SESSION
9
Are Pulmonary
Capillaries
Susceptible
to Mechanical
Stress?*
Oc/i/u’
T
tie
extreme
thinness
barrier
has
portiouis
of
of
omihy’ with
cellular
the
Forty
advent
years
asgo.
msmicreigraphms
of
mats
asmid
Fraunk
the
tlmat
Respiratory
gases
therefore
make
are
partial
increasedi
sumrfauce
atreal
Fick
In
law
time
large
(sup
thu
side
0.2
to
aumd
of
0.4
chmring
blood-gas
As
the
sausme
vemv
noted
extreme
stresses
0,
the
it
of
blood-gas
tar
On
ussatrix.4
nseust
ummembramies
The
electron
hramie,
or
fers
tensile
The
gas
time
three
barrier
*Froumm
the
thin
launina
of
side
the
densa,
unauimm forces
De’partosc’mst
of
to
our
oui
of pulmonam’v
Hg.’-’2
the
stress
to
to
which
that
following
capillary
in
time
tin’
the
imi-
we
stress
H,0,
wall
52.5
radius
of
of the
at
per
failusre
a capillary
40
time
curvature
of
9 x 10’ N/mn2
high
stress.
humasn
mm
H,O,
cm
aorta,’
transmural
wall
summa-
abotmt
ie,
of
hoop
of
that
of 0.3
(.tni is
is an extremely
higher
ratio
occurs
cm
the
teuision
section,
showing
pressumre
thickness
which
a much
52.5
cinder
wall
is
5
(or
It is
which
pressumre
(100
the
the
blood-gas
to
amid
of
barrier,
the
the
extracellufused
the
base-
endothiehiatl
layers.
of the
bassement
collaugemi
IV
mem-
whichi
ENDOTHELIUM
con-
usuattrix.49
Medicine,
summmarize
capillaries
the
consistently
of
that
of
:3) predis-
\Ve
showing
fails
on
lung,
at a nonsinal
comparable
is subjected
the
rabbit
transmural
of
wall
stress
capillaries
this
tension
puslmonarv
capillary
wall
pressure
At
that
transmural
(force
stress
failumre.
osur laboratory
of
(force
fact
capillarY
watt
alveolar
the
iongitumdinal
miot depend
In
in
oui
time
volume.’’
thickness.
studies
tension
ACTING
strength
INTERSTITIUM
oum the
identified.’
Sclmool
pulmonary
First,
blood
the
of Mediciuse,
versitv
of Cauhiforusiau,
Sauus Diego,
Las Jolla,
Calif.
This
stuudy wats suupported
by NIlI
prograuus
project
amumd HO1
1IL46190.
Repriu,t
requests:
Dr
Z%Iat/uieuu-Cu.ste//o,
Deparinueuut
c/tue.
Uuuit:ei’.s’itj
of Ca/iforuuia.
Sa,u Diego
.9209.3-0623
1 O2S
rather
in
putmimonaury
FoRcEs
from
portiomi
the’
not
to
hiniuig
Seurfauce
alveolar
failure
1) does
be
wall
of
or
the
the
aulveolasr
recognized.
ANu)
epitisehial
been
(if
high
in
lung
h.tm anci
a wall
9 x 10 dynes/cmn2),
spite
contrary.
The
time
tensioui
at high
prod-
curvature.
based
alveoli
is tIn’
of
conditiomis
redsuced
actimig
1) have
must
in
hut
tension
wall
the
stress
(force
rize
protective,
wall
from
hugh
of
inflation.
the
relationship
WALL
the
of
At
stremigth
nieclmanical
coustains
to
exercise.
the
fasilumre
comes
ceumter
strengths
(Fig
the
is uruainlv
demise
at
transmural
the
feur-
harrier
previd)ushy
harrier
unatrix
that
heavy
The
is
imi elite
without
withstand
Auxeou,.Aus
that
there
uptake
thicker
BsRusuEB
lIE
is evidence
of
tensiomi
into
time capillary
experiments
Laplace
ratdius
is caused
omi time ceurveci
tension
longitudinal
be
On
\Vhietlier
Se,
very
of omihy
imitegrity
stress
umot been
is
to
watt1
actimig
time
and
luuig
elememits
creases
is oui tIme
pathiophmvsiologic
Bu.ooD-CAs
pulmoumarv
extracehiumlaur
to
the
hecausse
ON’!’
There
mncidemice
of which
blood-gas
activity.
and
have
OF
amsv
structuraul
and
area
suggesting
duuring
its
iustense
fails
STuSENGTIt
umot be
pulmonary
barrier.4
capillaries,’-
the
a thickness
0,
exercise,5-5
maintaimi
ciurimig
where
pose
below
to
however,
of
uptake
thinness,
blood-gas
with
elsewhere,’-4
c’oumld
of
tdi
and
greater
is time
bulge
tissue
via
surface
with
thought
catpillar
circumferential
time
third
the
pressumre
calculated
the
is
presssure.3-’#{176}
according
surfatc’e
half
barrier
ussaximaul
tiusme,
strong
alveolamr
diffusion-limitation
himmiitautiouis
is
the
across
with
and
in
pressure
associated
the
diffusioum.
be
that
force
capillaries
Since
diffusiomi
tlsickmiess,
mmm2), approximately
barrier
titer
the
blood-gass
tmii.1
athletes
for
occurs
as
can
transmural
tension
Iuung,
150
of
tissue
of
2)
of
cliffereuice
gasses
wall
blood-
terms
of
layer,
asmi-
diffusion.
of the
evidence
\vall.
tensiomi
transmural
states
secomid
electrous
pulnieinarv
It
which
uct
tise
presemice
isassive
is
ehumcidasted.
first
effective
by
cif
reduced
Iiuuimatus
to
so
surface.
