Microvascular pressures measured by micropuncture
in isolated perfused lamb lungs
J. USHA RAJ AND P. CHEN
Department
of Pediatrics, Harbor- UCLA Medical Center, University of California,
Los Angeles, School of Medicine, Torrance, California 90509
pulmonary circulation;
pulmonary
nary vasomotor tone; pulmonary
compliance; neonatal lungs
vascular resistance;
arterial compliance;
pulmovenous
IT IS CLEAR that the arterioles are the major
site of resistance in the systemic circulation (6), there is
still some confusion as to the longitudinal distribution
of vascular resistance in the pulmonary circulation (11).
Estimates of the contribution of pulmonary arteries,
microvessels, and veins to total vascular resistance derived from indirect measurements have assigned a major
fract)ion of the resistance to the arterial segment (1, 5,
13, 14). More recently, by direct measurement of pressures in the small subpleural arterioles and venules using
the micropipette servo-nulling technique, the microvessels (vessels ~20 pm diam) were determined to be the
major site of resistance to blood flow in the lung (4, 22,
23
All these studies have been done in adult animals and
can be applied only generally to the newborn. There are
several reasons why the distribution of segmental vascular resistance in the lung is likely to be different in the
newborn. The high vascular resistance in the fetus (9,
10) falls dramatically at birth (9, 10) but remains higher
ALTHOUGH
2194
0161-7567/86
$1.50
than in the adult during the neonatal period. A high
basal vasomotor tone (27) and differences in the morphology of the pulmonary vasculature contribute to the
higher pulmonary vascular resistance in the neonate.
After birth, with progressive involution of the medial
smooth muscle in the small blood vessels (16), there is a
slow fall in pulmonary vascular resistance until the final
low adult value is reached at -3-6 mo of age (26).
In this study, we have used the technique of lung
micropuncture to directly determine the longitudinal
distribution of vascular pressures in isolated blood-perfused lungs of newborn lambs. To investigate the contribution of smooth muscle tone to base-line arterial and
venous resistance in the lungs, we paralyzed the vasculature with papaverine and repeated the microvascular
pressure measurements. We also determined the slope
and intercept of the vascular pressure flow relationship
before and after elimination of smooth muscle tone. In
addition, to study the influence of transmural pressure
on segmental vascular resistance, we determined the
microvascular pressure profile in the lungs during reverse
perfusion. We found that under base-line conditions, the
pressure drop
. across the pulmonary circulation occurs in
roughly equal proportions across the arteries, microvessels, and veins. Vessel tone contributes much more toward base-line arterial resistance than toward venous
resistance. In lungs with no smooth muscle tone, at the
same transmural pressure, the pressure drop across arteries and veins is similar, indicating that the distensibility and vessel geometry of arteries and veins is similar
in lungs of newborn lambs.
MATERIALS
AND
METHODS
Isolated Lung Preparation
The lungs of 20 newborn lambs, whose average age
and body weight were 8.4 t 4.5 days and 5.32 t 0.93 kg,
respectively, were isolated and perfused. Initially, the
lambs received ketamine (25 mg/kg body wt im) and
breathed 100% O2 during placement of catheters. Via a
neck incision under local anesthesia with 2% lidocaine,
catheters were inserted into the carotid artery and jugular vein, and an endotracheal tube was tied into the
trachea. We infused 20 ml/kg body wt of a plasma
expander [5% dextran (mol wt 70,000, Sigma Chemical,
St. Louis, MO) in Ringer lactate solution] intravenously
to prevent ketamine-induced systemic hypotension that
Copyright 0 1986 the American Physiological Society
Downloaded from http://jap.physiology.org/ by 10.220.33.2 on September 13, 2016
RAJ, J. USHA, AND P. CHEN. Microvascular
pressures measured by micropuncture
in isolated perfused lamb lungs. 3. Appl.
