The Acute Effects of Atelectasis on thePulmonary Circulation

Albert H. Niden

J Clin Invest. 1964;43(5):810-824. https://doi.org/10.1172/JCI104967.

Research Article

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Journal of Clinical InvestigationVol. 43, No. 5, 1964

The Acute Effects of Atelectasis on the PulmonaryCirculation *

ALBERT H. NIDEN(From the Department of Medicine, University of Chicago, Chicago, Ill.)

There is little doubt that pulmonary arterialblood flow is diverted away from chronically col-lapsed lung tissue. The earlier literature has beenextensively reviewed by Berggren (1), and morerecently other investigators have confirmed thisfinding (2-9). The effects of acute atelectasison pulmonary blood flow are not, however, so wellestablished (1, 4, 5, 7, 10, 11). Acute atelectasishas been induced by pneumothorax (1), by bron-chial occlusion with chest wall intact (4), and bybronchial occlusion with chest opened wide andlungs ventilated by intermittent positive pressure(5, 7, 10, 11). It is generally assumed that thepulmonary hemodynamic changes with acuteatelectasis are similar regardless of the method ofinducing atelectasis. However, each of the abovemethods for producing local collapse of lung tis-sue (segment, lobe, or one lung) produces dif-ferent "intrathoracic" pressure changes, differenteffects on left atrial pressure and on the non-collapsed lung tissue, and possibly noncomparablehemodynamic consequences. Since the early pul-monary vascular changes after endobronchial oc-clusion in the intact animal have not been welldelineated, the following study was undertaken.The effects on the pulmonary circulation of acuteatelectasis by endobronchial obstruction were in-vestigated in fourteen intact lightly anesthetizeddogs breathing spontaneously and six innervatedperfused dog lungs ventilated by means of a wholebody negative pressure respirator. In addition,the hemodynamic response to local pulmonary hy-poxia and hypercapnea was contrasted with that oflocal collapse of lung tissue.

* Submitted for publication July 17, 1963; acceptedDecember 26, 1963.

Supported by grants f rom the National Heart In-stitute (H-3878) (H-6918) and the Schweppe Foundation.

Presented in part at Federation Meetings of Ameri-can Societies for Experimental Biology (Fed. Proc. 1961,20, 105).

Methods

Mongrel dogs (15.6 to 22.8 kg) were anesthetized withmorphine sulfate (2 mg per kg subcutaneously) anda-chloralose (50 to 100 mg per kg intravenously). Hep-arin (5 mg per kg, iv) was used for anticoagulation; ad-ditional heparin (2.5 mg per kg, iv) was administeredevery 2 to 3 hours. The trachea was cannulated rou-tinely. Systemic blood pressure was measured withpolyethylene tubing inserted into the carotid artery, pul-monary arterial blood pressure by cardiac catheter in-serted into the pulmonary artery via the external jugularvein, and left auricular blood pressure by polyethylenetubing inserted into the left auricular appendage. Per-fused pulmonary arterial (vide infra) blood pressure wasdetermined by polyethylene tubing inserted into a sidearm of the perfusion tubing and extending one-eighth toone-fourth inch beyond the orifice of the perfusion can-nula (12). All pressures were measured by Stathamstrain gauge transducers and recorded on a Grass poly-graph instrument. Peripheral arterial and mixed venousblood from the pulmonary artery were analyzed in dupli-cate for oxygen content and oxygen capacity by VanSlyke determinations (13). [In dogs no. 79, 80, and 81oxygen saturation was determined with the Beckmanspectrophotometer (14).] 1

Experiments were performed on fourteen dogs breath-ing spontaneously with chest wall intact, subsequentlyreferred to as "intact dog" preparations. In an additionalsix dogs with chest wall opened, innervated left middleand lower lobes of the lung were perfused with a con-stant flow of blood (vide infra). These dogs will bereferred to as "perfusion" experiments. In eleven ofthe fourteen intact dog preparations as well as all of theperfusion experiments, acute atelectasis was produced bya balloon-tipped single lumen polyethylene catheter (i.d.,0.07 inch; o.d., 0.11 inch). The catheter with balloondeflated was inserted into the trachea below the trache-ostomy and positioned in the bronchus with the aid ofbronchoscopy.

In three intact dog experiments the right lung wasseparated from the left by a modified Wright trachealdivider (15) or a Zavod-type bronchospirometer tubepositioned under fluoroscopic control. When utilizingeither the tracheal divider or the bronchospirometertube, complete separation of the two lungs was con-firmed by monitoring the nitrogen content in the ex-

1 Analyses kindly performed by Gladys Mims.

810

ACUTEATELECTASIS AND THE PULMONARYCIRCULATION

MIXED VENOUSBLOOD

FIG. 1. SCHEMATICDIAGRAMOF THE INNERVATEDPERFUSIONOF LEFT MIDDLE ANDLOWERLOBES. Left upper lobe artery cannulated; see text for details. P = con-stant flow perfusion pump, PA= pulmonary artery, RA= right auricle, RL =right lung.

pired air 2 from each lung while giving 100% oxygen toone lung. As a result of tracheobronchial tree distor-tion with atelectasis, it was difficult to maintain separa-tion of the right and left lungs with the tracheal divideror bronchospirometer tube. For this reason the balloon-tipped single lumen catheter was preferred to the trachealdivider or bronchospirometer tube.