It
laboratory
in
pressure
passage
limit
alveolar
the
viewed
transferred!
aut as given
harrier,
the
of
it
aut the
time
cif
beemi
asre
time
in
cleuiionstrated
usmaimily’
large
that
circumferential
by time capillary
fact.
wats
publishiedl
or
blood-gas
Its
umiicroscopv
parenchsvuiia
limming
P/u.D.
microscope.
barrier
thiinness
lists
clmaracteristics
the
Low’
and
they’
light
electromi
luumsg
reusuarkable
harrier
that
the
blood-gaus
epithseliall
the
gas
of
\I.D.,
%Vc.s’t,
puuluimonarv
so thin
of
of the
lmuumauis,
comitiustuotus
theum,
are
B.
recognized.
resohsutiomi
strumctcmre
the
beesm
batrrier
power
uuud Johuu
of
lomig
of the
time
its
P/iD.;
A. ltIat/uiu’u-Co.sts’//o,
Ummi-
HL
of
EPITHELIUM
hoop
17331
?Iedi-
Fucu se 1. Putunonauy
capillary
iii an alveolar
watll, simowiusg the three
maims forces
actiusg on tise blood
gas barrier.
(1) Circuusiferential
or
isoop tension
is given
by capillary
tramssumiural
pressure
x rascihus of
cuurs’ature;
(2) surface
teosioum of the aslveolasr liniusg layer is ttmooghst
to be protective;
and (3) longitudinal
teussion
in the aulveolar
wall
associated
with tumng inflatiomi
increauses
hoop tension
aimcl therefore
the likelihood
of stress
fauilure.
(With
permission.3)
36th
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21692/ on 06/18/2017
Annual
Aspen
Lung
Conference
mm
Hg)
(1.3
and
but
cm)
has
a
also
has
harge
amounts
high
stress
imposedl
of its
small
radius
thinness,
greater
a much
of collagen
one
transfer
mucim
of
of
of
the
by
and
teumtly
the
layer
words,
the
requirements
passive
mm)
capihiary,
to
ahcive,
curvature
(2
In other
elastin.
is due
design
of
wall
pulmonary
curvature,
the
gas
and
on
radiums
thicker
in
for
or
or
time
aui adequate
alveolaur
basement
dir
FAILURE
OF
PULMONARY
CAPILLARIES
IN
We
examined
rier
in
the
rabbit
transmuurai
preparation
known
animals
were
inflow
artery
and
hung
in
was
1 mm,
left
first
to
perfused
followed
by
buffered
glumtaraldehyde
sanue
pressure.
Puilmonary
and
80
cm
H,0
pressures
5
cells
alveolar
pressure
transmuratl
pressures,
tweems
32.5,
of
the
inside
52.5,
atnalyzed
and
at
transmumral
5
the
72.5
outside
± 2.5
pressure,
pressure
(Ptm)
H,0.
Three
for
where
20,
six
Isigimest
sigisificauut
animals
cm
were
ing
were
the
H,O
stud-
to
greater
was
ied.
In
tue
lungs
exposed
to
a
Ptm
of
52.5
cm
H,O
amnd
leaust
restult
htlf
strength
cellular
entirely
of
time
dume
of eclensa,
markedly’
to
the
while
svidemsing
thuickmmess
32.5
of
suggest-
was
were
contimmu-
epithelial
underlining
mnatrix
compared
of
blood-gas
tIme
cmii 1-1,0
of
umo
was
aund
time
greater
at
the
stresses
sectioms.
thickumess
above
time
time
extraceilumlar
TIn’
of
imicreasing
epithsehiummi,
the
the
2 to :3
omilv
There
ermdotlmeliai
of
to
of
and
with
miiemnhratmme
of the
plane
linings.
iuucreasecl
Ptmsm).
iengthm
i)atsemmsent
ims time
length
Iimicroscopv
imaudi occurred,
The
to
± 4.3
significantly
or
few
omie
mmtummmber
10.4
time
11,0
emidothehiumis
approximately
at
the
barrier
fcir
a
in
the
enciotimehiummn
break
chisruptiomis
relieved.
in
breaks,
emit
in
Ptm.
audi
± 3.2(SE)
from
being
of
nuumn-
usiostly
electroum
to
of
emmelothiehial
for eneiothehiuum
lemigtis
(72.5
eithmer
once
greatl’
mis
break
comparedi
the
8.5
average,
1 to 2 Inn
extent
that
cmii H,O.
auscl
transussissid)Ii
the
cums H,O
frons
site
basement
increaseei
Ptmn,
72.5
rose
On
difference
that
12.5,
by
about
pressuure
pressure
an
be-
animals
epitheliumsi.
