In the Pulmonary Arteries, Capillaries, and Veins

Longitudinal Distribution of Vascular Resistance in the Pulmonary Arteries, Capillaries, and Veins

JEROME S. BRODY, EDWARD J. STEMMLER, and ARTHu B. DuBois From the Department of Physiology, Division of Graduate Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

A B S T R A C T A new method has been described monary artery pressure averaged 20.4 cm H2O, for measuring the pressure and resistance to blood and pulmonary vein pressure averaged 9.2 cm flow in the pulmonary arteries, capillaries, and H2O. These techniques also provide a way of ana- veins. Studies were performed in dog isolated lyzing arterial, capillary, and venous responses to lung lobes perfused at constant flow with blood various pharmacologic and physiologic stimuli. from a donor dog. Pulmonary artery and vein volume and total lobar blood volume were mea- INTRODUCTION sured by the ether plethysmograph and dye- dilution techniques. The longitudinal distribution The arterioles are the major resistance vessels in of vascular resistance was determined by analyzing the systemic vascular bed (1, 2), but it is uncer- the decrease in perfusion pressure caused by a tain whether the greatest resistance to blood flow bolus of low viscosity liquid introduced into the in the lungs is in the arteries, capillaries, or veins vascular inflow of the lobe. (1, 3, 4). The pulmonary arteries were responsible for Piiper (5), in 1958, reasoned from Poiseuille's 46% of total lobar vascular resistance, whereas law that, during constant perfusion, injection into the pulmonary capillaries and veins accounted for the bloodstream of a bolus of fluid with viscosity 34 and 20% of total lobar vascular resistance different from that of blood would cause a per- respectively. Vascular resistance was 322 dynes fusion pressure change proportional to the re- * sec* cm-5/ml of vessel in the lobar pulmonary sistance of the vessels through which the bolus arteries, 112 dynes sec.cm-5/ml in the pulmonary passed. Piiper considered that the major part of capillaries, and 115 dynes- sec* cm5/ml in the vascular resistance was located at one point in the lobar pulmonary veins. Peak vascular resistivity lung, and that the mean appearance time of the (resistance per milliliter of volume) was in an area viscosity-induced pressure change, multiplied by 2 ml proximal to the capillary bed, but resistivity flow, gave the volume to the "site of main resist- was high throughout the pulmonary arterial tree. ance" to blood flow. Piiper, however, did not re- The pulmonary arteries accounted for approxi- late the "site of main resistance" to an anatomic mately 50% of vascular resistance upstream from site because he was unable to further subdivide the sluice point when alveolar pressure exceeded pulmonary vascular volume; furthermore he did venous pressure. not describe the longitudinal distribution of pul- The method described provides the first mea- monary vascular resistance. surements of pulmonary capillary pressure. Mid- In the present study the volume to the midpoint capillary pressure averaged 13.3 cm H2O, pul- of vascular resistance in isolated lung lobes of dogs has been measured by modification of the viscosity- Dr. Brody is a postdoctoral fellow of the National In- described We related stitutes of Health. change technique by Piiper. Received for publication 11 September 1967 and in re- the resistance midpoint, 50%o of vascular resistance vised form 4 December 1967. upstream and 50%o of vascular resistance down- The Journal of Clinical Investigation Volume 47 1968 783 stream from this point, to pulmonary artery Plexiglas and was perfused by a constant flow pump with volume and total blood volume of the lobe during blood drawn from catheters placed in the inferior vena cava and femoral artery of a heparinized donor dog (Fig. forward perfusion, and to pulmonary vein volume 1). Total ischemic time of the lobe was less than 30 min. and total blood volume of the lobe during reverse The donor dogs, weighing 15-25 kg, were anesthetized perfusion. The resistance and pressure at intervals with sodium pentobarbital, 25 mg/kg, and were allowed along the pulmonary vessels have been calculated to breath spontaneously through a tracheal cannula. The blood from the donor dog was heated to 370C, passed by an analysis of the time course of pulmonary through the lobe, collected in a cylindrical venous reser- artery pressure change recorded as a bolus of low voir, and drained by gravity back into the jugular veins viscosity, 2 ml of saline solution, passed through of the same donor dog. The average oxygen pressure the vascular bed. This technique provides a way (Po2) of blood perfusing the lobe was 70 mm Hg. Aver- age carbon dioxide pressure (Pco2) was 38 mm Hg, pH of measuring resistance and pressure throughout 7.30. the pulmonary vascular bed without requiring Differential transducers with one side connected to direct pressure measurements from multiple points the plethysmograph were used to measure pulmonary within'the lung vessels. artery, pulmonary vein, and bronchial pressures. Lateral pressures in the pulmonary artery and vein were obtained METHODS from side-hole catheters placed just inside the artery and vein and were referred to the height of the center The left basal lobe was exposed through a left lateral of the lobe. Plethysmograph pressure was monitored by thoracic incision in seven 10-14-kg mongrel dogs anes- a differential transducer with one side open to the at- thetized with sodium pentobarbital, 25 mg/kg. The pul- mosphere. The plethysmograph was calibrated with the monary arterial and venous vessels and the bronchi to lobe in place and the bronchus clamped so that a 1 ml the left upper and middle lobes were isolated, tied, and volume change would produce a 25 mm deflection on the severed. The left basal lobe artery, vein, and bronchus recorder. The lobe was ventilated with room air by a were isolated and cannulated with polyethylene tubes positive pressure pump at a rate of 20 breaths/min with a while we made sure that no air was introduced into the constant tidal volume that produced transpulmonary pres- vascular system. The lobe was placed in an airtight box sure of 8-10 cm H20 at peak inspiration. End expira- (17.5 cm X 17.5 cm X 10.0 cm) constructed of 0.25 inch tory pressure was kept constant at 3-5 cm H20.

