Download The Effects of Radio-Opaque Contrast Media on the

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The
Effects
Media
on
of
the
Radio-Opaque
Structure,
and
Fibrin
By
KARL
VEREBELY,
ATER-SOLUBLE
with
such
frequency
as cerebral
been
found
that
In the presence
RICHARD
contrast
in
of
the
M.
TORACK
AND
MCDOWELL
radio-opaque
increasing
Solubiity
Clot
Kurr,
HENN
FLETCHER
W
Contrast
clinical
or
cardiac
the
of
radio-opaque
chemicals
these
compounds
the
angiography
( Fig.
media
medicine
and
for
1 ) are
diagnostic
intravenous
interfere
clotting
being
used
procedures
pyelography.
It has
with blood
coagulation.’
mechanism
in plasma
and
COOH-N-CH2(CHOH)4CH2OH
CH3
COONa
x
oI11l9
CH3
H
I
H3CN-LJ-C”CH3
H
H
HYPAQUE
Sodium salt of 3,5-Bisacetamido-2,46triiodobenzoic acid
j
0
CONRAY
N-Methylglucamine
salt of 5-acetamido-2,4,6triiodo-N-methylisophthalamic
acid
COONa
CH2COONH2-(CH2CH2OH)2
1l#{252}
LJNCCH3
0
I
UROKON
Sodium salt of 3-Acetamido-2,4,6-tridobenzoic acid
Fig. 1.-The
=sodium
DIODRAST
Diethanolamine
N-acetic acid
structures of radio-opaque
diatrizoate;
Conray=meglumine
salt of 3,5-Diiodo-4-pyridone-
contrast media
iothalamate;
used in this
study.
Urokon=sodium
Hypaque
acetrizoate;
Diodrast=iodopyracet.
From
New
the
York,
Departments
of
Neurology
and
Pathology,
Cornell
University
Medical
College,
N. 1.
Supported
in part
by Research
Grants
HE-04872
and NB-03346,
NB-04161
from USPHS
and from
the Winthrop
Laboratories.
Dr. Kutt
is a recipient
of a Research
Career
Development Award
JKO 3 NB 35003,
NINDB,
USPH.
First submitted
October
2, 1968; accepted
for publication
December
13, 1968.
KARL
VEREBELY,
MA.:
Research
Associate,
Department
of Neurology,
Cornell
University
Medical
College.
HENN
Kurr,
M.D.: Associate
Professor
of Neurology,
Cornell
University
Medical
College.
RICHARD
TORACK,
M.D.: Assistant
Professor
of Pathology,
Cornell
University
Medical
College.
FLETCHER
MCDOWELL,
M.D.:
Professor
of Neurology,
Cornell
University
Medical
College.
468
BLOOD,
VOL.
33,
No.
3
(MARCH)
1969
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EFFECYS
OF RADIO-OPAQUE
fibrinogen
clots
that
centration
pound,
solutions
formed
reached
no
in
ionic
In
this
studs’
of
clots,
at
polymerized
study
( 0.25
those
observed
that
the
before
fibrin
fibers.
to
40
per
in
patients
the
following
thought
delayed
and
the
When
the confor each
corn-
to be
related
concentration
considered
as
optical
density
evidence
contrast
and
or
been
thrombin
experimental
radio-opaque
plasma
formation
pH,
factors
were
in reduced
direct
clotting
time
was
the normal
control.
which
was
different
took
place.
of clots have
temperature,
These
manifested
presence
and
at all
opacity
strength,
inhibitors.26
which
were
469
MEDIA
was
disturbed,
the
were
less opaque
than
a certain
magnitude
clotting
in the
Decreases
CONTRAST
leading
of the
causes
a variety
to structural
clots.
is presented
media
to changes
and
indicating
structural
of
changes
that
changes
the
in
fibrin
the contrast
chemicals
interfere
with
normal
clot
stage
of lateral
aggregation
of the longitudinally
The
concentrations
of contrast
media
used
in this
cent
by
)
volume
during
below
were
cerebral
or
within
the
( 22
arteriography
to
range
65
of
per
cent
by volume).7
MATERIALS
The
effects
vestigated:
of
Sodium
iothalamate
(Conray
50 per cent,
Winthrop
60
Mallinckrodt
Pharmaceuticals
Laboratories,
N.Y.C.