60,
to
epithiehiuni.
lImms for
the
52.5
endlothmehi,um
seen
at
of
12.5
Also,
time
atndi
with
H,O
cm
for
was
40,
capiliarv
32.5
as
32.5
unullimeter
sectiomis,
of
niarkeeilv
per
for
ims epithietiumm
venous
were
1.4
at
a Ptmn
atnd
and
differences
except
cm
From
breaks
blood
seems
breaks
a
miii)
capillary,
ammiunal.
±
Therefore,
time
were
13.6
pressumre
pressure
of
breaks
at
showed
at a, Ptmsu of
2).
exposed
of epithehiath
increaused
emidobutt
(Fig
seen
tIle
barrier’2
mnihiimneter
\vats foumnd
breatk
to control
cannula
per
No
± 8.6
own
of
breaks
(iftcmm
of
eif tIme
disrupted,
Qumamitification
blood-gass
length
of
the
pulmnonary
11,0.
for
(3 miii)
(10
with
it
pressure.
animal’s
arterial
cm
each
and
pressures
below
Ic,
anel
the
a
of
2B).
time
were
were
layers
capihiaurx’
cd)mmtin(uous
WtS
vicinity
boundary
27.8
alveolar
fixative
used,
11,0
fix
openeci,
soiutionldextran
artery
were
cni
was
cannulated
with
saline
then
chest
control
to
Anesthetized
pressumres,
trachea
isung
themu
pressure.
atrium
her
experi-
the
and
same
perfusion
time
expose
the
and
outflow
placed
The
the
barcapihiary
following
pressure
at
exsanguinated,
pulmonary
was
to
blood-gas
increased
the
used
tramisunural
microscopy
the
to
Briefly,
was
capillary
electron
of
exposed
pressumre.1-’2#{176}
mental
for
ultrastructure
lumngs
of
the
coimsis-
eneiothmehial
at11
that
layers
imm close
were
of the
sousmetimnes
wats
epithehial
(Fig
damage
or
finding
red blood
memnbrane
RABBIT
harrier
chisruptiomi
meusibrause
clisreuption.
STRESS
blood-gas
lay’er,
alveoIasr
platelets
diffusion.
time
inclumded
A frequemit
theliah
wall
of
They’
the
wall.3-’2’-’
spite
extreme
ciisrumptions
found.
Ptns.
This
imiterstitimmumu
both
as
time emidothe-
A
Fuccusu;
2. Traussumiissioms
elec’troum
micrographis
shsowiumg
disruption
of thue blood-gas
baurrier
iuu rabbit
bug
exposed
to a capillary’
transumiural
pressiure
of 52.5
cmii 11,0.
A
/uft), capihlarv
eumdothsehiuuuis
is
disrupted
(amrrow),
bumt alveolar
epitheliuuumm
ammd two basenmeuut
uisenmiiraumes
are coumtinuuouus
iii tlme plaume
of time sectiomi.
B (rig/it),
atlveolar
epithehiuun
(open
aurrows)
asmmd catpillarsemmciothehia,l
layer
(solid
arrows)
aure disrupted;
note
a platelet
protruding
into tise eumelothsetiatl
openiumg
and closely
applied
to
tIme exposed
basement
ussensbramse.
Transpumhmmmonasrv
pressuure
was 5 cull 11,0.
(Witlm peruuuissioum.
I)
CHEST
/ 105
/ 3 / MARCH.
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21692/ on 06/18/2017
1994
/ Supplement
103S
a
hiumn
amid
epithmehiumn
Fuirther
blciod-gas
edit
was
iumsighut
harrier
by
of
temstly
mmsajoritv
barrier.
(if
breaks
to
complete
time
shmows
several
immterceltular
jummctiomss
at
the
slits
lengths
for
pressutre,
umsissi(in
relief’
were
due
tIme
of
were
examimimseci
greatly’
cliffereimt
by
the
71.1111 in
withs
transthe
varied
occtmrred.
Further
TEM
the
sttmdies’-’2
blood-gas
basrrier
of the
of
their
two
as
breaks,
and
frauctional
inciicated
the
tissue
about
little
This
‘‘
meof
observation
by
and
suggestimug
estimsuates
TEM.
with
ruuptsures
were
has
of
to
break
dhiuiuensions
appearance
mmsorphmommmetric
no
previoums
disruuptioms
comsipared
almost
ltmms. They
our
into
vicinity
greater
TIme
1.5
breaks
lulood-gas
protrudimsg
suggesting
previous
(TEM)
tIme SEM
time
in close
B),
barrier
with
Ptun.
of
close
demmsity
atl’ter
itself,
ommce disrumption
extemst
a fuunctioms
aundi
junction.
of aubout
similarities
cell
The
oriemuted
Most
of
were
of time blood-gas
of stresses
strikimmg
3A).
blood
3A
consis-
above.
slits,
layers
breaks
confirmnimmg
oumr
electromm
nsicroscopy
aund
(Fig
all
a red
att time
width
at
H,O
the
adja-
(SE M ). ‘
was
elongated
(Fig
of
of
surface
axis
jumnction
c’hmaummic’al stremmgth
elomsgattedl
cmss
of
3B
seen
52.5
capillary
\Vhsile
disruption
examimuation
microscopy
alveolar
were
time alveolus.
was
by
the
disruptions
Figumre
of
electron
of
Ptusm
tIme
perpemudicuulatr
were
scanusing
att
of
pattern
obtairsed
disrumptiomu
foummici
‘
changed.
the
svats
saumuptes
Evielemuce
uiot
iisto
thsaut simnular
techniques,
processing
and
even
preparation
proceduires.
