Effect of lung surface tension on bronchial collapsibility in excised dog lungs M. NAKAMURA, First Department
H. SASAKI, AND of Internal Medicine,
T. TAKISHIMA Tohoku University
NAKAMURA, M., H. SASAKI, AND T. TAKISHIMA. Effect of lung surface tension on bronchial collapsibility in excised dog Lungs. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 47(4): 692-700, 1979.-Bronchial collapsibilities were studied in air- and saline-filled excised dog lungs. The intrapulmonary bronchi were isolated from the rest -of the lung parenchyma with beads placed at their tributary bronchi as described previously by Takishima et al. (J. AppZ. Physiol. 38: 875-881, 1975). Pressure-volume relations of the isolated bronchi were obtained while lung volume (VL) was kept constant. When lung recoil pressure (PL) was reduced by filling the lung with saline at a given VL, bronchial areas were smaller and bronchial collapsibilities were larger than in the air-filled lung. When bronchial areas and bronchial collapsibilities in air- and salinefilled lungs were compared at a given PL, they were approximately identical. We concluded that bronchial areas and collapsibilities were primarilv determined by PL rather than VL, and lung surface tension itself made bronchial collapsibility equal to or even less than the degree of collapsibility due to forces applied from surrounding lung tissues that distended the bronchi. airway mechanics; limitation
pulmonary
interdependence;
expiratory
flow
determinants of diameters of intrapulmonary airways have been reported: one is lung volume (VL), suggested by Hughes et al. (6), and the other is lung recoil pressure (PL), suggested by Caro et al. (2) and Hyatt et al. (9). Using bronchograms in excised dog lungs, Hughes et al. (6) observed that with regard to relative airway hysteresis, at the same VL but with PL'S that differed by 1.0-7.0 cmHz0, due to inflation-deflation lung volume history, all bronchial lengths and diameters were essentially identical. On the other hand, Caro et al. (2) reported that airway conductance was dependent on PL rather than on VL in normal subjects studied with or without chest strapping. Recently, Hyatt et al. (9) reported that, using bronchograms of excised dog lungs before and after cooling and ventilation that increased lung surface tension, bronchial diameter corresponded best to PL and bronchial length to VL. Using bronchograms of the excised dog lung Hughes et al. (7) reported that the deflation curves for airway diameter in the airfilled and the saline-filled lung coincided at all PL, whereas the large difference in lung distending pressure appeared to have little influence on inflation curves of airway diameters when compared with the effect of lung volume. Because two conflicting determinants of airway
TWO CONTROVERSIAL
692
School of Medicine,
Sendai,
Japan
diameters have been reported, we reinvestigated the effect of the loss of lung surface tension on airway diameters. The second purpose of the present study is to estimate the effect of lung surface tension on bronchial collapsibility. In a theoretical study of the interdependence of expansion of structures within the lung, Mead et al. (11) suggested that peribronchial parenchyma could change its radial traction on the bronchi due to the stress-density effect of lung parenchyma. Hughes et al. (8) and the present investigators (23) observed that intrapulmonary bronchi were distended radially by forces applied from surrounding lung parenchyma and this characteristic tended to increase with decreasing bronchial diameter. However, it is not known how lung surface tension contributes to the radial traction of lung parenchyma when the bronchi collapse. Inasmuch as lung surface tension is influenced by lung hysteresis (I), shape of alveoli, and size of alveoli, the effect of lung surface tension on bronchial collapsibility will not be simple. Using beads we isolated the intrapulmonary bronchi from the rest of the lung parenchyma as previously described by Takishima et al. (23). We first obtained pressure-volume relations of the isolated bronchi in an air-filled lung. Second, to eliminate lung surface tension, the lung was filled with saline and bronchial pressurevolume relations were also obtained. Bronchial areas and collapsibilities in the air- and saline-filled lungs were compared with regard to PL or VL. METHODS
We performed complete studies on eight right lower lobes from eight mongrel dogs weighing 13-17 kg exsanguinated after intravenous injection of pentobarbital sodium with heparin. The lobes were suspended in the Lucite box with the extrapulmonary bronchus bound to a metal tube 8 mm in length and 14 mm OD. The lobe was inflated by box pressure (Pbox) -30 cmH20 and the lobar main bronchi 5-6 cm in length were glued airtight with Alonalpha (Sankyo, Japan) at the orifices of their tributary branch bronchi with lo-15 beads of 2-9 mm OD. A segmental bronchus near the airway opening was wedged airtight with a catheter (PE-240) having a bead of 7-9 mm OD for collateral ventilation of the lobe. Then, we could obtain bronchial pressure-volume relations independently of the lung parenchyma, which was inflated by means of negative box pressure while alveolar pressure (PA) was kept at atmospheric level through collateral
0161-7567/79/0000-0000$01.25
Copyright
0 1979 the American
Physiological
Society
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BRONCHIAL
COLLAPSIBILITY
AND
LUNG
SURFACE
693
TENSION
ventilation. Bronchial volume (Vbr) was measured with a 3O-ml syringe coupled with a linear displacement transducer (Hewlett-Packard ‘IDCDT-1000) and bronchial pressure (Pbr) with a pressure transducer (Hewlett-Packard 267BC). The bronchi and the apparatus were filled with saline. PA was measured at the catheter for collatera1 ventilation with a pressure transducer (HewlettPackard 267BC) and recorded on a pen-writing oscillograph (Sanei 8s). Pbox was measured with a water manometer and a pressure transducer (Hewlett-Packard 267BC). Pbr-Vbr curves were recorded on an X- Y plotter (Hewl&t-pa&ard 7045 A) during gradual deflation of Vbr 0.03 ml/s from Pbr-PA 0 to -60 cmHa0. It took about 2-3 min to record each Pbr-Vbr curve. First, Pbr-Vbr curves were obtained from an air-filled lung. The lobe was floated flat on the saline in the Lucite box and zero reference of Pbr was at the horizontal midline of the bronchi (Fig. 1A). VL was measured with a 2-liter Benedict-Ross respirometer coupled with a linear displacement transducer (Hewlett-Packard 7DCDT-1000). PL was defined as PA-Pbox. The lobe was slowly ventilated between PL 30 and 5 cmHe0 three times and Pbr-Vbr curves were recorded at PL 30, 10, and 5 cmHn0, respectively. The lobe was inflated once to PL 30 cmHz0 before recording Pbr-Vbr curves at PL 10 and 5 cmHa0. It took about 15 min to record these three Pbr-Vbr curves. Second, Pbr-Vbr curves were obtained from a salinefilled lung. The lobe was deflated to PL 0 cmHz0 and residual volume ,was measured by the water-displacement method, subtracting lobe weight and assuming the density of lung tissue as 1.0. The lobe was degassed with a vacuum pump with Vbr being kept in a collapsed state and all arrangements, including the measurement system, left unchanged. Then, the lobe was filled with saline through the collateral catheter (Fig. U?). The Lucite box was also filled with saline in order to avoid any effect from the gravity of the saline. PL in the saline-filled lung was defined as PA-Pbox minus the height of the saline from the midhorizontal level of the bronchi (Ps) while PA was kept at atmospheric. During the recording of the Pbr-Vbr curves and the ventilating of the lung with saline, PA was also kept at zero by means of the negative Pbox. Before recording Pbr-Vbr curves, the history of lung ventilation was kept in the same way as in the airfilled lung. Pbr-Vbr curves were obtained at three levels of VL corresponding to the volume at PL 30 (high VL), 10 (middle VL), and 5 cmHa0 (low VL), respectively, in the air-filled lung. Time courses of measurement were also taken in the same way as in the air-filled lung. At the end of measurement possible leaks of saline from the lung parenchyma were checked by means of the waterdisplacement method. In preliminary studies we observed that saline leak was greater at a higher VL. We kept the lobe at each VL for about 5 min and the leaks of saline from the lungs were 1.2 t 0.7% high VL (mean t SD, n = 8). Third, the bronchi were carefully dissected from the surrounding parenchyma, including the large pulmonary vessels. The dissected Pbr-Vbr curves were obtained in the same way as were the intact bronchi in the salinefilled lung. Zero Vbr was defined as Vbr at Pbr -60
A
Air
- filled
1~ ng
c
.
. . . . . . . . . . . :::: .
. .
B
Saline-
filled
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
::
.
.
.
.
lung
.
"L
l
:.*::: .