A.
Observation
contrast
To
mixture
0.1
Laboratories
fuged
of
lyophilized
at
1000
large
particles
fibrin
formation
The
pH
of
0.6
rpm.
values
were
plasma,
2.0
VX
professional
color
2. Electron
as
the
in
1 per
stained
B. Optical
(35
graded
3-C
Density
sets
of
24
to
solution
electron
of
of
0.6
Expandomatic
Zeiss Standard
phase
fibrin
was
added.
formation
clot
of
and
most
of contrast
pH
CF
meter.
research
formation
up
to
plus
suspended
of
containing
media
X,
millicentri-
media.
samples
contrast
10
the
visualization
M
Kodak
Fifty
water
objectives
using,
in
Chilcott
manner.
free
plasma
A control
Wamer
microscopic
presence
tube
the
Clot
distilled
was
contrast
ml.
camera
and
25
30
or
2.0
0.4
ml.
microscope
with
X and bOX).
minutes
X or
with
an
Kodachrome
II
and
Normal
as
7.2-7.4
pH
of
alcohols,
of
uranyl
in part
abnormal
1. Ten
with
Dalton’s
and
embedded
acetate
or
clots using sodium
later these clots
Chromate.
The clots
minutes
with
diatrizoate
were fixed
were
then
in
Epon.
Thin
sections
were
lead
citrate
and
examined
with
microscope.
Measurement
spectrophotometer
Cl.
large-volume
0.4
centrifuge
mm.).
prepared
series
phase
and
a glass
following
4 ml.
prepared
the
reflex
observations.
a saturated
EMU
X
buffered
a
after
in the
or in the
similarly
lens
Na
cent,
Research
( FSF).
3 minutes
media
M
supernatant
the
II,
in
for
( Simplastin,
with
and
taken
single
were
0s04
in
with
two
films
medium
cent
RCA
mm.,
0.6
resulting
(condenser
microscopic
contrast
dehydrated
In
35
contrast
prepared
with a Beckman
through
a Carl
were
ha,
M
of
conditions
in
attachment
0.6
per
(Mann
Formation
Clot
RPM
in-
( Diodrast
50
Factor
collected
ml.
were
; Meglumine
iodopyracet
Sodium
Stabilizing
thromboplastin
was
thromboplastin
the control
was viewed
photomicrographs
Exacta
of
of
with
normal
measured
ml.
ml.
formation
ethylester
Plasma
were
of
0.02
The
Fibrin
on the
reconstituted
interfere
glycine
at 2000
ml.
used
5 minutes.
under
the
blood
and
0.1
was
would
either
a phase-contrast
an
for
which
and
of
of
0.02
plasma
clot
Laboratories)
( Urokon
acetrizoate
Media
ml.
fibrin
Pharmaceuticals);
sodium
centrifuged
plasma,
of
Winthrop
methylester
Five
simplastin
l’sl Na Cl for
Clot formation
Still
the
ml.
and
cent,
per
inhibitors
then
was activated
by
The thromboplastin
).
grams
of
0.1
systems
ml.
ml.
);
as
),
plasma
Mallinckrodt
of Contrast
( Na
EDTA
contained
above
used
Effect
50
Glycine
microscopy.
9 mg.
removed.
were
of the
1. Phase
containing
per cent,
Laboratories
).
)
on
( Hypaque
diatrizoate
METHODS
AND
compounds
of Fibrin
cuvettes,
Clots
2.5
with
ml.
of
and
700
without
mg.
per
Contrast
cent
bovine
Media
fibrinogen.
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470
VEREBELY
ET AL.
Fig. 2.-(A
and B) Normal
control
clots.
1.0 ml. plasma
+ 0.2 ml. saline + 0.1 ml.
simplastin
Magnification:
1280X
.
(C) clot formed
in the presence
of sodium
diatrizoate.
1.0 ml. plasma
+ 0.2 ml. sodium
diatrizoate
+ 0.1 ml. simplastin
Magnification:
1280X.