The anatomic shunting of blood through the lungs canbe estimated from the "shunt equation" (16):

~, Cc'2 - Gao2D

C1O2 - Ct02' [1]

where Q and Q8 are the total pulmonary blood flow andblood flow shunted past nonventilating alveoli, respec-tively, and C102, Cao2, and C002 are the oxygen content ofpulmonary end capillary, peripheral arterial, and mixedvenous bloods, respectively.

The increased mixed venous blood shunted as a result ofobstructing portions of lung was determined in the follow-ing manner. After insertion of the endobronchial tube(balloon-tipped, tracheal divider, or bronchospirometertube) but before bronchial occlusion, the intact animals,breathing spontaneously, were ventilated with 100%oxygenfor 15 minutes, and the oxygen content of the peripheralarterial blood was determined as a control value. After

2 Nitralyzer Model 100 A, Custom Engineering andDevelopment Co., St. Louis, Mo.

the animal had been returned to ventilation with room airfor 10 minutes, portions of lung (segment, lobe, or wholelung) were made atelectatic by obstructing the bronchus.In four of the intact dogs, atelectasis was also inducedwhile the animal was being ventilated with 100% oxygen,after which the nonobstructed lung was immediately re-turned to ventilation with room air. Peripheral arterialoxygen saturation was continuously monitored by a cuvetteoximeter inserted between a femoral artery and vein andrecorded on the Grass polygraph. At varying intervalsafter endobronchial obstruction, samples of peripheralarterial blood from the femoral artery and mixed venousblood from the pulmonary artery were obtained simultane-ously for oxygen content determinations. To assessanatomic shunting, all blood samples were collected afterthe noncollapsed lung had been ventilated with 100%oxygen for 10 to 15 minutes. Thus in all experiments non-obstructed portions of lung were ventilated with room airexcept for 15-minute periods at the time of blood samplecollections.

In these experiments the peripheral arterial blood oxygencontent obtained as a control value while breathing 100%oxygen (CaO2 control) is used as an estimate of the pul-monary end capillary blood oxygen content. By sub-stituting the CaO2 control for C602 in Equation 1, we have:

0, _ Ca2eontro 1 - Cao2 [2]- CaOvontro1 - Cl0o22

which is then an estimate of the blood flow shunted as a

811

ALBERT H. NIDEN

PRESSURE

TO PUMP

TOVACUUM

FIG. 2. WHOLEBODY NEGATIVE PRESSUREANIMAL RESPIRATOR.

result of collapsing lung tissue. Since the Cao2 controlis less than the true pulmonary end capillary blood oxy-

gen content, Equation 2, which was used for the calcu-lations to be reported, would give an underestimate ofthe total shunt present after atelectasis. However, ifthe oxygenation of pulmonary end capillary blood is thesame during the control and test periods while breathing100%o oxygen, this equation does give a close approxi-mation of the shunt resulting from the endobronchialocclusion.

To assess the magnitude of change in the oxygenationof end capillary blood from the control to the test pe-

riods (whether the intermittent use of 100%o oxygen

produced sufficient atelectasis in the nonoccluded por-

tions of lung to affect the results), control experimentswere performed on four intact dogs. The dogs were

prepared for endobronchial occlusion as outlined above.One hundred per cent oxygen was administered to thefour dogs for 20 minutes alternately with room air for30 minutes for total periods of 200, 200, 250, and 200minutes, respectively. Peripheral arterial and mixedvenous blood samples were collected while the animalswere breathing 100% oxygen at the end of the initial(Cao2 control) and final (Cao2, CVo2) 20-minute periodsof oxygen breathing. The percentage of shunting of

blood past nonventilating alveoli was then calculated asin the experimental animals.

In the perfusion experiments, innervated left middleand lower lobes were perfused after opening the chestwith a left fourth intercostal incision and while ventilat-ing the lung with a Harvard positive pressure respirator.The perfusion cannula, directed towards the pulmonaryarterial bifurcation, was tied into the left upper lobe ar-tery. The left main pulmonary artery was ligated byan intrapericardial ligature. Thus the left middle andlower lobes could be perfused without manipulation ofor interference with their nerve supply or bronchialcirculation. The perfused pulmonary venous outflowdrained normally into the left auricle and thence to thesystemic circulation. Blood flow to the right lung wasmaintained by the animal's own heart (Figure 1) (17).Perfusion blood flow was kept constant with a modifiedDale-Schuster pump (12) primed with heparinized blood(10 mg heparin per 100 ml blood) or dextran.3 Bloodflow was continuously monitored and recorded on theGrass polygraph by a Shipley-Wilson rotameter insertedinto the inflow side of the circuit. Perfusion was begun

3Generously supplied by Abbott Laboratories, NorthChicago, Ill.