1 pVbr
“L
FIG. 1. Block diagram of apparatus in air-filled lung (A) and in saline-filled lung (B). In air-filled lung excised lower lobe was laid flat on saline in Lucite box. Lung was inflated by negative box pressure (Pbox). Lobar main bronchi were obstructed airtight with beads and segmental bronchus with catheter and bead for collateral ventilation. Isolated bronchial pressure-volume (Pbr-Vbr) relations were obtained with pressure transducer and syringe coupled with linear displacement transducer, respectively. Isolated lobar main bronchus, pressure transducer and syringe were filled with saline. Lung volume (VL) was measured with a Benedict-Ross respirometer coupled with linear displacement transducer. Alveolar pressure (PA) was measured at catheter for collateral ventilation with pressure transducer. Lung elastic recoil lung, lobe was pressure (PL) was defined as PA - Pbox. In saline-filled dipped in saline and VL was inflated with saline of lOO-ml syringes. PL in saline-filled lung was defined as PA at atmospheric pressure minus Pbox minus height of saline (Ps) from the midhorizontal line of bronchi.
cmHzO at PL or distending pressure 0 cmHz0. The differences of zero Vbr among the air-filled lung, the saline-filled lung, and the dissected bronchi were less than 2% of the maximum Vbr defined as Vbr at Pbr-PA = 0 cmHzO at PL 30 cmHa0 in the air-filled lung. We took the leaks of saline from the lung parenchyma and bronchi to be negligible. It has been considered that bronchial lengths are proportional to the cube root of VL in an air-filled lung (6). However, it has not been reported whether bronchial length even in a saline-filled lung is proportional to the cube root of VL. Because bronchial lengths were not controlled in this presentation due to difficulties in prep-
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694
NAKAMUHA,
aration, we measured the bronchial length at Pbr-PA = 0 cmHZO in the air- and saline-filled lungs in five additional lobes from five dogs. The lobes were laid flat in the Lucite box in the same way as described above. A bead 9 mm OD with a thin straight enamel wire 12 cm in length was glued on to the lobar main bronchi 6-7 cm in depth from the airway opening. The position of the enamel wire could be read to 0.5 mm with the unaided eye through a translucent plastic adapter connected to the airway opening at a given VL in both the air- and saline-filled lungs. During bronchial collapse bronchial length may be shortened. Furthermore in the dissected bronchi, bronchial length might be different from intact bronchial length. In three additional lobes from three dogs we studied the effect of bronchial length on Pbr-Vbr curves in intact and dissected bronchi in the air-filled lung. The lobe was laid flat in the Lucite box as described above with the lobar main bronchi obstructed airtight with beads. A catheter for collateral ventilation was introduced as described previously. The bottom bead was connected with a thin straight steel rod to an iron core 3 g in wt to measure the length of the obstructed lobar main bronchi with a linear differential transducer (Linear, Kyoto, Japan). The linear differential transducer was waterproofed and was laid horizontally inside the plastic adapter connected to the airway opening in a straight line with the main lobar bronchi. The position of the iron core was controlled by an adjustable stop as necessary and was changed smoothly inside the linear differential transducer. The positioning corresponded to the displacement of bronchial length. Dog B-W-
High
SASAKI,
AND
TAKISHIMA
After the intact Pbr-Vbr curves were obtained in the air-filled lung, the peribronchial parenchyma were dissected away from the obstructed main lobar bronchi in the same way as described above. In the dissected bronchi, length was measured or controlled during bronchial collapse in the same way as in intact bronchi. RESULTS
An example of Pbr-Vbr curves is shown in Fig. 2. In the saline-filled lung the initial Vbr at Pbr-PA = 0 cmHz0 were smaller and the Pbr-Vbr curves were more collapsible than in the air-filled lung at a given VL, although they were less collapsible than the dissected bronchi. Because bronchial length differed with different VL, bronchial areas (Abr) were calculated from Vbr with the assumption that bronchial length was proportional to the cube root of VL in both air- (6, 9) and saline-filled lungs. The characteristics of the bronchial length in the salinefilled lung and during bronchial collapse will be presented later. The initial Abr at Pbr-PA = 0 cmHz0 thus calculated were plotted with regard to VL and PL in Fig. 3. The Abr at high VL in the air-filled lung were standardized as 100% (5%maximum Abr). At all VL, Abr in the saline-filled lung were significantly smaller than Abr in the air-filled lung (paired t test, 0.001 < P c 0.005). On the other hand, when the Abr’s in both conditions were compared with regard to PL, although the Abr’s in the saline-filled lung were slightly smaller than Abr’s in the air-filled lung, both were nearly the same. Unfortunately, we could not check Abr statistically at any PL, because no PL in the saline-filled lung was identical with PL in
8 fn air-filled In saline
lung -filled
lung
“L
Middle
-60
-30 Pbr -
2. Example of Pbr-Vbr curves in air-filled lung (continuous Lines), saline-filled lung (dashed Lines), and dissected bronchi (interrupted Line). Pbr-Vbr curve in dissected bronchi is at distending pressure of 0 cmH20. Note that at corresponding VL initial Vbr in salineFIG.
+30
0 pA
(cmHz0)
filled lung at Pbr - PA = 0 cmH20 were lung and Pbr-Vbr curves in saline-filled than those in air-filled lung.
smaller lung
than were
those more
in air-filled collapsible
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BRONCHIAL
COLLAPSIBILITY
AND
LUNG
SURFACE
695
TENSION
In air-filled
--We
In saline
o At high
lung -filled
lu ng
l
VL
At middle
x At low
VL VL
0
t
[;-I
0
0
0
0
0
0
0
0
0
0
0 0 0 0 0
6C
0
f_
4( 40
60
80 VL
3. Initial bronchial VL (0), middle VL (o), and and PL. Abr at high VL in Means k SD (n = 8) were FIG.
( ‘10 maximum
area (Abr) at Pbr - PA = 0 cmH20 at high low VL (x) were plotted with regard to VL air-filled lung were standardized as 100%. shown. Note that Abr in saline-filled lung
the air-filled lung, and PL'S in the saline-filled lung were 10.9 t 1.9,6.0 t 1.1, and 3.0 t 1.5 cmHz0 in high, middle, and low VL, respectively. Bronchial collapsibilities in the air- and saline-filled lungs were compared in terms of VL and PL. Abr’s were calculated on several points of the Pbr-Vbr curve and were plotted on a logarithmic scale. Figure 4 shows that Pbr-Abr curves in both the air- and saline-filled lung are linear, except near the beginning of the curve, in a way similar to the Pbr-Vbr curves previously shown in the air-filled lung (20, 23). We took the linear slopes thus obtained as bronchial collapsibility. Slopes in the air- and saline-filled lungs were compared with regard to VL and PL (Fig. 5). Slopes at high VL in the air-filled lung were standardized as 100%. Slopes showed inverse proportion with VL or PL. At all VL, slopes in the saline-filled lung were significantly larger than in the airfilled lung (paired t test, 0.005 < P < 0.01). On the other hand, when slopes were compared with regard to PL, they were almost identical. PL in the air-filled lung was composed of both the lung tissue and the lung surface tension components of PL. The lung surface tension component of PL was obtained by the subtraction of PL in the saline-filled lung from PL in the air-filled lung and they were 19.1 t 1.9, 4.0 t 1.2, and 2.0 t 0.6 (mean t SD) at high, middle, and low VL, respectively. Similarly, in the air-filled lung Pbr was composed of three pressures: the dissected bronchial component, the lung tissue component, and the lung surface tension component. In the saline-filled lung Pbr
100 )
0
5
10
30
20 PI
L
(cmH70) L
were significantly lower than that in air-filled lung with regard to VL and both Abr’s were almost identical with regard to PL. Lines were the same as in Fig. 2.
was composed of the dissected bronchial component and the lung tissue component. The lung surface tension component of Pbr was obtained by the subtraction of Pbr in the saline-filled lung from Pbr in the air-filled lung at the same Abr at corresponding VL in the same manner as the analysis of the components of PL. The relations of the lung surface tension component of Pbr to VL, or to the lung surface tension component of PL, were plotted at 50 and 30% maximum Abr in Fig. 6. The lung tissue components of Pbr and PL were also plotted in Fig. 6, in which the lung tissue component of Pbr was made by the subtraction of the dissected bronchial component of Pbr from intact Pbr in the saline-filled lung at the corresponding distending pressure of intact and dissected states. The subtractions of dissected Pbr from intact Pbr were made at the same Vbr at the comparable PL or distending pressure and then Vbr was converted into Abr. The lung surface tension component of Pbr was increased nonlinearly with increased VL. At 50% maximum Abr at high and middle VL the lung surface tension component of Pbr-PA was significantly larger than the lung tissue component of Pbr-PA (paired t test, 0.001 < P < 0.005 and 0.025 < P < 0.050 at high and middle VL, respectively) whereas at 50% maximum Abr at low VL and at 30% maximum Abr at middle and low VL they were not significant (paired t test, 0.100 < P), which suggested that at 50% maximum Abr at high and middle VL the contribution of lung surface tension on Pbr-PA was significantly larger than the contribution of lung tissue. Both lung surface tension and lung tissue contributions
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696
NAKAMURA,
Dog
5
-
In
---
In saline-filled
air-filled
lung lung
At middle
l
x At X I
-60
low
VL VL
/
I
I
40
1
I
-20 Pbr
- ?A
I
0 ( cmH20)
FIG. 4. Pbr-Abr curves in air- and saline-filled lungs were replotted on logarithmic scale of Abr. Note that Pbr-Abr curves in saline-filled lung were linear as they also were in air-filled lung as previously reported by Takishima et al. (23). Symbols were the same as in Fig. 3.
