RICHARD V. EBERT, CRAIG W. BORDEN, WENDELL H. HALL and ...

A Study of Hypotension (Shock) Produced by Meningococcus Toxin
RICHARD V. EBERT, CRAIG W. BORDEN, WENDELL H. HALL and DAVID GOLD
Circ Res. 1955;3:378-384
doi: 10.1161/01.RES.3.4.378
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A Study of Hypotension ^Shock) Produced by
Meningococcus Toxin
By RICHARD V. EBERT, M.D., CRAIG W. BORDEN, M.D., WENDELL H. HALL, M.D. AND
DAVID GOLD, M.D.
Hemoclynamic alterations were produced in dogs by injecting meningococcus toxin. Hypotension
and u decrease in cardiac output occurred without significant reduction in blood volume. These
changes were accentuated by small hemorrhage. Increasing the blood volume above normal led to
marked increase in cardiac output with slight increase in arterial pressure. The arterial pressure was
markedly increased by the administration of levarterenol but large doses were required. Cortisone
did not modify the effect of meningococcus toxin on the circulation. Meningococcus toxin apparently
produced its effect by increasing the volume of blood in small blood vessels.
A ACUTE
circulatory disturbance
characterized by hypotension and,
at times, by a clinical picture resembling
traumatic shock is observed in
patients with serious acute infections. It is
most frequently seen in association with
bacteremia. A number of instances of the
syndrome have been observed following the
accidental introduction of large numbers of
bacteria into the blood stream through the
administration of contaminated blood. 121
The circulatory failure associated with
acute infection appears to differ from traumatic
shock in that it is not initiated by a diminution
in blood volume.' 4 Relatively little is known of
the hemodynamics of this type of circulatory
failure because of the difficulty in studying
these extremely ill patients.
A knowledge of the effect of bacteria on the
circulation of the experimental animal should
aid in the understanding of this problem.
Relatively few studies of this type are available.
It was found that severe hypotension
could be produced in the dog by the intravenous
injection of meningococcus toxin. A study of
the hemodynamics of this circulatory disturbance
was carried out.
METHODS
Mongrel clogs weighing from 6 to 12 Kg. were
used. Local anesthesia was used in all experiments.
From the Variety Club Heart Hospital, Minneapolis,
the Surgical Research Laboratory, Ancker
HoHpital, St. Paul, and the Department of Medicine
of the University of Minnesota.
Received for publication April 4, 1955.
378
General anesthesia was avoided because of lack of
knowledge of the influence of anesthesia on the effect
of the bacterial toxin. The measurements prior to
administration of toxin may have been modified by
the restlessness of the animals. After production of
circulatory failure by the toxin the animals were
stuporous or comatose.
The cardiac output was measured by the dye
method of Moore and associates. 6 Plasma volume
was measured by the T-1S24 dye method. 1 Pressures
in various portions of the circulatory system and the
intrapleural pressure were measured by the use of a
strain gauge and direct writing Sanborn Poly-Viso.
Arterial mean pressure was measured in the carotid
artery. Right atrial, pulmonary arterial and left
atrial pressures were measured by standard catheterization
procedures.
Meningococcus toxin was prepared by a modification
of the method of Thomas and Good. 7 Adequate
potency of the toxin was assured by inoculating
eight large slants of Mueller-Hinton agar medium
with meningococci. After 24 hours at 37 C. the
growth was harvested with a small amount of 0.S5
per cent saline. The suspension was inoculated into
a Kolle flask containing Mueller-Hinton agar medium
with 0.7 per cent glucose. Incubation was
then carried out at 37 C. for4S hours in 10 per cent
carbon dioxide. The growth was harvested with 10
ml. of 0.85 per cent saline. The suspension was centrifugal
at 4000 R.P.M. for 45 minutes. The supernatant
fluid was aspirated and tested for sterility.
This material was used for the experimental studies.
The toxin was stored at 10 C. and used within 4S
hours.