Physiol. 61(6): 2194-2201, 1986.-To
investigate the influence
of vasomotor tone and vessel compliance
on pulmonary
segmental vascular resistance, we determined
the longitudinal
distribution
of vascular pressures in 15 isolated blood perfused
lungs of newborn lambs. We measured pulmonary arterial and
left atria1 pressures and by micropuncture
the pressures in 20to 80-pm-diam
subpleural
arterioles and venules, both before
and after paralyzing
the vasculature with papaverine
hydrochloride. In five lungs we also determined
the microvascular
pressure profile during reverse perfusion. In lungs with baseline vasomotor tone, -32% of the total pressure drop was in
arteries, -32% in microvessels, and -36% in veins. With elimination of vasomotor
tone, arterial
and venous resistances
decreased to one-fifth and one-half of base-line values, respectively, indicating
that vasomotor tone contributed
mainly toward arterial resistance. During reverse perfusion, the pressure
drop in veins was similar to that in arteries during forward
perfusion, suggesting that the compliance of arteries and veins
is comparable. We conclude that vascular tone and compliance
are important
factors that determine the distribution
of segmental vascular resistance in lungs of the newborn.
LUNG
MICROVASCULAR
PRESSURE
Thermistor
Venous
reser voif
FIG.
1.
Pump
Blood perfusion circuit for lamb lungs. See text for details.
IN NEWBORN
LAMBS
2195
reservoir by a roller pump (Integral variable drive, ColeParmer). We calibrated the roller pump by timed collections of the outflow. Pulmonary arterial and left atria1
pressures were measured continuously with pressure
transducers (Gould Statham P23) that were connected
to polyethylene tubing, the tips of which were located in
the pulmonary arterial and left atria1 cannulas. Zero
reference level for vascular pressures was the top surface
of the lung (the site of all micropunctures). Left atria1
pressure was set by adjusting the height of the venous
reservoir, and the pulmonary arterial pressure was controlled by adjusting blood flow. We measured perfusate
02 and CO, tensions and pH every 10 min using standard
electrode techniques (Radiometer BMS 3MIC2, Copenhagen, Denmark) and adjusted pH to 7.40-7.50,
when
necessary, by the addition of sodium bicarbonate. Perfusate hematocrit
and glucose concentrations
(by
Dextrostix) were monitored every 20 min and blood
glucose concentration was kept between 90 and 130 mg/
dl by periodic addition of 50% glucose in water.
Initially, the collapsed lungs were perfused at a low
flow rate, then the flow increased gradually as the lungs
were inflated. The lungs were ventilated with appropriate
gas mixtures between micropuncture and during micropuncture were kept steadily inflated at an airway pressure of 7 cmH20.
Experimental Protocol
Base-line normoxia. During a base-line normoxic period, the lungs were ventilated by hand at 25/5 cmHzO
airway pressure (inspiratory and expiratory pressures)
at a rate of 30 breaths/min with a gas mixture of 30%
02-6% CO:!-74% N, for a few minutes, then switched to
a constant airway pressure of 7 cmH20. We adjusted
blood flow to raise pulmonary arterial pressure to 30
cmHzO and adjusted the height of the venous reservoir
to maintain left atria1 pressure at 8 cmHzO. The lungs
were perfused under zone 3 conditions; i.e., the left atria1
pressure was kept greater than airway pressure throughout the height of the lungs. Once established, blood flow
was kept constant for the rest of the experiment, at 69
t 21 ml. kg body wt-’ 0min-’ (354 t 63 ml/min). In 15
lungs we measured pressures by the micropuncture servonulling technique in 20- to SO-pm-diam subpleural arterioles and venules, as well as in l50- to 2OO-pm venules.
Low vascular tone. To study the influence of vascular
tone on base-line segmental vascular resistance in the
lungs, we used hyperoxia plus papaverine to eliminate
vascular smooth muscle tone. In 15 lungs, after the baseline normoxic period, the lungs were ventilated at the
same airway pressures and rate with a gas mixture containing 6% C02-94% O2 until blood Po2 was >200 Torr,
then switched to a constant airway pressure of 7 cmH20.