Time effect
of
blooci-gats
cmii
1-1,0
time
for
capillary
solumtiomm
or
fixattiomm
hatrrier
was
blood
pressure
of
for
H,O)
in at lesser
epithielial
breaks
breauks
were
mmseumsbraumme
tIme
was
lowered,’4
ihiatry’
ods
previous
of
observed
Imigim vascuuiar
iimstillamtioum
presssmre.t
i imsmuuediattely’
Imighm pressumre.
‘‘
simsuilatr
seemu
to
fixuttioum
tisat
att
fauulumre
of
mumimmute
of
perfumsioms
simuce
vascular
time
hyde
104S
the
a msumsuber
e1)itlmehtuumm
was
aufter
sviths
fixative
sahimse
at
high
I
at
that
tIle
lower
musin
in
blood
blood
soltmtioum
pressure.
h’
breaks
\vats
lungs
on
be
mmecessarv
fatihumre
f(ir
of
epithmelial
puhimmommary
tIme accimmssuhatieimm
EFFECT
high
At
a
the
saiuse
immcidemsce
of fluid!
immflatecl
l)reaks
was
Ic, withuosut
11,0,
comssparee!
(Fig
4).
both
emidothueliatl
instillation
for
its
sure
those
glumtaraidethat
addi-
dir
a
rupture
to
capillaries.
dc-
ims time iuiterstitiuumm.
Ptmss
columuimus,
(20
Fig
4).
sammue
5 to
H,O,
It
lummg
ilicreasse
fromms
suggests
rise
20
ui
was
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21692/ on 06/18/2017
(5
to
Annual
ie,
20
cumu
cmms 11,0
f’reqiiemscy
a,hxicmt
of
the
same
transpuulmmsomsary
cmmm 11,0:
32.5
time
previous
52.5
mimi equuivahemit
36th
(if
ims time
brc’atks
H,O,
increased
lummg voltumsse,
volummue
imm ciur
epithielial
thse
cuss
greatly
pressure
uused
from
52.5
att highm
low
time
atnd
ciii
or
was
perfused
the
Interestingly,
cmii H,O,
32.5
failure
pressumre)
approximsuately
(15
of
\‘oi,UmuE
traumspulussonary
to
traumssptmimomsary
Luxc
stress
luuumgs were
to
Hmcu
Ptnu
capillary
rabbit
disruptions
OF
capihlaury
of
wlsile
tisami
amsd thems
suggested
pending
whiemm
with
perfsusion
This
oumt
Amuother
of
stress
first
at
pressure.
mncidemice
mssatv
sifter
previous
in the
imsstiliation,
time
occur
stress
the
ruled
of endothelial
tional
perfusion-
perfusiomm
failure
(3 mum)
airway
thiast
it
3)
at
within
Isigh
cap-
Fucu: use 3. Sc’auuiui umg elec’troum
iumic’rograuphs
showiumg
disruuptioums
of’
the blouicl_gas
l)arrier
jul rabbit
luuumgs exposed
to a Ptumm of 72.5
(A) amid 52.5 (B) c’mnH,O.
A (top),
elomigatted
slit of’ tIme btooel_gas
barrier
(unbid arrow)
very close
(about
(1.4 fun) to aum intercellular
juuumc’tion (white
aurrow).
B (bottom),
disruptioum
of tIme blood
gas
baurrier
c’rossimmg
aim iumtercellumlar
juuuuctium,u (white
arrow)
atnd
shmowiuig a reel bldmodl cell (asterisk)
protruuding
ilutem tIme alveolus.
Note
abumusdamumce of proteiumaceoums
ummaterial (A atumd B) ammd red
blood
cell (A) ous tIme alveolaur
surface.
Traimspulmmtoiuaury
pressure
waus 5 cmmm11,0.
(With
permmmiSSiOum.
peru-
perfusion
with
Also,
the
which
short
indicated
auins’ays
fixation
was
aufter
occurred
stress
to
pressure
imucreased
study
This
this
the
stuidies
ghuutauralclehyde
by
f’indimsg
attrihumted
emuclotheliat
blood.
caupillar\’
fixatiomi
iuumusmeciiately
perfuused
of
perfusion
imuterestimug
of
with
ass great
aufter
‘
immitially
basement
fixation
mjms
of
with
were
atfter
iumng
previotus
capillaries
in causimmg
2
1
msuumber
pressure.
effect
pressumre
found
high
Ve
After
after
us time
puulmmsonaury
sigmuificatmst
stimcly,
the
that
of the
imm the
and
Interestiuigly,
fusnctiousal
reversibility’
cmii
endothelial
comitimmuuous
2
with
Ptmsm (12.5
perfuusions
breaks
withs
rapid
permeability’
those
a
somuse
comusistemst
the
Perfeusion
the
with
saline
pressure,’4
pressure.
study.
of
with
of both
were
52.5
reducing
lower
reduced
with
seen’4
reversibility
docuummsemmted
at
to
then
airways.
at high
associatted
imm tile
rapid
and
at
number
mimic! fixative
uso longer
smmuatll amici
the
its the
Ptm
perfusion
fixastive
comnpasred
sohumtion
mum)
either
via
tlsems
of breauks
raisiusg
fixative
fixautive
amid
resuitteel
by
(1
ammsdl glutarasldeisyde
imistillatioms
time
imicidence
perfuusion
sathimme sohuutiomm
sahimme
the
on
imivestigated
Aspen
Fig
pres-
4. left
ecu
patmmei)
1-1,0;
effect
Lung
opemm
of
Conference
tlse
increase
in
traumspuhmomiary
comuditiomss.