(D)
Clot
formed
in
+ 0.4 ml. meglumine
contrast
( Fraction
I, Mann
media
used
in
Research
(025
similar
bovine
C. Protein
360
In
5 minutes
10
ml.
the
excess
fluid
was
placed
in
10
minutes
in
0.8
ml.
distilled
Co.).
m
ratio
in
Junior
The
30 per
cent
ml.
plasma
1280X,
4 ml.
contained
clot
of
bovine
The
.
phase
and
activated
optical
by
densities
of
0.6
1 ml.
of
0.6
M
of 0.2
60
M
con-
NaCl
was
per
cent
minute
clots
spectrophotometer.
4 ml.
plasma,
4 ml.
in
them
from
the
clot
1 ml.
cooling,
ml.
5 per
ml.
cent
content
ml.
Solubility
plasma,
0.6
0.6
ml.
plasma
permitted
of
and
ml.
to
it with
was
were
read
values
from
the
test
for
the
final
filter
paper.
The
clot
added
and
boiled
for
against
obtained
Nils
times
After
buffer
(0.163
acid
were added.
reagent
(1:3)
was
The
M,
pH
The test tubes
added
(Fisher
a reagent
were
samples
12+),
blank
expressed
and
at
as
standards
a
(1
I).
Clots
described
0.6
0.6
M
glycine
0.6
ml.
of
sets
continue
proteins.
OH
Dr.
three
Clycine
samples
of
identical
Na
by
washed
nonfibrin
N
phenol
of Plasma
(preparation
modified
were
pressing
2.5
trichloracetic
(Fraction
plasma
minutes
most
determined
fibrinogen
method
60
by
of
4.6
diluted
15 minutes
the
Two
was
Folin-Ciocalteau’s
spectrophotometer.
Urea
thromboplastin.
formation
)
volumes
.Sml.),
were
formed
free
1.5
protein
anticoagulated
contained
ml.
1.5
the
which
After
and
standing
of
system
and
After
5 mg)
contained
and
1.0
increasing
.4m1.;
mixtures
from
to
bath.
clot
to
removed
tube
mixed
the
clots
saline
was
water
and
mixture
by
which
a Coleman
between
Fresh
0.1
iothalamate.
Magnification:
with
.3ml.;
Junior
the
a test
a water
thoroughly
Scientific
mixed
Laboratory
a Coleman
determined
normal
then
were
in
was
.2m1.;
These
Research
method
wash
D.
meglumine
simplastin.
of Clots
this
in
)
.bml.;
a control.
m
was
content
Bang.
for
( Mann
at
Content
Protein
.OSml.;
volumes
measured
mg
of
+ 0.1 ml.
Laboratory
ml.;
thrombin.
were
650
presence
microscopy.
trast
U.
the
iothalamate
M
0.6
of
for
in
contrast
methyl
M
the
60
Na
Cl.
above
minutes.
was
section
Al)
media;
the
and
ethylesters;
All
FSF
and
mixtures
reaction
One
used.
were
systems
set
of
The
inhibitor
the
control
activated
were
clots
test
system
was
by
prepared
immed-
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EFFECTS
OF
RADIO-OPAQUE
Fig.
3.-(A
and
ate. Magnification:
aciform
structures
0.2
ml.
trast
sodium
CONTRAST
B) Aciform
(A) 3200X;
formed
structures
(B) 1280X.
the presence
in
471
MEDIA
formed
in the presence
(C and D) Amorphous
of
sodium
+ 0.1 ml. simplastin
acetrizoate
of sodium
acetrizoprotein
masses
and
acetrizoate.
1.0
Magnification:
ml.
1280X.
plasma+
Phase
con-
in 30 per
cent
microscopy.
iately
washed
and
( Urevert,
urea
24
hours
the
its protein
Travenol
clots
content
determined.
Laboratories,
were
Inc.,
( as
washed
The
Morton
described
other
set was
Grove,
in
section
)
and
their
)
C
placed
Illinois
After
.
an
protein
exposure
of
content
de-
termined.
