Print - Circulation Research

Butter, Corn Oil and Fibrinolysis in Rats
By
ROOSEVELT L. TILLMAN, B.A.,
WILBUR A. THOMAS, M.D.,
M.D.,
B.S.
reasonable reprodueibility. Furthermore, 3
samples of plasma can be tested simultaneously with the Thrombelastograph, thus making it possible to make direct comparisons of
samples from animals from 3 different groups.
We applied the above method for the study
of fibrinolysis to 3 groups of rats in 2 separate,
consecutive experiments. One group was fed
a diet containing propylthiouracil, cholesterol,
sodium cholate, and a large amount of butter, which in previous experiments has produced infarcts in 43 of 218 rats. Another
group was fed the same diet, except that corn
oil was substituted for butter; no thrombi or
infarcts were found among 25 rats fed this
modification previously. A third group was
offered a " n o r m a l " semisynthetic diet. The
purpose of this report is to present the results
of studies of fibrinolysis in these 3 groups in
each of 2 experiments.
C
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ONSIDERABLE evidence has accumulated suggesting that 2 factors are involved in coronary thrombosis in man: (1) a
local factor (usually atherosclerosis) ; and (2)
a hematologic factor (procoagulative, antifibrinolytic, or both). 1 " 3 Data obtained from
this and other laboratories during the past
several years indicate that the ingestion of
certain fatty substances might be involved in
both the local and hematologic factors. 1
We have recently reported a dietary method
for the production of coronary thrombosis and
myocardial infarction in rats. 4 ' 5 In those experimental animals, the degree of arteriosclerosis (local factor) has been surprisingly minimal at even the sites of thrombosis and has
led us to believe that the diet was affecting
principally the hematologic factor.
Our attention has been directed toward the
development of methods for the study of
fibrinolysis.0 A method was needed that was
as nearly objective as possible, reproducible,
and capable of comparisons of rats on thrombogenic diets with those on nonthrombogenic
diets. For objectivity we chose to use an
electronic device called a Thrombelastograph,*
which provides a permanent, measurable record of at least certain aspects of blood clotting
and clotlysis.7' 8 For reprodueibility and comparability, we have utilized several purified or
semipurified additives that permit clotting
and lysis of plasma from rats at will. Thus
standard conditions can be created under
which clotting and lysis times and clot-firmness9 of normal plasma can be measured with
Methods
Sixty male rats (Wistar albinos) were used, 30
in each of the 2 consecutive experiments, herein
referred to as Experiment I and Experiment II.
They were housed in individual wire-bottom cages
and offered water ad libitum. All were weighed
weekly in Experiment I and at the beginning and
end of the short-term Experiment II (table 1).
Each day food not consumed was weighed and
discarded and measured portions of fresh diet
were placed in sterilized glass containers, thus
providing a daily record of food intake. Pair
feeding on either a food-weight or body-weight
basis was not done, all rats being offered more
than they could eat.
Diets
Three semisynthetic diets were prepared, as
• indicated in table 2. Dry ingredients were thoroughly blended in a Hobart food mixer. Various
supplements as listed were mixed in a mortar
with small portions of dry ingredients and blended
with the remainder in the mixer. Fats were added
last and if solid they were warmed until liquid.
Diets were stored in closed plastic containers at
4 C.
From the Department of Pathology, Washington
University School of Medicine, St. Louis, Mo.
Supported by Public Health Service Grant H-1820
from the National Heart Institute, Institutes of
Health, Bethesda, Md., and by a. grant from the
Nutrition Foundation.
Received for publication November 19, 1959.
*Sold by the Haemoscope Corporation, 866 Willis
Ave., Albertson, N. Y.
Circulation Research, Volume VIII, March 1960
ROBERT M. O'NEAL,
AND BARBARA BARTELS HIXON,
423
TILLMAN, O'NEAL, THOMAS, HIXON
424
Table 1
Weights, Dietary Intakes and Plasma Cholesterol Levels of Bats in the Three Experimental Groups of Two Consecutive Experiments
Groups
4-6 weeks
Start End
Av. plasma cholesterol levels at
end of experiment with ranges
Av. daily food intake
by weeks (Gm.)