DANPC E

DENSITOtlETER 4- DYE

AIR -4~~~OOR P 45MIXING C ONDENSER \ CHAMBER IIR \ n. -e r

+- 4~~~~ VENTILATE PRESSURE FIGURE 1 Diagram of experimental setup. Ppv and Ppa are lobar pulmonary vein and artery pressures, respectively. Pt is lobar bronchial pressure. The pulmonary veins may be connected directly 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 lung and Karsch (13) calculated that greater than 90%o of the volume in the dog and presumably 25%o of pulmonary injected ether equilibrates in the first hundredth length blood flow (6, 7). Average blood flow through the iso- of the capillaries. Therefore the ether method measures lated lobes in seven experiments was 13.6 ml/min per kg, the vascular volume proximal to the pulmonary capil- somewhat less than 20% of normal cardiac output (8). laries. However, flow at this level has been shown to completely 0.20 ml of a 1: 4 ether-Lipomul solution (12) was placed perfuse isolated lung lobes without the appearance of in one side channel of the perfusion apparatus while all edema (9). Blood flow was measured by occluding the blood was flowing through the opposite symmetrically outflow from the venous reservoir and recording the rate constructed side channel (Fig. 1). After the plethysmo- of rise of hydrostatic pressure at the bottom of the reser- graph had been sealed and respiration of the lobe stopped, voir. Flow could be measured this way to within + 2%o a 3-way stopcock was turned diverting all flow through of flow determined by direct collections in a graduated the side channel containing the ether-Lipomul solution, cylinder. Venous pressure was held constant by making moving the solution into the pulmonary artery. The mean the venous reservoir airtight and submitting it to a con- appearance time of the plethysmograph pressure vs. time stant air pressure of about 9 cm H20. This technique curve multiplied by flow gave the volume from the site ensured that venous pressure exceeded the alveolar pres- of ether injection to the beginning of the pulmonary capil- sures of 3-5 cm H20, and therefore "nonsluice" condi- lary bed. The volume of the apparatus dead space between tions existed throughout the lobe (10). In four lobes the site of ether injection and the pulmonary artery was measurements were also made during forward perfu- measured and subtracted from the volume measured with sion with the venous reservoir open to the atmosphere ether to give Vpa. Because of the small volume of the and with end expiratory pressure constant at 3-S5 cm ether-Lipomul solution (0.2 ml) dispersion of the solu- H20, these being "sluice" conditions (10). tion in transit to the end of the pulmonary artery can- Lobar pulmonary artery and vein pressures, plethysmo- nula was ignored. A similar method, but with reverse graph pressure, bronchial pressure, and dye concentrations perfusion, was used to measure the volume of the pulmo- were recorded on a Grass direct writing instrument. nary veins. The standard deviation of duplicate determi- Total lobar blood volume, lobar pulmonary artery volume, nations of Vpa was 0.2 ml. The coefficient of variation of and the volume to the midpoint of vascular resistance duplicates around the mean was 3.8%o. were each determined in duplicate during short periods of apnea at an end expiratory pressure of 3-5 cm H20 and Volume to the midpoint of lobar vascular resistance. after a prior inflation of the lobe to about 20 cm H20. The volume to the midpoint of lobar vascular resistance Total lobar blood volume. Total lobar blood volume (Vmp) was measured by a modification of the viscosity (VL) was determined by the Stewart-Hamilton indicator change method described by Piiper. The method is based dilution method (11) with indocyanine green as the indi- on Poiseuille's law: cator dye. With respiration stopped the dye was flushed into the arterial inflow (Fig. 1) and passed through a A\P = Q X- X h/r4 X 71. (1) mixing chamber before moving into the lung lobe. The ir concentration of the dye was measured by a Waters XP This law staates that the pressure drop (AP) across a 250A Densitometer in blood drawn from a catheter placed circular tube during steady laminar flow is equal to the in the pulmonary vein. The mean appearance time of the flow in that system (Q) multiplied by: a numerical term dye curve multiplied by flow was the volume of the pul- (8/ir) which results from the mathematical analysis of monary vessels plus the dead space of the tubing. The flow in a cylindrical tube; a geometric factor (I/r'), I tubing dead space volume was determined after each ex- being the length of the tube and r4 being the radius raised periment, with the lung removed from the apparatus, by to the fourth power; and the viscosity (,I) of the fluid the same dye injection technique. The dead space volume perfusing the tube. If all other factors remain constant a was subtracted from the total volume measured during change in the viscosity of the perfusate will cause a the experiment to give VL. The absolute accuracy and change of the pressure in the system proportional to the reproducibility of this method were tested with duplicate h/r factor. Laminar flow was present in both lung lobes determinations in tubes of known volume. Tube volumes and model tubes since the Reynold's numbers for the were measured with no systematic error and with a stand- largest pulmonary vessel (diameter equal to the pulmo- ard deviation of 0.7 ml. The standard deviation between nary artery cannula, 0.4 cm) and for all the model tubes duplicate determinations in the lung lobes was 0.8 ml, were well below the critical number for the occurrence of and the coefficient of variation of duplicates around the turbulent flow (14). mean was 3.5%. 2 ml of 0.9% NaCl (saline), warmed to 37°C, was Lobar pulmonary artery volume. Lobar pulmonary placed in the perfusion apparatus side channel through artery volume (Vpa) was measured by the technique of which blood was not flowing (Fig. 1). Respiration was Feisal, Soni, anrd DuBois (12). Ether injected into the stopped, and the 3-way stopcock was turned so that all pulmonary artery moves from the dissolved state in blood blood flowed through the channel containing the saline to the gaseous state on contact with alveolar air. A solution, moving the saline into the pulmonary artery. plethysmograph is used to record the rise in alveolar Since flow and venous pressure were constant, the de- pressure as ether enters the gas phase. Sackner, Feisal, 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 to resulting pressure curve (Fig. 2) was a profile of vis- the resistance of the vessels through which the saline was cosity change vs. volume in the bolus. The pressure curve passing. The median appearance time of the curve of reflecting the distribution of bolus