Papaverine hydrochloride was added to achieve a concentration of 100 pg/ml in the perfusate. Our conclusion
that this concentration was sufficient to effectively paralyze the vasculature was based on the observation that
there was no pressor response to a bolus injection of 200
pg of angiotensin into the pulmonary artery. Blood flow
remained constant (69 & 21 ml kg body wt-l. min-‘)
during this period. Microvascular pressures were meal
Downloaded from http://jap.physiology.org/ by 10.220.33.2 on September 13, 2016
may result in the release of vasoactive agents into the
circulation. Once the lambs’ blood pH and gas tensions
were within normal limits, they received 25 mg/kg body
wt of pentobarbital sodium and 1,000 IU/kg of heparin
sodium (Liquemin, Organon) intravenously, followed by
rapid exsanguination through the carotid artery catheter.
We collected the drained blood to prime the perfusion
circuit. Via a midline sternotomy the superior and inferior vena cava were ligated near their entry into the right
atrium, and the heart and lungs removed. Cannulas
(Silastic tubing, 4.68 mm ID, 7.81 mm OD, Dow Corning,
Midland, MI) filled with 5% dextran in Ringer lactate
solution were tied into the pulmonary artery via the right
ventricle and into the left atria1 appendage. By occluding
the distal pulmonary artery with a vascular clamp, we
prevented air bubbles from entering the lungs. The ductus arteriosus, the aortic root, and the azygous veins were
ligated, and a ligature was placed around the atrioventricular groove to occlude the lumen of the ventricles. In
the newborn lamb, as the ductus arteriosus and foramen
ovale are patent, the systemic veins and aorta have to be
tied to prevent leakage of blood. The lungs were placed
on a Plexiglas table, the vascular cannulae connected to
the perfusion circuit, and the endotracheal tube attached
to a source of gas supply. The average time interval from
death of the lamb to perfusion of the lungs was 12 min.
The perfusion circuit (Fig. 1) was filled with -200 ml
of blood and the level of blood in the venous reservoir
kept constant by addition of blood whenever necessary.
By noting the volume of blood added to the reservoir, we
could assessthe rate of weight gain in the lungs during
perfusion. Heparin was added to make a final concentration of 30 IU heparin/ml of blood. The perfusate temperature was kept at 38-39 “C (the body temperature of
lambs) with a heat exchanger (Miniprine,
Travenol,
Deerfield, IL) and the perfusate continuously filtered of
clots and bubbles with a filter (Ultipore, Pall Biomedical,
Easthills, NY). A thermistor probe placed near the outlet
of the heat exchanger allowed continuous monitoring of
the temperature. To decrease pulsations, a bubble trap
was placed in the circuit before the pulmonary arterial
cannula. A Starling resistor prevented pressures from
rising above 60 cmHzO within the circuit. Blood was
circulated through the pulmonary artery into the lungs
and back through the pulmonary veins into a venous
PROFILE
2196
LUNG
MICROVASCULAR
PRESSURE
l
Microvascular Pressure Measurement
To measure lung microvascu lar pressures we micropunctured the lung-using a modification of the technique
described by Bhattacharya and Staub (4). We used a
pipette puller to make micropipettes from glass tubing
(vertical pipette puller model 700D, David Kopf, Tujunga, CA) and bevelled the tip to a diameter ranging
between 2 and 4 pm on a pipette beveller (Diamond
Abrasive plate, David Kopf). Because the pleura of the
lamb is thick (2) and the arterioles are situated deep, a
thick glass tubing (0.6 mm ID, 1.2 mm OD, Frederick
Hauer, Brunswick, ME) was used to construct sturdy
80
s
I”
E
u
;
L
70
60
BASELINE
NORMOXIA
ci
*
ii
5
*
&
3020-
WITH
PAPAVERINE
AND HYPEROXIA
IO-
0
200
Blood
300
Flow
500
700
(ml/min)
2. Typical
vascular
pressure
flow data
normoxia
and hyperoxia
plus papaverine.