The undiluted toxin was injected intravenously
or into the right atrium. The amount used varied
from 0.4 to 2.0 ml. per Kg. Most animals received
1 ml. per Kg. A large inoculum of meningococci was
of critical importance. Results of preliminary tests
of the toxin in rabbits often failed to agree with the
results in dogs.
At the conclusion of the experiment the dogs were
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Circulation Reirard, Vriume III, Jtili IBSi

examined at autopsy. Small visceral hemorrhages
were noted in most instances. The most frequent
location was in the endocardium and lungs. The adrenals
exhibited small, never massive, hemorrhages
in about one-half of the animals studied.
RESULTS
Following intravenous injection of meningococcus
toxin into the dogs there was a gradual
fall in arterial pressure. The maximum decline
in pressure usually occurred 45 minutes to
one hour after injection. The animals became
stuporous. Vomiting and diarrhea were often
present. The effect of early lots of toxin was
variable in spite of efforts to insure a uniform
preparation. Certain lots produced little effect
on the arterial pressure whereas other lots
in identical volumes produced severe hypotension.
In evaluating the effect of the toxin on the
arterial pressure, cardiac output, blood volume
and right atrial pressure, it was arbitrarily
decided to select for analysis the results in 15
animals in which the arterial pressure fell
below 80 mm. Hg.
The results given in Table 1 show that the
decline of mean arterial pressure found in
every experiment was accompanied by a
reduction in cardiac output in all except two
instances (dogs 3, 6). Since the heart rate
Dog
1
2
3
4
6
7
9
10
12
13
14
15
16
20
22
Weight
9.5
6.4
7.7
7.0
9.5
10.0
8.6
S.4
9.1
10.9
12.7
12.7
9.1
17.0
S.2
Mean
Arterial
Pressure
mm. Hg
Before
176
182
124
156
130
145
124
130
128
143
136
117
117
133
143
After
76
73
78
53
74
64
63
42
75
55
52
65
55
78
78
EBERT, BORDEN, HALL AND GOLD 379
TABLE 1.—Effect of Meningococcus Toxin on the Circulation
Cardiac Output
L./Kg./mm.
Before
.143
.190
.176
.306
.248
.206
.326
.274
.238
.226
.12S
.145
.147
.164
.204
After
.116
.128
.187
.144
.315
.077
.107
.063
.105
.080
.035
.057
.045
.094
.128
Total Peripheral
Resistance
dynes/seconds/
cm "*
Before
10270
11921
72S6
5794
4409
5621
3530
4502
4715
4649
6673
5062
0980
9244
6846
After
5461
7113
4329
41%
1971
6647
5475
6287
6260
504S
9231
7113
10723
9444
5874
Right Atrial
Pressure
mm. Hg
Before
0
-0.5
-2.6
0
+0.5
+2.0
+2.6
-1.3
0
+0.6
—
+ 1.6
-0.6
-1.9
-1.0
increased in all but two animals, the stroke
volumes were obviously reduced. Since right
atrial pressure in all but two animals, and
effective right atrial pressure measured in five
dogs, decreased, the reductions in cardiac
output and stroke volumes were obviously
associated with reduction in venous return,
as is the case in oligemic shock. This deduction
is confirmed by the reduction of pulmonary
arterial pressure measured in ten animals and
of left atrial pressure recorded in eight animals.
The data on plasma volume and hematocrit
readings indicate that total blood volume
calculated therefrom increased in eight and
decreased slightly in seven experiments, but the
variations were not significant. In other words,
the acute reduction in mean arterial pressure
appears to be caused by acute reduction of
cardiac output without reduction in blood
volume.