RESULTS
I. Clot
Formation
The
type
in the
coagulation
and
When
process
concentration
visualized
trations
of
cent
contrast
contrast
the
of
altered
contrast
phase
of
cific chemical
optical
density
to
Media
various
medium
contrast
chemicals
caused
by
contained
of contrast
volume,
degrees
in the
present
microscope
the
depending
on
reaction
increasing
mixture.
concen-
morphologic
increasing
the
the
constitution
and the
normal
fibrin
network
an optically
denser
fibrin
media
did not greatly
clotting
mixtures.
ranged
between
7.18 and 7.35 (Table
Equimolar
Na Cl (0.78
M) was
zoate
(0.78M)
to determine
whether
centration
Contrast
the
distortion
of
containing
17-37
per cent contrast
media
by volume
showed
(Fig.
2), occasional
aciform
structures,
or both,
among
the
of fibrin
fibers
(Fig.
3). At low concentrations,
e.g., 2-5 per
media
mixture
addition
was
of the
under
the
the clot. Samples
protein
aggregates
reduced
amount
control
The
Presence
of the
abnormal
The pH
2).
compared
the high
compounds
morphologic
clot.
alter
values
was
the
of
the
hydrogen
reaction
with
50 per cent
molar
concentration
was
responsible
appearance
visible
of
but
ion
the
con-
mixtures
sodium
diatrior the spefor the reduced
the fibrin
clot.
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472
VEREBELY
Table
1.-Cross
M
and
Microscopic
Cl and 0.78
Na
Reaction
Group
A
0.02
ml
M
Changes
Diatrizoate
Na
Observed
Compared
Appearance
Mixture
Sodium
Microscopic:
diatrizoate
(0.78M)
occasional
ml
Plasma
and
0.1
ml
Simplastin
Gross:
ml
NaCl
aciform
Plasma
0.1
ml
Simplastin
Clot
amounts
of
masses
structures.
Transparent
Gross:
ml
of 0.78
protein
clear
Microscopic:
(0.78M)
0.1
of
small
AL.
Normal
Dense
clot.
fibrin
opaque
network.
clot.
CONTROL
C
ml
02
Fig.
The
fiber
reaction
ml
Simplastin
clot.
as the
sodium
Ultra
width
shows
( Group
B
although
the
micrographs
with
no
micrograph
are
present.
periodicity
were
)
diatrizoate
Structure
Electron
structure
micrographs
(a) An electron
uniform
mixtures
clot
distortion
virtually
0.1
which
plasma
logic
Gross:
Plasma
of
Microscopic:
Saline
ml
fibers
a normal
Normal
0.1
4.-Control
numerous
II.
fibers
0.1
0.02
B
in the Presence
to the Control
ET
prepared
showed
the
and
neither
as
(b)
uniform
width.
presented
had
mixture
( Group
clot
in
which
magnification
of
X37,000.
optical
the
network.
clot.
fibrin
A higher
in
reduced
fibrin
opaque
of a normal
X30,000.
preparation
plasma
Normal
Dense
Table
density
same
molar
1. The
nor
Na
Cl-
morpho-
concentration
A).
of Clots
of normal
fibrin
clots
revealed
a fairly
uniform
width
of 100 m1 (Fig.
of clots
formed
in the presence
of sodium
fibers
of this
type.
The
fibers
were
always
a periodic,
striated
4a and 4b).
diatrizoate
thinner
than
fiber
Similar
revealed
100
m1
the thinnest
fibers
being
about
50A#{176}in width
(Fig.
5a).
The
thicker
fibers
had occasional
gaps
in their
continuity
and at this point
the ends
had
a frayed
appearance
(Fig.
5b).
The
smaller
fibers
assumed
irregular
shapes
(Fig.
Sc)
which
were
quite
different
from
the linear
orientation
of normal
fibers.
Some
periodic
structure
however
could
still
be seen
in these
fibers.
with
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
OF RADIO-OPAQUE
EFFECTS
Fig.
graph
An
5.-Clot
of a clot
abnormal
X58,000.
but
eral
fiber
(c)
having
mass
of
containing
in which
An
thin
defined
Optical
The
fact
structure
(Arrow).
interruption
periodic
some
of
which
measure
are
(a) An
present.
appearance
a greatly
X46,000.
about
(d)
50A#{176}, with
electron
micro-
X40,000.