Measumremsient
reveaheci
a
volimmsue,
thsickening
into
thsick
tlse
sides
previous
was
brane
at
breaks.
crosc’op
reveauled
temucled
to
be
blood-gas
in
at
simsmilatr
for
a
voluuusie,
tmmsiformiu
of
that
endothiehiat
and
alveolar
hreauks
waull
ait
1)51 SE
anasIy’zed
by
of
thue
M amid
TE
the
Time
M
stress
physiologic
mnicrovascuiar
hams
imusportant
where
greaut
lung
As
situmsstion
studies
to
arterial
capihlasrs’
Ptmus,
chamuges
IV
elsewhere,7
imuflaution
msmsukes
tlse
this
ascceptambie
it
s’umhmmerable
to
at process
fumrther
accelerated
hatve
occurred.
ie,
l)lo(ud-gaus
are
weakemsed.
tIme
to
vemsti-
msecessarx’
to
ruuptture
baurrier
sine1
wlmite
tIme
witis
edt-
are
its
the
the
of
h)l(iOdi
sire
tummmgs sifter
stress
fsuitumre
csupillsur’
cell
dif
Other
stress
catumses
B,
ti-pc’
fsuitumre’
ass tIme
type
rathibit
of
c’ciemsma,
atmuci
pIstt’let
imiflatuumumiatory’
ussarker
tuumsgs
tise’
withm
umuec’hmauumisui, of
siusdi epithic’hiatl
mmmemmmhirstmuc’s triggeriumg
stIle1
of
),23
atusd
comssisteuut
time emudotlmehial
ii#{128}’tiVsttl(ili
of
fluuid
( RAPE
eeic’umia
sire
amid
atmscl c’ommmple-
edc’ummat
of
of
cells,
laiVaige
unairkers
ummm-
Istiluurt’
t\pe’
hiooei
ium luuumg
of imuflamsi nuatom’’
flsuici
edu’mtuat
dluue’ to
permsse’stbihity
permsueamhuihit’
wsus receistly’
amppeatraummces
HAPE
eif HAPE.5
high
presc’umc’e
rsuh)l)it
putlmmsommairy
psulmmuommairy
hasemmmemmt
lauvasge
lueums-
paurtic’ulaurly
,
proteimms.
pe’russe’ahiihitv
f’or
re’lesuse
l’ratmsk
leuukotriemme
altitude
amid
svus(lroumme
p’#{176}1’11y
su high
foumsci
iumflammsmmuattory’
Thue
the
or
umiairkers
C5a
caiusimsg
exposumre
attitiucle’
pit1-
c’dlemiiau.
prc’ssuure’).
\‘atsocommstric’tiomm,22
stisd
hweim
c’atumsilmg
puuluii(mmiatr
stemmosus).
pressuure’.
weight
hmigim
time
B4)
if pastimologic
high
psitmssomsstry
catpihlaurv
stress
HAPE,
time’ chisruuptiomm
of
lressuure
strumctumral
a lower
is
f’suihumre
lmase
catc’chsolammsiuse’
vauscullar
ims umsitrash
caspillsiric’s
high
of
levels
of
at
thse
1)resemmc’e
umiaius-
However,
hiecasuse
with
c’esses.
at catchm-22
mimic! lsighs
c’auusiumg
stre’ss
muc’uurogeumic’
distress
misoiecuilsmr
imiflammummsattors’
lining
setting
usseclsanicaul
level.
harrier
It
datussasge
is often
are
blood-gats
psul‘‘
care
1)rcveuit
pressumres
pressumre
sin
criticsul
to
at
eXsiuuuple.
rc’s1)irsutory’
pulmommary
High
u’
iii’;
c’ommehitioums
puuhuimousatr
d’atpillatrv
puulmmsoiiarv
Bothm
caupiltaurprovides
increased
(eg,
mmsemst frstguisemut
two
o’erimsf1atiomm,
citmrimug
out
oms tise
immflation
sisowiusg
in
high
at
pumiumsomman’
of
tsikeuu
overdistemusioms
Po,
stress
the
withu
lie
emud-expiratorv
inflaution
lagen
for
slsouuld
poimuted
imscreaseci
highs
degree
immiplicsutions
becaumse
of positive
of
high
pernueabmiit
casre
clue
lation.
tasium
at
msuechsanismss
mssomsarx’
the
vumimierabihitv
failure
botis
hsy’poxic
thse
(for
imu pullumiommaury’
c’(imsdiitidims
pautiemitS
mncreaused
to
or
ec!emmsa.
techniques.’’
ies
rise
immc’huucie
ultitsucle
trstuuusmai
imscrestsed
evemi
luusg
suduuit
Fsuiu
a role
plays
(aSs seemm iim exercise-immduuc’e(l
imuterestimsg
clue
high
of
following
s’lsere
muot seems
with
exatniple
orrimsuge)
breaks
possibl’
causes
hsemssorrisaige
we’re’
while
edleumsa
high
Sru,ess
immwhich
likely
Thmev
eclemims,.
summel trstmssiemut
hireatks
thmamu sit low
directions
were
miii-
the
commciitiomms
lsighs-perumseasbilitv’
somsue
ou.