Calculations of total peripheral resistance
(T.P.R.) presented in table 1 show a definite
reduction in four experiments (dogs 1, 2, 3, G),
a significant increase in seven (dogs 7, 9, 10,
12, 14, 15, 16), and doubtfully directed changes
in the four remaining dogs. While induction of
peripheral arteriolar dilation may thus have
contributed to the hypotension in a few animals,
it was certainly not the main causative
After
-0.2
-1.5
-1.3
-2.0
-2.5
-0.5
-2.6
-0.2
0
-2.6
—
-0.6
-4.0
-2.1
-3.8
Left Atrial
Pressure
mm. Hg
Before
—
—
—
—
+ 11.0
+5.2
—
+ 1.6
+5.2
+5.1
—
+5.S
+5.3
—
After
—
—
—
—
+S.0
+2.6
—
0
0
+4.3
—
+2.2
+3.1
—
Mean
Pulmonary
Artery
Pressure
mm. Hg
Before
17
13
22
12
19
15
17
—
13
17
17
—
—
—
—
After
15
9
13
11
13
10
13
—
7
S
14
—
—
—
—
Plasma
Volume
ml.
Before
379
301
545
353
507
521
540
3SS
459
469
460
3S0
—
460
—
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After
426
414
563
467
459
459
602
438
529
420
360
360
—
500
—
Hematocrit
Reading
Before
47.0
46.7
19.2
47.0
39.0
54.5
41.0
42.8
50.5
4S.4
47.0
49.0
56.0
50.0
53.0
After
4S.0
40.3
16.3
42.3
39.2
59.0
3S.0
42.8
52.0
49. S
55.0
48.0
62.0
4S.5
59.0

380 SHOCK DUE TO BACTERIAL TOXIN
TABLE 2.—Effect of Hemonhage (10 ml. per Kg.) on
Hypotension Produced by Meningococciis Toxin
DOE
5
6
S
12
Cardiac Output
L./Kg./Min.
Before
.716
.315
.134
.105
After
.060
.077
.065
.071
Total Periphera
Mean Arterial Resistance
Pressure mm. Hg dynes/seconds/
cm." 1
Before
97
74
S6
75
After
56
55
4S
50
Before
7594
1971
4916
6260
After
S623
5957
5658
6595
.factor for the hypotension induced by the
toxin.
The effect of reduction of blood volume on
the hypotension produced by toxin was
studied. Four animals were given toxin intravenously.
After the maximum decline in
arterial pressure had occurred, blood in the
amount of one per cent of the body weight
was removed. The observations were repeated
ten minutes later (table 2). The further decline
in arterial pressure was principally associated
with a marked further reduction in cardiac
output in all four animals consequent to
further impairment of venous return by the
hemorrhage. Calculation of the T.P.R., which
showed a marked increase in one experiment
(dog 6), and probably insignificant increases
in the three others, supports this contention.
A hemorrhage of this magnitude in the normal
animal would have relatively little permanent
•effect on cardiac output and arterial pressure.
Inasmuch as the hypotension and reduction
in cardiac output following the administration
of toxin was accompanied by a reduction in
Don
1
2
4
6
7
10
13
15
16
22
systemic and pulmonary venous pressure, an
experiment was performed to determine the
effect of increasing the blood volume on the
circulation. Hypervolemia was produced by
the intravenous infusion of 6 per cent dextran
in 0.85 per cent saline. Toxin was first administered
to the animals. When a maximum
decline in arterial pressure had occurred,
dextran solution in the amount of 30 ml. per
Kg. was administered. Observations were
made immediately before and after the infusion
of dextran. The results on 10 animals
are given in table 3. The right atrial pressure
and the cardiac output increased after dextran
infusion to above the control level, while the
increase in arterial pressure was of a lesser
degree. This was apprently due to the fact
that there was a marked decline in total
peripheral resistance after administration of
dextran in the majority of experiments.
