Life Sciantes Vol . 17, pp . 1855-1860 Printed in the U .S .A .
Pergamon Press
METABOLIC CHANGES IN DOGS DURING ANAPHYLACTIC SHOCK John J. Spitzer Department of Physiology, Louisiana State University Medical Center New Orleans, Louisiana 70112 (Received in final form November 17, 1975) SUMMARY Hemodynamic and metabolic parameters were studied in conscious dogs during anaphylactic shock. Mean arterial blood pressure and cardiac output decreased and heart rate increased during shock . FFA flux and 02 consumption decreased significantly shortly after the challenging injection. RQ was elevated indicating a shift in metabolite utilization towards carbohydrates . Although changes in substrate metabolism have been investigated during experimentally produced hemorrhagic (1) and endotoxic (2) shock, similar information is lacking during anaphylactic shock. The aim of the present investigation was to produce anaphylactic shock in the conscious dog and to study the effect of shock on some selected hemodynamic and metabolic variables . Materials and Methods Seven mongrel dogs weighing 24 .3 t 1 .9 kg were used in these studies . The animals were sensitized simultaneously with 5 ml of horse serum intravenously and a mixture of 5 ml of horse serum plus 1 ml of Freund's adjuvant subcutaneously (3) . Approximately two to three weeks later the dogs were deprived of food for 16 hrs, and under local anesthesia (2$ epinephrine-free procaine) a femoral artery was cannulated for measuring blood pressure and sampling of arterial blood . A catheter was also advanced into the pulmonary artery via the femoral vein . Mean arterial blood pressure, heart rate, pH and hematocrit were monitored from the femoral artery . Cardiac output was measured by the dye dilution method (4) . An infusion of albumin bound 1- ia -C palmitic acid was started at least 90 minutes prior to the first control blood sample and was continued throughout the experiment . Following the removal of control blood samples (arterial and mixed venous samples, taken simultaneously), 5 ml of horse serum was injected intravenously . Additional pairs of blood samples were taken approximately 15, With 30, 90 and 140 minutes following the challenging dose of horse serum . No antieach pair of blood samples, cardiac output was also estimated . coagulant was used in the animals . Each blood sample was anticoaqulated _in vitro with heparin and kept and handled in the cold . FFA, la C-FFA, lactate, glucose, oxygen, C02 , and 14 C02 were estimated as described previously (2) . 1855
Metabolic Changes in Anaphylactic Shock
1856
data :
Vol . 17, No . 12
The following calcualtions were performed utilizing the experimental 1.
FFA flux
(5), or total body FFA turnover (u mole/min) _
rate of palmitate- 14 C infusion (cpm/min ) arterial FFA specific activity (cpm/u mole) 2.
Total body Oz consomption (u mole/min) _ [OZa - OZv cardiac output
(u mole/ml)] x
(ml/min)
Subscripts "a" and "v" represent arterial and venous blood . significance was determined using the Student paired t test .
Statistical
Results The hemodynamic changes during anaphylactic shock in the conscious dog are shown in Table 1. The mean arterial blood pressure decreased following the challenging injection . This decrease was especially significant in the first half hour . Heart rate increased and remained . elevated throughout the experiment . Cardiac output was markedly depressed for more than an hour and a half following the challenging dose . The fluctuation in arterial hematocrit was not statistically significant . Arterial pH decreased significantly in the early part of the experiment and returned to control later on . The changes of arterial metabolite concentrations are shown in Table 2 . Arterial :FA glucose and lactate concentrations did not change significantly . Arterial lactate. .]