Csi’uu.u.-sutuu.:s
capillaries
elsewlsere.’
mssomm.srv
mmuemiu-
were
au
tisimu
imu ouur
electron
pathsophs’siologie
puulmmsomiarv
reviewed
batsemuuemmt
axis
They
time
ruptlmres
the
oriemutaitiomu,
in
Time
cells
As
Fewer
cif msseasuuremsmesmts
simsuilar
on
muasrro\s’er
differemut
iuuusg
blood
scamsmuimug
capillary
stress
of
Commuparison
indicated
both
Ptnu.
foummud.
svssll
stretchsiuig
voluumue.
foumudl
humt
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high
harrier.
highs
lemmgtls
segmsuents
lung
tlse
with
half
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abouut
in
tluickmuess
at
of
lumumg
thiast
of
mmuultipie
low
to
were
time
low
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interstitium
presence
opening
perpendictular
vithm
barrier
Exasmmsinautiouu
s’ohuunme,
oriented!
at
the
continuouus
epithselial
or
eiuciothehitmmuu
of
sttmdv
pressumre
blood-gas
due
with
of the
protruding
hsmusg
of
consistent
Disruptions
mine!
of
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c’oumulitiomms
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pre’ssuure
simggests
se’emm ium
tlmsit
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Epi50
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low
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CHEST
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Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21692/ on 06/18/2017
1994
I Supplement
105S
tions
where
ample
attack
also
the
extracehlular
matrix
in Goodpasture’s
syndrome
type
causing
IV collagen,25
weakened,
where
for
ex-
autoantibodies
bleeding
in the
lung
and
glomeruli.
We
recently
pulmonary
obtained
horses
is caused
ies.26 This study
Birks,
James
Jones,
of Veterinary
Davis.
The
known
EIPH
croscopy
16 m/s)
John
race-
failure
of pulmonary
in collaboration
with
capillarDrs. Eric
of
were
Walter
and
had
horses
fixed
galloped
Evidence
for
evidence
presence
(two
at high speed
(13 to
of intrapulmonary
animals).
disruption
alveolar
of
epithehial
blood
cells
layers,
in the
found
exposed
lungs
capillary
amid
interstitial
edema,
of the endothelium
into
the same
appearances
to high
was
in
capillary
vascular
thoroughbred
pressures
horses
measured
up
during
120
very
arterial
mm
Hg
and
high
time,
vascular
the
hypoxemia
the
and
high
barrier
could
not
to VO2m’ax.
In
barrier.
for
a
to 10 rn/s,27
be very high.
are
thicker
other
In
high
summary,
mechanical
curvature,
wail, which
not
barrier
but
turn require
number
enormous
only
also extremely
pulmonary
the
mechanical
causing
failure
hemorrhage.26
Interestingly,
were
found
a very
epithehial
uptake
strength
of
of
pulmonary
the
the
because
in turn
thin
edema
has
rates,
were
difficult
to
reversibility
of
only
limit
that
the
stress
mechanism
diffusion
high
been
capillaries
of
the
role
in
a
several
A dramatic
example
in
thorough-
for
extreme
number
of
generations
system
of the
same
such
Stress
breeding
large
cardiovascular
strength
a
hemorrhage
selective
a
at the
high-permeability
hemorrhage.
over
design
which
across
plays
to
of
alveolar
transfer
recognized.
causing
pulmonary
where
but
stresses
recently
pulmonary
horses
witim Michael
Yasuo
to
aerobic
develop
pulmonary
This
Costello,
Namnba,
has
beyond
blood-gas
the
barrier.
Ann
Koicimi
work
was
Elliott,
done
in collaboratioms
Zhenxing
Tsukinuoto,
and
Fu,
Reoato
Sanli
Kurdak,
Prediletto.
REFERENCES
1 Low
FN.
The
pulmonary
amid
man.
mammals
2 Gehr
failure
alveolar
Anat
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M,
and
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epithelium
1953;
Weibel
of
ER.
The
normal
human
eutimation
of
Respir
Physioh
1978;
32:121-40
Tsukimoto
K, Mathieu-Costelbo
0,
J AppI
capillaries.
laboratory
117:241-63
morpisometric
in pulmonary
4 West
reof
thorpro-
which
JB,
Mathieu-Costello
blood-gas
5
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Dempsey
JA,
hypoxemia
Physiol
(Lond)
6 Wagner
Physiol
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JB,
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1991;
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and
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show-
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RE,
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KS.
huuman
the
88:141-48
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355:161-75
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of
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Stress
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of pulmonary
Schweiz
Med
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8 West
JB,
Mathieu-Costetto
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blood-gas
PC,
Gale
in
Strength
Physiol
in healthy
1984;
PD,
exchange
0.
Respir
Hanson
alveolar
capillaries
which
in
that they
of red blood
in areas
ruptures
to
withstand
conditions
and
allowed
in-
capillaries
to find.
not
strong
capacity.