The effect of levarterenol on the arterial
pressure and cardiac output was studied in
eight animals. Observations on the effect of
levarterenol prior to the administration of
toxin revealed that a moderate pressor response
was produced by infusion at the rate of 20
tig. per min. A marked pressor response was
produced by infusion at the rate of 40 ^g- per
min. Following administration of toxin and
development of hypotension, a larger quantity
of levarterenol was required to produce a
pressor response in some of the animals. The
course of a typical experiment is shown in
figure 1. The amount of levarterenol required
to produce a rise in arterial pressure of 20
TABLE 3.—Effect of Dextran (SO ml. per Kg.) on Hypotension Produced by Meningococciis Toxin
Mean Arterial Pressure
mm. Hg
Before
76
73
53
74
64
42
55
65
55
78
After
129
130
102
S2
6S
63
125
104
91
107
Right Atr al Pressure
mm Hg
Before
-0.2
-1.5
-2.0
-2.5
-0.5
-0.2
-2.6
-0.6
-4.0
-3.S
After
+0.5
+ 14.3
+2.0
+0.2
0
0
-0.2
+0.5
+0.5
+0.7
Before
.116
.128
.144
.315
.077
.063
.OSO
.057
.045
.128
Cardiac output
L./Kg /min.
After
.218
.410
.318
.274
.103
.200
.280
.322
.364
.305
Total Peripheral Resistance
dynes/ seconds/cm."*
Before
5475
7113
4196
1971
6647
6274
504S
7113
10723
5874
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After
4955
3969
3650
2504
5275
2997
3290
2025
21S5
3423

Arterial
Pratsure
Heart Rate
per rain.
Cardiac Output
l./mln.
tAQ
iao
&o
too
too
4
Atrial Pressure 4
mm. Hq
t -
ml.
Procedure
Tirao minutei
.1
: I •
||
|
: • t t
ft'
III
EBERT, BORDEN, HALL AND GOLD 381
I
•
Mil
Illl
. 1
• •
|
t t to
1
s.
s
FIG. 1. Graphic representation of the course of a
typical experiment (dog No. 15) showing response of
the mean arterial pressure, heart rate, cardiac output,
effective right atriul pressure and blood volume
to injoctions of meningococcus toxin, levarterenol
and doxtrun.
mm. Hg or more was 20 ng. per min. in two
animals, 40 jug- per min. in two animals, 80
fig. per min. in two animals and 320 fig. per
min. in two animals. The average increase in
arterial pressure in these 8 animals was 38
mm. Hg. The average increase in cardiac
output was 29.5 ml./min./Kg. The cardiac
output increased in six of the eight animals.
The increase was statistically significant for
the group (p < .02).
Because of the relationship of the adrenal
cortex to the integrity of the vascular system,
the effect of cortisone on the response of the
circulation to meningococcus toxin was studied.
The animals were given cortisone acetate
10 mg. per Kg. intramuscularly. One half of
the total dose was given 12 hours prior to the
administration of the toxin and the remainder
one-half hour before injection of the toxin.
Because of the variation in potency of various
lots of toxin, 7 pail's of animals were studied.
These received the same dose of the same lot
of toxin on the same day. The results are
given in table 4. The average mean arterial
pressure was 184 mm. Hg in the cortisonetreated
animals prior to the administration of
toxin. This was significantly higher than the
average pressure in the control group of 142
mm. Hg (p < .05). The average cardiac
output was also slightly higher in the cortisonetreated
animals but this was not statistically
significant. The values were .253 L. per Kg.
per minute for the cortisone group and .223
L. per Kg. per minute for the controls. Following
administration of toxin, the arterial pressure
fell in all animals and was lower in 4 of
the cortisone-treated dogs than in their untreated
controls (pairs 1, 4, 5, 7). Although
the percentage decrease in cardiac output in
the cortisone-treated dogs was less than in
the untreated controls with two exceptions
(pairs 1 and 4), this was not significant. The
average mean arterial pressure for the cortisone-treated
group of dogs after the administration
of toxin was 85 mm. Hg and for the
control group it was 81 mm. Hg. Corresponding
average values for cardiac output were
.111 L. per Kg. per minute and .103 L. per
Kg. per minute respectively. It is evident that
cortisone therapy did not protect the animals
from the hypotensive effect of toxin. This is
TABLE 4.—Effect of Previous Administration of
Cortisone on Arterial Pressure and Cardiac Output
Following Administration of Meningococcus Toxin.
