. Peak vascular resistivity(resistance per milliliter of volume) was in an area2 ml proximal to the capillary bed, but resistivitywas high throughout the pulmonary arterial tree.The pulmonary arteries accounted for approxi-mately 50% of vascular resistance upstream fromthe sluice point when alveolar pressure exceededvenous pressure.

The method described provides the first mea-surements of pulmonary capillary pressure. Mid-capillary pressure averaged 13.3 cm H2O, pul-

Dr. Brody is a postdoctoral fellow of the National In-stitutes of Health.

Received for publication 11 September 1967 and in re-vised form 4 December 1967.

monary artery pressure averaged 20.4 cm H2O,and pulmonary vein pressure averaged 9.2 cmH2O. These techniques also provide a way of ana-lyzing arterial, capillary, and venous responses tovarious pharmacologic and physiologic stimuli.

INTRODUCTION

The arterioles are the major resistance vessels inthe systemic vascular bed (1, 2), but it is uncer-tain whether the greatest resistance to blood flowin the lungs is in the arteries, capillaries, or veins(1, 3, 4).

Piiper (5), in 1958, reasoned from Poiseuille'slaw that, during constant perfusion, injection intothe bloodstream of a bolus of fluid with viscositydifferent from that of blood would cause a per-fusion pressure change proportional to the re-sistance of the vessels through which the boluspassed. Piiper considered that the major part ofvascular resistance was located at one point in thelung, and that the mean appearance time of theviscosity-induced pressure change, multiplied byflow, gave the volume to the "site of main resist-ance" to blood flow. Piiper, however, did not re-late the "site of main resistance" to an anatomicsite because he was unable to further subdividepulmonary vascular volume; furthermore he didnot describe the longitudinal distribution of pul-monary vascular resistance.

In the present study the volume to the midpointof vascular resistance in isolated lung lobes of dogshas been measured by modification of the viscosity-change technique described by Piiper. We relatedthe resistance midpoint, 50%o of vascular resistanceupstream and 50%o of vascular resistance down-

The Journal of Clinical Investigation Volume 47 1968 783

stream from this point, to pulmonary arteryvolume and total blood volume of the lobe duringforward perfusion, and to pulmonary vein volumeand total blood volume of the lobe during reverseperfusion. The resistance and pressure at intervalsalong the pulmonary vessels have been calculatedby an analysis of the time course of pulmonaryartery pressure change recorded as a bolus of lowviscosity, 2 ml of saline solution, passed throughthe vascular bed. This technique provides a wayof measuring resistance and pressure throughoutthe pulmonary vascular bed without requiringdirect pressure measurements from multiple pointswithin'the lung vessels.

METHODSThe left basal lobe was exposed through a left lateralthoracic incision in seven 10-14-kg mongrel dogs anes-thetized with sodium pentobarbital, 25 mg/kg. The pul-monary arterial and venous vessels and the bronchi tothe left upper and middle lobes were isolated, tied, andsevered. The left basal lobe artery, vein, and bronchuswere isolated and cannulated with polyethylene tubeswhile we made sure that no air was introduced into thevascular system. The lobe was placed in an airtight box(17.5 cm X 17.5 cm X 10.0 cm) constructed of 0.25 inch

AIR -4~~~OOR P

DENSITOtlETER

IIR

Plexiglas and was perfused by a constant flow pump withblood drawn from catheters placed in the inferior venacava and femoral artery of a heparinized donor dog (Fig.1). Total ischemic time of the lobe was less than 30 min.The donor dogs, weighing 15-25 kg, were anesthetizedwith sodium pentobarbital, 25 mg/kg, and were allowedto breath spontaneously through a tracheal cannula. Theblood from the donor dog was heated to 370C, passedthrough the lobe, collected in a cylindrical venous reser-voir, and drained by gravity back into the jugular veinsof the same donor dog. The average oxygen pressure(Po2) of blood perfusing the lobe was 70 mmHg. Aver-age carbon dioxide pressure (Pco2) was 38 mmHg, pH7.30.

Differential transducers with one side connected tothe plethysmograph were used to measure pulmonaryartery, pulmonary vein, and bronchial pressures. Lateralpressures in the pulmonary artery and vein were obtainedfrom side-hole catheters placed just inside the arteryand vein and were referred to the height of the centerof the lobe. Plethysmograph pressure was monitored bya differential transducer with one side open to the at-mosphere. The plethysmograph was calibrated with thelobe in place and the bronchus clamped so that a 1 mlvolume change would produce a 25 mmdeflection on therecorder. The lobe was ventilated with room air by apositive pressure pump at a rate of 20 breaths/min with aconstant tidal volume that produced transpulmonary pres-sure of 8-10 cm H20 at peak inspiration. End expira-tory pressure was kept constant at 3-5 cm H20.

C EDANP

4- DYE

45MIXINGCONDENSER \ CHAMBER\ n. -e r

+- 4~~~~VENTILATE

PRESSURE

FIGURE 1 Diagram of experimental setup. Ppv and Ppa are lobar pulmonary vein and arterypressures, respectively. Pt is lobar bronchial pressure. The pulmonary veins may be connecteddirectly to the pump dispensing with the venous reservoir and donor dog if desired. See Meth-ods for explanation.

784 J. S. Brody, E. J. Stemmler, and A. B. DuBois

The left basal lobe accounts for 25%o of total lungvolume in the dog and presumably 25%o of pulmonaryblood flow (6, 7). Average blood flow through the iso-lated lobes in seven experiments was 13.6 ml/min per kg,somewhat less than 20% of normal cardiac output (8).However, flow at this level has been shown to completelyperfuse isolated lung lobes without the appearance ofedema (9). Blood flow was measured by occluding theoutflow from the venous reservoir and recording the rateof rise of hydrostatic pressure at the bottom of the reser-voir. Flow could be measured this way to within + 2%oof flow determined by direct collections in a graduatedcylinder. Venous pressure was held constant by makingthe venous reservoir airtight and submitting it to a con-stant air pressure of about 9 cm H20. This techniqueensured that venous pressure exceeded the alveolar pres-sures of 3-5 cm H20, and therefore "nonsluice" condi-tions existed throughout the lobe (10). In four lobesmeasurements were also made during forward perfu-sion with the venous reservoir open to the atmosphereand with end expiratory pressure constant at 3-S5 cmH20, these being "sluice" conditions (10).

Lobar pulmonary artery and vein pressures, plethysmo-graph pressure, bronchial pressure, and dye concentrationswere recorded on a Grass direct writing instrument.Total lobar blood volume, lobar pulmonary artery volume,and the volume to the midpoint of vascular resistancewere each determined in duplicate during short periodsof apnea at an end expiratory pressure of 3-5 cm H20 andafter a prior inflation of the lobe to about 20 cm H20.