3 West
JB,
blood-gas
actual
is
of the extreme
thinness
of the
is required
for the adequate
is exercise-induced
role
in
0.
lung
and
Stress
failure
heart
of
disease.
puilmonary
Lancet
1992;
340:762-67
9 Crouch
In:
number
interstitium
suggesting
capillaries
lungs
42
for
of
thin
rabbit
pulmonary
capillaries
are subjected
stress
in spite
of their
small
radius
ultrastructure
further
cardiac
outputs,
to be so high
of
bronchoalveolar
enough
indicating
pulmonary
macroscopically,
breaks
to
generations
as in
of an
inflamma-
passive
diffusion.
The
contradictory
imposed
on the blood-gas
barrier,
was
selection
of
fluid
as well
the
platelet
initiation
earlier,
in lavage
in
at
suggesting
the
found
ACKNOWLEDGMENTS:
exercise
0,
thin
high
pressures
while
a large
in the alveoli
and
abnormalities
due
selective
seen
of gases
by
requirements
during
without
words,
and
As mentioned
with
achieved
limitation,25
were
pres-
associated
heavy
wall,
HAPE,23
gallop
platelets
membrane
capillary
with
of the
leukocytes
basement
activation
pulmonary
mechanical
up
also
end
HAPE.
bred
in
the
In addition,
pressure,24
patients
of
pulmonary
speeds
must
be any
The
large
with
necessitate
1 OBS
high
of
respectively,
during
of diffusion
animals
probably
of
failure
failure
mI/mm/kg)
requires
that the bloodthin.
However,
exercise-induced
result
oughbreds
and
were
at
pathophysiologic
atrium
breeding
hal
markers
perfused
of
exposed
process.26
red
heft
VO,max
to be the
blood-gas
clear
inflammatory
and
Hg,
the
ing
cell
blood
have
and
contradictory
In thoroughbreds,
point
of failure
barrier,
alveolar
of the
white
barrier,
cowork-
creased
aerobic
performance
imposes
quirements
on the heart-lung
system.
those
requirements
have
reached
the
exceed
of disruption
and
thin
high
Jones
the
or
outputs
(>750
mI/mimi/kg)
which
require
very high
left
ventricular
filling.26
At the
in thoroughbreds
limitation
vided
to
be
transmurai
extremely
pressures
extremely
maximal
exercise
(180
gas barrier
be extremely
shown
site
tory
fronu
extension
vicinity
very
mm
70
galloping
at
capillary
pressures
the extremely
high
cardiac
achieved
in these
animals,
atrial
pressure
for adequate
same
are
galloping.
pulmonary
to
in thoroughbreds
indicating
that
These
cytoplasmic
must
the capilwe have
reduced,
close
performance
Pulmonary
of
and
was
60 to 70 mi’tin later.
time
.
sures
fixation
the
the
endothehiai
material
spaces,
are
in rabbit
the
solution
capillaries
blood
cells
protemneous
alveolar
fluid-filled
protrusions
lary lumen.26
These
pressure
animal,
(one
Ultrastructural
of stress
failure
of pulmonary
of a large
number
of red
interstitium,
mi-
in one
instillation
pressure
to tissue
fluid
with
electron
of glutaraldehyde
Ptm
of the
of California,
thoroughbred
perfusion
H,O
Tyler
University
three
removed
or vascular
30 ± 5 cm
that
and
Medicine,
lungs
exercise-induced
thoroughbred
was confirmed
by bronchoscopy
fixation
was either
by airways
animal)
ers27
in
Pascoe,
after the horse
on a treadmill.
bleeding
Tissue
that
(EIPH)
by stress
was done
School
at
evidence
hemorrhage
vascular
EC, Martin CR,
Crystal
scientific
RC,
West
foundatiomis.
Brody
JB,
jS. Basement
Barnes
New
York:
PJ,
et
Raven
membranes.
al,
eds.
Press
The
Ltd.
lung:
1991;
42 1-37
10 Glazier JB, Hughes
This
was
of capillary
once
the
lumsgs.
J
dimensions
AppI
Physiol
JMB,
Maloney
and
1969;
36th
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blood
JE. et al. Measurements
votuume
in rapidly
frozen
26:65-76
Annual
Aspen
Lung
Conference
11
Z, Costello
ML, Tsukimmioto
K, et al. Highs Ismmsg voluumne
increases
stress
failure
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caupillaries.
J AppI
Fu
Physiol
1992;
73:123-33
12 Tsukimoto
K, Mathieu-Costeilo 0, Prediietto
B, et aI. Ultrastructural
appearances
of pumlmnonary
capillaries
at hmighs
transunural
pressures.
J AppI Physiol
1991;
71:573-82
13 Costello
ML, Mathieu-Costetho
0, Vest JB. Stress failure of
alveolar
epithehial
copy.
Am
cells
Rev
studied
Respir
Dis
by scannimsg
1992;
electron
mmsicrou-
145:1446-55
14 Elliott AR, Fu Z, Tsukimoto
K, et al. Short-term
reversibility
of ultrastructural
changes
in pulmssonarv capillaries
caused by
stress failure.
J AppI Plsysiol
1992;
73:1150-58
15 Fu Z, Kurdak
5, Namba
Y, et at. Effect
of flxatiouu
by airway
instillation
on
capillaries
16
the
immcidence
[abstracti.