With
motor tone, slope of pressure flow line decreased
change in pressure
intercept.
FIG.
NEWBORN
LAMBS
pipettes, with the taper length ranging between 200 and
300 pm. The pipette was filled with 1.2 M NaCl solution
colored with green dye (Guinea Green B, Aldrich Chemical) and connected to a servo-nulling pressure measuring
system (model 4A, Instruments for Physiology and Medicine, San Diego, CA). The dye enabled us to see the tip
of the pipette easily and to perform a dye flow test during
micropuncture. To facilitate micropuncture of the lung,
the lung surface was stabilized by lightly placing a metal
ring ‘(attached to a stand) on the pleura; the ring also
held a pool of normal saline on the lung surface for
obtaining the zero reference pressure. The lung surface
was viewed through a stereomicroscope (Zeiss) at ~80 or
~120 magnification with illumination from a cold light
source (Intralux 5000, American Volpi, Auburn, NJ).
Subpleural venules, ranging from 10 to 250 pm diam are
numerous and easily visible, especially near the lung
edges; on the other hand only a few arterioles, ranging
from 20 to 100 pm diam were visible and were found in
a random distribution on the lung surface. Venules are
more superficial and hence easier to micropuncture. We
measured pressures in 20- to 80-pm-diam arterioles and
venules during each experimental period and pressures
in 150- to 200-pm venules also only during the base-line
normoxic period.
To micropuncture venules, we positioned the pipette
at a 30 Oangle to the pleural surface, whereas to puncture
arterioles we approached the pleura with the pipette at
a 45 O angle. Venules were identified by observing the
direction of flow of erythrocytes from small vessels into
large ones; for arterioles blood flowed in the opposite
direction. Because arterioles were deepseated, a dye flow
test was essential to determine the direction of blood
flow.
We accepted microvascular pressure measurements
that fulfilled the following criteria: 1) reproducible zero
reference pressure obtained both before and after the
pressure measurement, 2) an immediate response in the
microvascular pressure tracing when either the pulmonary artery or left atria1 pressure is perturbed, 3) immediate washout of injected dye from the pipette by the
flowing blood, indicating that the pipette tip was lying
freely in the vessel lumen, and 4) a pressure measurement
that is independent of small changes in the optimal
servo-null gain setting, indicating that the pipette tip is
in liquid.
Blood Flow Measurements
4o
E
E
3
a.
IN
in lamb lung during
elimination
of vasowithout
a significant
In five lungs, we used the radiolabeled microsphere
technique described by Heymann and associates (15) to
determine the distribution of blood flow within the lungs
during the normoxic and hyperoxic plus papaverine periods (low and high blood flow). During each experimental period, when vascular pressures and blood flow were
stable, we made an injection of 15pm-diam radionuclide
microspheres. The microspheres were injected rapidly
retrograde to blood flow, through a thin catheter inserted
via a T-piece into the perfusion circuit 15 cm from the
pulmonary artery. This created turbulence, allowing for
adequate mixing of the microspheres. After the injections, blood flow was stopped, the trachea clamped at 7
Downloaded from http://jap.physiology.org/ by 10.220.33.2 on September 13, 2016
sured in the 20- to 80-pm arterioles and venules again.
During both normoxia and hyperoxia plus papaverine
periods, we examined the vascular pressure flow relationships of the lungs. Blood flow rates were varied from 80
to 680 ml/min, as this range of flow rates usually yielded
a linear pressure flow relationship (correlation coefficient >0.99) (Fig. 2). Left atria1 pressure was 8 cmH20
and airway pressure was 7 cmH20 (zone 3 conditions).
Flow rate was incre ased in discrete steps every 30 s by
adjusting the pump speed, and pulmonary arteri al pressure was recorded.
High blood flow in lungs with low vascular tone. To
study the effect of blood flow and the total arteriovenous
pressure drop on segmental vascular resistance in the
lungs, we doubled blood flow to 138 t 26 ml= kg body
wt-l min-’ (616 t 42 ml/min) and measured microvascular pressures again.