Total lobar blood volume. Total lobar blood volume(VL) was determined by the Stewart-Hamilton indicatordilution method (11) with indocyanine green as the indi-cator dye. With respiration stopped the dye was flushedinto the arterial inflow (Fig. 1) and passed through amixing chamber before moving into the lung lobe. Theconcentration of the dye was measured by a Waters XP250A Densitometer in blood drawn from a catheter placedin the pulmonary vein. The mean appearance time of thedye curve multiplied by flow was the volume of the pul-monary vessels plus the dead space of the tubing. Thetubing dead space volume was determined after each ex-periment, with the lung removed from the apparatus, bythe same dye injection technique. The dead space volumewas subtracted from the total volume measured duringthe experiment to give VL. The absolute accuracy andreproducibility of this method were tested with duplicatedeterminations in tubes of known volume. Tube volumeswere measured with no systematic error and with a stand-ard deviation of 0.7 ml. The standard deviation betweenduplicate determinations in the lung lobes was 0.8 ml,and the coefficient of variation of duplicates around themean was 3.5%.

Lobar pulmonary artery volume. Lobar pulmonaryartery volume (Vpa) was measured by the technique ofFeisal, Soni, anrd DuBois (12). Ether injected into thepulmonary artery moves from the dissolved state in bloodto the gaseous state on contact with alveolar air. Aplethysmograph is used to record the rise in alveolarpressure as ether enters the gas phase. Sackner, Feisal,

and Karsch (13) calculated that greater than 90%o of theinjected ether equilibrates in the first hundredth lengthof the capillaries. Therefore the ether method measuresthe vascular volume proximal to the pulmonary capil-laries.

0.20 ml of a 1: 4 ether-Lipomul solution (12) was placedin one side channel of the perfusion apparatus while allblood was flowing through the opposite symmetricallyconstructed side channel (Fig. 1). After the plethysmo-graph had been sealed and respiration of the lobe stopped,a 3-way stopcock was turned diverting all flow throughthe side channel containing the ether-Lipomul solution,moving the solution into the pulmonary artery. The meanappearance time of the plethysmograph pressure vs. timecurve multiplied by flow gave the volume from the siteof ether injection to the beginning of the pulmonary capil-lary bed. The volume of the apparatus dead space betweenthe site of ether injection and the pulmonary artery wasmeasured and subtracted from the volume measured withether to give Vpa. Because of the small volume of theether-Lipomul solution (0.2 ml) dispersion of the solu-tion in transit to the end of the pulmonary artery can-nula was ignored. A similar method, but with reverseperfusion, was used to measure the volume of the pulmo-nary veins. The standard deviation of duplicate determi-nations of Vpa was 0.2 ml. The coefficient of variation ofduplicates around the mean was 3.8%o.

Volume to the midpoint of lobar vascular resistance.The volume to the midpoint of lobar vascular resistance(Vmp) was measured by a modification of the viscositychange method described by Piiper. The method is basedon Poiseuille's law:

A\P = Q X- X h/r4 X 71.ir

(1)

This law staates that the pressure drop (AP) across acircular tube during steady laminar flow is equal to theflow in that system (Q) multiplied by: a numerical term(8/ir) which results from the mathematical analysis offlow in a cylindrical tube; a geometric factor (I/r'), Ibeing the length of the tube and r4 being the radius raisedto the fourth power; and the viscosity (,I) of the fluidperfusing the tube. If all other factors remain constant a

change in the viscosity of the perfusate will cause a

change of the pressure in the system proportional to theh/r factor. Laminar flow was present in both lung lobesand model tubes since the Reynold's numbers for thelargest pulmonary vessel (diameter equal to the pulmo-nary artery cannula, 0.4 cm) and for all the model tubeswere well below the critical number for the occurrence ofturbulent flow (14).

2 ml of 0.9% NaCl (saline), warmed to 37°C, wasplaced in the perfusion apparatus side channel throughwhich blood was not flowing (Fig. 1). Respiration was

stopped, and the 3-way stopcock was turned so that allblood flowed through the channel containing the salinesolution, moving the saline into the pulmonary artery.Since flow and venous pressure were constant, the de-crease in pulmonary artery pressure was proportional to

Longitudinal Distribution of Vascular Resistance in the Lung 785

the change in viscosity caused by the saline bolus and tothe resistance of the vessels through which the saline waspassing. The median appearance time of the curve ofpressure decrease vs. time, multiplied by flow, gave thevolume from the injection site to the resistance midpointof the lung. The saline bolus did not appear to alter theresistance of the pulmonary vessels since perfusion pres-sure returned to the base line after the saline had passedthrough the lung. In order to determine the effective sa-line dead space, a saline injection was made without thelobe in place and with a short artificial resistance betweenthe pulmonary artery and pulmonary venous cannulae.The median appearance time of the curve of pressurechange vs. time multiplied by flow gave the effective sa-line dead space which, subtracted from the volume mea-sured with the lung in place, gave the volume to the mid-point of lobar vascular resistance.

Longitudinal distribution of vascular resistance. In or-der to study the resistance to blood flow at points alongthe lung vessels rather than just the volume to the mid-point of vascular resistance, the saline-induced pressurecurves were analyzed by another method. The abscissaof the pressure curve was marked off in 2-ml increments(flow X time = volume) beginning with the start of thepressure decrease caused by the saline. These points wereequated with volumes at 2-ml intervals along the vascu-lar tree. The pressure decrease at each point was used tocalculate vascular resistances for each 2 ml segment.

The pressure change recorded with saline injection isdetermined by the shape of the saline bolus, i.e. the dis-tribution of viscosity change within the bolus, as well asthe distribution of resistances in the system. In order todefine the shape of the saline bolus, a short length of tub-ing with small radius and small volume was substitutedfor the lung lobe at the end of the pulmonary artery can-nula. A bolus of saline was injected during constant bloodflow as described above, and the decrease in perfusionpressure was recorded. Because there was virtually nolongitudinal distribution of resistance in the small tube,the change in pressure vs. time as the saline bolus passedthrough the tube was directly proportional to the changein viscosity at each point in volume of the bolus. The

P(CM H20)

V(ML) ? 4 6 80 2

T(SEc) E

FIGURE 2 Shape of saline bolus. The curve shows thechange in perfusion pressure (P) produced as the salinebolus passed through a small volume, high resistancetube which replaced the lung lobe in Fig. 1. The abcissaof the curve is marked at 2-ml volume intervals (flow Xtime = volume). The viscosity change produced by anyportion of the bolus can be calculated from equation 2.

resulting pressure curve (Fig. 2) was a profile of vis-cosity change vs. volume in the bolus. The pressure curvereflecting the distribution of bolus viscosity change spreadthrough slightly more than 6 ml in volume even thoughonly 2 ml of saline were placed in the side channel. Thelengthening of the bolus was probably due to the parabolicfront created as blood moved through the channel con-taining the bolus. Since flow and the length and radius ofthe resistance tube at the end of the dead space wereknown, the change in viscosity in each portion of thesaline bolus could be calculated:

A-q saline = AP saline X X 11X0 . (2)

In order to simplify the calculations of vascular resistancethat follow, the saline bolus was divided into three 2-mlsegments. The average decrease in viscosity in the first2 ml segment was 0.020 poise, that in the second 2 mlsegment was 0.010 poise, and that in the third 2 ml seg-ment was 0.005 poise. The viscosity of the blood was cal-culated by substituting the pressure drop across the smalltube during blood flow for AP saline in equation 2. Bloodviscosity averaged 0.040 poise. The viscosity of water, at370C, would be 0.0069 poise. These values for blood vis-cosity and bolus-induced viscosity change were used inall subsequent calculations.