Av. weight
(Gm.)
1st
2nd
3rd
4th
5th
Experiment
I
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Normal
226
318
14.5
14.8
14.7
14.7
15.0
Butter
226
181
8.4
10.6
8.4
9.3
9.7
Corn oil
228
190
6.9
5.1
4.9
9.2
8.9
15.0
.8.8
14.8
12.8
82.5 (42-120) mg. 9!0
1192.3 (546-1656) mg.
%
168.0 (72-204) mg. %0
19 days
Start End
Experiment
II
Normal
Butter
258
296
263
209
Corn oil
261
225
7.43 10.5
Studies of Fibrinolysis
All studies were carried out with the Thrombelastograph, illustrated schematically in figure 1.
The principle of the machine is quite simple.
Blood plasma is placed in a cup rotating back
and forth constantly through an arc of 4 degrees
and 45 seconds; a pin, suspended by a torsion
wire, is immersed in the plasma and the surface
of the plasma covered with a layer of oil to prevent drying. As long as the contents are fluid,
the pin does not move with the rotation of the
cup. When the plasma filling the space between
the pin and cup clots, it adheres to their surfaces
and the pin (with torsion wire) tends to rotate
with the cup. The degree of rotation of the pin
depends upon the firmness and adhesiveness of
the clot.9 As the clot lyses, the pin and torsion
wire gradually decrease in degree of rotation and
finally their motion stops. A mirror mounted on
the torsion wire transmits, by means of a beam
of light, any motion of the wire to a slowly moving roll of photographic film; only the 2 extremes
of rotation are recorded. Three separate cups and
pins are mounted on 1 machine and recorded on a
single roll of film. Therefore, 3 specimens can be
tested and recorded simultaneously. Overlapping
of the 3 records on the film is easily separated by
the eye, since each has a different center point.
The method used for the comparative study of
fibrinolysis in the experiments reported herein
will be presented in a step-wise fashion.
66.6 (57-82) mg. %
659.4 (104-1480) mg. %
83.1 (69-106) mg. %
(1) Establishment of sets of three rats for testing
and time of testing
Tests on 3 rats, 1 from each group, were run
simultaneously. These sets of 3 were established
at the beginning of the experiment and matched
for weight, but as will be seen, the rats on the
"normal" diet soon became heavier than the other
2 during the course of the experiment. The tests
were performed within 12 to 40 days after beginning the diet. Usually only 1 set and never more
than 3 were tested in a single day.
(3) Method of obtaining blood
Each rat in the set of 3 was anesthetized with
3.75 mg. of sodium barbital per 100 Gm. body
weight. The peritoneal cavity was opened and
blood obtained by aortic puncture, using a 5 ml.
syringe (not siliconized) and a 21 gage needle.
Four ml. of blood were drawn into the syringe
containing 1.0 ml. of sodium citrate solution (3.8
Gm. in 100 ml. distilled water) to prevent clotting.
It usually took less than 30 minutes to obtain
blood from the 3 animals, but in order better to
control the time factor, the order in which the
animals were punctured was changed from set
to set (i.e., animals from the "butter" group would
be first in some sets and last in others).