Reverse perfusion in lungs with low vascular tone. To
determine the effect of transmural pressure on venous
geometry and resistance, we reversed blood flow in five
of the 15 lungs; i.e., blood entered the lungs through the
left atrium and drained from the pulmonary artery into
the blood reservoir. Blood flow rate was adjusted to
obtain the same total arteriovenous pressure drop during
reverse flow as during forward flow. Microvascular pressures were measured during both forward and reverse
flow.
PROFILE
LUNG
MICROVASCULAR
PRESSURE
cmHZO airway pressure, and the lungs frozen in liquid
N,. The average height of the lungs was 9 cm. The lungs
were cut into l-cm-thick horizontal slices. At the top of
the lungs, the site of micropuncture, a l-mm-thick slice
of the subpleural region was cut. The tissue was processedfor radionuclide counting of the three tracers (46Sc,
85Sr, 37Co) in a multiple-channel gamma counter (1282
Compugama, LKB Wallac). We determined the fractional blood flow to each -slice and expressed it as ml.
min
g dry lung-‘.
l
Data Analysis
RESULTS
Blood PO, averaged 130 t 13 Torr during the baseline normoxic period and 262 t 88 Torr during the
hyperoxic plus papaverine period. Blood hematocrit rose
from 17.0 t 4.8 to 17.8 t 5.2% by the end of the perfusion
period, suggesting fluid accumulation in the lungs. All
lungs gained weight slowly, at -0.5 t 0.8 g/min and had
gained 20-40% of their initial weight by the end of the
experiments. Airway edema did not occur in any of the
lungs.
Microvascular Pressures in Lamb Lungs
During Normoxia (Table 1)
During normoxia, blood flow averaged 69 t 21 ml. kg
body wt-l min-‘, and calculated pulmonary vascular resistance was 0.376 t 0.13 cmHZO
kg. Total
arteriovenous pressure drop was 22.2 t 2.4 cmHZO. The
pressure drop from the pulmonary artery to 20-pm arterioles was -32%,
from the 20-pm arterioles to 20-pm
venules was -32%
and from 20-pm venules to the left
atrium was -36% of the total pressure drop. Approximately 14% of the total pressure drop was in veins >2OO
IN
NEWBORN
2197
LAMBS
Microvascular Pressures in Lambs Lungs
with Low Vascular Tone (Table 2)
With elimination of vascular tone, at the same blood
flow, pulmonary arterial pressure fell to 20.5 t 3.3
cmH,O; a 44% decrease in total arteriovenous pressure
drop. This was associated with a significant decrease in
arteriolar and venular pressures. Pressure drop in arteries decreased much more than that in veins; arterial
resistance decreasing to one-fifth of the base-line value,
whereas venous resistance halved. Resistance in microvessels did not change significantly. Consequently, in the
absence of vascular tone, arteries represented only 11%
of total resistance, veins 29%, and microvessels 60%; the
microvessels becoming the major site of resistance to
blood flow.
Effect of Blood Flow and Total Arteriovenous
Pressure Drop on Microvascular Pressures
in Lamb Lungs with Low Vascular Tone (Table 3)
When we doubled blood flow, total arteriovenous pressure drop increased from 12.2 t 1.2 to 21.4 k 2.4 cmHZO,
approximating the total pressure drop during base-line
normoxic conditions. Total pulmonary vascular resistance decreased slightly but significantly. All segmental
pressure drops increased; pressure drops increased more
in arteries and veins than in microvessels. Now arteries
represented ~17%~ microvessels -44%, and veins -39%
of total vascular resistance.