Poiseuille's law is given in equation 1. If the initial vis-cosity (,i) of the fluid in a segment of the system isbrought to a new level (-q.) by a portion of the salinebolus, there is a change in pressure (Pi) to a new level(P.). Equation 1 for a segment of the system can be re-written with P, - P. = AP1 saline, and 7i - 71 = A71 saline.AP1 saline is the pressure drop in the segment caused bythe viscosity change, A1 saline, in the first 2 ml portion ofthe bolus.

AP1 saline = X X IX Ago saline- (3)

There is no need for absolute pressure or viscosity mea-surements in segments of the vascular bed since the equa-tions are now in terms of pressure change and viscositychange. By rearranging equation 3 one can solve for thegeometric factor characteristic for a segment in thesystem:

r4 API saline X 8 X XAx-. (4)

The pressure decrease recorded as a bolus of low vis-cosity moves through the lung vessels reflects the resist-ance of a cross-section of all the vessels in the circula-tion at a point in volume. The Irl factor calculated inequation 4 involves not only vessel length and radius butalso the number of vascular segments. Since resistancesin parallel add by reciprocals, I/r4= (vessel length/vessel radius') divided by the number of vascular seg-ments.

Assuming that the geometric factor does not change asthe bolus passes through the segment, the resistance (R)of the 2 ml segment with blood flowing through it (vis-

786 J. S. Brody, E. J. Stemmler, and A. B. DuBois

cosity = Ilblood) can be calculated:

R = 8,/7r X r4 X Ablood(5)

The actual pressure drop across that segment can be de-termined by multiplying R by Q/980.

This analysis is valid for the first 2 ml segment con-taining the first 2 ml of bolus which causes a viscositychange of 0.020 poise. But as the bolus moves on to thenext 2 ml segment, the 0.020 poise viscosity change willmove to this segment and the 0.010 poise viscosity de-crease of the second portion of the bolus will be in thefirst 2 ml segment, both segments contributing to thepressure drop measured at the 4 ml point. A correctionfor the amount of pressure change (AP2sal Ine) caused bythat part of the bolus in the first segment must be madeto determine the actual pressure drop and resistance inthe second 2 ml portion of the system. This correction

can be calculated since the geometric factor for the first2 ml segment has been calculated, and the change in vis-cosity (A72 saline) caused by the second portion of thebolus in that segment is known:

AP2 atline = Q X X r X AX72s aline.7 r

(6)

AP2 salne can be subtracted from the total pressure dropat the 4 ml point to give the pressure drop (API saline)caused by that part of the bolus in the second 2 ml seg-ment. The geometric factor and resistance of the secondsegment can then be calculated as in equations 4 and 5.A similar correction with a 0.010 decrease in viscosity inthe second 2 ml segment and a 0.005 decrease in the first2 ml segment of the system can be made when the bolushas moved on to the 6 ml mark, and so forth on downthe lung lobe.

Fahraeus and Lindquist found that the relative viscosity

VMP

ABC 5.7(5.4)

I, CmHMBAC 7.7(8.2)

CAB 10.2 (9.7)

A . ,T-IME (SEC)

FIGURE 3 Saline pressure curves from model

tubes in series. Resistance of tube A was 3880

dynes - sec -cm-, tube B was 1960 dynes * sect cm-5,

and tube Cwas 1090 dynessec-cmn. ABC, BAC,etc. represent the order in which the tubes were

placed. The arrows mark the measured volume

to the midpoint of vascular resistance in ml

(Vmp). The actual Vmp is in parenthesis.

Longitudinal Distribution of Vascular Resistance in the Lung

CBA 12.8 (12.6)

787

of blood decreased in tubes of radius less than 200 , (15).Relative viscosity in tubes with a radius of 25 /A is ap-proximately one-third less than in tubes with radiuslarger than 200 ,u, but it is not clear what the relativeviscosity is in vessels as small as the capillaries (16).The decrease in viscosity with the decreasing tube size ispresent at all hematocrits (16), and therefore A1saeinequations 3 and 4 and blbood in equation 5 will decreaseby the same proportion. Since A1mi,,. appears in the de-nominator of the equations and qblood appears in the nu-merator, the ratio between the two will remain unchangedin small vessels, and the Fahraeus-Lindquist effect willhave little influence on our calculations of resistance.

Total pulmonary vascular resistance was determinedby two methods. Resistance determined by summing vas-cular resistances calculated at 2-ml intervals throughoutthe lung from passage of a bolus whose viscosity wasmeasured in vitro will be referred to as "calculated re-sistance." "Measured resistance" was determined by sub-tracting pulmonary vein pressure from pulmonary arterypressure during nonsluice conditions, or subtracting al-veolar pressure from arterial pressure during sluice con-ditions, multiplying by 980 to convert to dynes per squarecentimeter and dividing by flow in milliliters per second.Since "calculated resistance" was determined by assumingthat blood viscosity was the same in lung vessels of allsizes, the close agreement between "calculated resistance"and "measured resistance" suggests that if there was alower viscosity in small vessels it was relatively unim-portant in our calculations of vascular resistance.

RESULTS

Model system. The accuracy of the viscosity-change method for measuring the volume to theresistance midpoint (Vmp) and the longitudinaldistribution of vascular resistance was tested inmodel tubes of known resistance. The tubes weresubstituted for the lung lobe in Fig. 1 and wereperfused with blood from a reservoir instead of adonor dog.

Three tubes of equal volume but different geo-metric characteristics can be used to illustrate thesignificance of the resistance midpoint measure-ment. Each tube had a volume of 6 ml, but at theflow and hematocrit during the experiment theresistance of tube A was 3880 dynes sec* cm-5,tube B was 1960 dynes-sec cm5, and tube C was1090 dynes -sec -cm-5. Since the tube volumes wereequal, the Vmp for each tube should be and wasmeasured to be the same. The magnitude of thepressure decrease caused by the saline bolus wasgreatest in the tube with the greatest resistance toblood flow. Fig. 3 shows the pressure tracings aftersaline injection when the tubes were arranged inseries in several combinations. The contours of

the pressure curves differed depending on theorder of placement of the tubes. The position ofthe high resistance tube most affects the shape andthe median appearance time of the pressure curves.

The accuracy of the method for measuring vol-ume to the resistance midpoint is demonstrated inFig. 4, a plot of measured vs. actual Vmp in a

variety of single tubes and combinations of tubes.There was no significant difference between actualand measured Vmp. The standard deviation of du-plicate determinations of Vmp in the lung lobeswas 0.2 ml. The coefficient of variation of dupli-cates around the mean was 2.6%.

The pressure curves after saline injection inseveral arrangements of tubes A, B, and C were

also analyzed to determine the longitudinal distri-bution of resistance. The resistance per millilitercalculated at 2-ml intervals is compared to actualresistance per milliliter in Fig. 5. There is a goodfit of calculated and actual resistances in all butFig. 5 CBAwhere the high resistance was down-stream. In this situation the downstream resistanceis grossly underestimated, whereas the generaltendency is to slightly overestimate downstreamresistance when it is small.