Pair 1*
No cortisone
Cortisone
Pair 2
No cortisone
Cortisone
Pair 3
No cortisone
Cortisone
Pair 4
No cortisone
Cortisone
Pair 5
No cortisone
Cortisone
Pair 6
No cortisone
Cortisone
Pair 7
No cortisone
Cortisone
Mean Arterial
Pressure mm. HR
Before After
121
165
133
163
143
166
143
175
163
156
146
20S
149
234
101
69
7S
104
7S
106
91
75
S5
67
54
97
S3
79
Cardiac Output
L./Kd./min.
Before
.164
.570
.164
.250
.204
.232
.220
.20S
.275
.133
.218
.265
.320
.125
After
.195
.052
.094
.177
.128
.140
.084
.066
.112
.06S
.062
.1S3
.047
.094
* Paired animals received the same lot of toxin
and the same dose of toxin per Kg. on the same day.
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382 SHOCK DUE TO BACTERIAL TOXIN
of interest because of the relationship of
acute circulatory failure in meningococcemia
in human beings to massive adrenal hemorrhage.
The combination of meningococcemia,
shock and adrenal hemorrhage has been
called the Waterhouse-Friderichsen syndrome.
It has been postulated that the circulatory
failure is caused by adrenal insufficiency.
This has been denied by other authors 8 who
have pointed out that acute circulatory failure
occurs in the absence of massive adrenal hemorrhage.
In these animals massive adrenal
hemorrhages were not seen. The ineffectiveness
of cortisone would suggest that adrenal insufficiency
was not playing an important role
in the production of circulatory failure following
the administration of meningococcus toxin.
DISCUSSIOX
The hemodynamic effects of meningococcus
toxin can best be explained by an increase in
volume of blood in peripheral vessels. The
resulting diminution in venous return would
account for the fall in right atrial and pulmonary
vascular pressures and the decrease
in cardiac output in the presence of a normal
total blood volume. This mechanism appears
to be the basic factor incuding hypotension
following administration of toxin. The critical
effect of changes in blood volume is also
compatible with this hypothesis. Diminution
in blood volume by a small hemorrhage caused
further decline in cardiac output and arterial
pressure. Increase of blood volume above
normal by dextran infusion raised the right
atrial pressure to normal or increased levels,
and led to a marked increase in cardiac output.
The arterial pressure also increased but to a
lesser extent.
Lack of conclusive directional change or
actual increase of the calculated T.P.R. following
administration of toxin suggests that there
was little change in resistance to flow at the
level of the arterioles. This is based on the
assumption that the arterioles contribute the
majority of the resistance reflected by the
calculated T.P.R. As emphasized by Green
and co-workers, 8 interpretations of changes in
vascular tonus based upon calculations of
T.P.R. should be made cautiously. Alterations
of cell plasma ratio and of blood flow will
influence the effective viscosity of the blood.
Changes in intravascular pressures will produce
passive changes in the size of the vessels.
It appears unlikely that the contribution of
these factors to the observed changes is of
sufficient importance to alter the main implications
of the data.
The basic mechanisms bj r which meningococcus
toxin produces its effect on the circulation
is unknown. Two possibilities may be
considered. The toxin may alter the elastic
properties of small vessels permitting them to
distend more completely at a given pressure.
This effect could be mediated through direct
damage to vascular endothelium or musculature
or indirectly through humoral, metabolic,
or nervous mechanisms. A second, and more
remote, possibility is that the toxin has no
effect on the elastic properties of small vessels
but induces active venoconstriction with subsequent
rise of pressure and distention of
distal small vessels. In regard to the above
possibilities, the following observations are of
interest. Bacterial toxins have been observed
to produce hemorrhage and necrosis in
tumors. 10 Direct observations of the effect
of the polysaccharide derived from Serralia
marcescens on tumor tissue and normal muscle
have been made. 11 Slowing of the arterial and
venous circulation with capillary stasis
occurred. Meningococcus toxin as well as
products from other bacteria produce the
Shwartzman phenomenon. Thomas 7 has observed
cortical necrosis of the kidneys of
rabbits following repeated injection of
meningococcus toxin. These observations suggest
a profound effect of bacterial toxins on
the small vessels.