viscosity change spread pressure decrease vs. time, multiplied by flow, gave the through slightly more than 6 ml in volume even though volume from the injection site to the resistance midpoint only 2 ml of saline were placed in the side channel. The of the lung. The saline bolus did not appear to alter the lengthening of the bolus was probably due to the parabolic resistance of the pulmonary vessels since perfusion pres- front created as blood moved through the channel con- sure returned to the base line after the saline had passed taining the bolus. Since flow and the length and radius of through the lung. In order to determine the effective sa- the resistance tube at the end of the dead space were line dead space, a saline injection was made without the known, the change in viscosity in each portion of the lobe in place and with a short artificial resistance between saline bolus could be calculated: the pulmonary artery and pulmonary venous cannulae. The median appearance time of the curve of pressure A-q saline = AP saline X X 1 (2) change vs. time multiplied by flow gave the effective sa- 1X0. the volume mea- line dead space which, subtracted from In order to simplify the calculations of vascular resistance sured with the lung in place, gave the volume to the mid- that follow, the saline bolus was divided into three 2-ml point of lobar vascular resistance. segments. The average decrease in viscosity in the first Longitudinal distribution of vascular resistance. In or- 0.020 poise, that in the second 2 ml along 2 ml segment was der to study the resistance to blood flow at points segment was 0.010 poise, and that in the third 2 ml seg- the lung vessels rather than just the volume to the mid- ment was 0.005 poise. The viscosity of the blood was cal- point of vascular resistance, the saline-induced pressure culated by substituting the pressure drop across the small curves were analyzed by another method. The abscissa tube during blood flow for AP saline in equation 2. Blood of the pressure curve was marked off in 2-ml increments viscosity averaged 0.040 poise. The viscosity of water, at (flow X time = volume) beginning with the start of the 370C, would be 0.0069 poise. These values for blood vis- pressure decrease caused by the saline. These points were cosity and bolus-induced viscosity change were used in equated with volumes at 2-ml intervals along the vascu- all subsequent calculations. lar tree. The pressure decrease at each point was used to calculate vascular resistances for each 2 ml segment. Poiseuille's law is given in equation 1. If the initial vis- The pressure change recorded with saline injection is cosity (,i) of the fluid in a segment of the system is determined by the shape of the saline bolus, i.e. the dis- brought to a new level (-q.) by a portion of the saline tribution of viscosity change within the bolus, as well as bolus, there is a change in pressure (Pi) to a new level the distribution of resistances in the system. In order to (P.). Equation 1 for a segment of the system can be re- define the shape of the saline bolus, a short length of tub- written with P, - P. = AP1 saline, and 7i - 71 = A71 saline. ing with small radius and small volume was substituted AP1 saline is the pressure drop in the segment caused by for the lung lobe at the end of the pulmonary artery can- the viscosity change, A1 saline, in the first 2 ml portion of nula. A bolus of saline was injected during constant blood the bolus. flow as described above, and the decrease in perfusion pressure was recorded. Because there was virtually no AP1 saline = X X IX Ago saline- (3) longitudinal distribution of resistance in the small tube, the change in pressure vs. time as the saline bolus passed There is no need for absolute pressure or viscosity mea- through the tube was directly proportional to the change surements in segments of the vascular bed since the equa- in viscosity at each point in volume of the bolus. The tions are now in terms of pressure change and viscosity change. By rearranging equation 3 one can solve for the geometric factor characteristic for a segment in the P system: (CM H20) r4 API saline X 8 X XAx-. (4) The pressure decrease recorded as a bolus of low viscosity moves through the lung vessels reflects the resist- of all the vessels in the circula- ? 4 6 8 ance of a cross-section V(ML) 0 2 tion at a point in volume. The Irl factor calculated in T(SEc) E equation 4 involves not only vessel length and radius but FIGURE 2 Shape of saline bolus. The curve shows the also the number of vascular segments. Since resistances change in perfusion pressure (P) produced as the saline in parallel add by reciprocals, I/r4= (vessel length/ bolus passed through a small volume, high resistance vessel radius') divided by the number of vascular seg- tube which replaced the lung lobe in Fig. 1. The abcissa ments. of the curve is marked at 2-ml volume intervals (flow X Assuming that the geometric factor does not change as time = volume). The viscosity change produced by any the bolus passes through the segment, the resistance (R) portion of the bolus can be calculated from equation 2. 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: can be calculated since the geometric factor for the first 2 ml segment has been calculated, and the change in vis- R = 8,/7r X r4 X Ablood(5) cosity (A72 saline) caused by the second portion of the bolus in that segment is known: The actual pressure drop across that segment can be determined by multiplying R by Q/980. AP2 atline = Q X X r X AX72s aline. (6) This analysis is valid for the first 2 ml segment con- 7 r taining the first 2 ml of bolus which causes a viscosity AP2 salne can be subtracted from the total pressure drop change of 0.020 poise. But as the bolus moves on to the at the 4 ml point to give the pressure drop (API saline) next 2 ml segment, the 0.020 poise viscosity change will caused by that part of the bolus in the second 2 ml seg- move to this segment and the 0.010 poise viscosity de- ment. The geometric factor and resistance of the second crease of the second portion of the bolus will be in the segment can then be calculated as in equations 4 and 5. first 2 ml segment, both segments contributing to the A similar correction with a 0.010 decrease in viscosity in pressure drop measured at the 4 ml point. A correction the second 2 ml segment and a 0.005 decrease in the first for the amount of pressure change (AP2sal Ine) caused by 2 ml segment of the system can be made when the bolus that part of the bolus in the first segment must be made has moved on to the 6 ml mark, and so forth on down to determine the actual pressure drop and resistance in the lung lobe. the second 2 ml portion of the system. This correction Fahraeus and Lindquist found that the relative viscosity