Table I lists total "calculated resistance," i.e.the sum of the resistances calculated at 2-mlintervals, and the calculated per cent of totalresistance in each tube, and compares these to

actual values. The results are relatively accurate

15

W ./0'2

2>

to

VMP ACTUAL(ML)

FIGURE 4 Actual Vmp vs. measured Vmp. Vmp= vol-ume to the midpoint of vascular resistance.

788 J. S. Brody, E. J. Stemmler, and A. B. DuBois

A B C

C A a}

I

/I

C B A

0 5 10 15 20 0 5 10 15 20

FIGURE 5 Longitudinal distribution ofresistance in model tubes in series.Actual (solid line) vs. calculated (in-terrupted line) resistivity (resistanceper milliliter) calculated at 2-ml vol-ume intervals in model tubes A, B, andC arranged in series.

VOLUME(ML)

except in sequence CBA where the large down-stream resistance is underestimated. In this case,

tube A was calculated to account for 37% insteadof the actual 56%o of total resistance. Although thiserror affected the calculation of the longitudinaldistribution of resistance in CBA, it did notappreciably alter the measurement of the midpointof vascular resistance, as can be seen in Fig 3CBA.

Isolated lung lobes. Table II contains a sum-

mary of the results of our studies in five isolatedlung lobes during forward perfusion and two lunglobes during reverse perfusion in nonsluice condi-tions, i.e., with downstream pressure (9 cm H20)greater than alveolar pressure (4 cm H20).Average total lobar blood volume (VL) during

forward perfusion was 26.6 ml. Lobar pulmonaryartery volume (Vpa) averaged 6.2 ml or 23%of VL. During reverse perfusion VL averaged 23.3ml, and pulmonary vein volume (Vpv) was 6.4 mlor 28% of VL.

Although forward and reverse perfusion in thelobes were not precisely comparable from thestandpoint of pressures applied to artery and vein,and although the studies were done in differentlungs, the results of the two experiments can becombined to give a gross estimate of lobar capil-lary blood volume (Vpc). Since Vpa during for-ward perfusion + Vpv during reverse perfusionaccount for 51% of VL, Vpc must be 49%of VLor 12.5 ml. The left basal lobe makes up 25%oof total lung volume in dogs and presumably the

TABLE I

Longitudinal Distribution of Resistance in Model Tubes

Resistance

Resistance Tube A Tube B Tube C

Tube Calcu- Calcu- Calcu- Calcu-sequence lated Actual lated Actual lated Actual lated Actual

dynes-sec -cm-6 %total %total % total

ABC 7050 6930 52 56 32 28 16 16BAC 7390 6930 47 56 30 28 23 16CAB 6935 6930 49 56 30 28 21 16CBA 6155 6930 37 56 50 28 13 16

Longitudinal Distribution of Vascular Resistance in the Lung

750

500p

Waz

0."a

w

z

n

n)w

250

750

500

250

I

I

B A C

789

AL

I

Ak

TABLE I IMeasurements in Lung Lobes under Nonsluice Conditions

Per- Down-fusion streampres- pres- Resistance Resistance Arterial Capillary Venous

Dog Weight Flow sure sure measured VL Vpa Vpc Vpv Vmp calculated resistance resistance resistance

kg ml/min cm H20 cm H20 dynes- ml ml ml ml ml dynes. %total resistancesec see

*cm-$ *cm-SForward perfusion

A 11.4 143 22.0 9.5 5140 24.4 7.3 9.0 6405 38B 11.4 96 18.5 8.5 6140 20.6 5.4 6.1 6535 48C 12.3 176 19.0 9.0 3340 25.3 4.9 5.7 2400 40D 11.4 176 19.0 9.0 3340 28.5 6.5 6.9 1970 51E 13.6 214 25.0 9.5 4260 34.0 6.8 6.5 4745 54

Mean 12.1 161 20.7 9.1 4446 26.6 6.2 12.8* 7.4* 6.8 4375 46 45* 9*

Reverse perfusionG 11.4 182 19.0 9.0 3220 23.4 6.7 13.6 3745 20H 12.3 160 20.0 10.5 3500 23.2 6.1 15.0 3700 20

Mean 11.9 171 19.5 9.8 3360 23.3 5.4$ 11.5: 6.4 14.3 3725 23t 57$ 20

Mean combined forward and reverse perfusion12.0 164 20.4 9.2 4136 25.6 5.9 12.5 7.2 4214 46§ 3411 20¶

VL, total lobar blood volume; Vpa, volume of the pulmonary artery; Vpc, capillary blood volume; Vpv, volume of the pulmonary vein; Vmp.volume to the midpoint of vascular resistance.* Based on assumption that Vpv is 28% of VL during forward perfusion.$ Based on assumption that Vpa is 23% of VL during reverse perfusion.§ From forward perfusion.11 Remainder.¶ From reverse perfusion.

same per cent of total pulmonary blood volume(6, 7). Therefore, total capillary blood volumewould be (12.5 ml x 100%o)/25%, or 50 ml inour dogs. Since pulmonary blood volume in dogsis 11 ml/kg x 100 (17) our estimated capillaryblood volume would be (50 ml . 132 ml) x 100 or

V(ML)P I'O -( cm "20) qr -14

21t t20 4,I4419V W

38% of total pulmonary blood volume in the dogsused. The difference between lobar capillary bloodvolume, which was 49%o of lobar blood volume,and total capillary blood volume, which was 38%oof total pulmonary blood volume, can be explainedby the presence of the lobar cannulae which ex-

0 10I I I

20 30

FORWARD

LVPA vPc+V:v

T(sec) I I I I I I I I a I

REVERSE

I VPV | VPC+VPA l

frFIGURE 6 Saline curves in lung lobes. Curves on left show saline-induced pressure curve in one forwardperfusion (dog C) and one reverse perfusion (dog G) experiment. Vmp is marked with an arrow. Diagramon right represents the average vascular volumes and Vmp in five forward and two reverse perfusion ex-periments. Vpa, volume of the pulmonary artery; Vpc, capillary blood volume; Vpv, volume of the pulmonaryvein.

790 1. S. Brody, E. J. Stemmler, and A. B. DuBois

o-o FORWARDPERFUSION

..-.REVERSE PERFUSION

KipvS VPFIGuRE 7 Resistivity in lung lobes. Av-erage resistivity (resistance per milliliter)is calculated at 2-ml intervals in five for-ward perfusion and two reverse perfusionexperiments. Vpa marks the average vol-ume of the pulmonary artery during for-ward perfusion (reading from left toright). Vpv marks the average volume ofthe pulmonary vein during reverse perfu-sion (reading from right to left).

cluded portions of the large conducting arteriesand veins in our experiments.

The average volume to the resistance midpoint(Vmp) during forward perfusion was 6.8 ml or24%o of VL. Since Vpa averaged 23%o of VL itwould appear that the pulmonary artery was re-sponsible for a large portion of total lobar vascularresistance. During reverse perfusion at comparableflow rates Vmpwas 14.3 ml or 62%o of VL. Exam-ples of forward and reverse perfusion saline in-jection curves with Vmp marked for each areshown in Fig. 6.