(S) Method of obtaining plasma
The blood obtained in step 2 was placed in
15 ml. plain centrifuge tubes and centrifuged at
2,000 r.p.m. for 15 minutes. The plasma was then
Circulation Research, Volume VIII, March 1960
425
BUTTER, CORN OIL AND FIBRINOLYSIS
Table 2
Composition of Diets in the Three Experimental Groups of Rats in Per Cent by Weight
"Butter"
"Normal"
Corn oil
Casein
Sucrose
Celluflour
Salt mixture*
Vitamin mixture t
Choline chloride
2.0
20.0
65.8
6.0
4.0
2.0
0.2
"Corn oil"
Butter
Cholesterol
Na cholate
Propylthioura ci 1
Casein
Sucrose
Celluflour
Salt mixture*
Vitamin mixture t
Choline chloride
40.0
5.0
2.0
0.3
4.0
20.7
5.0
4.0
2.0
1.0
Corn oil
Cholesterol
Na cholate
Propylthioura cil
Casein
Sucrose
Celluflour
Salt mixture*
Vitamin mixture t
Choline chloride
40.0
5.0
2.0
0.3
20.0
20.7
5.0
4.0
2.0
1.0
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*This salt mixture is the Wesson modification of Osborne and Mendel Salt Mixture (Science
75: 339, 1932). The composition in per cent by weight is as follows: Calcium carbonate, 21;
copper sulfate (5H»O), 0.039; ferric phosphate, 1.47; manganous sulfate (anhydrous), 0.02;
magnesium sulfate (anhydrous), 9; potassium aluminum sulfate, 0.009; potassium chloride, 12;
potassium dihydrogen phosphate, 31; potassium iodide, 0.005; sodium chloride, 10.5; sodium
fluoride, 0.057; tricalcimn phosphate, 14.9.
tEach kilogram of the vitamin mixture contained the following, triturated in dextrose:
Vitamin A concentrate, 4.5 Gm. (200,000 units per 6m.); Vitamin D concentrate, 0.25 6m.
(400,000 units per Gm.); alpha tocopherol, 5.0 Gm.; ascorbic acid, 45.0 Gin.; inositol, 5.0
Gm.; menadione, 2.25 Gm.; P aminobenzoic acid, 5.0 Gm.; niacin, 4.5 Gm.; riboflavin, 1.0 Gm.;
pyridoxine hydrochloride, 1.0 Gm.; thiamme hydrochloride, 1.0 Gm.; calcium pantothenate, 3.0
Gm.; biotin, 0.02 Gm.; folic acid, 0.09 Gm. .
drawn off with a syringe and needle and placed
in a 3 ml. tube. The entire procedure from aortic
puncture to drawing off the plasma usually required less than 1 hour and during this period
the blood was at room temperature, about 26 C.
After the plasma was drawn off, it was kept at
4 C. until used in the test. One ml. of plasma was
stored at —20 C. and total cholesterol determinations were performed later by the method of
Pearson, Stern and McGavack.30
(4) Method of preparing ingredients to he mixed
with the plasma in the test
(a) Calcium chloride. Anhydrous calcium chloride was added to 1,000 ml. of distilled water until
a specific gravity reading of 1.0835 was obtained
at 20 C, indicating a 10 per cent solution. This
10 per cent solution was then diluted to 1.29 per
cent and used as a stock solution, (b) Streptokinase. 100,000 units of a purified streptokinasestreptodornase preparation (Varidase*) were diluted to 100 units/ml, as a stock solution. Streptokinase was used as in a previous method to activate
fibrinolysis." (c) "Diagnostic Plasma."t One 2.5
*The Varidase was made available by the courtesy
of Lederle Laboratories through Dr. Sol Sherry.
•(•The Diagnostic Plasma was kindly supplied by
Warner-Chilcott Laboratories, Morris Plains, N. J.
The 2.5 ml. vial is the "Bacteriologic size," sold
commercially for use in the coagulase test. However,
the dilution used in our procedure is not that recommended for the coagulase test.
Circulation Research, Volume VIII. March I960
ml. vial of lyophilized wThole human plasma was
added to 3.25 ml. of distilled water and used as
a stock solution. In a preliminary experiment,
comparing the effect of the "butter" diet with
the "normal" diet, Diagnostic Plasma was not
used and it was possible to demonstrate a significant difference in the firmness of clots in the 2
groups. However, complete lysis did not occur
even after 24 hours. We then found that the
addition of Diagnostic Plasma would result in
complete lysis and it was used in all experiments
reported herein.
(5) Mixing of various ingredients
One ml. of test plasma was mixed with 0.5 ml.
of the Diagnostic Plasma stock. Of this mixture,
0.7 ml. was added to 0.3 nil. of streptokinase
stock. Then 0.3 ml. of the resulting test plasma—
Diagnostic Plasma—streptokinase solution was
placed in 1 of the 3 cups of the Thrombelastograph for each of the 3 rats in the test set.