_ncreased markedly and remained elevated throughout the experiment . However, the degree of increase at 140 min following albumin injection was greatly variable from one animal to the other . Changes in FFA flux, oxygen consumption, and respiratory quotient are shown in Table 3. FFA turnover decreased significantly shortly after the challenge and returned to normal and in many cases was elevated above control levels later on in the experiment . Oxygen consumption decreased significantly in the early part of the experiment and returned toward control values subsequently . The respiratory quotient increased significantly through 90 minutes of the observation period and was still elevated 140 min later in three out of four experiments . Discussion In recent years attention has been focused to the metabolic alterations accompanying various forms of shock . Thus it was found that hemorrhagic hypotension in conscious dogs produced quite marked alterations of substrate utilization, characterized by increased arterial FFA concentration, increased FFn flux with a decreased oxygen consumption and an increase in carbohydrate metabolism by the body as indicated by an elevated RQ (6, 7) . Anaphylactic shock in the dog is a relatively short lasting condition which exhibits a much milder form of circulatory disturbance than some other types of experimentally produced shock . The current studies indicate that during anaphylaxis very little change in arterial FFA concentration occurs but the FFA flux is significantly decreased . Oxygen consumption of the animal is decreased and RQ ie increased. Thus, comparing anaphylactic shock and hemorrhagic hypotension in the conscious dog, one notices a number of similarities (and also differences) both in the area of metabolic changes and also hemodynamica (increased heart
Vol . 17, No . 12
1857
Metabolic Changae in Anaphylactic Shock
rl ., v ~ W z ~, o -r-I ~o
z
s mrn
r r-i ~N 1 +I
Nc'1 r-i r rr-I + +i
m~o 0o 00+I 1
m ~n
o rl ~-I O
ino
Orl + +i
o~r 00 00+i 1
W
a - a a+ o ~C ~ô
~xzII
W .-I o z
xO O
N U " .i ++U ro
r-I
H
~Q
x
mU
o ~o rm rl +1 I
rrl + +1 o ~o
r v 00
00 I +~
rl ~o V~N+i +
m ~n
rr rl o
fyl
m
~n o~ m
1
+i
O O
ro 01N
rIN f+1O rO
00 1 +I
c~
z_ r M3x .. NO a a
Uo~ N
0
i'~z
~N ~f1N 1f11 r-I +I
r~o Nr
orl rl o
vi rl N rl ~1
m ~o
v rl ar O
+I
+ +~
O I +I
O~
O~ ~ü
0o NM " "
~ r-1 + ü
10 O~
OO I ü
~ m
r-I r-I + +I
OO 1 ?1
N
OO
b+ O
q " rl "H N
 UÓ m
N N b+,s~ qH ro
.C O U I-I
o
a b ar x
a H zz o u --
O .~
N+1 rl
ri
OO
f+1
0 0 a
x
~w ro ~ N m d Cl +~ H
ta â --
°~ a~a
--
N +~
++ O O ro
ó
w
v
ro
a~a a
a
x
~
O O a I
N
+I " rl f-I
~
w m a ro â
Metabolic Changes in Anaphylactic Shock
1858
~Iw
In 10 ao~ rl N
M
~O
e! V~
M
r
Vol . 17, No . 12
M o0 M
01 O
00
NN + +i
Mrl I +I
O~
M ~O
O r-I
r 10 r-I 10
MN 1 N ü
r r1
W .-I
ri
z C9 " z
I
+i
aor
OO
++~
w a
- a_
O ~ ~O II Ixz o ~o z
mU
x q
U-
M II 13 z v N pv
ro S-I
a
a~ U
a 0
a0
N
z_
O~ H r
O " rl
" .i 01 r-I OO A " ~I
N
sr lD
0o 1 +i
MM M r-I + +I
~(1 M 00 + +I
O rl 0o
Mv ul r rl M vi~
MM 1 rl ü
o+ao
10 ri 01 O
rN 01 O~
+ +I
MM OO
~o r
in v r rl ON
Mv rl +I
rao ~O N I +i
00 1 +1
+ +1
er ~
00 1 ++
I +1
NO + +~
+ rol m
E
~ r-I
Ó U
ro~ " rl ,l~ f-I N
a~ +~
a
M
q 1-i
a O -~ r
H
zz o -U
rl M O~ rl O" O" +i
r-I
rl O" +I
~n v
rl M 00 O +I
Ol b~ O ro
U
0
0v
a w
w~ ro~ ".i N f-i
r-I
U
â~
"ro~ ~I N fa ri
v Ú ~~
roo o " .~
N r-I
ó~
m~ " ~I N
vi
G1
r-I
â~
rov
q
Vol . 17, No . 12
Metabolic Changea in Anaphylactic Shock
~o
â
I r~ n z M~~ r-I z
0o N 10
+ +1
r~r~ OO
rrn
N V~ O O OO
.-1 V~ NO OO
ui ~o
00 I ++
OO
ó0 + +,
W
-O~
a
a_ OA~,10 W ri ~ II Ixz C7 ~o mU
z
z
U-
a
~+
n
13z
b
N~v
a a
a o âó ~ca
ââ 0 0
U " .i U
óó + +i
I
++
++~
0
x a
O 01 N f+1 NN
- °
~w~
N
z
r o ~ ~o
ON
0o OO
ao v rl o
o~r rao
a~o ~o
Na, No
0 o + +1
No
0o I +i
I +i
00 I ++
OO + +i
00 ++a
O ~ O U N wE
~a ww H H W Gl a ro x U
ao -. pd r E II zz ~ `r U
a~ o ~orl ~D rl 00
ri ~o vo 00 +i
o ~
ro 00 ++
0 O v a ~i 0 0 v a
â .~ a~ w~ w } w --
óx ++ . aa a a~ o~ U ~ N 7. o --
w v~ O x
q ro
1859
1860
Metabolic Changes in Anaphylactic Shock
Vol . 17, No . 12
rate, decreased cardiac output) . The major change in metabolism appears to be an elevated RQ indicating increased reliance by the body on carbohydrate metabolism . The changes in FFA flux in the present study were similar to those found by Paul, et al (B) . It is of interest to point out that conscious dogs subjected to anaphylactic shock behave similarly to anesthetized ones in showing a decreased cardiac output, decreased FFA flux, and increased lactate concentration (9) . The major hemodynamic difference between the two groups of animals is shown in changes of heart rate . The latter variable increases during anaphylactic shock in the conscious dogs while it decreases 1n the anesthetized animals . In conclusion, our studies indicate that the metabolic alterations that characterize anaphylactic shock in the conscious state consist of a shift in metabolism towards an increased utilization of carbohydrates and a decreased turnover of FFA. Acknowledgement These studies were supported by Grant HL 16850 from the National Institutes of Health . References 1.