Calculation of vascular resistance at 2-ml inter-vals in the lungs allows a more precise estimate ofthe vascular resistance of the pulmonary arteryand vein. During forward perfusion, lobar pul-monary artery resistance calculated from seg-mental resistances averaged 46%o of total vascularresistance with a range of 38-54%o. If one assumesthat Vpv was 28%o of VL, as measured from reverseperfusion, then lobar venous resistance and lobarcapillary resistance during forward perfusion can

be subdivided. Lobar venous resistance averagedapproximately 9%o, and capillary resistance aver-

aged approximately 45%o of total vascular resist-ance. During reverse perfusion venous resistanceaccounted for 20%o of total vascular resistance.Arterial resistance was approximately 23% andcapillary resistance approximately 57% of totalvascular resistance. Reverse perfusion of the lobeis analogous to model CBA in Fig. 5 CBAwherethe high resistance tube was downstream. Calcu-lation of the distribution of resistance was inaccu-rate distal to the initial low resistance (tube C inthe models or the pulmonary veins in the lungs) inboth the models and the lung lobes.

Average "calculated resistance" closely approxi-mated average "measured resistance" in the sevenlungs (Table II). However "calculated" and"measured" resistance differed slightly in eachindividual experiment. In order to compare theresults of all the experiments in terms of absoluteresistance at 2-ml intervals, the calculated valuesin each experiment were multiplied by a factor

Longitudinal Distribution of Vascular Resistance in the Lung

4001

3001-iI

I

w40hizahiUz4t0~V)

0 5 10 15 20 25 30

VOLUME(ML)

791

which corrected "calculated" to "measisistance. This correction did not changetion between calculated resistances throulobe but rather raised or lowered a

proportionately.Fig. 7 shows the average resistance pei

(resistivity) calculated at 2-ml intervalfive forward perfusion and the two re-fusion experiments. During forward perfcular resistance was relatively high throtpulmonary arterial tree. Resistivity reacdslightly before the end of the pulmonaand fell throughout the remainder ofmonary vascular bed.

The accuracy of the analysis of segmeibution decreased as the bolus moved dc(see Discussion), and therefore the resthe pulmonary veins was probably estimaccurately in the reverse perfusion exSince the pulmonary arteries accounted

ARTERIES CAPILLARIES

0N4

x

U

(I)

0..

0

FIGURE 8 Intravfor arteries fromfrom reverse perfi

ured" re-the rela-

ghout the1i1 values

r milliliterIs, for theverse per-usion vas-ighout theled a peaktry artery

the pul-

_d-1 2z

TABLE I I IMeasurements in Lung Lobes under

Sluice Conditions

Perfusion ResistanceDog pressure measured VL Vpa Vmp

cm H20 dyne -sece ml ml mlcm-6

A 21.0 6740 19.2 6.5 7.5C 16.0 4000 24.4 4.7 4.8D 21.0 5660 25.5 6.1 5.8E 23.0 4660 32.5 6.0 5.4

Mean 20.5 5265 25.4 5.8 5.7Mean nonsluice 21.4 4020 28.1 6.4 7.0

Change + 0.9 -1245 + 2.7 +0.6 +1.3

itai amstri-...of vascular resistance during forward perfusion)wnstream and the pulmonary veins for 20% of total vascular

ataed mofe resistance during reverse perfusion, the capillariesated more would be responsible for approximately 34%o of

forim ts. vascular resistance. Using these figures for thefor 46% relative distribution of pulmonary vascular re-

sistance, resistance was 322 dynes sec cm-5/ml inVEINS the pulmonary arteries, 112 dynes -seC -cm-5/ml

in the pulmonary capillaries, and 115 dynes sec*cm-5/ml in the pulmonary veins. Fig. 8 showsthe average intravascular pressures throughout thepulmonary vascular tree.

Table III shows the data obtained in four lungsduring forward perfusion under sluice conditions,i.e., when alveolar pressure exceeded venous pres-sure. Under these conditions venous resistance wasnot measured. The resistance midpoint was at theend of the pulmonary artery suggesting that thearteries were responsible for about 50% of totalvascular resistance upstream from the sluice point.On changing to nonsluice conditions by raisingvenous pressure above alveolar pressure, the re-sistance midpoint moved downstream away from

44 .the pulmonary artery.

DISCUSSION

IS Errors in analysis of the distribution of resist-ances to blood flow. Perfusion pressure decreases

I I J| during constant blood flow 'as a bolus of fluid withI

0 - 20 25 a viscosity less than that of blood passes through a10.2 series of resistances (5). The shape of the curve

VOLUME(ML) plotting the decrease in perfusion pressure (AP)

ascular pressure in lobar vessels. Data against time (or volume) is related to the distribu-

forward perfusion and data for veins tion of resistance in the system and the distribu-usion. tion of viscosity change (An) within the bolus.

792 1. S. Brody, E. J. Stemmler, and A. B. DuBois

The distribution of resistance along a series oftubes or in the lung can be calculated from thecurve of AP vs. volume if the distribution of vis-cosity within the bolus is known.

For maximum accuracy the AP vs. volumecurve of the lobe and Aq vs. volume plot of thebolus should be analyzed continuously or at leastat very small volume intervals. The analysis of theAP vs. volume curve of the lobe was simplified bycalculating resistance at 2-ml intervals along thecurve. The low viscosity bolus was spread outover a 6 ml volume as it entered the lung. An ap-proximate correction for the shape of the bolus wasmade by dividing the Aid volume plot of the bolusinto three 2 ml segments. The average Anq in eachsegment was used in making the calculations ofresistance to blood flow. These simplifications inthe calculation of the distribution of vascular re-sistance tended to decrease slightly the precisionof the method in measuring resistance changesoccurring over small volume intervals. This de-crease is illustrated in Fig. 5 where the actual re-sistance to flow in model tubes is plotted againstresistance calculated from the AP vs. volume curveresulting from the injection of the low viscositybolus in the same models. Because the method ofanalysis did not allow greater precision than 2 ml,the exact site of peak resistance to blood flow inthe isolated lung lobe could not be placed moreclosely than 2 ml in a specific anatomic segment ofthe pulmonary arterial tree.

For the purpose of calculating resistance it wasassumed that the distribution of viscosity changewithin the bolus, i.e. the shape of the bolus, wasconstant. However, a change in the shape of thebolus did occur as a result of the effects of laminarflow as the bolus passed through the resistancecircuit. The front of the bolus moved more rapidlythan the body of the bolus, and the tail of thebolus moved at a slower rate than the body of thebolus (14). As a result some viscosity change waspresent in downstream vessels before it was as-sumed to be there, and some viscosity change waspresent in upstream vessels after the bolus hadbeen assumed to have passed through these areas.When downstream resistance was high it wasgrossly underestimated because the rapidly movingfront of the bolus had passed through the highresistance downstream areas and the remaindercaused a relatively small pressure drop. The pre-

mature passage of the bolus caused an early pres-sure drop erroneously attributed to the low re-sistance upstream areas. This phenomenon is il-lustrated in Fig. 5 CBA and the data recordedduring reverse perfusion of the lung lobes.