VMP

ABC 5.7(5.4)

I, CmHM BAC 7.7(8.2)

CAB 10.2 (9.7)

CBA 12.8 (12.6) 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 C was 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 A . T-IME, (SEC) (Vmp). The actual Vmp is in parenthesis.

Longitudinal Distribution of Vascular Resistance in the Lung 787 of blood decreased in tubes of radius less than 200 , (15). the pressure curves differed depending on the Relative viscosity in tubes with a radius of 25 /A is ap- order of placement of the tubes. The position of proximately one-third less than in tubes with radius the high resistance tube most affects the shape and larger than 200 ,u, but it is not clear what the relative curves. viscosity is in vessels as small as the capillaries (16). the median appearance time of the pressure The decrease in viscosity with the decreasing tube size is The accuracy of the method for measuring vol- present at all hematocrits (16), and therefore A1saein ume to the resistance midpoint is demonstrated in equations 3 and 4 and blbood in equation 5 will decrease Fig. 4, a plot of measured vs. actual Vmp in a by the same proportion. Since A1m i,,. appears in the de- variety of single tubes and combinations of tubes. nominator of the equations and qblood appears in the nu- merator, the ratio between the two will remain unchanged There was no significant difference between actual in small vessels, and the Fahraeus-Lindquist effect will and measured Vmp. The standard deviation of du- have little influence on our calculations of resistance. plicate determinations of Vmp in the lung lobes Total pulmonary vascular resistance was determined was 0.2 ml. The coefficient of variation of dupli- by two methods. Resistance determined by summing vas- cates around the mean was 2.6%. cular resistances calculated at 2-ml intervals throughout the lung from passage of a bolus whose viscosity was The pressure curves after saline injection in measured in vitro will be referred to as "calculated re- several arrangements of tubes A, B, and C were sistance." "Measured resistance" was determined by sub- also analyzed to determine the longitudinal distri- tracting pulmonary vein pressure from pulmonary artery bution of resistance. The resistance per milliliter pressure during nonsluice conditions, or subtracting al- intervals is to actual veolar pressure from arterial pressure during sluice con- calculated at 2-ml compared ditions, multiplying by 980 to convert to dynes per square resistance per milliliter in Fig. 5. There is a good centimeter and dividing by flow in milliliters per second. fit of calculated and actual resistances in all but Since "calculated resistance" was determined by assuming Fig. 5 CBA where the high resistance was down- that blood viscosity was the same in lung vessels of all stream. In this situation the downstream resistance sizes, the close agreement between "calculated resistance" the and "measured resistance" suggests that if there was a is grossly underestimated, whereas general lower viscosity in small vessels it was relatively unim- tendency is to slightly overestimate downstream portant in our calculations of vascular resistance. resistance when it is small. Table I lists total "calculated resistance," i.e. RESULTS the sum of the resistances calculated at 2-ml Model system. The accuracy of the viscosity- intervals, and the calculated per cent of total change method for measuring the volume to the resistance in each tube, and compares these to resistance midpoint (Vmp) and the longitudinal actual values. The results are relatively accurate distribution of vascular resistance was tested in model tubes of known resistance. The tubes were substituted for the lung lobe in Fig. 1 and were 15 perfused with blood from a reservoir instead of a donor dog. Three tubes of equal volume but different geo- W ./0 metric characteristics can be used to illustrate the '2 significance of the resistance midpoint measure- > ment. Each tube had a volume of 6 ml, but at the 2 flow and hematocrit during the experiment the resistance of tube A was 3880 dynes sec* cm-5, tube B was 1960 dynes-sec cm 5, and tube C was 1090 dynes -sec-cm-5. Since the tube volumes were equal, the Vmp for each tube should be and was measured to be the same. The magnitude of the pressure decrease caused by the saline bolus was to greatest in the tube with the greatest resistance to blood flow. Fig. 3 shows the pressure tracings after VMP ACTUAL(ML) saline injection when the tubes were arranged in FIGURE 4 Actual Vmp vs. measured Vmp. Vmp = vol- series in several combinations. The contours of ume to the midpoint of vascular resistance. 788 J. S. Brody, E. J. Stemmler, and A. B. DuBois I A B C B A C 750 AL

500I p 250 az I W

0." a C A a} C B A w 750 z I FIGURE 5 Longitudinal distribution of n 500 resistance in model tubes in series. n) w /I Actual (solid line) vs. calculated (in- terrupted line) resistivity (resistance 250 per milliliter) calculated at 2-ml volume intervals in model tubes A, B, and Ak C arranged in series. 0 5 10 15 20 0 5 10 15 20

VOLUME (ML) except in sequence CBA where the large down- forward perfusion was 26.6 ml. Lobar pulmonary stream resistance is underestimated. In this case, artery volume (Vpa) averaged 6.2 ml or 23% tube A was calculated to account for 37% instead of VL. During reverse perfusion VL averaged 23.3 of the actual 56%o of total resistance. Although this ml, and pulmonary vein volume (Vpv) was 6.4 ml error affected the calculation of the longitudinal or 28% of VL. distribution of resistance in CBA, it did not Although forward and reverse perfusion in the appreciably alter the measurement of the midpoint lobes were not precisely comparable from the of vascular resistance, as can be seen in Fig 3 standpoint of pressures applied to artery and vein, CBA. and although the studies were done in different Isolated lung lobes. Table II contains a sum- lungs, the results of the two experiments can be mary of the results of our studies in five isolated combined to give a gross estimate of lobar capil- lung lobes during forward perfusion and two lung lary blood volume (Vpc). Since Vpa during for- lobes during reverse perfusion in nonsluice condi- ward perfusion + Vpv during reverse perfusion tions, i.e., with downstream pressure (9 cm H20) account for 51% of VL, Vpc must be 49% of VL greater than alveolar pressure (4 cm H20). or 12.5 ml. The left basal lobe makes up 25%o Average total lobar blood volume (VL) during of 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 16 BAC 7390 6930 47 56 30 28 23 16 CAB 6935 6930 49 56 30 28 21 16 CBA 6155 6930 37 56 50 28 13 16

Longitudinal Distribution of Vascular Resistance in the Lung 789 TABLE I I Measurements in Lung Lobes under Nonsluice Conditions

Per- Down- fusion stream pres- 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 resistance sec see *cm-$ *cm-S Forward perfusion A 11.4 143 22.0 9.5 5140 24.4 7.3 9.0 6405 38 B 11.4 96 18.5 8.5 6140 20.6 5.4 6.1 6535 48 C 12.3 176 19.0 9.0 3340 25.3 4.9 5.7 2400 40 D 11.4 176 19.0 9.0 3340 28.5 6.5 6.9 1970 51 E 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 perfusion G 11.4 182 19.0 9.0 3220 23.4 6.7 13.6 3745 20 H 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 perfusion 12.0 164 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 38% of total pulmonary blood volume in the dogs (6, 7). Therefore, total capillary blood volume used. The difference between lobar capillary blood would be (12.5 ml x 100%o)/25%, or 50 ml in volume, which was 49%o of lobar blood volume, our dogs. Since pulmonary blood volume in dogs and total capillary blood volume, which was 38%o is 11 ml/kg x 100 (17) our estimated capillary of total pulmonary blood volume, can be explained blood volume would be (50 ml . 132 ml) x 100 or by the presence of the lobar cannulae which ex-

V(ML) 0 10 20 30 I I I P I'O- ( cm "20) qr -14 2021t t 4, FORWARD I4419V W LVPA vPc+V:v

REVERSE

I VPV | VPC +VPA l

T(sec) I I I I I I I I a I fr FIGURE 6 Saline curves in lung lobes. Curves on left show saline-induced pressure curve in one forward perfusion (dog C) and one reverse perfusion (dog G) experiment. Vmp is marked with an arrow. Diagram on right represents the average vascular volumes and Vmp in five forward and two reverse perfusion experiments. Vpa, volume of the pulmonary artery; Vpc, capillary blood volume; Vpv, volume of the pulmonary vein. 790 1. S. Brody, E. J. Stemmler, and A. B. DuBois 4001

o-o FORWARD PERFUSION -i I 3001 ..-.REVERSE PERFUSION

w 40 hi zI a hi U SKipvVP z 4t FIGuRE 7 Resistivity in lung lobes. Av- 0~ erage resistivity (resistance per milliliter) V) is calculated at 2-ml intervals in five forward perfusion and two reverse perfusion experiments. Vpa marks the average volume of the pulmonary artery during forward perfusion (reading from left to right). Vpv marks the average volume of the pulmonary vein during reverse perfusion (reading from right to left). 0 5 10 15 20 25 30