J. J . Spitzer and J . A. Spitzer, Am . J . Physiol . 222
101 (1972) .
2.
J . J . Spitzer, A. A. Bechtel, L . T . Archer, M. R. Black, and L . B. Hinshaw, Am . J. Ph~iol . 227 132 (1974) .
3.
N. Back, H . Wilkins, and R. Steqer, An . of N. Y . Aced . Sc . 146
4.
J. M. Kinsman, J. W . Moore, and W. F . Hamilton, Am . J. Physiol . 89 (1929) .
5.
D. T . Armstrong, R. Steele, N. Altszuler, A . Dune, J . S. Bishop, and R . C . DeBodo, Am . J . Phys iol . 201 9 (1961) .
6.
R. ::iener and J . J. Spitzer, Am . J . Physiol . 227
7.
J. J . Spitzer, R. Wiener, and E. H . Wolf, in Neuroh injury, (P . 221) Plenum Press, New York (1973) .
8.
P. Paul and W. L. Holmes, Lipid s 8
9.
J . J . Spitzer, Proc . Soc. Exper . Biol . Med . 15 1 in press (1976) .
491 (1968) .
5 (1975) . oral Aspects of
142 (1973) .
322
Pergamon Press
METABOLIC CHANGES IN DOGS DURING ANAPHYLACTIC SHOCK John J. Spitzer Department of Physiology, Louisiana State University Medical Center New Orleans, Louisiana 70112 (Received in final form November 17, 1975) SUMMARY Hemodynamic and metabolic parameters were studied in conscious dogs during anaphylactic shock. Mean arterial blood pressure and cardiac output decreased and heart rate increased during shock . FFA flux and 02 consumption decreased significantly shortly after the challenging injection. RQ was elevated indicating a shift in metabolite utilization towards carbohydrates . Although changes in substrate metabolism have been investigated during experimentally produced hemorrhagic (1) and endotoxic (2) shock, similar information is lacking during anaphylactic shock. The aim of the present investigation was to produce anaphylactic shock in the conscious dog and to study the effect of shock on some selected hemodynamic and metabolic variables . Materials and Methods Seven mongrel dogs weighing 24 .3 t 1 .9 kg were used in these studies . The animals were sensitized simultaneously with 5 ml of horse serum intravenously and a mixture of 5 ml of horse serum plus 1 ml of Freund's adjuvant subcutaneously (3) . Approximately two to three weeks later the dogs were deprived of food for 16 hrs, and under local anesthesia (2$ epinephrine-free procaine) a femoral artery was cannulated for measuring blood pressure and sampling of arterial blood . A catheter was also advanced into the pulmonary artery via the femoral vein . Mean arterial blood pressure, heart rate, pH and hematocrit were monitored from the femoral artery . Cardiac output was measured by the dye dilution method (4) . An infusion of albumin bound 1- ia -C palmitic acid was started at least 90 minutes prior to the first control blood sample and was continued throughout the experiment . Following the removal of control blood samples (arterial and mixed venous samples, taken simultaneously), 5 ml of horse serum was injected intravenously . Additional pairs of blood samples were taken approximately 15, With 30, 90 and 140 minutes following the challenging dose of horse serum . No antieach pair of blood samples, cardiac output was also estimated . coagulant was used in the animals . Each blood sample was anticoaqulated _in vitro with heparin and kept and handled in the cold . FFA, la C-FFA, lactate, glucose, oxygen, C02 , and 14 C02 were estimated as described previously (2) . 1855
Metabolic Changes in Anaphylactic Shock
1856
data :
Vol . 17, No . 12
The following calcualtions were performed utilizing the experimental 1.