Effect of Increased Transmural Pressures
on Venous. Resistance
Microvascular pressures measured during forward and
reverse flow in five lungs with paralyzed vasculature are
summarized in Table 4. VVith the vasculature paralyzed,
we were able to reverse perfuse the lungs at similar flow
rates to achieve the same total arteriovenous pressure
drop as during forward perfusion. We found that with
the same distending pressure in veins as in arteries,
venous pressure drop was similar to that in arteries.
l
l
minml-’
l
Pm*
TABLE
Vascular Pressure Flow Relationship of Lamb Lungs
With and Without Vascular Tone
Typical pressure-flow relationship in a lamb lung during base-line normoxia and after elimination of vascular
tone are shown in Fig. 2. The effect of hyperoxia plus
papaverine was to significantly decrease the slope of the
pressure flow lines in the lungs from 0.047 t 0.016 to
1. Pulmonary microvascular pressure profile in 15 isolated blood-perfused lamb lungs
Pulmonary
Artery
Pressures
Pressure drop in vascular
segments,
cmH20
Total pressure drop in
Venules
Arterioles
(20-80 pm)
30.2t3.4
20430
23.0t2.5
7.2
32.4
pm
150-200
16.0t2.2
7
31.5
Values are means t SD. Pressures
a re given in cm Hz0 relative
to pleural pressure (atmospheric)
vessels. n = 8 for arterioles;
n = 24 for 20- to 80-pm venu les; IZ = 12 for 150- to 200-pm venules.
Left
Atrium
pm
11.2kO.8
8.0tO.O
4.8
3.2
21.6
14.4
at level of micropuncture.
n, no. of punctured
Downloaded from http://jap.physiology.org/ by 10.220.33.2 on September 13, 2016
All data are expressed as means t SD. We used an
analysis of variance for multiple comparisons and a
paired t test to compare differences between normoxic
and hyperoxic plus papaverine periods. Linear regression
analysis was used to determine a correlation between
blood flow and lung height. For the pressure flow points
we performed linear regression analysis and obtained a
slope and intercept in each lung for both base-line normoxie and hyperoxic plus papaverine periods. Mean data
for both slopes and intercepts during each experimental
period were compared using a paired t test. We accepted
a P value of <0.05 as indicative of statistical significance.
PROFILE
2198
LUNG
MICROVASCULAR
PRESSURE
PROFILE
IN
NEWBORN
LAMBS
2. Pulmonary microvascular pressure profile in 15 perfused lamb lungs
with normal and low vascular tone
TABLE
Pulmonary
Vascular
Resistance,
cmHaO . min. ml-l.
Condition
Normal
vascular
tone
Pressures
kg
Pulmonary
artery
Arterioles
(20430 pm)
30.2t3.4
0.376t0.13
Venules
(20430 pm)
23.0-r-2.5 (12)
16.0t2.2
7.2
AP
Low
vascular
tone
0.209t0.06*
20.5t3.3*
AP
Values
19.lt3.1*
means
& SD; values
at level of micropuncture.
are
(10)
vessels. Pressures
kg body wt-l -min?
8.OkO.O
8
11.6t2.5* (26)
7.5
in parentheses
indicate
no. of punctured
Blood flow was constant
at 69 t 21 ml
(24)
7
1.4
(atmospheric)
Left
atrium
8.0tO.O
3.6
are in cmHpO
relative
to pleural
pressure
AP, pressure drop in vascular segments.
* P
c 0.05.
3. Effect of blood flow on pulmonary vascular resistance and
microvascular pressures in 15 perfused lamb lungs with low vascular tone
TABLE
Condition
flow
69*21
0.209kO.06
Pressures
kg
Pulmonary
artery
Arterioles
(20-80 pm)
20.5t3.3
AP
High
Venules
(20430 pm)
19.1-c-3.1 (10)
1.4
blood
flow
138*26
0.198t0.05*
25.8t3.2* (9)
29.4&3-l*
AP
7.5
in parentheses
AP, pressure
indicate
no. of punctured
drop in vascular
segments.
(26)
8.0tO.O
3.6
16.4&4.3* (21)
3.6
Values
are means t SD; values
(atmospheric)
at level of micropuncture.
11.6k2.5
Left
atrium
8.0k0.0
9.4
vessels. Pressures
* P < 0.05.