(6) Performing the test in the Thromielastograph
As a last step, the rotating mechanism of the
machine was started, including the turning of the
film, and the 0.05 ml. of the stock calcium chloride
solution (1.29 per cent) was added to each cup.
Immediately afterwards, the pin attached to the
toi-sion wire was lowered into the cup and recording started immediately. Paraffin oil was quickly
layered over the top of the plasma to prevent
drying and preparation of the test was complete.
TILLMAN, O'NEAL, THOMAS, HIXON
426
Light Source
Mirror
Plunger (Pin)
* * " I mm between cup and plunger
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Constont rototion ( 4 ^° to and fro
every 9 seconds) of motor driven
base- Heated to 37°C.
Figure 1
Diagrammatic illustration of the thrombelastograph
apparatus. The mechanism is more fully described
in the text under "Methods."
The progress of clotting and lysis could be followed visually as part of the reflected light from
the mirror, attached to the torsion wire, appeared
on a frosted glass panel, graduated in mm., at
the front of the machine. Time of clotting and
lysis could be recorded from observing this panel.
However, it was actually unnecessary to determine
the times in this fashion because rotation of the
wire was recorded on film moving at a constant
speed of 2 mm./min. Thus, the time of any change
could be determined later from the permanent
record by simply measuring the distance of the
starting point.
(7) End of test
After lysis was complete, the machine was
turned oil. The cups were removed, cleaned with
a barium sulfate-soap solution, dried and polished
for the next test. Two tests were performed on
the plasmas of each set of 3 rats and the average
of the 2 tests was used in preparing the tables
presented herein. Autopsies were performed on
all rats, which had been sacrificed by exsanguination following the aortic puncture. Their viscera
were examined for infarets as in previous experiments,1"3 but none was either expected or seen in
this early period.
(8) Measurements of photographic record
After development and drying of the roll of
photographic paper used in a test, three measurements were made (fig. 2). The first was a measure of time in seconds that elapsed from the
beginning of the record (lowering of the pin into
plasma) to the beginning of motion of the pin,
torsion wire and mirror, herein defined as "clotting
time." (This corresponds to the "reaction time"
of other authors.)7 The second measurement was
the "maximum amplitude," the greatest rotation
obtained at any point during recording, measured
on the thrombelastograph as millimeters between
the 2 lines of the tracing. The third measurement,
"lysis time," was the time in minutes from the
beginning of motion of the pin to its cessation,
where a single line was reobtained on the recording.
Results
The results are summarized in tables 1 to 3
and illustrated in figure 2. Experiments T
and II will be considered together. In the first
experiment, 2 sets of animals were discarded
because of deaths in 1 of the groups and 1
set was discarded because, after photographing the plasmas under photoflood lamps, the
"normal" plasma failed to clot. In the second
experiment, 1 set of animals was discarded
because of the death of 1 animal. The 16 sets
left were comprised of 48 rats. Plasmas from
these animals were tested after 12 to 40 days
on the diets (table 3). The rats fed the normal
diet (table 2) grew rapidly, ate more than the
other rats, had serum cholesterol levels in the
normal range and appeared in good condition
(table 1). The rats fed the butter and corn
oil diets stopped growing (probably because of
the propylthiouracil), ate only about half as
much as the normal rats and appeared at least
somewhat debilitated. The only distinguishing
features (other than clotting and lysing characteristics) noted between the "butter"' rats
and the "corn oil" rats were the significantly
higher levels of cholesterol and grossly greater
turbidity of the plasmas of the rats in the
butter groups. The plasma cholesterol levels
of the rats fed the corn oil diet were only
slightly higher than those of the rats on the
normal diet (table 1).