on Pbr-PA were compared with both corresponding components of PL to determine the possible influence of structural or material differences between them (Fig. 6). Both components of Pbr-PA increased linearly with the corresponding component of PL. At 30% maximum Abr both components of Pbr-PA increased more steeply than at 50% maximum Abr with regard to both VL and PL. In the air-filled lung the relations of the lung parenchymal compo nent of Pbr-PA .nd PLW ‘ere approximate ly simil .ar to the relations show on the right-hand side of Fig. 6. Though the lung surface tension components of Pbr-PA were slightly larger than the lung tissue components of Pbr-PA with considerable standard deviations, they were nearly the same. Figures 5 and 6 suggest that lung surface tension itself makes bronchial collapsibility equal to or even less than the degree of collapsibility due to forces applied from surrounding lung tissues that distended the bronchi In the saline-filled lung the average bronchial lengths were shorter by 2.2 t 0.8% (mean t SD, n = 15) than in the air-filled lung even though the lung volume was kept the same at Pbr-PA = 0 cmHa0. We neglected the effect of small differences in bronchial length on the calculation of Abr at Pbr-PA = 0 cmHa0. During deflation of Vbr from Pbr-PA = 0 to -50
SASAKI,
AND
TAKISHIMA
cmHa0 intact bronchial length decreased by approximately 3-6s of initial bronchial length at Pbr-PA = 0 cmHz0 at each PL. Bronchial length decreased less at high PL. When the bronchial length was fixed at initial bronchial length of Pbr-PA = 0 cmHz0, Pbr-Vbr curves were almost identical to Pbr-Vbr curves obtained without fixed bronchial length in the intact bronchi. The semilogarithmic slopes of Pbr-Abr curves without fixed bronchial length showed no difference from those with fixed bronchial length. Because of decreased PL, in the saline-filled lung during bronchial collapse at a given VL, bronchial length might become shorter than in the air-filled lung. However, during bronchial collapse bronchial length would be shortened in both air- and saline-filled lungs, though varying in magnitude. Then, the difference of the effect of shortening bronchial length on Pbr-Abr curves between air- and saline-filled lungs might be reduced. The small difference of Pbr-Vbr curves between fixed and nonfixed bronchial length at initial bronchial length would make the error of the subtraction of Pbr in the saline-filled lung from Pbr in the air-filled lung insignificant. In the dissected bronchi the initial bronchial length were shorter by 14.5 t 3.5% (mean t SD) than the intact bronchial length at the corresponding distending pressure of approximately 30 to 5 cmHa0. With fixed bronchial length with an intact initial bronchial length of PbrPA = 0 cmH20, Pbr-Vbr curves of dissected bronchi indicated slightly less collapsibility than those without fixed bronchial length by Pbr 1.1 t 0.8 and 2.0 t 1.4 cmHs0 (mean t SD), at 50 and 30% maximum Abr, respectively. The differences of pressure were larger at higher PL. Therefore, we might have overestimated the lung tissue component of Pbr-PA by approximately l-2 cmHa0 in Fig. 6. DISCUSSION
In the present study the determinants of the initial bronchial area at Pbr-PA = 0 cmH20 and bronchial collapsibility were studied with regard to VL and PL in the air- and saline-filled lungs. First, we will consider possible errors and limitations in the present study. Alveolar pressure was assumed to be at atmospheric during bronchial collapsing. In the air-filled lung collateral channels were suggested as being enough to keep alveolar pressure at atmospheric even during dynamic bronchial collapse (20). During bronchial collapse in the saline-filled lung, however, alveolar pressure might not be at atmospheric, depending on the time constant of the collaterally ventilated segment. In two lobes from two dogs we measured flow resistance of collateral channels of segments in the air- and saline-filled lungs. The lobes were suspended in the Lucite box and laid flat in the way previously described here. A double-lumen polyethylene catheter (a small catheter (PE-90) inside a larger one of OD 7 mm) was wedged into a segmental bronchus in the way described above, but without obstructing the other tributary bronchi with beads. A small catheter that had several lateral holes and was closed at the end was used for measurement of pressure at the segmental bronchus. Flow was measured with a Fleisch pneumotachograph in
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BRONCHIAL
COLLAPSIBILITY
AND
LUNG
SURFACE
TENSION
697 -
In air-filled
----
In saline-filled
-0‘0 400 V
lung
0 At high l
VL
At middle
x At
h CI .-.*i
lung
low
VL VL
300
a
5
3 .x “c
200
0 ii
100 40
60
80
100
( o/Omaximum
VL
Lung
tissue
. . . . . . . . Lung
5
10
)
(cmH20
0 At high
component tension
l
component
30’/.maximum Abr
\s\, ir I ,H’
0
VL
At middle
x At low
Abr
1
lung were considerably larger than in air-filled lung with regard to VL and approximately the same with regard to PL. Symbols were the same as in Fig. 3.
surface
30’1. max,imum
30
20 PL
FIG. 5. Bronchial collapsibilities were compared with regard to VL and PL. Bronchial collapsibilities at high VL in air-filled lung were standardized as 100%. Note that bronchial collapsibilities in saline-filled
w-e-
0
VL VL
T
A
l
0
:
0
’
T/ 0 .** 0
,**
maximum 50.J. 5O.J. maximum 4
I
I
60 VL
1
r
80 100 ( ‘Jomaxi mum )
0
FIG. 6. Radial tractions on bronchi of both lung tissue component (dashed lines) and of lung-surface tension component (dotted lines) of Pbr-PA were plotted with regard to VL on left. PL in air-filled lung were divided into two components of lung-surface tension and lung tissue. Relations of lung tissue component and lung surface tension component of Pbr-PA to their corresponding components of PL were plotted on right. Note that with regard to VL, radial tractions of lung surface
Abr
Abr v
I
r
5 10 20 Lung tissue or lung surface tension component of PL (cmH20)
1
30
tension component were roughly the same as those of the lung tissue component except at 50% maximum Abr at high VL, and with regard to PL they were almost the same and were linearly related. See text for statistical descriptions. Radial tractions increased more steeply with increased PL at smaller Abr, than at larger Abr. Symbols are the same as in Fig. 3.
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698 the air-filled lung and in the saline-filled lung with a 50ml syringe the scale of which could be read to 1 ml by the naked eye. Saline flow was obtained five times during 1-min intervals after saline flow became a steady state. The driving pressure of 2 cmH20 as the pressure difference from -pressure at the segmental bronchus to the airway opening pressure was made by an air pump in the air-filled lung and two saline reservoirs in the saline-filled lung, respectively. In the air-filled lung the mean airflow resistances from the segment were 144 and 232 cmHaO/(l/s) at PL 10 (middle VL) and 5 cmHz0 (low VL), respectively. In the saline-filled lung the mean flow resistances from the segment increased by 8 and 10 times the resistance in the air-filled lung at mid .dle and low v ‘L, respectively. If both airway and collateral resistances were simply determined by the differences of viscosity of air (1.86 X 10s4 poise) and saline (1.002 x lo-’ poise), the airway and collateral resistances in the saline-filled lung would increase 54 times that of the air-filled lung at a given VL. Menkes et al. (13) reported that collateral resistance decreased with increased PL. Because in the saline-filled lung PL decreased at a given VL, collateral resistance should also increase more than expected due to the difference in viscosity. Menkes et al. (13) su .ggested that collateral channels could not be opened even with a driving pressur beof 190 cm Hz0 once th .ey w ‘ere occluded in the a.ir-filled lung I. In the saline-fill .ed lung an increased number of collateral channels due to loss of surface tension at the air-liquid interface or meniscus of liquid of collateral channels could be one of the reasons for such lower collateral resistances than expected due to the difference in viscosity and PL. Supposing the segmental compliances in the saline-filled lung were three times the compliance in the air-filled lung, collateral time constants of the segment in the saline-filled lung were around 30 times the time constant in the air-filled lung. In the present preparation, Vbr were deflated slowly at 0.03 ml/ s; therefore, the collateral ventilation would not be disturbed because of PA being kept at atmospheric even in the saline-filled lung. Low initial bronchial area at Pbr-PA = 0 cmHz0 in the saline-filled lung at a given VL would not be due to increased bronchial tone because in the preliminary experiment we instilled atropine and isoproterenol of final concentrations of 5 and 1 pg/ml, respectively, into intact bronchi isolated by beads in three lobes. Comparisons of Pbr-Vbr curves of the isolated bronchi before and after instillation of bronchodilators made no systematic difference. Presumably, unless otherwise specifically designed preparations such as gas supply, nutritious solutions, and temperature supply are made to maintain main lobar bronchial tone, bronchial tone might diminish as time elapses during the isolating of the lobal main bronchi. Because Pbr-Abr relations in the saline-filled lung were obtained later than in the air-filled lung, bronchial tone in the sal ine-filled lu w might decrease more, if it changed at all. Smaller PL was accompanied by large narrowing of of Abr at a given VL and a much smaller narrowing Abr at a given PL (Fig. 3), which were approximately similar to the findings by Hyatt et al. (9) except for the fact that they studied the branch ial dia meter at increa .sed
NAKAMURA,
SASAKI,
AND
TAKISHIMA