(b)
at this
point.
irregular
shape
An
intertwined
virtually
no
lat-
X 42,000.
The
micrographs
polymerized
fibers
Sd).
III.
of
sodium
diatrizoate.
of varying
width
with
a frayed
a thin
fiber
with
micrograph
fibers,
aggregation.
an
473
MEDIA
6.0X102M
numerous
fibers
showing
electron
a poorly
very
CONTIIAST
always
Density
that
contained
showed
which
no
numerous
tendency
extremely
for lateral
thin
longitudinally
aggregation
(Fig.
of Clots
the
presence
of
contrast
media
reduced
the
optical
density
of the clot,
led us to study
the
relationship
between
optical
density
and
the
quantity
of fibrinogen
incorporated
into the fibrin
clot. Figures
6 and 7 show
the effect
of all compounds
tested.
At a contrast
media
concentration
of 5 per
cent by volume
(3.0 X 102M),
most
of the fibrinogen
was incorporated
into
the
fibrin
clot
(Fig.
6).
Conversely
at the
same
except
sodium
acetrizoate
caused
considerable
(Fig.
7).
At a concentration
of 10 per
cent by
trast
media
the optical
density
of all clots was
concentration
all of the
reduction
in optical
volume
(6.0 X 102M)
reduced
below
18 per
agents
density
of concent of
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474
VEREBELY
El’
AL.
E
a)
0
0
0.25 1.25
2.5
5.u
Concentration
Fig.
6.-Protein
content
various contrast media.
of
of 0.6M
clots
in
contrast
the
media
in volume
presence
of
%
increasing
concentrations
NaCI control
O.6M Na acetrizoate
0.6M Na diatrizoate
#{149}
0.6M lodopyracet
#{176} 0.6M
meglu mine iothala
of
A
mate
0
0.25 1.25
2.5
Concentration
Fig.
7.-Optical
density
7.5
5.0
of O.#{212}M
contrast
of clots
with
only
the fibrin
clot’s
mer incorporation
NaCl
control,
yet
with
iodopyracet.
optical
into
the
in volume
increasing
media. At each
dilution
the OD of clots
formed
was calculated
as the percentage
of the equimolar
the equimolar
ably
lower
10.0
media
%
concentrations
in the
Na
incorporation
These
results
density
was not paralleled
the clot’s structural
protein.
of various
presence
Cl control’s
of
contrast
media
OD.
of fibrinogen
showed
that
by a decrease
An extreme
contrast
was considera reduction
in
in fibrin
example
monoof this
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
EFFECTS
OF
RADIO-OPAQUE
CONTRAST
475
MEDIA
Protein
content
of clot
80
‘
0
60
0
E
0
L)
0
a)
0
0
0
400
Optical
density
of clot
20
0
0.25
1.25
2.5
5.0
Concentration
of
0.6M
7.5
meglu
mine othalamate in volume %
Fig.
8.-Protein
content
and
optical
density
meglumine
iothalamate
in increasing
concentrations.
Table
2.-Urea
Solubility
FSF
Chemical
in the
mixture.
Na
agent
reaction
Cl
Methyl
Ethyl
was
Ester
Ester
0.6M
0.6M
0.6M
0.6M
Saline
Normal
0
0.6M
diatrizoate
Each
less
value
±0.04
mg
nonparallel
relationship
iothalamate
the
crease
in
decreased
Iv.
Urea
Plasma
diatrizoate
represents
in the
the
formed
Presence
Chloride
in
the
presence
of Contrast
Media,
of
Controls
Protein
Content(mg.)#{176}
of 60 mm.
clot
at ter 24
hrs.
in
30%
urea.
% of fibrin
pH of
protein
reaction
dissolved
in mixture
30%
urea
in 24 hrs.