The effect of meningococcus toxin on the
circulation is similar to the effect of the toxin
of Clostridium oedematiens. In the experiments
of Aub, Zamecnik and Nathanson a marked
fall in arterial pressure and cardiac output
followed the injection of the toxin of Clostridium
oedemalien8. n There was only a slight
decrease in blood volume. Increase in blood
volume by transfusion with blood or albumin
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led to an immediate rise in arterial pressure
and cardiac output. The right atrial pressure
remained low. In the heart-lung preparation
the toxin produced pulmonary edema, but the
effect on cardiac function was minimal."
The heart was capable of increased work at a
time when the pulmonary circulation was
greatly impaired.
The hemodynamic changes produced by
bacterial toxins also resemble those described
in irreversible hemorrhagic shock. Following
severe hemorrhage and prolonged hypotension
in dogs, reinfusion of blood restores the blood
volume to normal. The arterial pressure and
cardiac output rise initially but later decline
to low levels. Wiggers H reviewed the experimental
evidence on this type of shock and
concluded that stagnation and pooling of
blood in minute vessels are dominantly concerned
in reducing venous return. Fine and
his co-workers 16 • 16 ' 17 have recently shown that
the dog in hemorrhagic shock loses its normal
ability to destroy bacteria. They demonstrated
that during hemorrhagic shock a bacterial
factor develops in the dog's tissues and is
responsible for the irreversibility to transfusion.
A marked reduction in the incidence of irreversible
shock was achieved by treatment of
the dogs with antibiotics prior to hemorrhage,
provided the bacterial flora of the animals
had not become resistant to the antibiotic
used.
SUMMARY AND CONCLUSIONS
Meningococcus toxin was administered to
unanesthetized dogs. Hypotension and a decrease
in cardiac output were produced. The
blood volume did not decrease significantly.
Right and left atrial pressures and pulmonary
arterial pressure decreased.
A small hemorrhage following administration
of toxin produced a further decline in
arterial pressure and cardiac output. Increase
in blood volume produced by administration
of dextran solution led to a marked increase
in cardiac output. The arterial pressure increased
but to a lesser degree.
Levarterenol increased arterial pressure in
animals made hypotensive by toxin, A com-
EBERT, BORDEN, HALL AND GOLD 383
parison was made of the amount of levarterenol
required to produce a given rise in
arterial pressure before and after the administration
of toxin. In the majority of instances a
larger dose was required after the administration
of toxin.
The administration of cortisone did not
modify the effect of meningococcus toxin on
the circulation.
The observations made in this study are
compatible with the hypothesis that meningococcus
toxin produces its effect on the circulation
by increasing the volume of blood in
small blood vessels.
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reactions from massive bacterial contamination
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•BRAUDE, A. I., WILLIAMS, D., SIEMIENSKT, J. AND
MURPHY, R.: Shock-like state due to transfusion
of blood contaminated with gram-negative bacilli.
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arterenol. Arch. Int. Med. 92: 75, 1953.
1 STEVENS, A. R., JR., LEGO, J. S., HENRY, B. S.,
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6 MOORE, J. W., KINSMAN, J. M., HAMILTON, W. F.
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'GIBSON, J. G., JR. AND EVELYN, K. A.: Clinical
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concerning the phenomenon. J.
Rxper. Med. 96: 605, 1952.
•KINSMAN, J. M., D'ALONZO, C. A. AND RUSSI, S.:
Fulminating meningococci septicemia associated
with adrenal lesions; analysis and discussion of
7 cases. Arch. Int. Med. 78: 139, 1946.