PL. Therefore, we might say that there was little tone in the present lobar main bronchi. In the present study we found that elimination of lung surface tension reduced the initial bronchial area at PbrPA = 0 cmHZO and increased bronchial collapsibility. Both initial bronchial diameter at Pbr-PA = 0 cmH20 and bronchial collapsibility were well related to PL but not to VL. The contribution of lung parenchyma to the radial traction on the bronchi was well documented using the lung parenchymal model presented by Mead et al. (11). The contribution of lung tissue to the radial tracti .on on the bronchi could be similarly analyzed by the lung parenchymal model constructed by Mead et al. (11). However, it was unknown whether or not lung surface tension contributed to parenchymal radial traction in the same way that lung tissue did depending on the magnitude of the lung surface tension component of PL. Hughes et al. (6) reported that the determinant of bronchial diameter was VL. On the other hand, Caro et al. (2), Hughes et al. (7), and Hyatt et al. (9) found a close correlation between bronchial diameter and PL. We found results similar to those of Caro et al. (2) and Hvatt et al. (9) in that bronchial area was well related to PLYbut not to VL, except that they found close relations between bronchial area and PL in th e lung with increased PL. The present results confirmed the finding by Hugh .es et al. (7)) although their results did not demonstrate differences in expiratory pressure-volume curves between airand saline-filled lungs below moderate lung volumes. Because at Pbr-PA = 0 cmHe0 both the bronchi and the lung parenchyma would expand homogeneously ( 19)) lung surface tension might contribute to the radial traction of lung parenchyma on the bronchi, and depending on the magnitude of the component of lung surface tension of PL, lung tissue also might make a contribution. During bronchial collapse, peribronchial lung parenchyma would be unhomogeneously deformed, -which raised the question of whether or not lung surface tension contributed to the radial traction of lung parenchvma bv the magnitude of contributions of lung surface tension to PL. Radial traction of lung parenchyma on the bronchi was defined as interdependence of lung parenchyma by Mead et al. (11). Mead and associates (11) defined the interdependence as an inversely proportional increase of radial traction depen ding on the d ecreased bronchial diameter due to stress density theory and Taki shima and Mead (21) proved their theory experimentally. Menkes et al. (14) developed the theory of the interdependence of adjacent lung parenchyma. Hughes et al. (8) and the authors (19, 20, 23) observed the magnitude of peribronchial radial traction on the bronchi when collapsing; both groups showed considerably larger values than the stress density theory by Mead et al. (11). Prediction of elasticity based on the lung parenchyma as an isotropic elastic continuum shows that parenchymal distortion falls off rapidly (5). Morphological studies of distortions occurring as a result of locally indenting the pleura have shown that distortion does not extend far into the parenchyma from the site of indentation (3, 18). Because local peribronchial parenchyma would determine the radial traction of the lung parenchyma, deformation of the air space of the peribronchial parenchyma might reduce lung sur-
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BRONCHIAL
COLLAPSIBILITY
AND
LUNG
SURFACE
699
TENSION
face tension; if the lung surface tension component of PL were primarily determined by the conditions described in the formula of Laplace, radial expansion of alveoli would be accompanied by a larger curvature of alveoli in the radial direction of the bronchi, resulting in a decrease of radial forces applied by the lung surface tension if surface tension were kept the same. However, in the present study, we found that radial tractions on the bronchi, due to both lung tissue and lung surface tension, showed the same magnitude as in the air-filled lung with regard to the respective components of PL. Then, the mechanisms responsible for the distending forces applied from the lung surface tension are probably different from those responsible for lung tissue forces. Radial forces applied from the lung tissue to the bronchi would have the same characteristics as described in the spring model of interdependence by Mead et al. (11). The volume of the air spaces of the peribronchial parenchyma would increase during bronchial collapse, resulting in local inflation of lung parenchyma. Inflation of lung parenchyma was accompanied by an increase in lung elastic recoil. Furthermore, the surface tension had a larger hysteresis than the lung tissue had between the periods of lung inflation and deflation (1). Thus, the radial forces applied by the lung surface tension would be larger than that by the lung tissue during the periods of local lung inflation by the amount of larger hysteresis. Therefore, inflation of local parenchyma during bronchial collapse might produce enough local radial traction by the lung surface tension rath .er than decreased local radial traction of lung surface tension described in the formula of Laplace due to a larger curvature of alveoli in the radial direction to the bronchi. The exact mechanisms of radial traction of parenchyma on the bronchi are not known, nor are the mechanisms of radial tractions made by lung surface tension. Histological study might be on .e of the methods needed for analysis of the interdependence of parenchyma. The theoretical analysis of maximum expiratory flow was intensively studied by many investigators. (vrnax) Mead et al. (12) proposed an equal pressure-point theory
that described V maxto be proportional to PL and inversely proportional to upstream resistance (Rup). There are many studies that support the equal pressure-point theory. Vincent et al. (24) found that during lung inflation and deflation in human subjects Vm,x increased by the amount of increased PL. Park et al. (16) made pulmonary emphysema in papain-inhaled hamster lungs. They observed that Vm,, was also proportional to PL. Paying attention to the bronchial narrowing that occurs during maximum forced expiratory maneuvers, Pride et al. (17) proposed the Starling resistor theory that pointed out the importance of bronchial collapsibility. Recently, theoretical analysis of V maxalso described bronchial collapsibility as a primary determinant of Vmax (4, 15, 22). However, it has not been reported whether bronchial collapsibility is related to PL or not. In the present study, we found that bronchial collapsibility was well related inversely to PL in air- and saline-filled lungs (Fig. 5). In normal lungs (24) or experimental pulmonary emphysema made by papain (16), PL, as a determinant of Vmax in equal pressure-point theory, seemed to be inversely proportional to bronchial collapsibility. The present result suggests that in human pulmonary emphysema one of the determinants of decreased Vm,, seems to be decreased PL. In terms of decreased PL, a saline-filled lung seemsto be a model of pulmonary emphysema. However, we have not obtained any information from emphysema patients to indicate whether or not bronchial collapsibility is inversely proportional to PL. Maisel et al. (10) reported atrophy of the bronchial wall structures in some emphysematous patients. In that case, bronchial collapsibility in some emphysematous patients might be greater than expected from the present results. Because the present preparation for studying bronchial collapsibilities can be applied only to the normal structures of parenchyma, further work may be needed for application to the wide variety of human lung diseases. The authors are appreciative of Mr. B. Breneman, Ms. B. Hayashi, and Ms. K. Toda for their assistance in the preparation of this paper. Received
11 January
1979; accepted
in final
form
1 June 1979.
REFERENCES 1. BACHOFEN, H., J. HILDEBRANDT, AND M. BACHOFEN. Pressurevolume curves of air- and liquid-filled excised lungs-surface tension in situ. J. AppZ. Physiol. 29: 422-431, 1970. 2. CARO, C. G., J. BUTLER, AND A. B. DUBOIS. Some effects of restriction of chest cage expansion on pulmonary function in man: an experimental study. J. CZin. Invest. 39: 573-583, 1960. 3. D’ANGELO, E., AND S. MICHELINI. Alveolar morphology under localized distorting forces. J. AppZ. PhysioZ. 34: 809-815, 1973. 4. DAWSON, S. V., AND E. A. ELLIOTT. Wave-speed limitation on expiratory flow-a unifying concept. J. AppZ. Physiol.: Respirat. Environ. Exercise PhysioZ. 43: 498-515, 1977. 5. HOPPIN, F. G., JR., AND J. HILDEBRANDT. Mechanical properties of the lung. In: Bioengineering Aspects of the Lung, edited by J. B. West. New York: Dekker, 1977, vol. III, chapt. 2, p 83-162. 6. HUGHES, J. M. B., F. G. HOPPIN, JR., AND J. MEAD. Effect of lung inflation on bronchial length and diameter in excised lungs. J. AppZ. PhysioZ. 32: 25-35, 1972. 7. HUGHES, J. M. B., H. A. JONES, AND A. G. WILSON. Bronchial hysteresis in excised lung. J. Physiol. London 249: 435-443, 1975. 8. HUGHES, J. M. B., H. A. JONES, A. G. WILSON, B. J. B. GRANT, AND N. B. PRIDE. Stability of intrapulmonary bronchial dimensions during expiratory flow in excised lungs. J. AppZ. Physiol. 37: 684694, 1974.
9. HYATT, R. E., J. R. RODARTE, AND T. A. WILSON. Effect of increased static lung recoil on bronchial dimension of excised lungs. J. AppZ. Physiol. 39: 429-433, 1975. 10. MAISEL, F. C., G. W. SILVERS, R. S. MITCHELL, AND T. L. PETTY. Bronchial atrophy and dynamic expiratory collapse. Am. Rev. Respir. Dis. 98: 988-997, 1968. 11. MEAD, J., T. TAKISHIMA, AND D. LEITH. Stress distribution in lungs: a model of pulmonary elasticity. J. Appt. PhysioZ. 28: 596608, 1970. 12. MEAD, J., J. M. TURNER, P. T. MACKLEM, AND J. B. LITTLE. Significance of the relationship between lung recoil and maximum expiratory flow. J. AppZ. PhysioZ. 22: 95-108, 1967. 13. MENKES, H., A. GARDINER, G. GAMSU, J. LEMPERT, AND P. T. MACKLEM. Influence of surface forces on collateral ventilation. J. AppZ. Physiol. 31: 544-549, 1971. 14. MENKES, H., D. LINDSAY, L. WOOD, A. MUIR, AND P. T. MACKLEM. Interdependence of lung units in intact dog lungs. J. AppZ. Physiol. 32: 681-686, 1972. 15. PARDAENS, J., K. P. VAN DE WOESTIJINE, AND J. CLI~MENT. A physical model of expiration. J. AppZ. Physiol. 33: 479-490, 1972. 16. PARK, S. S., I. P. GOLDRING, C. S. SHIM, AND M. H. WILLIAMS, JR. Mechanical properties of the lung in experimental pulmonary emphysema. J. AppZ. Physiol. 26: 738-744, 1969.