812

ACUTEATELECTASIS AND THE PULMONARYCIRCULATION

30[ 4 RESPIRATIONS/MIN

20[

3--V.(cc)

3 - MEAN PAPTmmHG)5

MINUTES 0 K) 20 30 40 50 60 70 80 90 100 110 130 150 170 190tOCCLUSION DOG86 3-1-60 17.5 KG.

FIG. 3. ACUTE COLLAPSE OF THE RIGHT LOWERLOBE WHILE BREATHING

ROOMAIR (DOG 86). In this and all subsequent figures, Sao2= peripheralarterial oxygen saturation while ventilating noncollapsed lung with 100%ooxygen. TV=tidal volume; mean PAP=mean pulmonary arterial pres-sure. Endobronchial occlusion at time "O." Anatomic shunt calculated atthe arrow.

before tying the intrapericardial ligature about the leftmain pulmonary artery so that blood flow to the per-fused area was uninterrupted. In all perfusion experi-ments ventilation was maintained without interruptionof ventilation or perfusion by a box respirator (Fig-ure 2) with the trachea opened to the atmosphere, the

lung being ventilated with rhythmic changes of negativepressure within the box (11). Catheters for measuringcarotid arterial, pulmonary arterial, left auricular, andperfusion blood pressures as well as the balloon-tippedsingle lumen endobronchial catheter were brought outthrough rubber stoppers inserted into openings in the

MINUTES 0 10 20 30 40 50 60 70 80 90 100 110 130150 70 190f OCCLUSION DOG82 1-26-60 18.2 KG.

FIG. 4. ACUTECOLLAPSEOF LEFT LOWERLOBE WHILE BREATHINGROOMAIR(DOG 82). Note the reduction in anatomic shunt after 3 hours and 10minutes.

813

-1

6Z SHUNT

814 ALBERT H. NIDEN

FIG. 5. TYPICAL AUTOPSY FINDINGS (DOG 109) 4 HOURS AND 20 MINUTES AFTER ENDO-

BRONCHIALOCCLUSIONOF LEFT LOWERLOBE BRONCHUSREVEALING COMPLETEATELECTASIS OF LEFT

LOWERLOBE.

TABLE I

Acute atelectasis versus percentage of blood shunted in intact dogs

Dog Duration %Lungno. Lung collapsed* collapsed collapsed %Shunt

minutes79 Segment left lower lobe 120 15 40t80 Segment left lower lobe 30 15 30t81 Right lung 30 55 8382 Left lower lobe 10 30 65

Left lower lobe 200 30 3284 Right lung or lesst 45 55 or less 6385 Right lower and middle lobes 100 40 5186 Right lower lobe 110 30 5187 Right lower lobe 20 30 40

Right lower lobe (100% 02)§ 25 30 50.599 Left lung 45 45 49

101 Left lung 25 45 36.5Left lung (100% 02)§ 25 45 35

109 Left lower lobe 260 30 50Left lower lobe (100% 02)§ 15 30 40

115 Left lung or less4 10 45 or less 47123 Left lung 20 4311 53

Left lung (100% 02)§ 20 41 11 63129 Segment left lower lobe 35 15 36

* Lungs collapsed while breathing room air unless otherwise noted.t No mixed venous sample. a-v 02 gradient assumed to be 5 vol per 100 ml.t Balloon broke after blood determinations. Maximal possible percentage of lung collapsed estimated by position

of balloon at autopsy (terminal portion of lower lobe bronchus).§ Lung collapsed after ventilation with 100% 02-11 Determined from percentage of ventilation to each lung with bronchospirometer tube.

aL&J

-JI

0U0zD

Ij

9

el

74

3C

20

IC

ACUTEATELECTASIS AND THE PULMONARYCIRCULATION

o % BLOODSHUNTEDvs.

70 LUNG COLLAPSED0-

0

so~~~~~VW 00

D _ / 00

0 00

%SHUNT/ 1O0 2I0 310 40 Ni 6i0 710 8,0 9p0

FIG. 6. SUMMARYOF ACUTE ATELECTASIS IN INTACT DOGS. 0 = endo-bronchial occlusion after ventilation with room air. * = endobronchialocclusion after ventilation with 100% oxygen. All points below the diag-onal line indicate a greater percentage of anatomic shunting than percentageof lung tissue collapsed.

box. After a 15- to 30-minute control period, occlusionof the left middle and lower lobe bronchi was producedby inflation of the balloon at the tip of the endobronchialcatheter. The extent of atelectasis was directly visual-ized through a clear plastic window in the respirator box.