In general, the further downstream the bolusmoved the less compact it was and the less itsshape resembled the bolus shape used in the cal-culations of resistance at 2-ml intervals. In thelungs the problem of bolus distortion was mag-nified by the multiple parallel channels throughwhich the bolus traveled. Therefore the resistancecalculations became less accurate as the bolusmoved downstream. For this reason pulmonaryartery resistance was most accurate when calcu-lated from the forward perfusion experiments andpulmonary venous resistance most accurate whencalculated from the reverse perfusion experiments.

The decrease in perfusion pressure producedby the saline bolus will cause a decrease in thevolume of the highly compliant lung vessels. Vas-cular resistance will increase at the smaller vas-cular volume abolishing a portion of the saline-induced pressure change. Since the pressurechange will be less than it should be, calculatedresistance will be underestimated throughout thevascular bed. A method for calculating the ap-proximate degree of underestimation of vascularresistance is described in the Appendix. Arterialresistance was underestimated by about 3%o of itsresistance, capillary resistance by 1o%, and venousresistance by about 3%. Since resistance was un-derestimated in all vessels these corrections do notsignificantly alter the calculated longitudinal dis-tribution of resistance in the lung vessels.

Inherent in the isolated lung lobe preparationused in this study are several conditions which mayaffect the distribution of pulmonary vascular re-sistance and limit extrapolation of the present re-sults to the intact animal.

A portion of pulmonary artery and pulmonaryvein was excluded from the preparation in theprocess of cannulating the lobe. As a result "lobar"pulmonary artery and vein volume and "lobar"pulmonary arterial and venous resistance were lessthan they would be in the whole lung. The resist-ance to blood flow in the large conducting arteriesand veins is not known, but an estimate can be madeof the pressure drop across these vessels by us-ing Poiseuille's law. Values for main pulmonary,

Longitudinal Distribution of Vascular Resistance in the Lung 793S

artery, left pulmonary artery, and venous trunkdiameter were taken from the measurements ofMiller (18), and values for vessel length from theestimates of Schleier (1). At the average flow inour experiments the pressure drop across the mainpulmonary artery would be 0.08 cm H2O and thepressure drop across the left pulmonary arterywould be 0.12 cm H2O. The excluded arteriestherefore account for approximately 4% of totalpulmonary artery resistance. The pressure dropacross the excluded portion of the pulmonary veinwould be 0.05 cm H20 or 2% of total venous re-sistance. These corrections do not significantlychange the per cent of resistance in each of thevascular beds.

Total vascular resistance of the lung lobes in thepresent study was similar to or less than that foundin other studies of excised and intact lungs at com-parable levels of blood flow (4, 19, 20). The mea-surements reported were made after perfusionpressure had been constant for 5 min usually 30-40 min after the beginning of lobar perfusion.The authors have shown, in the following paper(21), that vascular tone and reactivity are presentin both arteries and veins in the isolated lunglobe preparation, and that constriction of either thepulmonary arteries or the pulmonary veins canmarkedly affect the longitudinal distribution ofvascular resistance within the lung. Whether thedistribution of vascular resistance in the isolatedlung differs from that in the intact lung is notknown.

Increasing the pulmonary blood flow or the leftatrial pressure has been shown to lower pulmonaryvascular resistance (20, 22). Kuramoto and Rod-bard (23), using catheters placed in the pulmonaryartery, small pulmonary veins, and the left atriumto measure pressure gradients across segments ofthe pulmonary vascular tree, concluded that allvascular segments share equally in the decrease inresistance associated with increasing blood flow.The effect of changing the blood flow on the dis-tribution of segmental vascular resistance was notspecifically studied in our preparations. There ap-pears to, be no relation between blood flow, whichranged from 96 to 214 ml/min in the five lungsduring forward perfusion, and the per cent of totalvascular resistance in the pulmonary arterial orvenous vessels.

Pulmonary vein pressure was set, and it aver-

aged 9.1 cm H2Oduring forward perfusion; it was19.5 cm H2O during reverse perfusion. Kuramotoand Rodbard (23) found that pulmonary venousresistance [(small vein pressure-left atrial pres-sure)/flow] decreased about 30% as left atrialpressure was raised from 10 to 20 cm H2O. If thiscorrection is applied to the results of the presentstudy, venous resistance would account for 26%of pulmonary vascular resistance at normal leftatrial pressure, rather than the 20% found at thepressure of reverse perfusion.

End expiratory pressure was kept constant at3-5 cm H2O. The lung volume at this transpulmo-nary pressure corresponds to the volume of air inthe lungs at functional residual capacity in the in-tact animal (24). What effect lung inflation hason arterial, capillary, and venous resistance is notknown, although it has been shown that smallvessel volume decreases and large vessel volumeincreases with increasing degrees of lung inflation(25, 26).

Longitudinal distribution of pulmonary vascu-lar resistance. The results of the present studyindicate that the pulmonary arteries are responsiblefor an average of 46%o of lobar vascular resistance.The pulmonary capillaries account for 34% andthe pulmonary veins for 20%o of total lobar vas-

cular resistance. Expressed as resistance per mil-liliter of each vascular bed, arterial resistance isapproximately three times capillary or venous re-

sistance. Peak vascular resistivity, i.e. resistanceper milliliter, is in an area about 2 ml proximal to

the capillary bed, but resistivity is high through-out the pulmonary arterial tree. There does not ap-pear to be a vascular segment in the lung analo-gous to the high resistance muscular arterioles ofthe systemic circulation. The pulmonary arteriesalso contribute about half of vascular resistanceupstream from the sluice point when alveolarpressure exceeds venous pressure.

Schleier (1) and more recently Piiper (5, 27)have argued that the capillaries are the major re-

sistance vessels in the lung. Schleier made a de-tailed mathematical analysis of the distribution ofvascular resistance in the human lung usingPoiseuille's law. He employed Miller's measure-ments of vessel diameter (18) and assumed fig-ures for vessel length in his calculations. He con-cluded that, in contrast to the systemic vascularbed where the muscular arterioles are the major

794 J. S. Brody, E. J. Stemmler, and A. B. DuBois

resistance vessels, in the lung the capillaries arethe major- site of vascular resistance.

Schleier's calculated values for resistance ac-tually do not differ greatly from the values mea-sured in the present study. He calculated that thearteries account for 40% of the total pressuredrop across the lung, the capillaries 53%o, and theveins 7%o of the total pressure drop across thelung, whereas we calculated that the arteries ac-counted for 46%o, the capillaries 34%o, and theveins 20%o of the total pressure drop. The differ-ences between Schleier's figures and ours can beexplained by small errors in values used for ves-sel radius in Schleier's study, and by the fact thathe underestimated the cross-sectional area of thecapillary bed and therefore overestimated capil-lary resistance (28).