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700 17. PRIDE, N. B., S. PERMUTT, R. L. RILEY, AND B. BROMBERGERBARNEA. Determinants of maximal expiratory flow from the lungs. J. AppZ. Physiol. 23: 646-662, 1967. 18. ROBERTSON, C. H., D. L. HALL, AND J. C. HOGG. A description of lung distortion due to localized pleural stress. J. Appl. Physiol. 34: 344-350, 1973. 19. SASAKI, H., F. G. HOPPIN, JR., AND T. TAKISHIMA. Peribronchial pressure in excised dog lungs. J. AppZ. Physiol.: Respirat. Environ. Exercise Physiol. 45: 858-869, 1978. 20. SASAKI, H., T. TAKISHIMA, AND T. SASAKI. Influence of lung parenchyma on dynamic bronchial collapsibility of excised dog lungs. J. AppZ. Physiol.: Respirat. Environ. Exercise Physiol. 42:
NAKAMURA,
SASAKI,
AND
TAKISHIMA
699-705, 1977. 21. TAKISHIMA, T., AND J. MEAD. Tests of a model of pulmonary elasticity. J. AppZ. Physiol. 33: 576-581, 1972. 22. TAKISHIMA, T., AND H. SASAKI. Two-dimensional flow-model for analysis of expiratory check valve. BUZZ. Physio-PathoZ. Respir. 8: 361-374, 1972. 23. TAKISHIMA, T., H. SASAKI, AND T. SASAKI. Influence of lung parenchyma on collapsibility of dog bronchi. J. AppZ. PhysioZ. 38: 875-881, 1975. 24. VINCENT, N. J., R. KNUDSON, D. E. LEITH, P. T. MACKLEM, AND J. MEAD. Factors influencing pulmonary resistance. J. AppZ. PhysioZ. 29: 236-243, 1970.
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H. SASAKI, AND of Internal Medicine,
T. TAKISHIMA Tohoku University
NAKAMURA, M., H. SASAKI, AND T. TAKISHIMA. Effect of lung surface tension on bronchial collapsibility in excised dog Lungs. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 47(4): 692-700, 1979.-Bronchial collapsibilities were studied in air- and saline-filled excised dog lungs. The intrapulmonary bronchi were isolated from the rest -of the lung parenchyma with beads placed at their tributary bronchi as described previously by Takishima et al. (J. AppZ. Physiol. 38: 875-881, 1975). Pressure-volume relations of the isolated bronchi were obtained while lung volume (VL) was kept constant. When lung recoil pressure (PL) was reduced by filling the lung with saline at a given VL, bronchial areas were smaller and bronchial collapsibilities were larger than in the air-filled lung. When bronchial areas and bronchial collapsibilities in air- and salinefilled lungs were compared at a given PL, they were approximately identical. We concluded that bronchial areas and collapsibilities were primarilv determined by PL rather than VL, and lung surface tension itself made bronchial collapsibility equal to or even less than the degree of collapsibility due to forces applied from surrounding lung tissues that distended the bronchi. airway mechanics; limitation
pulmonary
interdependence;
expiratory
flow
determinants of diameters of intrapulmonary airways have been reported: one is lung volume (VL), suggested by Hughes et al. (6), and the other is lung recoil pressure (PL), suggested by Caro et al. (2) and Hyatt et al. (9). Using bronchograms in excised dog lungs, Hughes et al. (6) observed that with regard to relative airway hysteresis, at the same VL but with PL'S that differed by 1.0-7.0 cmHz0, due to inflation-deflation lung volume history, all bronchial lengths and diameters were essentially identical. On the other hand, Caro et al. (2) reported that airway conductance was dependent on PL rather than on VL in normal subjects studied with or without chest strapping. Recently, Hyatt et al. (9) reported that, using bronchograms of excised dog lungs before and after cooling and ventilation that increased lung surface tension, bronchial diameter corresponded best to PL and bronchial length to VL. Using bronchograms of the excised dog lung Hughes et al. (7) reported that the deflation curves for airway diameter in the airfilled and the saline-filled lung coincided at all PL, whereas the large difference in lung distending pressure appeared to have little influence on inflation curves of airway diameters when compared with the effect of lung volume. Because two conflicting determinants of airway
TWO CONTROVERSIAL
692
School of Medicine,
Sendai,
Japan
diameters have been reported, we reinvestigated the effect of the loss of lung surface tension on airway diameters. The second purpose of the present study is to estimate the effect of lung surface tension on bronchial collapsibility. In a theoretical study of the interdependence of expansion of structures within the lung, Mead et al. (11) suggested that peribronchial parenchyma could change its radial traction on the bronchi due to the stress-density effect of lung parenchyma. Hughes et al. (8) and the present investigators (23) observed that intrapulmonary bronchi were distended radially by forces applied from surrounding lung parenchyma and this characteristic tended to increase with decreasing bronchial diameter. However, it is not known how lung surface tension contributes to the radial traction of lung parenchyma when the bronchi collapse. Inasmuch as lung surface tension is influenced by lung hysteresis (I), shape of alveoli, and size of alveoli, the effect of lung surface tension on bronchial collapsibility will not be simple. Using beads we isolated the intrapulmonary bronchi from the rest of the lung parenchyma as previously described by Takishima et al. (23). We first obtained pressure-volume relations of the isolated bronchi in an air-filled lung. Second, to eliminate lung surface tension, the lung was filled with saline and bronchial pressurevolume relations were also obtained. Bronchial areas and collapsibilities in the air- and saline-filled lungs were compared with regard to PL or VL. METHODS
We performed complete studies on eight right lower lobes from eight mongrel dogs weighing 13-17 kg exsanguinated after intravenous injection of pentobarbital sodium with heparin. The lobes were suspended in the Lucite box with the extrapulmonary bronchus bound to a metal tube 8 mm in length and 14 mm OD. The lobe was inflated by box pressure (Pbox) -30 cmH20 and the lobar main bronchi 5-6 cm in length were glued airtight with Alonalpha (Sankyo, Japan) at the orifices of their tributary branch bronchi with lo-15 beads of 2-9 mm OD. A segmental bronchus near the airway opening was wedged airtight with a catheter (PE-240) having a bead of 7-9 mm OD for collateral ventilation of the lobe. Then, we could obtain bronchial pressure-volume relations independently of the lung parenchyma, which was inflated by means of negative box pressure while alveolar pressure (PA) was kept at atmospheric level through collateral
0161-7567/79/0000-0000$01.25
Copyright
0 1979 the American
Physiological
Society
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BRONCHIAL
COLLAPSIBILITY
AND
LUNG
SURFACE
693
TENSION
ventilation. Bronchial volume (Vbr) was measured with a 3O-ml syringe coupled with a linear displacement transducer (Hewlett-Packard ‘IDCDT-1000) and bronchial pressure (Pbr) with a pressure transducer (Hewlett-Packard 267BC). The bronchi and the apparatus were filled with saline. PA was measured at the catheter for collatera1 ventilation with a pressure transducer (HewlettPackard 267BC) and recorded on a pen-writing oscillograph (Sanei 8s). Pbox was measured with a water manometer and a pressure transducer (Hewlett-Packard 267BC). Pbr-Vbr curves were recorded on an X- Y plotter (Hewl&t-pa&ard 7045 A) during gradual deflation of Vbr 0.03 ml/s from Pbr-PA 0 to -60 cmHa0. It took about 2-3 min to record each Pbr-Vbr curve. First, Pbr-Vbr curves were obtained from an air-filled lung. The lobe was floated flat on the saline in the Lucite box and zero reference of Pbr was at the horizontal midline of the bronchi (Fig. 1A). VL was measured with a 2-liter Benedict-Ross respirometer coupled with a linear displacement transducer (Hewlett-Packard 7DCDT-1000). PL was defined as PA-Pbox. The lobe was slowly ventilated between PL 30 and 5 cmHe0 three times and Pbr-Vbr curves were recorded at PL 30, 10, and 5 cmHn0, respectively. The lobe was inflated once to PL 30 cmHz0 before recording Pbr-Vbr curves at PL 10 and 5 cmHa0. It took about 15 min to record these three Pbr-Vbr curves. Second, Pbr-Vbr curves were obtained from a salinefilled lung. The lobe was deflated to PL 0 cmHz0 and residual volume ,was measured by the water-displacement method, subtracting lobe weight and assuming the density of lung tissue as 1.0. The lobe was degassed with a vacuum pump with Vbr being kept in a collapsed state and all arrangements, including the measurement system, left unchanged. Then, the lobe was filled with saline through the collateral catheter (Fig. U?). The Lucite box was also filled with saline in order to avoid any effect from the gravity of the saline. PL in the saline-filled lung was defined as PA-Pbox minus the height of the saline from the midhorizontal level of the bronchi (Ps) while PA was kept at atmospheric. During the recording of the Pbr-Vbr curves and the ventilating of the lung with saline, PA was also kept at zero by means of the negative Pbox. Before recording Pbr-Vbr curves, the history of lung ventilation was kept in the same way as in the airfilled lung. Pbr-Vbr curves were obtained at three levels of VL corresponding to the volume at PL 30 (high VL), 10 (middle VL), and 5 cmHa0 (low VL), respectively, in the air-filled lung. Time courses of measurement were also taken in the same way as in the air-filled lung. At the end of measurement possible leaks of saline from the lung parenchyma were checked by means of the waterdisplacement method. In preliminary studies we observed that saline leak was greater at a higher VL. We kept the lobe at each VL for about 5 min and the leaks of saline from the lungs were 1.2 t 0.7% high VL (mean t SD, n = 8). Third, the bronchi were carefully dissected from the surrounding parenchyma, including the large pulmonary vessels. The dissected Pbr-Vbr curves were obtained in the same way as were the intact bronchi in the salinefilled lung. Zero Vbr was defined as Vbr at Pbr -60
A
Air
- filled
1~ ng
c
.
. . . . . . . . . . . :::: .
. .
B
Saline-
filled
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
::
.
.
.
.
lung
.
"L
l
:.*::: .