All intact dogs were autopsied (the chest being openedwith the trachea occluded) immediately after blood gaseswere obtained. The extent of atelectasis was notedgrossly and the lung photographed. The lung was re-moved with trachea occluded and fixed in formalin.Both the overdistended and collapsed lung tissues werethen sectioned and stained with hematoxylin and eosinfor examination with the light microscope.

Results

Acute pulmonary atelectasis in the intact dog.The over-all response to atelectasis by endo-bronchial occlusion of portions of the lung (seg-ment, lobe, or whole lung) was observed in four-teen intact dogs for periods of from 20 minutesto 4 hours and 20 minutes. With endobronchialobstruction there was a fall in peripheral arterialoxygen saturation beginning within 1 to 2 minutes

and reaching a low value (47 to 89.5 % whilebreathing 100%o oxygen) within 10 to 20 minutes.This was accompanied regularly by an immediateslight fall in mean pulmonary arterial blood pres-sure that was usually but not always followed bya moderate increase in pressure. Respiratoryminute volume increased two- to fourfold as aresult of an increase in respiratory rate or tidalvolume or both (Figures 3, 4).

The calculated percentage of blood flow shuntedthrough nonventilating alveoli as a result of theocclusion ranged between 30 and 83 %. Exceptfor one dog (no. 101), the percentage of bloodflow shunted was equal to or greater than theamount of lung tissue collapsed, as ascertained atautopsy (Figure 5). The extent of atelectasiswas sharply outlined and limited to anatomic seg-ments or lobe(s). The data are summarized inTable I and Figure 6. One dog (no. 82) ob-served over a protracted period of time showed achange in the percentage of blood shunted froman initial 65 to 32% at 3 hours and 20 minutes

815

6c

5c

4C

ALBERT H. NIDEN

> : 2$< t to R^~~~~~~~~~~~~~~~~~~~~~~~~~~~0FIG7TYICL ISTLOICAPPARNC OFTH AUTEY TELCTTI LUG RIHT OWR ND IDLELOBSDO

85) 1 HOURAND 40 MINUTES AFTER COLLAPSE. Note dilated vascular bed filled with red blood cells (X 500).

after collapse of the left lower lobe (approximately30%o of the lung) (Figure 4).

In one dog (no. 109) intrapleural pressurewas measured through a Harvard pleural can-nula. Mean intrapleural pressure was - 9.0 cmH2O before and - 14.0 cm H2O after collapse ofleft lower lobe.

With acute atelectasis the a-v oxygen gradientacross the lung while breathing 100% oxygen (16determinations) ranged between 4.43 and 9.80 volper 100 ml oxygen, with an average value of 7.27.The oxygen gradient while ventilating one lungwith 100% nitrogen (six determinations) rangedbetween 7.88 and 10.43, with an average of 9.01vol per 100 ml oxygen.

The histologic appearance of the acutely atelec-tatic lung revealed, in addition to complete atelec-tasis of the alveoli, marked congestion of thepulmonary vascular bed with dilated arterioles andcapillaries filled with red blood cells. A typicalmicroscopic section is shown in Figure 7.

Acute pulmonary atelectasis in the intact dogwhile breathing 100% 0,2 In four dogs the ef-fect of acute bronchial obstruction while breathingroom air was compared to that while breathing100% oxygen (Figures 6, 8; Table I). Exceptfor the delay of 4 to 8 minutes before a fall inperipheral arterial oxygen saturation with thedogs breathing 100% oxygen, there was no dif-ference in response.

This venous admixture, greater than predictedfrom the percentage of lung tissue collapsed whilebreathing room air or 100% oxygen, could haveresulted from a) atelectasis in the dependent por-tions of nonoccluded lung as a result of anesthesiaand 100%o oxygen or b) the opening of anatomicshunts in the noncollapsed lung as a consequenceof overdistention or c) the decreased pulmonaryvascular resistance in the acutely collapsed lungbecause of hypoxia, hypercapnea, neurogenicstimuli, and/or mechanical effects. Further ex-periments were designed to determine the mecha-

816

ACUTEATELECTASIS AND THE PULMONARYCIRCULATION

QZ 80 < 153, RJNT

5020

P 15' aA.

P 10 -8S 130

s. 110

B.9Q - f COLLAPSEL LUNGp ROOMAIR

COLLAPSE L LUNGlOO5 °2

1 I I~

MIN 0 4 8 12 16 20' 0 4 8 12 16 20DOG 123 19.81KG 9-19-60FIG. 8. ACUTE ATELECTASIS OF LEFT LUNG (DOG 123). Lung filled

with room air before collapse compared to lung filled with 100%o oxygen

before collapse. Sys. BP = peripheral arterial blood pressure.

nism of this early increased venous admixture inacute pulmonary atelectasis by endobronchialocclusion.

Intermittent 100%70 oxygen to control dogs. Al-ternate administration of 100% oxygen for 20minutes and room air for 30 minutes to fouranesthetized dogs for 200, 200, 250, and 200 min-utes, respectively, produced a calculated shunt ofpulmonary blood flow through nonventilated al-veoli ranging between 0 and 6%o (Table II).