In 12 of the 16 sets of rats, the plasmas of
those on the butter diet had longer lysis times,
greater maximum amplitudes and shorter clotting times than the plasmas of those in the
other 2 groups. Factors such as hemolysis,
resulting from technical difficulties, may account for the rapid lysis of clot of an occaCirculation Research, Volume VIII, March 1960
BUTTER, CORN OIL AND PIBRINOLYSIS
427
B"22.5mins.
C= 16.0 mins.
N" 3.25mins.
N» 5.5 mins.
B»27.5 mins.
C" 9 0 mins.
A.
s\
C« 3.75 mins.
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B-75.0 mins.
N" 6.0 mins.
B s 45.0 mins.
Ns
3.5 mins.
C s 34.0 mins.
Figure 2
Thrombelastographs from 3 sets of animals, each set being composed of 3 rats, 1 from
the "normal" group (N), 1 from the "butter" group (B), and 1 from the "corn oil"
group (C). Clot-lysis time in minutes is given for each rait. Upper. The set of tracings
labeled A is from the initial test and B is a repeat test on duplicate plasmas which had
been kept at 4 C. until the initial test was complete. Note that the maximum amplitude
and clot-lysis times are greater in the repeat test. This was a uniform occurrence, probably the result of loss of activity of the streptokinase. Also notice the clotting times,
the "normal" being longer than the other two plasmas. Middle. There is a strikingly
greater clot-lysis time for the plasma clot of the rat in the "butter" group than for those
of the other 2 groups. Lower. Clotting time is approximately the same for each plasma,
and the clot-lysis time of the plasma from the "corn oil" group lies between those of the
other 2.
sional rat from the butter group. All these
data, with averages, are given in table 3 and
will not be repeated in the text. Differences
among means were tested by the analysis of
variance of a randomized block, with pairs of
means compared by Tukey's method. Homogeneity of variances was tested by Bartlett's
Circulation Research, Volume VIII, March 1960
chi-square method.11 Because of the skewed
distribution of the lysis times, various transformations were tried in order to produce
samples which could be considered to be from
a normal population. The logarithmic transformation reduced the skewness and produced
homogeneous variances in the 3 groups
TILLMAN, O'NEAL, THOMAS, HIXON
428
Table 3
Complete Data Obtained with the Thrombelastograph on the Forty-Eight Experimental
Animals
N*
Experiment
I
Experiment
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II
Mean
Maximum amplitude
in mm.
Clotting time
in sees.
Days
B
C
40
38
37
37
37
36
35
150.0
180.0
150.0
172.5
165.0
165.0
159.5
127.5
120.0 .
97.5
157.5
120.0
135.0
97.5
172.5
127.5
127.5
165.0
150.0
3 80.0
127.0
19
18
17
16
152.5
180.0
180.0
157.5
120.0
172.5
210.0
180.0
150.0
135.0
105.0
90.0
105.0
105.0
82.5
105.0
105.0
97.5
82.5
150.0
150.0
112.5
150.0
120.0
120.0
195.0
150.0
35
14
13
13
12
165.28; 111.12 142.47
Geometric
Mean
Lysis time
in min.
B
C
N
6.3
8.0
14.3
5.0
8.3
13.3
8.8
13.8
14.5
11.0
16.5
14.3
21.0
21.5
10.5
6.3
19.5
10.3
10.0
12.0
17.0
18.5
3.5
20.0
11.7
5.0
27.5
4.4
27.5
150.0
13.0
162.5
25.0
48.8
25.0
20.0
55.0
1.6
4.6
21.0
13.3
12.5
9.3
7.0
5.8
6.0
8.0
8.3
6.5
12.5
9.5
10.5
15.0
31.3
23.0
24.0
18.0
17.0
18.0
22.0
12.5
9.0
23.8
11.5
13.5
8.8
14.8
10.0
15.5
165.0
70.0
25.0
19.5
15.0
4.0
3.3
32.5
20.0
300.0
50.0
2.8
40.0
25.0
101.5
75.0
115.0
53.8
3.0
77.5
32.0
3.5
1.3
63.5
37.5
33.3
63.8
18.21
12.81
8.56
27.8
75.93
27.7
15.0
46.9
14.7
*The letter designations correspond to the experimental groups defined in the text.
for " n o r m a l , " B for " b u t t e r , " and C for "corn o i l . "
(P>0.50). The antilogarithm of the mean
logarithm is the geometric mean close to the
medium and thus a better estimate of a central
value than the arithmetic mean in a skewed
distribution. The differences between the lysis
times for rats on the butter diet and either of
the other 2 groups is statistically significant
(P<0.05). The average lysis time for rats on
corn oil diet is almost identical to that for
rats on the normal diet (table 3).