1 pVbr
“L
FIG. 1. Block diagram of apparatus in air-filled lung (A) and in saline-filled lung (B). In air-filled lung excised lower lobe was laid flat on saline in Lucite box. Lung was inflated by negative box pressure (Pbox). Lobar main bronchi were obstructed airtight with beads and segmental bronchus with catheter and bead for collateral ventilation. Isolated bronchial pressure-volume (Pbr-Vbr) relations were obtained with pressure transducer and syringe coupled with linear displacement transducer, respectively. Isolated lobar main bronchus, pressure transducer and syringe were filled with saline. Lung volume (VL) was measured with a Benedict-Ross respirometer coupled with linear displacement transducer. Alveolar pressure (PA) was measured at catheter for collateral ventilation with pressure transducer. Lung elastic recoil lung, lobe was pressure (PL) was defined as PA - Pbox. In saline-filled dipped in saline and VL was inflated with saline of lOO-ml syringes. PL in saline-filled lung was defined as PA at atmospheric pressure minus Pbox minus height of saline (Ps) from the midhorizontal line of bronchi.
cmHzO at PL or distending pressure 0 cmHz0. The differences of zero Vbr among the air-filled lung, the saline-filled lung, and the dissected bronchi were less than 2% of the maximum Vbr defined as Vbr at Pbr-PA = 0 cmHzO at PL 30 cmHa0 in the air-filled lung. We took the leaks of saline from the lung parenchyma and bronchi to be negligible. It has been considered that bronchial lengths are proportional to the cube root of VL in an air-filled lung (6). However, it has not been reported whether bronchial length even in a saline-filled lung is proportional to the cube root of VL. Because bronchial lengths were not controlled in this presentation due to difficulties in prep-
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694
NAKAMUHA,
aration, we measured the bronchial length at Pbr-PA = 0 cmHZO in the air- and saline-filled lungs in five additional lobes from five dogs. The lobes were laid flat in the Lucite box in the same way as described above. A bead 9 mm OD with a thin straight enamel wire 12 cm in length was glued on to the lobar main bronchi 6-7 cm in depth from the airway opening. The position of the enamel wire could be read to 0.5 mm with the unaided eye through a translucent plastic adapter connected to the airway opening at a given VL in both the air- and saline-filled lungs. During bronchial collapse bronchial length may be shortened. Furthermore in the dissected bronchi, bronchial length might be different from intact bronchial length. In three additional lobes from three dogs we studied the effect of bronchial length on Pbr-Vbr curves in intact and dissected bronchi in the air-filled lung. The lobe was laid flat in the Lucite box as described above with the lobar main bronchi obstructed airtight with beads. A catheter for collateral ventilation was introduced as described previously. The bottom bead was connected with a thin straight steel rod to an iron core 3 g in wt to measure the length of the obstructed lobar main bronchi with a linear differential transducer (Linear, Kyoto, Japan). The linear differential transducer was waterproofed and was laid horizontally inside the plastic adapter connected to the airway opening in a straight line with the main lobar bronchi. The position of the iron core was controlled by an adjustable stop as necessary and was changed smoothly inside the linear differential transducer. The positioning corresponded to the displacement of bronchial length. Dog B-W-
High
SASAKI,
AND
TAKISHIMA
After the intact Pbr-Vbr curves were obtained in the air-filled lung, the peribronchial parenchyma were dissected away from the obstructed main lobar bronchi in the same way as described above. In the dissected bronchi, length was measured or controlled during bronchial collapse in the same way as in intact bronchi. RESULTS
An example of Pbr-Vbr curves is shown in Fig. 2. In the saline-filled lung the initial Vbr at Pbr-PA = 0 cmHz0 were smaller and the Pbr-Vbr curves were more collapsible than in the air-filled lung at a given VL, although they were less collapsible than the dissected bronchi. Because bronchial length differed with different VL, bronchial areas (Abr) were calculated from Vbr with the assumption that bronchial length was proportional to the cube root of VL in both air- (6, 9) and saline-filled lungs. The characteristics of the bronchial length in the salinefilled lung and during bronchial collapse will be presented later. The initial Abr at Pbr-PA = 0 cmHz0 thus calculated were plotted with regard to VL and PL in Fig. 3. The Abr at high VL in the air-filled lung were standardized as 100% (5%maximum Abr). At all VL, Abr in the saline-filled lung were significantly smaller than Abr in the air-filled lung (paired t test, 0.001 < P c 0.005). On the other hand, when the Abr’s in both conditions were compared with regard to PL, although the Abr’s in the saline-filled lung were slightly smaller than Abr’s in the air-filled lung, both were nearly the same. Unfortunately, we could not check Abr statistically at any PL, because no PL in the saline-filled lung was identical with PL in
8 fn air-filled In saline
lung -filled
lung
“L
Middle
-60
-30 Pbr -
2. Example of Pbr-Vbr curves in air-filled lung (continuous Lines), saline-filled lung (dashed Lines), and dissected bronchi (interrupted Line). Pbr-Vbr curve in dissected bronchi is at distending pressure of 0 cmH20. Note that at corresponding VL initial Vbr in salineFIG.
+30
0 pA
(cmHz0)
filled lung at Pbr - PA = 0 cmH20 were lung and Pbr-Vbr curves in saline-filled than those in air-filled lung.
smaller lung
than were
those more
in air-filled collapsible
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BRONCHIAL
COLLAPSIBILITY
AND
LUNG
SURFACE
695
TENSION
In air-filled
--We
In saline
o At high
lung -filled
lu ng
l
VL
At middle
x At low
VL VL
0
t
[;-I
0
0
0
0
0
0
0
0
0
0
0 0 0 0 0
6C
0
f_
4( 40
60
80 VL
3. Initial bronchial VL (0), middle VL (o), and and PL. Abr at high VL in Means k SD (n = 8) were FIG.
( ‘10 maximum
area (Abr) at Pbr - PA = 0 cmH20 at high low VL (x) were plotted with regard to VL air-filled lung were standardized as 100%. shown. Note that Abr in saline-filled lung
the air-filled lung, and PL'S in the saline-filled lung were 10.9 t 1.9,6.0 t 1.1, and 3.0 t 1.5 cmHz0 in high, middle, and low VL, respectively. Bronchial collapsibilities in the air- and saline-filled lungs were compared in terms of VL and PL. Abr’s were calculated on several points of the Pbr-Vbr curve and were plotted on a logarithmic scale. Figure 4 shows that Pbr-Abr curves in both the air- and saline-filled lung are linear, except near the beginning of the curve, in a way similar to the Pbr-Vbr curves previously shown in the air-filled lung (20, 23). We took the linear slopes thus obtained as bronchial collapsibility. Slopes in the air- and saline-filled lungs were compared with regard to VL and PL (Fig. 5). Slopes at high VL in the air-filled lung were standardized as 100%. Slopes showed inverse proportion with VL or PL. At all VL, slopes in the saline-filled lung were significantly larger than in the airfilled lung (paired t test, 0.005 < P < 0.01). On the other hand, when slopes were compared with regard to PL, they were almost identical. PL in the air-filled lung was composed of both the lung tissue and the lung surface tension components of PL. The lung surface tension component of PL was obtained by the subtraction of PL in the saline-filled lung from PL in the air-filled lung and they were 19.1 t 1.9, 4.0 t 1.2, and 2.0 t 0.6 (mean t SD) at high, middle, and low VL, respectively. Similarly, in the air-filled lung Pbr was composed of three pressures: the dissected bronchial component, the lung tissue component, and the lung surface tension component. In the saline-filled lung Pbr
100 )
0
5
10
30
20 PI
L
(cmH70) L
were significantly lower than that in air-filled lung with regard to VL and both Abr’s were almost identical with regard to PL. Lines were the same as in Fig. 2.
was composed of the dissected bronchial component and the lung tissue component. The lung surface tension component of Pbr was obtained by the subtraction of Pbr in the saline-filled lung from Pbr in the air-filled lung at the same Abr at corresponding VL in the same manner as the analysis of the components of PL. The relations of the lung surface tension component of Pbr to VL, or to the lung surface tension component of PL, were plotted at 50 and 30% maximum Abr in Fig. 6. The lung tissue components of Pbr and PL were also plotted in Fig. 6, in which the lung tissue component of Pbr was made by the subtraction of the dissected bronchial component of Pbr from intact Pbr in the saline-filled lung at the corresponding distending pressure of intact and dissected states. The subtractions of dissected Pbr from intact Pbr were made at the same Vbr at the comparable PL or distending pressure and then Vbr was converted into Abr. The lung surface tension component of Pbr was increased nonlinearly with increased VL. At 50% maximum Abr at high and middle VL the lung surface tension component of Pbr-PA was significantly larger than the lung tissue component of Pbr-PA (paired t test, 0.001 < P < 0.005 and 0.025 < P < 0.050 at high and middle VL, respectively) whereas at 50% maximum Abr at low VL and at 30% maximum Abr at middle and low VL they were not significant (paired t test, 0.100 < P), which suggested that at 50% maximum Abr at high and middle VL the contribution of lung surface tension on Pbr-PA was significantly larger than the contribution of lung tissue. Both lung surface tension and lung tissue contributions
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696
NAKAMURA,
Dog
5
-
In
---
In saline-filled
air-filled
lung lung
At middle
l
x At X I
-60
low
VL VL
/
I
I
40
1
I
-20 Pbr
- ?A
I
0 ( cmH20)
FIG. 4. Pbr-Abr curves in air- and saline-filled lungs were replotted on logarithmic scale of Abr. Note that Pbr-Abr curves in saline-filled lung were linear as they also were in air-filled lung as previously reported by Takishima et al. (23). Symbols were the same as in Fig. 3.