1.0
1.03
0
1.0
1.0
0
7.30
1.03
1.02
0
7.22
0.83
0.82
0.0
0.0
100
100
7.20
0.93
0.94
0
7.25
mean
0.90
of at least
four
7.2
7.23
0
determinations
and
7.20
the S.D.
in each.
is
fibrin
contrast
clot
clots
0.90
milligram
than
of
Content(mg.)#{176}
mm.
clot,
0.6M
iothalamate
Metaglucamine
Glycine
Glycine
Formed
and Sodium
Protein
of 60
diatrizoate
Meglumine
Na
of Clots
Inhibitors
10.0
shown
in
incorporation
medium
concentration;
Figure
into
the
8. In the presence
clot hardly
changed
however
the
optical
of meglumine
with
the
in-
density
the
of
rapidly.
Solubility
clots
and
formed
in the
meglumine
30 per cent
urea
(Table
2).
demonstrated
that the Fibrin
fibrin
polymers.
The enzyme
presence
iothalamate
of sodium
were
found
diatrizoate,
insoluble
methylglucamin
in a solution
of
The
stability
of these
clots in 30 per cent
urea
Stabilizing
Factor
(FSF)
acted
upon
the altered
FSF
has been
known
to catalyze
covalent
bond
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476
VEREBELY
E’r
AL.
in the last
step
of fibrin
polymerization.
The plasma
clots
formed
presence
of glycine
methyl
and ethyl
esters,
however,
totally
dissolved.
control
clots which
contained
normal
saline
or 0.6 M NaCl
in their clotting
formation
in
the
The
mixture
were
also
stabilized
by
FSF
and
did
not
dissolve
in 30 per
cent
urea.
DIscussIoN
The
physical
and
significantly
chemical
altered
Abnormal
mainly
by
It is probable
that
these
meres
which
were
at
gether
in an
the
altered
showed
but that
the
finding
fibrin
stage
density
contrast
the
used.
of the
This
polymerization
This
of
contrast
clots
until
However,
not
in the
presence
clot
medium
no
clot
formed.
primary
fibrinogen
diatrizoate
very
either
appeared
before
to
or
with
the
consistent
preceded
caused
fewer
the
of sodium
from
sized
fibers
were
present
Since
these
small
fibers
was
the
topre-
in appearance
structural
abnormality
main
fibrin
bundle
of
be
to
media.
and
aggregated
believed
to be
were
different
change
density
drop
of the
to decrease
indicated
was
quite
the chief
to join the
appeared
with
the use of light
microof 9 to 37 per cent by volume.
from
intermediate
fibrin
poly-
intermediate
were
not found.
concentrations
structure.
sudden
started
and
clots
of contrast
polymerization
structures
were
aggregation.
medium
clot’s
parallel
the
incorporation
media
lateral
of
concentration
optical
higher
into
some
periodicity,
of these
fibers
that
a reduced
optical
monomer
incorporation.
Increased
the
which
fibrin
types
formed
contrast
media.
of a clot formed
that
numerous
very
thin
fibers
of normal
thickness
still exhibited
be the inability
at
masses
stages
of
The aciform
molecules
formed
from
micrographs
of
of various
were
observed
concentrations
protein
different
manner.
fibrinogen
crystals
Electron
presence
protein
aggregates
at contrast
medium
scopy
cipitated
characteristics
the
the
a sudden
This
diminished
decrease
suggested
fibrils
were
incorporation
in
that
with
incorporated
curve
did
not
optical
density
curve,
in that fibrin
monomer
only at the highest
concentrations
of contrast
that
blocked
at low
but the
altered.
Higher
concentrations
of
with
fibrin
monomer
incorporation
contrast
into
contrast
structural
medium
concentrations
arrangement
of the
media
polymerized
caused
fibrin
further
as
reduction
in the clot’s protein
content.
Several
investigators
have
shown
chemical
interference
with
formation.
Edsal2
demonstrated
that
the structural
properties
greatly
modified
by variations
of pH,
ionic
strength
of chemical
clot
fibrin
was
interference
evidenced
by
the
normal
fibrin
of fibrin
are
agents
and
other
factors.
He made
observations
on the gross
structure
of fibrin
clot. The
presence
of iodide,
thiocyanate,
urea
and
glucose
resulted
in the formation
of a fine transparent
clot grossly
similar
to those
we observed
in the presence
of contrast
media.