VOLUME (ML) cluded portions of the large conducting arteries be subdivided. Lobar venous resistance averaged and veins in our experiments. approximately 9%o, and capillary resistance aver- The average volume to the resistance midpoint aged approximately 45%o of total vascular resist- (Vmp) during forward perfusion was 6.8 ml or ance. During reverse perfusion venous resistance 24%o of VL. Since Vpa averaged 23%o of VL it accounted for 20%o of total vascular resistance. would appear that the pulmonary artery was re- Arterial resistance was approximately 23% and sponsible for a large portion of total lobar vascular capillary resistance approximately 57% of total resistance. During reverse perfusion at comparable vascular resistance. Reverse perfusion of the lobe flow rates Vmp was 14.3 ml or 62%o of VL. Exam- is analogous to model CBA in Fig. 5 CBA where ples of forward and reverse perfusion saline in- the high resistance tube was downstream. Calcu- jection curves with Vmp marked for each are lation of the distribution of resistance was inaccu- shown in Fig. 6. rate distal to the initial low resistance (tube C in Calculation of vascular resistance at 2-ml inter- the models or the pulmonary veins in the lungs) in vals in the lungs allows a more precise estimate of both the models and the lung lobes. the vascular resistance of the pulmonary artery Average "calculated resistance" closely approxi- and vein. During forward perfusion, lobar pul- mated average "measured resistance" in the seven monary artery resistance calculated from seg- lungs (Table II). However "calculated" and mental resistances averaged 46%o of total vascular "measured" resistance differed slightly in each resistance with a range of 38-54%o. If one assumes individual experiment. In order to compare the that Vpv was 28%o of VL, as measured from reverse results of all the experiments in terms of absolute perfusion, then lobar venous resistance and lobar resistance at 2-ml intervals, the calculated values capillary resistance during forward perfusion can in each experiment were multiplied by a factor Longitudinal Distribution of Vascular Resistance in the Lung 791 which corrected "calculated" to "measiured" re- TABLE I I I sistance. This correction did not change the rela- Measurements in Lung Lobes under tion between calculated resistances throughout the Sluice Conditions lobe but rather raised or lowered a 1i1 values Perfusion Resistance proportionately. Dog pressure measured VL Vpa Vmp Fig. 7 shows the average resistance peir milliliter cm H20 dyne -sece ml ml ml (resistivity) calculated at 2-ml intervalIs, for the cm-6 five forward perfusion and the two re-verse per- A 21.0 6740 19.2 6.5 7.5 C 16.0 4000 24.4 4.7 4.8 fusion experiments. During forward perfusion vas- D 21.0 5660 25.5 6.1 5.8 cular resistance was relatively high throtighout the E 23.0 4660 32.5 6.0 5.4 pulmonary arterial tree. Resistivity reacdled a peak Mean 20.5 5265 25.4 5.8 5.7 slightly before the end of the pulmonatry artery Mean nonsluice 21.4 4020 28.1 6.4 7.0 and fell throughout the remainder of the pul- Change + 0.9 -1245 + 2.7 +0.6 +1.3 monary vascular bed. _d-1itai 2z The accuracy of the analysis of segmei amstri-...of vascular resistance during forward perfusion bution decreased as the bolus moved dc)wnstream and the pulmonary veins for 20% of total vascular (see Discussion), and therefore the resataed mofe resistance during reverse perfusion, the capillaries the pulmonary veins was probably estimated more would be responsible for approximately 34%o of accurately in the reverse perfusion ex forim ts. vascular resistance. Using these figures for the Since the pulmonary arteries accounted for 46% relative distribution of pulmonary vascular resistance, resistance was 322 dynes sec cm-5/ml in ARTERIES CAPILLARIES VEINS 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 shows the average intravascular pressures throughout the pulmonary vascular tree. Table III shows the data obtained in four lungs during forward perfusion under sluice conditions, i.e., when alveolar pressure exceeded venous pres- 0 N4 sure. Under these conditions venous resistance was x not measured. The resistance midpoint was at the U end of the pulmonary artery suggesting that the arteries were responsible for about 50% of total vascular resistance upstream from the sluice point. (I) On changing to nonsluice conditions by raising venous pressure above alveolar pressure, the re- 0.. sistance midpoint moved downstream away from 44 .the pulmonary artery. DISCUSSION IS Errors in analysis of the distribution of resistances to blood flow. Perfusion pressure decreases II J| during constant blood flow 'as a bolus of fluid with I - a less than that of blood passes through a 0 0120 025 viscosity .2 series of resistances (5). The shape of the curve VOLUME (ML) plotting the decrease in perfusion pressure (AP) time is related to the distribu- FIGURE 8 Intravascular pressure in lobar vessels. Data against (or volume) for arteries from forward perfusion and data for veins tion of resistance in the system and the distribu- from reverse perfiusion. 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 of mature passage of the bolus caused an early pres- tubes or in the lung can be calculated from the sure drop erroneously attributed to the low re- curve of AP vs. volume if the distribution of vis- sistance upstream areas. This phenomenon is il- cosity within the bolus is known. lustrated in Fig. 5 CBA and the data recorded For maximum accuracy the AP vs. volume during reverse perfusion of the lung lobes. curve of the lobe and Aq vs. volume plot of the In general, the further downstream the bolus bolus should be analyzed continuously or at least moved the less compact it was and the less its at very small volume intervals. The analysis of the shape resembled the bolus shape used in the cal- AP vs. volume curve of the lobe was simplified by culations of resistance at 2-ml intervals. In the calculating resistance at 2-ml intervals along the lungs the problem of bolus distortion was mag- curve. The low viscosity bolus was spread out nified by the multiple parallel channels through over a 6 ml volume as it entered the lung. An ap- which the bolus traveled. Therefore the resistance proximate correction for the shape of the bolus was calculations became less accurate as the bolus made by dividing the Aid volume plot of the bolus moved downstream. For this reason pulmonary into three 2 ml segments. The average Anq in each artery resistance was most accurate when calcu- segment was used in making the calculations of lated from the forward perfusion experiments and resistance to blood flow. These simplifications in pulmonary venous resistance most accurate when the calculation of the distribution of vascular re- calculated from the reverse perfusion experiments. sistance tended to decrease slightly the precision The decrease in perfusion pressure produced of the method in measuring resistance changes by the saline bolus will cause a decrease in the occurring over small volume intervals. This de- volume of the highly compliant lung vessels. Vas- crease is illustrated in Fig. 5 where the actual re- cular resistance will increase at the smaller vas- sistance to flow in model tubes is plotted against cular volume abolishing a portion of the saline- resistance calculated from the AP vs. volume curve induced pressure change. Since the pressure resulting from