9 GREEN, H. D., LEWIS, R. N., NICKERSON, N. D.
AND HELLER, A. L.: Blood flow, peripheral resistance
and v;iscular tonus with observations
on the relationship between blood flow and cutaneous
temperature. Am. J. Physiol. 141: 518,
1944.
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384 SHOCK DUE TO BACTERIAL TOXIN
10 ZAHL, P. A., HUTNER, S. H., SPITZ, S., SUGIURA,
K. AND COOPER, F. S.: The action of bacterial
toxin on tumors. I. Relationship of the tuniorhemorrhagic
agent to the endotoxin antigens of
gram-negative bacteria. Am. J. Hyg. 36: 224,
1942.
11 ALGIRE, G. H., LKQALLAIS, F. Y. AND PARK, H. D.:
Vascular reactions of normal and malignant tissues
in vivo. II. The vascular reaction of normal
and neoplastic tissues of mice to a bacterial
polysaccharide from Serratia marcescens (Bacillus
prodigiosus) culture filtrates. J. Nat.
Cancer Inst. 8: 53, 1947.
U AUB, J. C, ZAMECNIK, P. C. AND NATHANSON,
I. T.: Phj-siologie action of Clostridium oedematiens
(novyl) toxin in dogs. J. Clin. Invest.
26: 404, 1947.
"KRAYER, 0., AUB, J. C, NATHANSON, I. T. AND
ZAMECNIK, P. C: Influence of antitoxin upon
action of Clostridium oedematiens toxin in
heart-lung preparation of dog. J. Clin. Invest. 26:
411, 1947.
" WIGGERS, C. J.: Physiology of Shock. New York
The Commonwealth Fund, 1950.
16 FRANK, H. A., JACOB, S. W., SCHWEINBURG, F. B.,
GODDARD, J. AND FINE, J.: Traumatic shock.
XXI. Effectiveness of an antibiotic in experimental
hemorrhagic shock. Am. J. Physiol. 168:
430, 1952.
lb JACOB, S., WEIZEL, H., GORDON, E., KORMAN, H.,
SCHWEINBURG, F., FRANK, H. AND FINE, J.:
Bacterial action in development of irreversibility
to transfusion in hemorrhagic shock in the
dog. Am. J. Physiol. 179: 523, 1954.
17 SCHWEINBURG, F. B., FRANK, H. A. AND FINE, J.:
Bacterial factor in experimental hemorrhagic
shock. Evidence for development of a bacterial
factor which accounts for irreversibility to transfusion
and for the loss of the normal capacity
to destroy bacteria. Am. J. Physiol. 179: 532,
1954.
Hemorrhagic Hypotension and Hepatic
Blood Flow
It appears to have been demonstrated in dogs that hepatic vascular resistance
increases during hemorrhagic hypotension and shock. Since the hepatic circulation in
this animal differs from that of man and most mammals in the enormous muscular
development in the hepatic vein, studies of hepatic flow have also been carried out on
rats, a species that resembles man as regards anatomy of the hepatic vein. Recently an
indirect method for estimating changes in regional flow has been used. It consists in
essence of determining the electric current required to maintain a + 1C thermal
equilibrium in a heater embedded in the liver (Grayson J. Physiol. US: 54, 1952).
Using this technic, it has been found that sudden reduction of arterial pressure
causes a transient reflex hepatic constriction initiated by the baroceptor mechanism
and mediated by adrenergic fibers in the hepatic nerves. However, without further
decline of arterial pressure, hepatic blood flow continues to diminish progressively.
This steady decline is not affected by nerve section or administration of agents blocking
impulses at ganglia or nerve terminals, hence is not of neurogenic origin. Anoxia
and mechanical closure of small vessels are both suggested as possible causes.
Since hepatic resistance is reduced again after reinfusion of drown blood, the progressive
decline of arterial pressure leading to death (normovolemic shock) does not
appear to be related to continued impairment of hepatic flow.
After Johnson, D. H.: J. I'hysiol. 126: 413, 19.S4.
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