8.4
are in cmHzO
relative
to pleural
pressure
4. Pulmonary microvascular pressures in 5 perfused lamb lungs
with low vascular tone during forward and reverse flow
TABLE
Condition
Forward
AI-’
flow
Pulmonary
Vascular
Resistance,
cmHzO - min - ml-’ - kg
Blood Flow,
ml - kg body
M-l. min-l
0.202t0.04
122238
Pressures
Pulmonary
artery
Arterioles
(20-80 pm)
29.722.1
26.8t1.6
Reverse
(4)
2.9
Left
atrium
flow
129t40
0.196&0.07
Venules
pm)
in parentheses
AP, pressure
indicate
no. of punctured
drop in vascular
segments.
0.028 t 0.005 cmHz0 ml min (P c 0.05) without a
significant change in the extrapolated pressure intercept
of the pressure flow line (11.8 t 3.4 vs. 10.2 2 2.7
cmHzO).
l
l
Blood Flow Distribution in Lamb Lungs With
and Without Vascular Tone
Blood flow distribution along a vertical gradient in five
lamb lungs (Fig. 3) was uniform during normoxia and
unchanged after paralysis of the vasculature. With increased blood flow, the distribution of blood flow in the
lung remained uniform. Blood flow in the top millimeter
of the lung, the site of micropuncture, was siknilar to that
in the lower slices.
DISCUSSION
Segmental Vascular Resistance in Lamb Lungs
We found that the pressure drop across the subpleural
microcirculation in the lamb lung occurs equally across
Pressures
8.0tO.O
(6)
8.1
Arterioles
pm)
Pulmonary
artery
16.8t1.4 (3)
8.9
vessels.
Left
atrium
(20-80
25.7t2.5 (6)
3.7
Values
are means i SD; values
(atmospheric)
at level of micropuncture.
16.lzt3.7
10.7
(20-80
29.4t2.5
AP
Venules
pm)
(20-80
are in cmHaO
8.0tO.O
8.8
relative
to pleural
pressure
the pulmonary arteries, microvessels, and veins. As blood
flow was uniformly distributed throughout the lung under the conditions of our experiment, and to the extent
that the blood flow through the top l-mm slice of the
lung was representive of the flow through the superficial
subpleural vessels that we micropunctured, our data in
the subpleural microcirculation can be extrapolated to
the entire lung. The distribution of segmental vascular
resistance in the newborn lamb lung is different from
that reported in the adult dog (4), cat (ZZ), and rabbit
(23) using similar techniques. In the adult lung, the major
site of ‘resistance to blood flow is the middle segment,
extending from the ZO-pm arteriole to the ZO-pm venule.
We have found in 3- to 4wk-old rabbits, that -50% of
the total pressure drop was in arteries and -24% in
veins, indicating that in younger animals, arteries and
veins are the major sites of resistance to blood flow in
the lung (unpublished observations). Venous resistance
has been reported to be very low in the dog lung [15%
(3)] as well as in the adult rabbit lung [7% (23)] by the
Downloaded from http://jap.physiology.org/ by 10.220.33.2 on September 13, 2016
Low blood
Blood Flow,
ml. kg body
w-l. mine1
Pulmonary
Vascular
Resistance,
cmH20.
min. ml-l.
LUNG
MICROVASCULAR
PRESSURE
ormal
PROFILE
VaspAar
IN
NEWBORN
LAMBS
2199
Tone
Low Vascular
Tone
(low blood flow)
@
Low Vascular
(high
blood
Tone
flow)
lb
BLOOD
FLOW
io
(ml
b min-’
=g dry
i5
fo
lung-‘)
direct measurement
of microvascular
pressures.
However, other investigators,
from measurement
of venular
pressures using small catheters, have found that a substantial portion of the total pulmonary
vascular resistance is in veins (l&21,30).