the injection of the low viscosity change will be less than it should be, calculated bolus in the same models. Because the method of resistance will be underestimated throughout the analysis did not allow greater precision than 2 ml, vascular bed. A method for calculating the ap- the exact site of peak resistance to blood flow in proximate degree of underestimation of vascular the isolated lung lobe could not be placed more resistance is described in the Appendix. Arterial closely than 2 ml in a specific anatomic segment of resistance was underestimated by about 3%o of its the pulmonary arterial tree. resistance, capillary resistance by 1o%, and venous For the purpose of calculating resistance it was resistance by about 3%. Since resistance was un- assumed that the distribution of viscosity change derestimated in all vessels these corrections do not within the bolus, i.e. the shape of the bolus, was significantly alter the calculated longitudinal dis- constant. However, a change in the shape of the tribution of resistance in the lung vessels. bolus did occur as a result of the effects of laminar Inherent in the isolated lung lobe preparation flow as the bolus passed through the resistance used in this study are several conditions which may circuit. The front of the bolus moved more rapidly affect the distribution of pulmonary vascular re- than the body of the bolus, and the tail of the sistance and limit extrapolation of the present re- bolus moved at a slower rate than the body of the sults to the intact animal. bolus (14). As a result some viscosity change was A portion of pulmonary artery and pulmonary present in downstream vessels before it was as- vein was excluded from the preparation in the sumed to be there, and some viscosity change was process of cannulating the lobe. As a result "lobar" present in upstream vessels after the bolus had pulmonary artery and vein volume and "lobar" been assumed to have passed through these areas. pulmonary arterial and venous resistance were less When downstream resistance was high it was than they would be in the whole lung. The resist- grossly underestimated because the rapidly moving ance to blood flow in the large conducting arteries front of the bolus had passed through the high and veins is not known, but an estimate can be made resistance downstream areas and the remainder of the pressure drop across these vessels by us- caused a relatively small pressure drop. The pre- ing Poiseuille's law. Values for main pulmonary, Longitudinal Distribution of Vascular Resistance in the Lung 793S artery, left pulmonary artery, and venous trunk aged 9.1 cm H2O during forward perfusion; it was diameter were taken from the measurements of 19.5 cm H2O during reverse perfusion. Kuramoto Miller (18), and values for vessel length from the and Rodbard (23) found that pulmonary venous estimates of Schleier (1). At the average flow in resistance [(small vein pressure-left atrial pres- our experiments the pressure drop across the main sure)/flow] decreased about 30% as left atrial pulmonary artery would be 0.08 cm H2O and the pressure was raised from 10 to 20 cm H2O. If this pressure drop across the left pulmonary artery correction is applied to the results of the present would be 0.12 cm H2O. The excluded arteries study, venous resistance would account for 26% therefore account for approximately 4% of total of pulmonary vascular resistance at normal left pulmonary artery resistance. The pressure drop atrial pressure, rather than the 20% found at the across the excluded portion of the pulmonary vein pressure of reverse perfusion. would be 0.05 cm H20 or 2% of total venous re- End expiratory pressure was kept constant at sistance. These corrections do not significantly 3-5 cm H2O. The lung volume at this transpulmo- change the per cent of resistance in each of the nary pressure corresponds to the volume of air in vascular beds. the lungs at functional residual capacity in the in- Total vascular resistance of the lung lobes in the tact animal (24). What effect lung inflation has present study was similar to or less than that found on arterial, capillary, and venous resistance is not in other studies of excised and intact lungs at com- known, although it has been shown that small parable levels of blood flow (4, 19, 20). The mea- vessel volume decreases and large vessel volume surements reported were made after perfusion increases with increasing degrees of lung inflation pressure had been constant for 5 min usually 30- (25, 26). 40 min after the beginning of lobar perfusion. Longitudinal distribution of pulmonary vascu- The authors have shown, in the following paper lar resistance. The results of the present study (21), that vascular tone and reactivity are present indicate that the pulmonary arteries are responsible in both arteries and veins in the isolated lung for an average of 46%o of lobar vascular resistance. lobe preparation, and that constriction of either the The pulmonary capillaries account for 34% and pulmonary arteries or the pulmonary veins can the pulmonary veins for 20%o of total lobar vas- markedly affect the longitudinal distribution of cular resistance. Expressed as resistance per mil- vascular resistance within the lung. Whether the liliter of each vascular bed, arterial resistance is distribution of vascular resistance in the isolated approximately three times capillary or venous re- lung differs from that in the intact lung is not sistance. Peak vascular resistivity, i.e. resistance known. per milliliter, is in an area about 2 ml proximal to Increasing the pulmonary blood flow or the left the capillary bed, but resistivity is high through- atrial pressure has been shown to lower pulmonary out the pulmonary arterial tree. There does not ap- vascular resistance (20, 22). Kuramoto and Rod- pear to be a vascular segment in the lung analo- bard (23), using catheters placed in the pulmonary gous to the high resistance muscular arterioles of artery, small pulmonary veins, and the left atrium the systemic circulation. The pulmonary arteries to measure pressure gradients across segments of also contribute about half of vascular resistance the pulmonary vascular tree, concluded that all upstream from the sluice point when alveolar vascular segments share equally in the decrease in pressure exceeds venous pressure. resistance associated with increasing blood flow. Schleier (1) and more recently Piiper (5, 27) The effect of changing the blood flow on the dis- have argued that the capillaries are the major re- tribution of segmental vascular resistance was not sistance vessels in the lung. Schleier made a de- specifically studied in our preparations. There ap- tailed mathematical analysis of the distribution of pears to, be no relation between blood flow, which vascular resistance in the human lung using ranged from 96 to 214 ml/min in the five lungs Poiseuille's law. He employed Miller's measure- during forward perfusion, and the per cent of total ments of vessel diameter (18) and assumed fig- vascular resistance in the pulmonary arterial or ures for vessel length in his calculations. He con- venous vessels. cluded that, in contrast to the systemic vascular Pulmonary vein pressure was set, and it aver- bed 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 are sels. Agostoni and Piiper (4) attempted to define the major- site of vascular resistance. midcapillary pressure by measuring the pressure Schleier's