Edsal
described
a coarse
opaque
control
clot similar
to
those that were
Our reaction
formed
mixtures
to 7.35. Although
Edsal
in his reaction
mixture,
control
clots
with
pH values
of our
in our control
samples.
were
prepared
with
proposed
we found
thick
fibers
test mixtures,
pH
values
a pH of 6.3 as optimal
that our systems
at pH
and high
optical
which
were
very
ranging
for
7.25
between
7.18
fibrin
formation
provided
good
density.
We believe
that
the
close to those
of the control,
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
EFFECTS
OF
were
not
The
media
RADIO-OPAQUE
CONTRAST
responsible
marked
and
cals
rather
other
distortion
contrast
than
fibrin
normal
polymerizing
reversibly
mobilities.8
that
they
arrangement
observed
of the
solution
alone
in the
fibrin
polymers.
equimolar
to the
is not responsible
presence
of meglumine
property
seems
of the contrast
to interfere
contrast
for the
iothalachemiwith
the
process.
studies
can
spatial
media.
Some
specific
high
molar
concentration
their
Electrophoresis
media
altered
conducted
with
NaC1
that high
ionic
concentration
morphologic
mate
the
for
experiments
suggested
477
MEDIA
this
from
bind
plasma
laboratory
demonstrated
proteins
Since
contrast
media
are
also reacted
with
fibrinogen
and
change
that
their
contrast
electrophoretic
capable
of binding
proteins,
or enzymes
which
catalyze
it is possible
fibrin
poly-
merization.
Lorand
and Jacobsen#{176} introduced
glycine
methyl
and ethyl
esters
as irihibiof FSF.
In the presence
of such inhibitors
the covalent
bond
formation
or
stabilization
of the plasma
clot was prevented;
thus the clots that formed
were
soluble
in 30 per cent urea or in 1 per cent monochloroacetic
acid.
We
performed
30 per cent urea solubility
tests to see whether
the abnormal
tors
fibrin
structures
FSF
ethyl
formed
upon
the
the
abnormal
ability
different
the
fibrin
structure
of the
As
a
joined
FSF
result,
plasma
normal
altered
the
clots
insoluble
enzyme
presence
arrangement
fibers
that
were
stabilizing
formed
in the
that
only
the
which
found
media
fibrin
of contrast
media
were
acted
upon
freely
soluble
as in the presence
of such experiments
would
also
to discriminate
We
contrast
that
presence
or became
The results
of FSF
clots.
the
in
and thus stabilized,
and methyl
esters.
control
not
clot
structures
in the
30 per cent
differentiate
in
could
polymer
formed
and
the
present
presence
of
in
three
urea.
This
indicated
between
the regular
abnormally
polymerized
of contrast
media.
However,
it is possible
of fibrin
monomeres
was altered
and
each
other
remained
catalyzed
covalent
by
of glycine
shed
light
unchanged
in the
bond
formation
as
clots
to postulate
the sites
abnormal
it does
at
polymer.
in normal
clots.
SUMMARY
Radio-opaque
and
contrast
plasma
the fibrin
amorphous
clot
fiber diameter
in the light
concentration
concentration,
With
2.0
102M,
optical
corporation
of fibrin
within
normal
limits.
was
duced
ence
LLF
changes
altered.
by
Electron
70 per
of 6.1 X
or Factor
in the
cent
102M
XIII)
clot.
with
morphologic
and an increase
microscope
and
agents
different
concentrations
the
interfered
The
of contrast
which
was
increasing
X
media
formation.
in
micrographs
to 90 per
the
that
medium
clots
of the
sodium
diatrizoate.
catalyzed
covalent
of
between
decreased
that
control
the
fiber
3.5
fibrin
diameter
of
appeared
with
the
a threshold
clot formed.
X
rapidly
The fibrin
stabilizing
cross
links
despite
fibrin
a decrease
10’3M
while
polymer
structure
of the
the spatial
arrangements
confirmed
cent
process
included
the reaction
mixture.
Above
for each
contrast
media,
no
of the
monomers
into
This
indicated
normal
of protein
aggregates.