on Pbr-PA were compared with both corresponding components of PL to determine the possible influence of structural or material differences between them (Fig. 6). Both components of Pbr-PA increased linearly with the corresponding component of PL. At 30% maximum Abr both components of Pbr-PA increased more steeply than at 50% maximum Abr with regard to both VL and PL. In the air-filled lung the relations of the lung parenchymal compo nent of Pbr-PA .nd PLW ‘ere approximate ly simil .ar to the relations show on the right-hand side of Fig. 6. Though the lung surface tension components of Pbr-PA were slightly larger than the lung tissue components of Pbr-PA with considerable standard deviations, they were nearly the same. Figures 5 and 6 suggest that lung surface tension itself makes bronchial collapsibility equal to or even less than the degree of collapsibility due to forces applied from surrounding lung tissues that distended the bronchi In the saline-filled lung the average bronchial lengths were shorter by 2.2 t 0.8% (mean t SD, n = 15) than in the air-filled lung even though the lung volume was kept the same at Pbr-PA = 0 cmHa0. We neglected the effect of small differences in bronchial length on the calculation of Abr at Pbr-PA = 0 cmHa0. During deflation of Vbr from Pbr-PA = 0 to -50
SASAKI,
AND
TAKISHIMA
cmHa0 intact bronchial length decreased by approximately 3-6s of initial bronchial length at Pbr-PA = 0 cmHz0 at each PL. Bronchial length decreased less at high PL. When the bronchial length was fixed at initial bronchial length of Pbr-PA = 0 cmHz0, Pbr-Vbr curves were almost identical to Pbr-Vbr curves obtained without fixed bronchial length in the intact bronchi. The semilogarithmic slopes of Pbr-Abr curves without fixed bronchial length showed no difference from those with fixed bronchial length. Because of decreased PL, in the saline-filled lung during bronchial collapse at a given VL, bronchial length might become shorter than in the air-filled lung. However, during bronchial collapse bronchial length would be shortened in both air- and saline-filled lungs, though varying in magnitude. Then, the difference of the effect of shortening bronchial length on Pbr-Abr curves between air- and saline-filled lungs might be reduced. The small difference of Pbr-Vbr curves between fixed and nonfixed bronchial length at initial bronchial length would make the error of the subtraction of Pbr in the saline-filled lung from Pbr in the air-filled lung insignificant. In the dissected bronchi the initial bronchial length were shorter by 14.5 t 3.5% (mean t SD) than the intact bronchial length at the corresponding distending pressure of approximately 30 to 5 cmHa0. With fixed bronchial length with an intact initial bronchial length of PbrPA = 0 cmH20, Pbr-Vbr curves of dissected bronchi indicated slightly less collapsibility than those without fixed bronchial length by Pbr 1.1 t 0.8 and 2.0 t 1.4 cmHs0 (mean t SD), at 50 and 30% maximum Abr, respectively. The differences of pressure were larger at higher PL. Therefore, we might have overestimated the lung tissue component of Pbr-PA by approximately l-2 cmHa0 in Fig. 6. DISCUSSION
In the present study the determinants of the initial bronchial area at Pbr-PA = 0 cmH20 and bronchial collapsibility were studied with regard to VL and PL in the air- and saline-filled lungs. First, we will consider possible errors and limitations in the present study. Alveolar pressure was assumed to be at atmospheric during bronchial collapsing. In the air-filled lung collateral channels were suggested as being enough to keep alveolar pressure at atmospheric even during dynamic bronchial collapse (20). During bronchial collapse in the saline-filled lung, however, alveolar pressure might not be at atmospheric, depending on the time constant of the collaterally ventilated segment. In two lobes from two dogs we measured flow resistance of collateral channels of segments in the air- and saline-filled lungs. The lobes were suspended in the Lucite box and laid flat in the way previously described here. A double-lumen polyethylene catheter (a small catheter (PE-90) inside a larger one of OD 7 mm) was wedged into a segmental bronchus in the way described above, but without obstructing the other tributary bronchi with beads. A small catheter that had several lateral holes and was closed at the end was used for measurement of pressure at the segmental bronchus. Flow was measured with a Fleisch pneumotachograph in
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BRONCHIAL
COLLAPSIBILITY
AND
LUNG
SURFACE
TENSION
697 -
In air-filled
----
In saline-filled
-0‘0 400 V
lung
0 At high l
VL
At middle
x At
h CI .-.*i
lung
low
VL VL
300
a
5
3 .x “c
200
0 ii
100 40
60
80
100
( o/Omaximum
VL
Lung
tissue
. . . . . . . . Lung
5
10
)
(cmH20
0 At high
component tension
l
component
30’/.maximum Abr
\s\, ir I ,H’
0
VL
At middle
x At low
Abr
1
lung were considerably larger than in air-filled lung with regard to VL and approximately the same with regard to PL. Symbols were the same as in Fig. 3.
surface
30’1. max,imum
30
20 PL
FIG. 5. Bronchial collapsibilities were compared with regard to VL and PL. Bronchial collapsibilities at high VL in air-filled lung were standardized as 100%. Note that bronchial collapsibilities in saline-filled
w-e-
0
VL VL
T
A
l
0
:
0
’
T/ 0 .** 0
,**
maximum 50.J. 5O.J. maximum 4
I
I
60 VL
1
r
80 100 ( ‘Jomaxi mum )
0
FIG. 6. Radial tractions on bronchi of both lung tissue component (dashed lines) and of lung-surface tension component (dotted lines) of Pbr-PA were plotted with regard to VL on left. PL in air-filled lung were divided into two components of lung-surface tension and lung tissue. Relations of lung tissue component and lung surface tension component of Pbr-PA to their corresponding components of PL were plotted on right. Note that with regard to VL, radial tractions of lung surface
Abr
Abr v
I
r
5 10 20 Lung tissue or lung surface tension component of PL (cmH20)
1
30
tension component were roughly the same as those of the lung tissue component except at 50% maximum Abr at high VL, and with regard to PL they were almost the same and were linearly related. See text for statistical descriptions. Radial tractions increased more steeply with increased PL at smaller Abr, than at larger Abr. Symbols are the same as in Fig. 3.
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698 the air-filled lung and in the saline-filled lung with a 50ml syringe the scale of which could be read to 1 ml by the naked eye. Saline flow was obtained five times during 1-min intervals after saline flow became a steady state. The driving pressure of 2 cmH20 as the pressure difference from -pressure at the segmental bronchus to the airway opening pressure was made by an air pump in the air-filled lung and two saline reservoirs in the saline-filled lung, respectively. In the air-filled lung the mean airflow resistances from the segment were 144 and 232 cmHaO/(l/s) at PL 10 (middle VL) and 5 cmHz0 (low VL), respectively. In the saline-filled lung the mean flow resistances from the segment increased by 8 and 10 times the resistance in the air-filled lung at mid .dle and low v ‘L, respectively. If both airway and collateral resistances were simply determined by the differences of viscosity of air (1.86 X 10s4 poise) and saline (1.002 x lo-’ poise), the airway and collateral resistances in the saline-filled lung would increase 54 times that of the air-filled lung at a given VL. Menkes et al. (13) reported that collateral resistance decreased with increased PL. Because in the saline-filled lung PL decreased at a given VL, collateral resistance should also increase more than expected due to the difference in viscosity. Menkes et al. (13) su .ggested that collateral channels could not be opened even with a driving pressur beof 190 cm Hz0 once th .ey w ‘ere occluded in the a.ir-filled lung I. In the saline-fill .ed lung an increased number of collateral channels due to loss of surface tension at the air-liquid interface or meniscus of liquid of collateral channels could be one of the reasons for such lower collateral resistances than expected due to the difference in viscosity and PL. Supposing the segmental compliances in the saline-filled lung were three times the compliance in the air-filled lung, collateral time constants of the segment in the saline-filled lung were around 30 times the time constant in the air-filled lung. In the present preparation, Vbr were deflated slowly at 0.03 ml/ s; therefore, the collateral ventilation would not be disturbed because of PA being kept at atmospheric even in the saline-filled lung. Low initial bronchial area at Pbr-PA = 0 cmHz0 in the saline-filled lung at a given VL would not be due to increased bronchial tone because in the preliminary experiment we instilled atropine and isoproterenol of final concentrations of 5 and 1 pg/ml, respectively, into intact bronchi isolated by beads in three lobes. Comparisons of Pbr-Vbr curves of the isolated bronchi before and after instillation of bronchodilators made no systematic difference. Presumably, unless otherwise specifically designed preparations such as gas supply, nutritious solutions, and temperature supply are made to maintain main lobar bronchial tone, bronchial tone might diminish as time elapses during the isolating of the lobal main bronchi. Because Pbr-Abr relations in the saline-filled lung were obtained later than in the air-filled lung, bronchial tone in the sal ine-filled lu w might decrease more, if it changed at all. Smaller PL was accompanied by large narrowing of of Abr at a given VL and a much smaller narrowing Abr at a given PL (Fig. 3), which were approximately similar to the findings by Hyatt et al. (9) except for the fact that they studied the branch ial dia meter at increa .sed
NAKAMURA,
SASAKI,
AND
TAKISHIMA