calculated values for resistance ac- under which Ringer's solution was absorbed by tually do not differ greatly from the values mea- subpleural capillaries. They found that 60% of sured in the present study. He calculated that the vascular resistance in the dog isolated lung lobe arteries account for 40% of the total pressure was on the venous side of the effective midpoint drop across the lung, the capillaries 53%o, and the of the pulmonary capillaries. This is the largest veins 7%o of the total pressure drop across the estimate of pulmonary venous resistance in the lung, whereas we calculated that the arteries ac- literature. Whereas the explanation for the differ- counted for 46%o, the capillaries 34%o, and the ence between these results and the results of the veins 20%o of the total pressure drop. The differ- present study is not clear it may be that the sub- ences between Schleier's figures and ours can be pleural vessels do not reflect true intrapulmonary explained by small errors in values used for ves- capillary pressure. sel radius in Schleier's study, and by the fact that The arguments favoring the pulmonary arteries he underestimated the cross-sectional area of the as the major resistance vessels in the lung have capillary bed and therefore overestimated capil- been indirect. Campbell in 1898 (3) reasoned that lary resistance (28). the large cross-sectional area of the capillary bed Piiper (5) in describing the viscosity-change offsets the effect of the small capillary vessel size technique for measuring the midpoint of vascular on resistance to blood flow. He concluded that the resistance, or as he called it the sife of maximal greatest resistance to blood flow in the lungs was resistance, was unable to place the resistance site in the pulmonary arterioles. Lawson, Duke, Hyde, in a particular anatomic segment of the pulmonary and Forster (29) found, by varying blood flow and vascular bed. However, he later concluded that left atrial pressure in the isolated cat lung, that the major portion of vascular resistance in the pulmonary vascular resistance and diffusing ca- lung was in the pulmonary capillaries (27). The pacity could vary independently. This finding sug- major difference between Piiper's conclusions and gested to them that the capillary bed was not the those of the present study lie not in the measure- major resistance site in the lungs. DeBono and ments of the viscosity-induced pressure curve but Caro (30) have argued that the relatively rigid in the measurement of total lobar blood volume smaller pulmonary arteries contribute the maj or (VL). Piiper used a photomultiplier to measure portion of pulmonary vascular resistance during the transit time of plasma or packed red blood sluice conditions, i.e., when alveolar pressure ex- cells through the lung. He found VL to average 1.6 ceeds venous pressure. As flow increases under ml/kg, whereas VL averaged 2.2 ml/kg in the these conditions, the relation between flow and present study. The latter figure fits closely with pulmonary artery pressure remains linear. This estimated VL based on total pulmonary blood vol- would not be the case if the larger pulmonary ume being 11 ml/kg in the dog (17) and the left arterial vessels which are more compliant con- basal lobe accounting for 25%o of total lung vol- tributed a major portion of vascular resistance. ume and presumably 25% of total pulmonary Pulmonary arterial wedge pressure (Pw) pro- blood volume (6, 7). We were unable to measure vides an approximate measure of venous pressure, known volumes accurately using plasma or packed but it is not clear which vessels are included in the red blood cells as an indicator and a photocell "arterial" [(Pulmonary artery pressure- Pw) / (Grass finger plethysmograph) or photomultiplier flow] and "venous" [(Pw-left atrial pressure)/ as a sensing device. All such measurements grossly flow] resistances measured by this method (31). underestimated actual volume in our hands prob- Direct measurements of pressure gradients along ably because the tail of the dilution curve was not pulmonary vessels with small catheters have not visualized. If VL in Piiper's study were increased provided consistent results in the pulmonary cir- to that found in the present study his results culation. True lateral pressures are not measured, would agree closely with ours. pressure gradients are small, and variations in There is only one study which suggests that pressure with tube placement and tube size and the pulmonary veins are the major resistance ves- difficulty 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, volume (Vc) was calculated to be 50 ml or 38% 33). "Venous resistance" has ranged from 4 to of total pulmonary blood volume. This calculation 20%o of total pulmonary vascular resistance in stud- presumes that Vpv accounted for the same per ies which assume the difference between arterial cent of VL during forward and reverse perfusion. wedge pressure and left atrial pressure to be the Some limit can be placed on the error inherent in gradient across the pulmonary veins (34, 35). this assumption. The volume of the capillaries and "Venous resistance" has ranged from 19 to 49%o veins increased by 2.1 ml after elevation of reser- of total pulmonary vascular resistance in studies voir pressure from 0 to 9 cm H20 during forward when the difference between pressures recorded perfusion (Table III). Since venous compliance is from small catheters threaded into pulmonary approximately four times capillary compliance veins and left atrial pressure was used as the (39), the veins would have increased by 1.7 ml. If gradient acrioss the pulmonary veins (36, 37). one assumes that a similar increase in Vpv would Connolly and Wood (38), using the difference occur if reservoir pressure was raised from 9 to 18 between pulmonary artery pressure and pressure cm H20, the difference in pulmonary vein pres- recorded from a catheter wedged in the pulmonary sure between forward and reverse perfusion, Vpv veins to estimate the pressure gradient across the could have been overestimated by a maximum of pulmonary artery, found "arterial resistance" to 1.7 ml. Therefore Vpc could not have been more be 68%o of total pulmonary vascular resistance in a than 14.2 ml nor Vc more than 43%o of total pul- group of patients. Aviado (37), however, found monary blood volume. virtually no pressure gradient across the pulmo- Weibel (28) found Vc to average 146 ml in ana- nary artery in dogs using the wedged venous tomic studies of five human lungs. Bates, Varis, catheter. No estimates of capillary resistance have Donevan, and Christie (40) found Vc derived been made from any of these studies. from steady-state diffusing capacity measured dur- The resistance to blood flow in a vascular bed ing exercise at two different oxygen tensions to is determined not only by the length and radius average 153 ml. Lewis, McElroy, Hayford-Wel- of the vessels in that bed, the l/r4 factor in sing, and Samberg (41) obtained similar values Poiseuille's law, but also by the number of vascu- for Vc in supine man using the rebreathing method lar segments in the bed. The h/r4 factor therefore for measuring diffusing capacity. If average pul- is multiplied by 1/n where n is the number of vas- monary blood volume in man is assumed to be cular segments. Weibel (28) has found capillary 450-500 ml (42, 43), Vc would account for about length to be 12 X 10-4 cm