Local hypoxia and hypercapnea in the intactdog without atelectasis. To ascertain whether thelocal effect of capillary or venous blood gas

changes (hypoxemia and hypercapnia) in theatelectatic lung tissue could account for the ap-

parent increase in blood flow through an acutelyatelectatic lung, ventilation of one lung with 100%

nitrogen either alone or with 7.5% carbon dioxidewas compared to acute atelectasis. Utilizing a

bronchospirometer tube to separate the left lungfrom the right, ventilation of the left lung withnitrogen, either alone or with 7.5 %carbon dioxide,produced less -shunting of blood through this lungthan acute collapse of the left lung in two dogs(Table III, Figure 9). Since oxygen is actuallyremoved from blood flowing past alveoli beingventilated with 100%o nitrogen, the calculated

percentage of blood shunted under these circum-stances is an overestimate of the true shunt.Thus the local effects of hypoxemia and hyper-capnia could not account for the increased shunt-ing of blood through acutely collapsed lung.

Acute pulmonary atelectasis in the innervatedlung perfusion. To measure directly changes invascular resistance in the atelectatic lung, constantflow perfusions of innervated left middle andlower lobes were performed in six dogs. Acutecollapse of these lobes perfused at a constantflow resulted in an immediate fall in perfusionpressure in five of the six dogs tested with eitherno change or more often a slight rise in pulmonary

TABLE II

Effect of intermittent ventilation with 100% oxygen on theshunting of blood

TotalDog Total durationno. time 100% 02 %Shunt*

minutes minutes

251 200 80 6253 200 80 0255 250 100 4257 200 80 4

* Assuming 0% shunt after 20 minutes of ventilationwith 100% oxygen [time of first (control) blood samples].See text for details.

817

ALBERT H. NIDEN

P20A

(InnH8,~s3ByS. I 10a qc~(mmlH

0-0- o-----<>0q&70-

1007* N2 LEFT LUNG COLLAPSE LEFT LUNG ROOMAIRt on 4off tcdlapse

KNO". U zq4 RIUDOG 123

I U 2 4 6 b 10 12 14 16 lb 2u19.8 K G. 1-19-60

FIG. 9. COMPARISONOF ACUTECOLLAPSEOF LEFT LUNGWITH UNILATERAL VENTILA-

TION WITH 100% NITROGEN (DOG 123).

arterial pressure of the noncollapsed lobes whoseblood supply came from the animal's own heart.There was no change or a slight increase in theleft atrial pressure. Re-expansion of the col-lapsed lung resulted in immediate return of pres-sures to the control level (Figures 10, 11). Sym-pathectomy (removal of thoracic sympatheticganglia 2 through 6) in four dogs and bilateralvagotomy alone or in combination with sympathec-tomy in two dogs did not alter the type of response(Figure 10).

In one experiment, blood flow through the leftlower and middle lobes was measured directly bycollecting the outflow from the left lower lobevein and that from the left middle lobe vein. Theleft lower and middle lobes were perfused in the

Acute atelectasis versus

TABLE III

ventilation withleft lung

100% nitrogen to

%Totalventilation, %Blood

Procedure left lung shunt

100% N2, 41 32left lung

Room air, 43 53collapse left lung

100% 02, 41 63collapse left lung

usual manner from a single pump at a constantflow while the lung was ventilated in the negativepressure animal respirator. Collapse of the leftlower lobe alone resulted in an increase in leftlower lobe venous outflow with an equal decreasein left middle lobe venous outflow, over-all flowthrough the two lobes being maintained constantby the perfusion pump.

Discussion

Acute pulmonary atelectasis by endobronchialocclusion in the intact dog results in an increasedvenous admixture of the peripheral arterial bloodout of proportion to the amount of lung tissuecollapsed. Constant-flow innervated lobe perfu-sions suggest that this is on the basis of an initialdecrease in pulmonary vascular resistance in theatelectatic lobes. Sympathectomy alone or com-bined with vagotomy does not alter the response.When compared to the effect of acute atelectasis,unilateral ventilation with 100%o nitrogen or92.5% nitrogen and 7.5% carbon dioxide in thesame dog reduces the amount of blood flow to theaffected lung, indicating that the decreased vas-cular resistance in acute atelectasis cannot be as-cribed to the associated alveolar hypoxia and hy-percapnea or to either separately.

818

ACUTEATELECTASIS AND THE PULMONARYCIRCULATION

9r

"R"

(PERF. BP-LA1I

5L

PERE BP7

0- wM HG) 4 .5

L A P raICM HG) L

- 3

-8

BOX p -70-(MM HG)

_ COLLAPSELL. OFF0 2I I 8II I I I

100 2 4 6 8 10 12 14 1B

DOG121

I

0F-UwI

a.

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14 -

13 -

i2

13

12 -jLI

2 2.8 KG

COLLAPSELL. OFFI I I-L- .