Piiper (5) in describing the viscosity-changetechnique for measuring the midpoint of vascularresistance, or as he called it the sife of maximalresistance, was unable to place the resistance sitein a particular anatomic segment of the pulmonaryvascular bed. However, he later concluded thatthe major portion of vascular resistance in thelung was in the pulmonary capillaries (27). Themajor difference between Piiper's conclusions andthose of the present study lie not in the measure-ments of the viscosity-induced pressure curve butin the measurement of total lobar blood volume(VL). Piiper used a photomultiplier to measurethe transit time of plasma or packed red bloodcells through the lung. He found VL to average 1.6ml/kg, whereas VL averaged 2.2 ml/kg in thepresent study. The latter figure fits closely withestimated VL based on total pulmonary blood vol-ume being 11 ml/kg in the dog (17) and the leftbasal lobe accounting for 25%o of total lung vol-ume and presumably 25% of total pulmonaryblood volume (6, 7). Wewere unable to measureknown volumes accurately using plasma or packedred blood cells as an indicator and a photocell(Grass finger plethysmograph) or photomultiplieras a sensing device. All such measurements grosslyunderestimated actual volume in our hands prob-ably because the tail of the dilution curve was notvisualized. If VL in Piiper's study were increasedto that found in the present study his resultswould agree closely with ours.

There is only one study which suggests thatthe pulmonary veins are the major resistance ves-

sels. Agostoni and Piiper (4) attempted to definemidcapillary pressure by measuring the pressureunder which Ringer's solution was absorbed bysubpleural capillaries. They found that 60% ofvascular resistance in the dog isolated lung lobewas on the venous side of the effective midpointof the pulmonary capillaries. This is the largestestimate of pulmonary venous resistance in theliterature. Whereas the explanation for the differ-ence between these results and the results of thepresent study is not clear it may be that the sub-pleural vessels do not reflect true intrapulmonarycapillary pressure.

The arguments favoring the pulmonary arteriesas the major resistance vessels in the lung havebeen indirect. Campbell in 1898 (3) reasoned thatthe large cross-sectional area of the capillary bedoffsets the effect of the small capillary vessel sizeon resistance to blood flow. He concluded that thegreatest resistance to blood flow in the lungs wasin the pulmonary arterioles. Lawson, Duke, Hyde,and Forster (29) found, by varying blood flow andleft atrial pressure in the isolated cat lung, thatpulmonary vascular resistance and diffusing ca-pacity could vary independently. This finding sug-gested to them that the capillary bed was not themajor resistance site in the lungs. DeBono andCaro (30) have argued that the relatively rigidsmaller pulmonary arteries contribute the maj orportion of pulmonary vascular resistance duringsluice conditions, i.e., when alveolar pressure ex-ceeds venous pressure. As flow increases underthese conditions, the relation between flow andpulmonary artery pressure remains linear. Thiswould not be the case if the larger pulmonaryarterial vessels which are more compliant con-tributed a major portion of vascular resistance.

Pulmonary arterial wedge pressure (Pw) pro-vides an approximate measure of venous pressure,but it is not clear which vessels are included in the"arterial" [(Pulmonary artery pressure- Pw) /flow] and "venous" [(Pw-left atrial pressure)/flow] resistances measured by this method (31).Direct measurements of pressure gradients alongpulmonary vessels with small catheters have notprovided consistent results in the pulmonary cir-culation. True lateral pressures are not measured,pressure gradients are small, and variations inpressure with tube placement and tube size anddifficulty with catheter wedging have limited con-

Longitudinal Distribution of Vascular Resistance in the Lung 795

fidence in the results of many of these studies (32,33). "Venous resistance" has ranged from 4 to20%o of total pulmonary vascular resistance in stud-ies which assume the difference between arterialwedge pressure and left atrial pressure to be thegradient across the pulmonary veins (34, 35)."Venous resistance" has ranged from 19 to 49%oof total pulmonary vascular resistance in studieswhen the difference between pressures recordedfrom small catheters threaded into pulmonaryveins and left atrial pressure was used as thegradient acrioss the pulmonary veins (36, 37).Connolly and Wood (38), using the differencebetween pulmonary artery pressure and pressurerecorded from a catheter wedged in the pulmonaryveins to estimate the pressure gradient across thepulmonary artery, found "arterial resistance" tobe 68%o of total pulmonary vascular resistance in agroup of patients. Aviado (37), however, foundvirtually no pressure gradient across the pulmo-nary artery in dogs using the wedged venouscatheter. No estimates of capillary resistance havebeen made from any of these studies.

The resistance to blood flow in a vascular bedis determined not only by the length and radiusof the vessels in that bed, the l/r4 factor inPoiseuille's law, but also by the number of vascu-lar segments in the bed. The h/r4 factor thereforeis multiplied by 1/n where n is the number of vas-cular segments. Weibel (28) has found capillarylength to be 12 X 10-4 cm and capillary radius4 x 10-4 cm in the human lung. But he has alsofound that there are 280 X 109 capillary segments.The effect of the very small capillary size is there-fore cancelled by the large cross-sectional area ofthe capillary bed. Similar figures for the arterialand venous vessels are not available. It seemsprobable that the most important determinant ofthe longitudinal distribution of vascular resistancein the lung is the relation between vessel size(mainly radius) and the total number of segmentsin a vascular bed.

Pulmonary capillary blood volume. Lobar capil-lary blood volume (Vpc) was calculated by sub-tracting lobar pulmonary artery volume, measuredin the forward perfusion experiments, plus lobarpulmonary vein volume (Vpv), measured in thereverse perfusion experiments, from total lobarblood volume (VL). Vpc calculated in this wayaveraged 12.5 ml. Total pulmonary capillary blood

volume (Vc) was calculated to be 50 ml or 38%of total pulmonary blood volume. This calculationpresumes that Vpv accounted for the same percent of VL during forward and reverse perfusion.Some limit can be placed on the error inherent inthis assumption. The volume of the capillaries andveins increased by 2.1 ml after elevation of reser-voir pressure from 0 to 9 cm H20 during forwardperfusion (Table III). Since venous compliance isapproximately four times capillary compliance(39), the veins would have increased by 1.7 ml. Ifone assumes that a similar increase in Vpv wouldoccur if reservoir pressure was raised from 9 to 18cm H20, the difference in pulmonary vein pres-sure between forward and reverse perfusion, Vpvcould have been overestimated by a maximum of1.7 ml. Therefore Vpc could not have been morethan 14.2 ml nor Vc more than 43%o of total pul-monary blood volume.

Weibel (28) found Vc to average 146 ml in ana-tomic studies of five human lungs. Bates, Varis,Donevan, and Christie (40) found Vc derivedfrom steady-state diffusing capacity measured dur-ing exercise at two different oxygen tensions toaverage 153 ml. Lewis, McElroy, Hayford-Wel-sing, and Samberg (41) obtained similar valuesfor Vc in supine man using the rebreathing methodfor measuring diffusing capacity. If average pul-monary blood volume in man is assumed to be450-500 ml (42, 43), Vc would account for about30-35%O of total pulmonary blood volume in thesestudies. Calculation of Vc derived from singlebreath diffusing capacity measurements have beensomewhat lower both during exercise and in thesupine position (41, 44). It is difficult to comparethe Vc measurements of the present study, thoseof Weibel (28), Bates and coworkers (40), andLewis and coworkers (41), which were done at alung volume equivalent to functional residual ca-pacity with Vc values determined by the singlebreath-diffusing capacity method which is done atpeak inspiration. The relation between degree oflung inflation and pulmonary vascular volume iscomplex. Macklin (25) and Howell, Permutt,Proctor, and Riley (26) have shown that largeand small lung vessels react in different ways toincreasing degrees of lung inflation, and Hamer(45) has found that Vc, as measured by singlebreath-diffusing capacity method, decreases withincreasing lung volume.