and capillary radius 30-35%O of total pulmonary blood volume in these 4 x 10-4 cm in the human lung. But he has also studies. Calculation of Vc derived from single found that there are 280 X 109 capillary segments. breath diffusing capacity measurements have been The effect of the very small capillary size is there- somewhat lower both during exercise and in the fore cancelled by the large cross-sectional area of supine position (41, 44). It is difficult to compare the capillary bed. Similar figures for the arterial the Vc measurements of the present study, those and venous vessels are not available. It seems of Weibel (28), Bates and coworkers (40), and probable that the most important determinant of Lewis and coworkers (41), which were done at a the longitudinal distribution of vascular resistance lung volume equivalent to functional residual ca- in the lung is the relation between vessel size pacity with Vc values determined by the single (mainly radius) and the total number of segments breath-diffusing capacity method which is done at in a vascular bed. peak inspiration. The relation between degree of Pulmonary capillary blood volume. Lobar capil- lung inflation and pulmonary vascular volume is lary blood volume (Vpc) was calculated by sub- complex. Macklin (25) and Howell, Permutt, tracting lobar pulmonary artery volume, measured Proctor, and Riley (26) have shown that large in the forward perfusion experiments, plus lobar and small lung vessels react in different ways to pulmonary vein volume (Vpv), measured in the increasing degrees of lung inflation, and Hamer reverse perfusion experiments, from total lobar (45) has found that Vc, as measured by single blood volume (VL). Vpc calculated in this way breath-diffusing capacity method, decreases with averaged 12.5 ml. Total pulmonary capillary blood increasing lung volume. 796 J. S. Brody, E. J. Stemnler, and A. B. DuBois Applications (49). Investigations into the mechanisms of ex- Vessel response to stimuli. The methods de- perimental pulmonary edema have been hampered scribed provide a way of measuring the pressure by the lack of accurate measurements of pulmonary drop and resistance to blood flow in each portion capillary pressure (50). Pulmonary capillary pres- of the pulmonary or systemic vascular beds with- sure measurements would also be of value in study- out requiring direct measurements of pressure ing the transudation of various substances through gradients within the vessels. This technique can the capillary wall and the bursting point of pul- be applied to analyzing arterial, capillary, and monary capillaries submitted to high transmural venous responses to a variety of pharmacologic pressures such as seen in mitral stenosis or under and physiologic stimuli. We report in the follow- gravitational stress. ing paper (21) the effects of several drugs on the The methods described in the present study al- individual vascular segments in the dog lung us- low for the first time accurate measurement of pul- ing the methods described in this paper. monary capillary pressure. Midcapillary pres The calculations involved can be simplified and sure averaged 13.3 cm H2O, whereas pulmonary the precision of the results improved if the shape artery pressure averaged 20.4 cm H2O, and pul- of the low viscosity bolus, the change in bolus monary vein pressure averaged 9.2 cm H20. shape as it passes through the lung, and the re- Under the circumstances of the experiments resulting change in perfusion pressure with time in ported, 63%o of the pressure drop in the pulmonary the vessels are analyzed with an analogue or digi- vessels occurred before the midpoint of the pul- tal computor. The preparation can be simplied as monary capillaries. Pressure at the arterial end of we found by perfusing the lobe of a dog with the the pulmonary capillaries averaged 15.3 cm H20, dogs own blood and without a donor dog in an whereas pressure at the venous end averaged 11.4 open (reservoir) or closed (no reservoir) system. cm H20. These values were determined during The techniques presumably can also be applied to steady nonpulsatile flow. Linderholm, Kimbel, the intact animal providing that flow and venous Lewis, and DuBois' (51) analysis of instantane- pressure are kept constant or measured continu- ous capillary flow and pulse pressure suggests ously. that the pressure-flow curve of the pulmonary ves- Pulmonary capillary pressure. Accurate -mea- sels is linear. If this is true the longitudinal dis- surements of capillary pressure in the systemic tribution of resistance determined during non- circulation have been available for many years pulsatile flow should not differ significantly from (46), but there are no methods for measuring mean values determined during pulsatile flow. capillary pressure in the lung. The pressure re- APPENDIX corded from a catheter wedged into small pulmo- The decrease in perfusion pressure caused by the low nary arterial vessels was initially thought to rep- viscosity bolus produced a decrease in the volume of the resent pulmonary capillary pressure (47), but highly compliant lung vessels. During forward perfusion further studies have shown that the arterial wedge the mean bolus-induced perfusion pressure change aver- pressure reflects pressure in vessels distal to the aged 1.3 cm H20 in the pulmonary arteries and 0.8 cm capillary bed (48). Pulmonary venous wedge H20 in the pulmonary capillaries. The mean pressure decrease in the pulmonary veins was 0.5 cm H20 during pressure appears to reflect pressure in vessels reverse perfusion. The vascular volume changes associ- proximal to the pulmonary capillaries (48). ated with these pressure changes can be estimated by us- Agostoni and Piiper (4) described an indirect ing the values for pulmonary vascular compliance deter- method for measuring pulmonary capillary pres- mined by Engelberg and DuBois (39). Vascular volume admit the decreased 0.2 ml in both the pulmonary arteries and veins sure from subpleural capillaries, but they and 0.1 ml in the pulmonary capillaries. subpleural capillary pressure could be quite dif- The error in the calculations of vascular resistance as- ferent from intrapulmonary capillary pressure be- sociated with the vascular volume changes can be de- cause of structural differences between the two rived if it is assumed that vascular conductance is pro- types of vessels. portional to vascular volume. Point A in Fig. 9 represents the average calculated conductance (Ge) for the Hydrostatic pressure in the pulmonary capillary pulmonary arteries and the average volume at which it bed is thought to be the most important-factor in was measured [pulmonary artery volume (V) minus the the etiology of most forms of pulmonary edema bolus-induced volume changes (AV)]. Point B represents Longitudinal Distribution of Vascular Resistance in the Lung 797 U. S. Public Health Service Grant 2 T 1-GM-957-05. Dr. DuBois is a recipient of a Research Career Award of the National Institutes of Health. REFERENCES ,, z~~60 / 1. Schleier, J. 1918. Der Energieverbrauch in der Blut- U 50 bahn. Pfleugers Arch. Ges. Physiol. 173: 172. 2. Rushmer, R. F. 1965. The arterial system: arteries and arterioles. In Physiology and Biophysics. T. C. Ruch and H. D. Patton, editors. W. B. Saunders Co., Philadelphia. 19th edition. 600. 0 4 o , . 3. Campbell, H. 1898. The resistance to the blood flow. J. 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