I I0 2 4 6 8 10 12 14

9-13-60FIG. 10. ACUTE ATELECTASIS OF THE INNERVATED PERFUSED (CONSTANT FLOW) LEFT MIDDLE

AND LOWERLOBES BEFOREAND AFTER SYMPATHECTOMY(DOG 121). R = perfusion arterial bloodpressure minus left atrial blood pressure, a measure of vascular resistance when blood flow isconstant. Perf. BP = perfusion arterial blood pressure. LAP = left atrial pressure. BoxP = intrabox pressure of the negative pressure whole animal respirator, i.e., "intrathoracic"pressure.

The histologic observations of the acutely col-lapsed lung reveal a dilated capillary bed filledwith red blood cells. These findings agree withthe physiologic findings indicating a decreased pul-monary vascular resistance. Passive congestion

30-

PERF BR 200-

480- RO(FLOW 300-_( CC/M IN) I60-

0-

PRESSURE _0(CM H20)

SYS. B.1? 120-Wm HG) 80-

40- tOCCLUSION L.L.

DOG107

cannot, however, be differentiated from an in-creased blood flow on the basis of histologic ap-pearance. In contrast, chronic atelectatic lunghas a reduced vascular bed histologically as wellas a reduced blood flow physiologically (18, 19).

1 -

DM AIR

_-l

RE ASE

7-12-6016.4 KGFIG. 11. ACTUAL TRACING FROMAN INNERVATED LEFT MIDDLE AND LOWERLOBE PERFUSION

(DOG 107).

--- 7"W-T--T.-. W-R, I I 0 A 0 WA i i iT -I- 1- - -11" I- -

819

ALBERT H. NIDEN

Several technical problems are apparent in astudy of this type. First, despite careful place-ment by bronchoscopy of the balloon-tipped cathe-ter, it is impossible to collapse a predeterminedamount of lung tissue with certainty. Thus per-forming routine autopsies immediately after thecollection of blood samples is essential to ascertainthe actual extent of atelectasis and the position ofthe balloon. In all cases the area of atelectasiswas sharply defined and limited to anatomic seg-ments or lobes. Second, endobronchial occlusionis used to produce atelectasis to eliminate anypossible injury to the nerve supply, to the bronchialcirculation of the collapsed lobes, or to both, whichmay occur with the use of a bronchial ligature.Third, cannulation for the constant flow perfu-tions of the left middle and lower lobes is im-portant. This approach eliminates manipulationof and injury to the vessels and nerves of theperfused lobes, which frequently occur when di-rect cannulation of the perfused lung is employed.Finally, as indicated by the results, the oxygena-v gradient across the lung in acute abnormalcardiopulmonary conditions such as acute lungcollapse may be increased above the normal aver-age of 4.2 vol per 100 ml [2.3 to 6.3 in dogs anes-thetized with Nembutal (20, 21)]. Therefore,assumption of a fixed a-v gradient under such cir-cumstances is invalid; a mixed venous blood sam-ple is necessary to determine accurately the per-centage of blood shunted. The reasons for theincrease in a-v oxygen gradient in these experi-ments are not clear. Chloralose anesthesia, hy-poxemia, and hyperventilation may have inducedan increase in oxygen consumption or a decrease incardiac output, or both. Neither of these param-eters was measured.

From the results, at least initially, there is ap-parently little difference between the blood flowthrough a partially collapsed lobe and through acompletely collapsed lobe after endobronchial oc-clusion. Although the lobes filled with room airat the time of the endobronchial obstruction didnot completely collapse for a few hours becauseof the nitrogen present, the lung filled with 100%coxygen became completely atelectatic within 10minutes (22). Despite this, there was no dif-ference between the shunting observed after endo-bronchial occlusion while breathing room air and

while ventilating with 100% oxygen, except forthe earlier appearance of peripheral arterial oxy-gen desaturation with the former (Figures 6, 8;Table I). The delayed appearance of arterialhypoxemia after obstruction of the oxygen-filledlungs is understandable. The partial pressureof oxygen in this lung remains high until all theoxygen is absorbed and alveoli completely collapse.In contrast, with nitrogen present in the lobesfilled with room air, the partial pressure of oxy-gen begins to decrease immediately as oxygen isremoved, resulting in an almost immediate arterialdesaturation after obstruction of those lobes.