PL. Therefore, we might say that there was little tone in the present lobar main bronchi. In the present study we found that elimination of lung surface tension reduced the initial bronchial area at PbrPA = 0 cmHZO and increased bronchial collapsibility. Both initial bronchial diameter at Pbr-PA = 0 cmH20 and bronchial collapsibility were well related to PL but not to VL. The contribution of lung parenchyma to the radial traction on the bronchi was well documented using the lung parenchymal model presented by Mead et al. (11). The contribution of lung tissue to the radial tracti .on on the bronchi could be similarly analyzed by the lung parenchymal model constructed by Mead et al. (11). However, it was unknown whether or not lung surface tension contributed to parenchymal radial traction in the same way that lung tissue did depending on the magnitude of the lung surface tension component of PL. Hughes et al. (6) reported that the determinant of bronchial diameter was VL. On the other hand, Caro et al. (2), Hughes et al. (7), and Hyatt et al. (9) found a close correlation between bronchial diameter and PL. We found results similar to those of Caro et al. (2) and Hvatt et al. (9) in that bronchial area was well related to PLYbut not to VL, except that they found close relations between bronchial area and PL in th e lung with increased PL. The present results confirmed the finding by Hugh .es et al. (7)) although their results did not demonstrate differences in expiratory pressure-volume curves between airand saline-filled lungs below moderate lung volumes. Because at Pbr-PA = 0 cmHe0 both the bronchi and the lung parenchyma would expand homogeneously ( 19)) lung surface tension might contribute to the radial traction of lung parenchyma on the bronchi, and depending on the magnitude of the component of lung surface tension of PL, lung tissue also might make a contribution. During bronchial collapse, peribronchial lung parenchyma would be unhomogeneously deformed, -which raised the question of whether or not lung surface tension contributed to the radial traction of lung parenchvma bv the magnitude of contributions of lung surface tension to PL. Radial traction of lung parenchyma on the bronchi was defined as interdependence of lung parenchyma by Mead et al. (11). Mead and associates (11) defined the interdependence as an inversely proportional increase of radial traction depen ding on the d ecreased bronchial diameter due to stress density theory and Taki shima and Mead (21) proved their theory experimentally. Menkes et al. (14) developed the theory of the interdependence of adjacent lung parenchyma. Hughes et al. (8) and the authors (19, 20, 23) observed the magnitude of peribronchial radial traction on the bronchi when collapsing; both groups showed considerably larger values than the stress density theory by Mead et al. (11). Prediction of elasticity based on the lung parenchyma as an isotropic elastic continuum shows that parenchymal distortion falls off rapidly (5). Morphological studies of distortions occurring as a result of locally indenting the pleura have shown that distortion does not extend far into the parenchyma from the site of indentation (3, 18). Because local peribronchial parenchyma would determine the radial traction of the lung parenchyma, deformation of the air space of the peribronchial parenchyma might reduce lung sur-
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BRONCHIAL
COLLAPSIBILITY
AND
LUNG
SURFACE
699
TENSION
face tension; if the lung surface tension component of PL were primarily determined by the conditions described in the formula of Laplace, radial expansion of alveoli would be accompanied by a larger curvature of alveoli in the radial direction of the bronchi, resulting in a decrease of radial forces applied by the lung surface tension if surface tension were kept the same. However, in the present study, we found that radial tractions on the bronchi, due to both lung tissue and lung surface tension, showed the same magnitude as in the air-filled lung with regard to the respective components of PL. Then, the mechanisms responsible for the distending forces applied from the lung surface tension are probably different from those responsible for lung tissue forces. Radial forces applied from the lung tissue to the bronchi would have the same characteristics as described in the spring model of interdependence by Mead et al. (11). The volume of the air spaces of the peribronchial parenchyma would increase during bronchial collapse, resulting in local inflation of lung parenchyma. Inflation of lung parenchyma was accompanied by an increase in lung elastic recoil. Furthermore, the surface tension had a larger hysteresis than the lung tissue had between the periods of lung inflation and deflation (1). Thus, the radial forces applied by the lung surface tension would be larger than that by the lung tissue during the periods of local lung inflation by the amount of larger hysteresis. Therefore, inflation of local parenchyma during bronchial collapse might produce enough local radial traction by the lung surface tension rath .er than decreased local radial traction of lung surface tension described in the formula of Laplace due to a larger curvature of alveoli in the radial direction to the bronchi. The exact mechanisms of radial traction of parenchyma on the bronchi are not known, nor are the mechanisms of radial tractions made by lung surface tension. Histological study might be on .e of the methods needed for analysis of the interdependence of parenchyma. The theoretical analysis of maximum expiratory flow was intensively studied by many investigators. (vrnax) Mead et al. (12) proposed an equal pressure-point theory
that described V maxto be proportional to PL and inversely proportional to upstream resistance (Rup). There are many studies that support the equal pressure-point theory. Vincent et al. (24) found that during lung inflation and deflation in human subjects Vm,x increased by the amount of increased PL. Park et al. (16) made pulmonary emphysema in papain-inhaled hamster lungs. They observed that Vm,, was also proportional to PL. Paying attention to the bronchial narrowing that occurs during maximum forced expiratory maneuvers, Pride et al. (17) proposed the Starling resistor theory that pointed out the importance of bronchial collapsibility. Recently, theoretical analysis of V maxalso described bronchial collapsibility as a primary determinant of Vmax (4, 15, 22). However, it has not been reported whether bronchial collapsibility is related to PL or not. In the present study, we found that bronchial collapsibility was well related inversely to PL in air- and saline-filled lungs (Fig. 5). In normal lungs (24) or experimental pulmonary emphysema made by papain (16), PL, as a determinant of Vmax in equal pressure-point theory, seemed to be inversely proportional to bronchial collapsibility. The present result suggests that in human pulmonary emphysema one of the determinants of decreased Vm,, seems to be decreased PL. In terms of decreased PL, a saline-filled lung seemsto be a model of pulmonary emphysema. However, we have not obtained any information from emphysema patients to indicate whether or not bronchial collapsibility is inversely proportional to PL. Maisel et al. (10) reported atrophy of the bronchial wall structures in some emphysematous patients. In that case, bronchial collapsibility in some emphysematous patients might be greater than expected from the present results. Because the present preparation for studying bronchial collapsibilities can be applied only to the normal structures of parenchyma, further work may be needed for application to the wide variety of human lung diseases. The authors are appreciative of Mr. B. Breneman, Ms. B. Hayashi, and Ms. K. Toda for their assistance in the preparation of this paper. Received
11 January
1979; accepted
in final
form
1 June 1979.
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9. HYATT, R. E., J. R. RODARTE, AND T. A. WILSON. Effect of increased static lung recoil on bronchial dimension of excised lungs. J. AppZ. Physiol. 39: 429-433, 1975. 10. MAISEL, F. C., G. W. SILVERS, R. S. MITCHELL, AND T. L. PETTY. Bronchial atrophy and dynamic expiratory collapse. Am. Rev. Respir. Dis. 98: 988-997, 1968. 11. MEAD, J., T. TAKISHIMA, AND D. LEITH. Stress distribution in lungs: a model of pulmonary elasticity. J. Appt. PhysioZ. 28: 596608, 1970. 12. MEAD, J., J. M. TURNER, P. T. MACKLEM, AND J. B. LITTLE. Significance of the relationship between lung recoil and maximum expiratory flow. J. AppZ. PhysioZ. 22: 95-108, 1967. 13. MENKES, H., A. GARDINER, G. GAMSU, J. LEMPERT, AND P. T. MACKLEM. Influence of surface forces on collateral ventilation. J. AppZ. Physiol. 31: 544-549, 1971. 14. MENKES, H., D. LINDSAY, L. WOOD, A. MUIR, AND P. T. MACKLEM. Interdependence of lung units in intact dog lungs. J. AppZ. Physiol. 32: 681-686, 1972. 15. PARDAENS, J., K. P. VAN DE WOESTIJINE, AND J. CLI~MENT. A physical model of expiration. J. AppZ. Physiol. 33: 479-490, 1972. 16. PARK, S. S., I. P. GOLDRING, C. S. SHIM, AND M. H. WILLIAMS, JR. Mechanical properties of the lung in experimental pulmonary emphysema. J. AppZ. Physiol. 26: 738-744, 1969.
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700 17. PRIDE, N. B., S. PERMUTT, R. L. RILEY, AND B. BROMBERGERBARNEA. Determinants of maximal expiratory flow from the lungs. J. AppZ. Physiol. 23: 646-662, 1967. 18. ROBERTSON, C. H., D. L. HALL, AND J. C. HOGG. A description of lung distortion due to localized pleural stress. J. Appl. Physiol. 34: 344-350, 1973. 19. SASAKI, H., F. G. HOPPIN, JR., AND T. TAKISHIMA. Peribronchial pressure in excised dog lungs. J. AppZ. Physiol.: Respirat. Environ. Exercise Physiol. 45: 858-869, 1978. 20. SASAKI, H., T. TAKISHIMA, AND T. SASAKI. Influence of lung parenchyma on dynamic bronchial collapsibility of excised dog lungs. J. AppZ. Physiol.: Respirat. Environ. Exercise Physiol. 42:
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AND
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699-705, 1977. 21. TAKISHIMA, T., AND J. MEAD. Tests of a model of pulmonary elasticity. J. AppZ. Physiol. 33: 576-581, 1972. 22. TAKISHIMA, T., AND H. SASAKI. Two-dimensional flow-model for analysis of expiratory check valve. BUZZ. Physio-PathoZ. Respir. 8: 361-374, 1972. 23. TAKISHIMA, T., H. SASAKI, AND T. SASAKI. Influence of lung parenchyma on collapsibility of dog bronchi. J. AppZ. PhysioZ. 38: 875-881, 1975. 24. VINCENT, N. J., R. KNUDSON, D. E. LEITH, P. T. MACKLEM, AND J. MEAD. Factors influencing pulmonary resistance. J. AppZ. PhysioZ. 29: 236-243, 1970.
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