Similarly, the average clotting time for rats
on the butter diet is significantly shorter than
that of rats on the corn oil diet (P<0.01) or
of rats on the normal diet (P<0.01). The
clotting times of rats on the corn oil diet were
also shorter (P<0.05) than the normal. Since
the variances were homogeneous (P>0.25)
and the distributions were not skewed, statistical analyses were performed using actual
values of the measurements of clotting times.
Also, the maximum rotation of the torsion
wire (maximum amplitude, the factor of the
firmness and adhesiveness of the clot) was
greater in the rats fed butter than in either of
the other 2 groups (P<0.01 for either). The
C
B
N
N is
maximum amplitudes of the corn oil groups
were significantly (P<0.05) greater than
those of the normal rat. The variances of the
maximum amplitudes showed a tendency toward heterogeneity (0.025<P<0.05), but the
distributions were not skewed and, therefore,
the actual measurements were used for
analysis.
Discussion
We have demonstrated, objectively, in experimental animals that (under the standardized conditions of this experiment) fibrinolysis is inhibited in rats fed a complex diet
containing large amounts of butter, as compared with rats fed a corresponding diet in
which corn oil was substituted for butter or
with rats fed a '' normal'' synthetic diet. The
test is highly artificial, involving citrating and
recalcifying the blood and adding other substances. But, in spite of the artificial nature
of the test, differences were not obscured but
could be demonstrated among the group in almost every instance when samples to be compared were subjected to precisely the same
treatment.
Circulation Research; Volume VIII, March I960
BUTTER, CORN OIL AND FIBRINOLYSIS
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It is important to note that the results of
this study of fibrinolysis in animals correlate
well with the thrombogenic properties of the
diet previously demonstrated.3 Approximate]y
20 per cent of rats fed the "butter" diet in
our laboratories have developed myocardial or
renal infarete, or both. None of 25 rats fed
the "corn oil" diet developed infarcts or
other thrombotic phenomena. Also, rats on
"normal" diets have never, in our experience,
developed thrombi or infarcts.
The role of the lyophilized human plasma in
the test is not clear. If it is omitted, complete
lysis has never occurred, even with samples
from normal rats, up to as long as 24 hours.
However, differences can still be demonstrated
in the characteristics of the clot that is formed.
In a preliminary experiment with rats on the
"butter" and the "normal" diets, we were
able to demonstrate statistically significant
differences in the clots formed (without the
use of lyophilized plasma) as demonstrated by
lesser rotation of the torsion wire in rats on
the "normal" diet. Although the clots did not
completely lyse, this difference in amplitude
of recordings may reflect some degree of lysis
going on at the time the clot was formed.
Tn the experiments reported herein, it will
be noted that the clotting time is significantly
shorter in the "butter" group as compared
with either of the 2 other groups. This observation could mean that the diet is affecting
clotting as well as lysis. However, before we
are justified in drawing this conclusion, it will
be necessary to demonstrate changes in clotting time without using streptokinase. It is
possible that lysis is active from the beginning
of clotting and, when not inhibited, could delay the formation of a clot. The same reasoning applies to the differences of maximum amplitudes of the recordings among the 3 experimental groups. Since the lysis times appear
to vary directly with the maximum amplitudes
and inversely with clotting times, under these
experimental conditions these measurements
may all be functions of a single process, i.e.,
lysis. It is also possible that the observed
differences in measurements may be the result
of differences in characteristics of the clots
Circulation Research, Volume VIII, March i960
429
rather than differences in the lytic factors in
serum.