These
showed
a linear
relationship
of contrast
density
the
changes
fibers
and
the
in-
clots
stayed
of the clots
were
in the
repres-
enzyme
(FSF,
the
structural
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478
VEREBELY
SUMMARIO
Esseva
trovate
que
substantias
de
IN
ET
AL.
INTERLINGUA
contrasto
a radio-opacitate
interfereva
in
le
processo
formation
de coagulos fibrinic e plasmatic.
Le alterationes
morphologic
includeva
un dedino
del diametro
del fibras de fibrina e un augmento
del aggregatos
de proteina.
Iste
ultimes
appareva
amorphe
in le microscopio
optic
e monstrava
un relation
lineari con le
concentration
del agentes
de contrasto
in le mixtura
de reaction.
Supra
un concentration
liminal,
le qual differeva
pro le vane substantias
de contrasto,
nulle
coagulo
se formava.
Con crescente concentrationes del substantia
de contrasto
inter 3,5 X 10’s e 2,0 X 102
M, le densitate
optic
del coagulos
decinava
rapidemente
durante
que le incorporation
de
monomeros
de fibrina ad in le structura
polymeric
del coagulos
se teneva
intra
limites
normal. Isto indicava
que le disposition
spatial del coagulos
esseva alterate.
Micrographias
electronic
confirmava
le facto que le fibras
de fibrina
esseva
reducite
in br
diametros
per
70 a 90 pro cento
in comparation
con be valores de controbo in le presentia
de 6,1 X 10-2
M diatnizoate
de natrium.
Le enzyma de stabilisation
de fibrina (FSF, LLF, o Factor XIII)
catalysava
covalente
nexos transversal
in despecto
del alterationes
structural
in le coagulo.
normal
del
ACKNOWLEDGMENT
The
cism
authors
in the
wish
to express
preparation
their
of this
gratitude
to Dr.
Koloman
Laki
for his
to
IV.
Reversible
advice
and
criti-
manuscript.
REFERENCES
1.
Kutt,
H.,
mechanism
Acta
2.
Verebely,
F., and
Streuli,
Radiol.
Edsall,
of
K.,
McDowell,
complications
Bang,
F.:
of
N.,
Possible
angiography,
Suppi.
Vol 5:277-289,
1966.
J. T., and Lever, W. F.: Effects
of ions and neutral molecules
on fibrin clotting. J. Biol. Chem. 191:735-756,
1951.
3. Ferry,
J. D., and Morrison,
P. R.: Preparation
and properties
of serum and plasma
proteins
VIII.
The
conversion
of human
fibrinogen
to fibrin under various conditions.
J. Amer.
Chem.
Soc.
69:388,
1947.
4. Shulman,
S., and
Ferry,
J. D.: The
conversion
of fibrinogen
to fibrin.
II Influence of pH and ionic strength
on clotting
time
and opacity.
J. Phys.
and Colloid,
Chem. 54:66,
1950.
5. Shulman,
S.: The conversion
of fibrin-
ogen
fibrin.
inhibition
of
the reaction.
Arch.
Biochem.
30:353-371,
1951.
6. Rosenfield,
L.: Clot opacity
and
the
thrombin-plasma
reaction.
Arch.
Biochem.
111:660-670,
7.
Kutt,
1985.
H.,
Schick,
B.
W.,
Rennie,
L.
E.,
and McDowell,
F.: The quantities
of sodium
diatnizoate
in cerebral
vessels during arteriography.
J. Nerosurg.
20:515-519,
1963.
8. Kutt, H., and McDowell,
F.: Effects
of ionized contrast
media
upon electrophoretic mobilities
of blood proteins
and lipoproteins. J. Lab. Clin. Med. 59:118,
1962.
9. Lorand,
L., and Jacobsen,
A.: Specific
inhibitors
and the chemistry
of fibrin polymerization.
Biochemistry
3:1939-1943,
1964.
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
1969 33: 468-478
The Effects of Radio-Opaque Contrast Media on the Structure, and
Solubility of the Fibrin Clot
KARL VEREBELY, HENN KUTT, RICHARD M. TORACK and FLETCHER MCDOWELL
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