Rippe
B, Townsley
pressure
on
the
of
Amn Rev
stress
Thmigpen
M,
pulmnonary
failure
Respir
Dis
J AppI Physiol
1984;
57:233-39
Nicolaysen
C, Waaler
BA, Aarseth
stretchable
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Lymphiology
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isolated
iii
dog
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17
18
Egamm
EA.
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imsflation,
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19 Parker JC, Townsley
cular
J
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huista-
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tif
mndile
time
his’-
by increasimsg
cells.
whelm
also
ims
chmaimm
with
retrsicti(imi
hiiumding
of
imi plaice
etal
cstlc’iuummu
tlmaut
siomm.
\Vc’
elmc’lattioms
retesuse
atllows
teumsioms.
However,
interrumpts
increases
sire’
forces
of
expressiuiui
Ims our
receumt
cell-
endotimehial
of
M LC
asked
if
tile
retrstetioms
with
cultmureei
coumsistemit
we
hiothu
cells.
ss’ithm
tlue
emidothuelial
of’ at e(immstitultive
centrip-
fouund
commstitumtive
0.20 ± 0.02
msmolP/ummolMLC,
atctommsy’osimi-mmsediatu’d
teum-
at
reclumctioum
respomise
aimscl conversely,
cell
tetlmerimug
report,
si c’onstituutive’
prevemmt
plmosphorylsitiomm
of
Ni LC
to
hmiststmmmimue or
phmosphorvhaitioum
if iuscrestsedi
wosmld
1mmcommtrot
cause
cell
amid huistsimimse-stuimiumlateel
clmsuin
calciuumui
comistitustive,
retrsictioms.
H UVE
Ni LC
of
1989;
(-12
withm tue
prevented
H UVE
± 1 percemmt).
huistsimisimse
the
imug calciumsu
imm
iii
chielsttiomm
Ni LC
mmmc! tIme
(14 ± 4
Simssihstrlv,
pretreatmsmemmt
bstssih MLC
phsplm-
tIle
amid
± 5
reduced
fohlowimsg
c’ommtrol
tIle
calciumms
response).
also
Pre-
reduced
mmsolP/miucil
msmousolaver
(47
also
its
± 0.04
muuolP/mmsolM
LC)
msuonolayer
permeability
of
IIUVE
Ni L-9,
imicreutse
cells
witls ML-9
(-0.13
± 0.02
imseresise
of
inhmihiitor,
stimsmulated
percemut
treatmuuemst
of PPAE
M LC phmosphmorvlation
reduced
withs
immcrease
Pretreatumiemut
(-0.16
± 0.O3molP/molM
LC)
in mmsoncilayer
permssesuhility
± 14
myosimi
cells
± 0.02 mmuolP/mssoIMLC)
ammcl
imscreasse
iii H UVE
cell
misonolaver
percemmt of time coumtrol response).
of PPAE
cells with
cAMP
reduced
(21
imm
(-0.08
pluosphmorylation
(-0.29
iumcrease
imu HUVE
cell
chelatioum
M LC
-dlepemudemut
cif
cathciumui-csulmnodulims
time
amid
(PPAE)
was phmos-
huistamnimme-stimsiuulatech
MLC phsosphmorylation
a huistsumuimme imuitiated
cells
that
Pretreatm#{236}ment
the
cells
eutdothmelissh
csulcisumss calmimoduhimi
kinase.
pres’emmtsc!
rylatiomm
increase
J1-1, Sussith
nary arterial
effects
periuueal)ility
N,
produced
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imm rabbit.
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of tpe
IV
collagen
TIse
light
256:63-9
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is consistemmt
calcitumsi
ceil-sul)strate
cells
light
phsosphmsitc’
euidothmehial
extracehlular
phmom’y’lamtecl by the
Mediut.
This
of
that
UVE)
thse
moles
temmsiomu within
amid
(I!
initiates
incresuse
retrstctioum
reported
of
± 0.02
0.18
timsit Imistamimme
of
recemstly
emidothueliash
(ussolP/nmolMLC).
chselatiomi
histaumsuiuue
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BA.;
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M. I).
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by
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(MLC)
woumld
433-49
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hugh
Institute
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vein
imucresuseci
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131-41
JAMA
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umsicrovatspeauk
Interumsittent
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itt situ
immperfumsed
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clog
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M LC)
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percent
of
atnel
fohlosv-
control
re-
5l)onse).
TIse
hstsai
level
sents
comustituitive
stcid
iumcreaseei
j.tM,
0.06
Ni LC
(289
okssciatic
6Frouus
stud
phmosplmoryhsutiomm
pImsplmsutsise
)
± 32
atcid
imscrestseci
thue Ummivc’rsity-
CHEST
10
but
hot
PPAE
of
Iowa
I
i.sM
1.tM,
simucl
perce’mmt)
College
of Mediciuue,
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(1
± 0.05
(4 ± 5
umueimmolsive’r
1994
cells
0.17
muistumumer,
cell
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rehireOkadstic’
ium i’PAE
siumel
su dose-depemsdemut
iii
1)ercemst)
likely
activity.
)imosphmorylsstiomm
± 0.O4mmsolP/mmuo1MLC
uiuotP/umsolMLC
f.LM
M LC
of
kiumatse
10
permumesthil-
Iowa
/ Supplement
City’.
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