The method for the study of fibrinolysis reported herein appears to be superior to that
previously reported by us.6 The end-point
with our previous method and with any other
method relying on visual disappearance of the
clot is to some extent subjective; with the
thrombelastograph it can be strictly objective.
Also, conditions can be more rigidly controlled
than with most other methods and results compared that were obtained on different days or
even in different places.
The test described herein should be useful
in exploring dietary factors associated with
thrombosis and infarction in experimental
animals. Since differences can be demonstrated
in a much shorter time (as early as 12 days)
than it takes rats to develop arterial thrombosis (usually at least 2 months), 1 - 4 ' 5 it will
be possible to screen many diets rapidly and
then selectively test the results in longer-term
experiments with in situ thrombosis and infarction as the morphologic end-point.
Perhaps even more important than the application of the method to experimental animals is its potential usefulness in studying
clot lysis in man. Investigation of fibrinolysis
in man, using this method, might elucidate
important hematologic factors in the production of arterial and venous thrombi.
Summary
We have recently reported a dietary method
for the production of thrombosis and infarcts
in rats and have- suggested that part of the
mechanism of thrombosis in these animals was
interference by the diet with some hematologic
factor, possibly fibrinolysis. In the study reported herein, we have developed a method
for studying fibrinolysis in rats in vitro, utilizing an electronic device called the Thrombelastograph. Results of this study correlate well
with the previously demonstrated thrombogenic properties of 2 of the diets. Rats on a
"butter-thiouracil-cholesterol-bile salt" diet
(known to produce thrombi and infarcts)
have prolonged clotlysis times, as compared
with rats on a similar diet (and not thus far
430
associated with thrombi and infarcts) in which
corn oil is substituted for butter. Although
the in vitro test is performed under highly
artificial conditions, they are carefully standardized and the fact that the results correlate
well with previously demonstrated thronibogenic properties of the diet would suggest that
it has practical value for the study of thrombogenic effects of various diets in experimental
animals. It is possible that it will prove to be
even more useful in the study of fibrinolysis
in man.
Summario in Interlingua
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Kecentemente nos reportava un methodo dietari pro
le production do thrombose e infarciiiiento in rattos
e suggereva que mi parte del mechanismo del thrombogenese in iste animates consisteva. dul interferentia
per le dieta con le un o le altere factor hematologic,
possibilemente le fibrinolyse. In le hie reportate
studio nos ha elaborate un inethodo pro le investigation in vitro del fibrinolyse de rattos, con le uso de
un dispositivo electronic que es designate como le
thrombelastographo. Le resultatos del studio revela
un alte correlation con le previemente demonstrate
proprietates thrombogenetic de 2 de nostre dietas
experimental. Kattos recipiente un dieta a butyro,
thiouracil, cholesterol, e sal de bile—que es cognoseiteinente responsabile pro le production de thrombos
e infarcimentos—ha prolongate tempores de lyse de
coagulos in comparation con rattos recipiente le
mesme dieta con le exception que oleo de mais es
substituite pro butyro. Iste dieta es non—usque
nunc—associate con le production de thrombos e infarcimeutos. Ben que le test in vitro es effectuate
sub conditiones altemente artificial, su methodologia
es meticulosemente standardisate, e le facto que le
resultatos monstra un marcate correlation con previemente demonstrate proprietates thrombogenetic
TILLMAN, O'NEAL, THOMAS, HIXON
del dieta pare indicar que le test es de valor
practie pro le studio del effectos throinbogenetie
de varie dietas in animales experimental. II es beu
possibile que le mesme test va provar se aneora plus
utile in le studio de fibrinolyse in subjectos human.
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Circulation Research, Volume VIU, March 1960
Butter, Corn Oil and Fibrinolysis in Rats
ROOSEVELT L. TILLMAN, ROBERT M. O'NEAL, WILBUR A. THOMAS and BARBARA
BARTELS HIXON
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Circ Res. 1960;8:423-430
doi: 10.1161/01.RES.8.2.423
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