From detailed morphometric
measurements
of the cat’s lung, Zhuang et al. (31) calculated that 49% of the total vascular resistance was in
veins, which they attributed to the branching pattern of
the veins and the viscoelastic
properties
of the vessel
walls. As the longitudinal
distribution
of resistance
through the pulmonary
circulation
depends on lung volume, transmural
pressures, and degree of vasomotor tone
as well as on the geometry of the vascular bed and the
properties of the vessel walls (II), it is very difficult to
make a meaningful comparison among studies by different investigators
that are done under different experimental conditions.
Influence of Vasomotor
Vascular Resistance
In the intact
nervous system
maintenance of
(8). Circulating
acid metabolites,
Tone on Segmental
fetal and newborn lamb, the autonomic
appears to play little or no role in the
normal resting pulmonary vascular tone
vasoactive agents, such as arachidonic
might be responsible for the high rest-
ing tone in the fetal period (29). We confirmed in this
study that vascular smooth muscle tone contributes
significantly to base-line arterial and venous resistance in
the lungs, though much more toward arterial resistance.
As pulmonary vascular resistance in the intact newborn
lamb (24) is lower than that of the isolated perfused
lungs in our experiments,
the high vasomotor tone may
be an artifact of the isolated lung preparation.
Nevertheless, it is of interest to note that there was much more
constriction
in arteries due to circulating
vasoactive
agents than in veins. With elimination
of vascular
smooth muscle tone, the microvessels
become the major
site of resistance to blood flow in the lungs. It appears
that when total pulmonary vascular resistance decreases,
the fractional
pressure drop in the microvascular
segment increases, although it decreases in both arterial
and venous segments. The slope of the pressure flow line
decreased significantly
after paralysis of vasculature with
papaverine,
indicating that the vessels in the segment
upstream from the site of critical pressure had increased
in caliber. Because elimination
of smooth muscle tone
did not change the extrapolated intercept of the pressure
flow line significantly
from base-line normoxic conditions, the site of critical pressure may be in the microvascular segment, which has little smooth muscle.
Downloaded from http://jap.physiology.org/ by 10.220.33.2 on September 13, 2016
FIG. 3. Blood flow distribution
in 5 lungs with
normal and low vascular tone. Vertical
distribution
of blood flow was uniform
under conditions
of normal and low vascular
tone. With increased
blood
flow in lungs with low vascular
tone, blood flow
distribution
remained
uniform.
Bars, mean values;
Lines, SD.
2200
LUNG
MICROVASCULAR
PRESSURE
When we increased blood flow after paralysis of the
vascular smooth muscle, the pressure drop across the
microvascular
segment increased far less than that across
the other segments, indicating that the microvessels
are
more distensible than the arteries and veins. With the
total arteriovenous
pressure drop the same as under baseline conditions, only -17% of the total pressure drop was
in arteries, whereas -39% was in veins.
Influence of Transmural
Pressure and Vessel
Distensibility
on Segmental Vascular Resistance
NEWBORN
LAMBS
This work was supported
in part by National
Heart,
Blood Institute
Grant HL-34606
and by the American
Lung
of Los Angeles County.
Address
for reprint
requests:
J. U. Raj, Harbor-UCLA
Center, 1000 W. Carson St., A-17, Torrance,
CA 90509.
Received
25 March
1986; accepted
in final
form
9 July
Lung, and
Association
Medical
1986.
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In the absence of smooth muscle tone, the resistance
of the arteries and veins will depend mainly on the
geometry of the vessels (i.e., the branching pattern and
vessel caliber) and on the viscoelastic
properties
of the
vessel walls. The caliber of the vessels will depend on the
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in the pulmonary
veins
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newborn
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will vary greatly depending on the degree of vasomotor
tone. In the newborn lamb under conditions of significant
basal vasomotor tone, the microvascular
pressure can be
calculated by assuming equal resistance *on the arterial
and venous sides. However,
if basal vasomotor
tone is
low, the resistance
is shifted to the venous side, and
calculated microvascular
pressures will be higher. Therefore the conventional
method of estimating microvascular pressure as the left atria1 pressure plus 0.4 times the
difference between pulmonary
arterial and left atria1
pressure (14) cannot apply to the newborn lamb.
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