Although the hemodynamic effects in the ven-tilated lung were not extensively investigated inthe present study, the marked peripheral arterialhypoxemia noted after bronchial occlusion of oneor more lobes of the lung could have resultedfrom changes in the noncollapsed lung. Possiblecauses of desaturation of blood leaving the ven-tilated lung are the maintenance or increase ofblood flow past poorly ventilated alveoli (physio-logic shunting), the spontaneous development ofatelectasis in the dependent portions of the ven-tilated lung secondary to anesthesia and oxygenbreathing, and the opening of a-v shunts in theventilating lung. For the following reasons,none of these mechanisms is believed to beof major importance in these experiments: a)Ventilating the noncollapsed lung with 100%oxygen before blood oxygen determinations shouldhave eliminated the effects of any physiologicshunting that might have been induced by over-distention of the ventilating lung. b) Since con-tinuous ventilation with 100% oxygen in an anes-thetized animal is apt to induce atelectasis of de-pendent portions of lung, it was necessary todetermine whether the intermittent use of 100%oxygen at the time of blood sampling might haveproduced enough atelectasis in the ventilated lungto produce venous admixture. For the followingreasons it is unlikely that atelectasis in the non-obstructed lung contributed significantly to theobserved venous admixture: 1) acuteness of theresponse, 2) the lesser degree of venous admixturewith 100% nitrogen to one lung compared to col-lapse of the same lung, 3) the marked hyperventi-lation noted in the ventilated lung secondary toacute atelectasis (this would tend to minimize the

820

ACUTEATELECTASIS AND THE PULMONARYCIRCULATION

development of hypostatic atelectasis), and mostimportant, 4) the minimal degree of shunting ob-served in the control animals ventilated with 100%ooxygen for long periods of time (Table II). c)The possibility that some of the venous admixturenoted was a result of the opening of a-v shuntsin the ventilated lung, which may open with pul-monary embolism (17) and with certain drugs(23), cannot be ruled out on the basis of the dataavailable. However, the perfusion studies re-vealed an increase in the pulmonary arterial pres-sure in the noncollapsed lung supplied by bloodfrom the animal's own heart, whereas there was afall in the vascular pressure of the collapsed lobesperfused at a constant blood flow. This increasein pulmonary arterial pressure in the noncollapsedlung supplied by the dog's own heart does not sug-gest opening of a-v shunts but could have resultedfrom an increase in cardiac output secondary toblood gas changes, an increase in pulmonary vas-cular resistance secondary to blood gas changes,or overdistention of the noncollapsed lung. Therewas no systematic change in left auricular pres-sure.

Regardless of the above, hemodynamic changesin the nonobstructed lung cannot be the sole causeof the marked venous admixture of peripheralblood noted in these experiments. Direct meas-urements in the perfused innervated lung un-equivocally demonstrate a fall in vascular resist-ance after bronchial occlusion of that lung. Inaddition, when over-all blood flow through theleft lower and middle lobes is kept constant, endo-bronchial obstruction of the left lower lobe re-sults in an increase in flow through the collapsedlobe as measured directly by collecting venous out-flow. At the same time, a concomitant decreasein blood flow occurs in the noncollapsed leftmiddle lobe.

There are several possible explanations for thisincrease in blood flow through and decrease in vas-cular resistance of the collapsed lung. These in-clude neurogenic stimuli, the local effects of hy-poxemia and hypercapnia, the effects of surfacetension alterations, and mechanical factors.

Denervation failed to alter the response. In-duced local hypoxia and hypercapnea without col-lapse resulted in reduced rather than augmentedblood flow through the affected lung. No at-

tempt was made to evaluate the possible effect ofsurface tension changes on pulmonary vascularresistance in the acutely atelectatic lung. Al-though surface forces may play a part, it hasbeen shown to be insignificant compared to theeffects of geometrical factors over the course ofnegative pressure inflation or deflation (24).Thus the increased blood flow through and re-duced vascular resistance in the atelectatic lungare apparently the result of passive geometric al-terations secondary to lung volume and pressurechanges.

Simple anatomic shortening and widening ofthe capillary bed with pulmonary collapse (25)could account for a significant reduction in pul-monary vascular resistance, since a major portionof the total pulmonary vascular resistance is lo-cated in the intra-alveolar vessels (26). In ad-dition, after endobronchial occlusion, intra-alveo-lar pressure is gradually reduced until, with com-plete collapse, the intra-alveolar pressure in theatelectatic lung approaches the intrathoracic pres-sure, and the transpulmonary pressure (the dif-ference between airway pressure and the pressuresurrounding the lungs) approaches zero. Thereduction in intra-alveolar pressure in the col-lapsed lung lowers perivascular pressure in thisarea, resulting in an increase in transmural pres-sure (the difference between intravascular andperivascular pressures). Both of these changes,a decrease in transpulmonary pressure and an in-crease in transmural pressure, have been shownto lower pulmonary vascular resistance (27, 28).

Although the above pressure alterations wouldoccur with or without intrathoracic pressurechanges, the reduced intrapleural pressure notedwith acute endobronchial obstruction in an intactanimal might preferentially accentuate the initialvascular changes in the collapsed lung, possiblydilating the larger blood vessels that might nor-mally collapse with deflation (25). The decreasein intrathoracic pressure would also tend to over-distend the ventilating lung. This would in-crease the pulmonary vascular resistance in thenoncollapsed lung (29), further enhancing theshunting of blood through the collapsed lung.