796 J. S. Brody, E. J. Stemnler, and A. B. DuBois

Applications

Vessel response to stimuli. The methods de-scribed provide a way of measuring the pressuredrop and resistance to blood flow in each portionof the pulmonary or systemic vascular beds with-out requiring direct measurements of pressuregradients within the vessels. This technique canbe applied to analyzing arterial, capillary, andvenous responses to a variety of pharmacologicand physiologic stimuli. Wereport in the follow-ing paper (21) the effects of several drugs on theindividual vascular segments in the dog lung us-ing the methods described in this paper.

The calculations involved can be simplified andthe precision of the results improved if the shapeof the low viscosity bolus, the change in bolusshape as it passes through the lung, and the re-sulting change in perfusion pressure with time inthe vessels are analyzed with an analogue or digi-tal computor. The preparation can be simplied aswe found by perfusing the lobe of a dog with thedogs own blood and without a donor dog in anopen (reservoir) or closed (no reservoir) system.The techniques presumably can also be applied tothe intact animal providing that flow and venouspressure are kept constant or measured continu-ously.

Pulmonary capillary pressure. Accurate -mea-surements of capillary pressure in the systemiccirculation have been available for many years(46), but there are no methods for measuringcapillary pressure in the lung. The pressure re-corded from a catheter wedged into small pulmo-nary arterial vessels was initially thought to rep-resent pulmonary capillary pressure (47), butfurther studies have shown that the arterial wedgepressure reflects pressure in vessels distal to thecapillary bed (48). Pulmonary venous wedgepressure appears to reflect pressure in vesselsproximal to the pulmonary capillaries (48).Agostoni and Piiper (4) described an indirectmethod for measuring pulmonary capillary pres-sure from subpleural capillaries, but they admit thesubpleural capillary pressure could be quite dif-ferent from intrapulmonary capillary pressure be-cause of structural differences between the twotypes of vessels.

Hydrostatic pressure in the pulmonary capillarybed is thought to be the most important-factor inthe etiology of most forms of pulmonary edema

(49). Investigations into the mechanisms of ex-perimental pulmonary edema have been hamperedby the lack of accurate measurements of pulmonarycapillary pressure (50). Pulmonary capillary pres-sure measurements would also be of value in study-ing the transudation of various substances throughthe capillary wall and the bursting point of pul-monary capillaries submitted to high transmuralpressures such as seen in mitral stenosis or undergravitational stress.

The methods described in the present study al-low for the first time accurate measurement of pul-monary capillary pressure. Midcapillary pressure averaged 13.3 cm H2O, whereas pulmonaryartery pressure averaged 20.4 cm H2O, and pul-monary vein pressure averaged 9.2 cm H20.Under the circumstances of the experiments re-ported, 63%o of the pressure drop in the pulmonaryvessels occurred before the midpoint of the pul-monary capillaries. Pressure at the arterial end ofthe pulmonary capillaries averaged 15.3 cm H20,whereas pressure at the venous end averaged 11.4cm H20. These values were determined duringsteady nonpulsatile flow. Linderholm, Kimbel,Lewis, and DuBois' (51) analysis of instantane-ous capillary flow and pulse pressure suggeststhat the pressure-flow curve of the pulmonary ves-sels is linear. If this is true the longitudinal dis-tribution of resistance determined during non-pulsatile flow should not differ significantly frommean values determined during pulsatile flow.

APPENDIXThe decrease in perfusion pressure caused by the lowviscosity bolus produced a decrease in the volume of thehighly compliant lung vessels. During forward perfusionthe mean bolus-induced perfusion pressure change aver-aged 1.3 cm H20 in the pulmonary arteries and 0.8 cmH20 in the pulmonary capillaries. The mean pressuredecrease in the pulmonary veins was 0.5 cm H20 duringreverse perfusion. The vascular volume changes associ-ated with these pressure changes can be estimated by us-ing the values for pulmonary vascular compliance deter-mined by Engelberg and DuBois (39). Vascular volumedecreased 0.2 ml in both the pulmonary arteries and veinsand 0.1 ml in the pulmonary capillaries.

The error in the calculations of vascular resistance as-sociated with the vascular volume changes can be de-rived if it is assumed that vascular conductance is pro-portional to vascular volume. Point A in Fig. 9 repre-sents the average calculated conductance (Ge) for thepulmonary arteries and the average volume at which itwas measured [pulmonary artery volume (V) minus thebolus-induced volume changes (AV)]. Point B represents

Longitudinal Distribution of Vascular Resistance in the Lung 797

,, 60 /z~~

o , .

U 50

0 4

0

0 2 4 6 .8 lo 12 14

VOLUME(ML)FIGURE 9 Conductance-volume plot of lung vessels.Average conductance values are taken from data in Fig.8. See Appendix for explanation of abbreviations.

the true volume of the pulmonary arteries. If we assumethat the conductance-volume curve of the pulmonary ar-teries is linear and goes through zero, the slope of theconductance-volume line at point B is Ge/V. Point C lieson the conductance-volume line and represents the trueconductance (Gt) of the pulmonary arteries at the vol-ume V -AV. The slope of the conductance-volume linethrough point C is Gt/(V -AV). Since the slope of theline through points B and C is the same, the true conduct-ance (Gt) at volume V -AV can be determined. Gt =(Ge/V) X (V -AV), and Gc, V, and AV are known.Gt = (30.7/5.9) X 5.7 = 29.7 ml * cm H20 min1. The over-estimate of pulmonary artery conductance or underesti-mate of artery resistance is (Gc- Gt)/Gt or 3.4%o. Simi-lar calculations for the pulmonary capillaries and veinsshow resistance underestimates of 0.7%o and 2.5% respec-tively.

ADDENDUM

Since this paper was submitted for publication two stud-ies of the distribution of pulmonary vascular resistancehave appeared. Garr, Taylor, Owens, and Guyton (52),using an isogravimetric method to estimate pulmonarycapillary pressure, found that 56%o of vascular resistancelies before the capillary midpoint in the isolated lung lobe,a result in close agreement with that (63%) of the pres-ent study. McDonald and Butler (53), employing the vas-cular waterfall effect, found arterial, capillary, and ve-nous pressure drops to be about equal.

ACKNOWLEDGMENTS

This work was supported by U. S. Public Health Serv-ice grants HE 4797 and HE 7397. Dr. Stemmler received

U. S. Public Health Service Grant 2 T 1-GM-957-05.Dr. DuBois is a recipient of a Research Career Awardof the National Institutes of Health.

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798 J. S. Brody, E. J. Stemmler, and A. B. DuBois

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