Present results agree with those of Bj6rk (4, 5)and with the findings of Aviado in some openchest dogs (10). On the other hand, numerous

821

ALBERT H. NIDEN

PULMONARYVASCULARRESIS TANCE A

LUNG VOLUME

PULMONARYVASCULARRESISTANCE B

PHYSIOLOGIC RANGE

LUNG VOLUME

FIG. 12. SCHEMATIC VASCULAR RESISTANCE-LUNG VOLUMECURVE. Drawn from Figure 6B, Thomas, Griffo, andRoos (29). Physiologic lung volume from personal observations in intact dogs; see text.

investigators have demonstrated only an increasein pulmonary vascular resistance in and a reducedblood flow through the acutely collapsed lungs ofdogs ventilated with chest open and intermittentpositive pressure (see Berggren for earlier refer-ences, 7, 11). In view of the findings of Thomas,Griffo, and Roos (29), it may be possible to recon-cile these seemingly divergent results.

These authors (29) have demonstrated that inthe excised dog lung, vascular resistance duringnegative pressure deflation is volume dependent.They also showed that with negative pressure in-flation or deflation, resistance falls to a minimumat moderate inflation of the excised lungs and riseswith further inflation or deflation. Thus the initialstate of the lung at the time of collapse would af-fect the direction of change in vascular resistance(28, 29). Assuming that the intact lung will re-spond similarly to excised lungs in this respect, wecan draw a schematic lung volume-vascular resist-ance curve based on the observations of Thomasand colleagues (29) (Figure 12). If the physio-logic lung volume in the intact dog is at point a

(Figure 12A), then with bronchial obstruction,the vascular resistance in the collapsed lung willfall to point b and in the overdistended ventilatinglung will rise to point c. This is compatible withobservations noted here. On the other hand, inthe open chest dog, the lung volume might be lessthan the physiologic lung volume (for example, atpoint x, Figure 12B). In this case, the vascularresistance in the atelectatic lung would increase topoint y (Figure 12B), whereas the nonobstructedlung would not change in size, and its vascular re-sistance would remain at point z (Figure 12B).This would explain the increased resistance and de-creased blood flow noted in some of the open chestexperiments. The lung volume of the intact dogbreathing spontaneously may be assumed to benormal. Unfortunately, lung volumes of the openchest dog are not available in these experiments,nor have they been reported in other studies ofatelectasis.

Although acute bronchial obstruction in the in-tact dog results in a reduced vascular resistancein and an increased blood flow through the col-

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ACUTEATELECTASIS AND THE PULMONARYCIRCULATION

lapsed lung, there is little doubt that pulmonaryvascular resistance is increased in and blood flowmarkedly reduced through the chronically atelec-tatic lung. The mechanism of this transition invascular resistance has not been studied. In onedog (no. 82) this transition was already occurringat 190 minutes (Figure 4). Possible mecha-nisms for the reduction in blood flow in chronicallycollapsed lung are a) neurogenic effects, b) fur-ther alterations in surface tension forces, c) re-turn of intrathoracic pressure to normal after agradual reduction in chest volume or a decreasein compliance of the overdistended lung, d) fur-ther geometric changes assuming that the lungdoes not become completely atelectatic for severalhours, and e) chronic organic vascular changes.Organic vascular changes apparently do occur,since a marked increase in vascular resistance per-sists even after 3 weeks following re-expansion ofa chronically collapsed lung (3). The hemo-dynamic changes that occur with time in atelectaticlung warrant further investigation.

Summary

The response to acute pulmonary atelectasis wasstudied in fourteen lightly anesthetized dogsbreathing spontaneously with chest wall intact.Portions of lung were made atelectatic by endo-bronchial occlusion.

Acute atelectasis produced a two- to fourfoldincrease in respiratory minute volume, a decreasein intrathoracic pressure, and an initial fall in pul-monary arterial pressure usually followed by aslight rise. The percentage of cardiac outputshunted during acute atelectasis was greater thanthe percentage of lung tissue collapsed. In con-trast, unilateral ventilation with 100% nitrogenor 92.5%o nitrogen and 7.5%o carbon dioxide re-duced the amount of blood flow through the af-fected lung. Except for a variation in the timeof response, there was no difference whether thelung was filled with room air or 100% oxygenbefore acute collapse.

Constant flow perfusions of innervated pul-monary lobes (negative intrathoracic pressurebreathing) revealed a sudden fall in perfusionpressure with acute collapse of the perfused areain five of six preparations. Vagotomy and sym-pathectomy did not eliminate the response. Di-

rect measurement of pulmonary venous outflowconfirmed the increase in blood flow through theacutely collapsed lobe.

After acute endobronchial occlusion in the in-tact dog, blood flow is initially increased throughatelectatic lung as a result of mechanical factors.Mechanisms of this effect are discussed.

Acknowledgments

The author is indebted to Dr. Benjamin Burrows forhis suggestions and criticisms and is grateful to WilliamPitts and David Tidaback for their technical assistanceand to Joan Denne for the blood gas analyses.

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