FFA flux
(5), or total body FFA turnover (u mole/min) _
rate of palmitate- 14 C infusion (cpm/min ) arterial FFA specific activity (cpm/u mole) 2.
Total body Oz consomption (u mole/min) _ [OZa - OZv cardiac output
(u mole/ml)] x
(ml/min)
Subscripts "a" and "v" represent arterial and venous blood . significance was determined using the Student paired t test .
Statistical
Results The hemodynamic changes during anaphylactic shock in the conscious dog are shown in Table 1. The mean arterial blood pressure decreased following the challenging injection . This decrease was especially significant in the first half hour . Heart rate increased and remained . elevated throughout the experiment . Cardiac output was markedly depressed for more than an hour and a half following the challenging dose . The fluctuation in arterial hematocrit was not statistically significant . Arterial pH decreased significantly in the early part of the experiment and returned to control later on . The changes of arterial metabolite concentrations are shown in Table 2 . Arterial :FA glucose and lactate concentrations did not change significantly . Arterial lactate. .]_ncreased markedly and remained elevated throughout the experiment . However, the degree of increase at 140 min following albumin injection was greatly variable from one animal to the other . Changes in FFA flux, oxygen consumption, and respiratory quotient are shown in Table 3. FFA turnover decreased significantly shortly after the challenge and returned to normal and in many cases was elevated above control levels later on in the experiment . Oxygen consumption decreased significantly in the early part of the experiment and returned toward control values subsequently . The respiratory quotient increased significantly through 90 minutes of the observation period and was still elevated 140 min later in three out of four experiments . Discussion In recent years attention has been focused to the metabolic alterations accompanying various forms of shock . Thus it was found that hemorrhagic hypotension in conscious dogs produced quite marked alterations of substrate utilization, characterized by increased arterial FFA concentration, increased FFn flux with a decreased oxygen consumption and an increase in carbohydrate metabolism by the body as indicated by an elevated RQ (6, 7) . Anaphylactic shock in the dog is a relatively short lasting condition which exhibits a much milder form of circulatory disturbance than some other types of experimentally produced shock . The current studies indicate that during anaphylaxis very little change in arterial FFA concentration occurs but the FFA flux is significantly decreased . Oxygen consumption of the animal is decreased and RQ ie increased. Thus, comparing anaphylactic shock and hemorrhagic hypotension in the conscious dog, one notices a number of similarities (and also differences) both in the area of metabolic changes and also hemodynamica (increased heart
Vol . 17, No . 12
1857
Metabolic Changae in Anaphylactic Shock
rl ., v ~ W z ~, o -r-I ~o
z
s mrn
r r-i ~N 1 +I
Nc'1 r-i r rr-I + +i
m~o 0o 00+I 1
m ~n
o rl ~-I O
ino
Orl + +i
o~r 00 00+i 1
W
a - a a+ o ~C ~ô
~xzII
W .-I o z
xO O
N U " .i ++U ro
r-I
H
~Q
x
mU
o ~o rm rl +1 I
rrl + +1 o ~o
r v 00
00 I +~
rl ~o V~N+i +
m ~n
rr rl o
fyl
m
~n o~ m
1
+i
O O
ro 01N
rIN f+1O rO
00 1 +I
c~
z_ r M3x .. NO a a
Uo~ N
0
i'~z
~N ~f1N 1f11 r-I +I
r~o Nr
orl rl o
vi rl N rl ~1
m ~o
v rl ar O
+I
+ +~
O I +I
O~
O~ ~ü
0o NM " "
~ r-1 + ü
10 O~
OO I ü
~ m
r-I r-I + +I
OO 1 ?1
N
OO
b+ O
q " rl "H N
 UÓ m
N N b+,s~ qH ro
.C O U I-I
o
a b ar x
a H zz o u --
O .~
N+1 rl
ri
OO
f+1
0 0 a
x
~w ro ~ N m d Cl +~ H
ta â --
°~ a~a
--
N +~
++ O O ro
ó
w
v
ro
a~a a
a
x
~
O O a I
N
+I " rl f-I
~
w m a ro â
Metabolic Changes in Anaphylactic Shock
1858
~Iw
In 10 ao~ rl N
M
~O
e! V~
M
r
Vol . 17, No . 12
M o0 M
01 O
00
NN + +i
Mrl I +I
O~
M ~O
O r-I
r 10 r-I 10
MN 1 N ü
r r1
W .-I
ri
z C9 " z
I
+i
aor
OO
++~
w a
- a_
O ~ ~O II Ixz o ~o z
mU
x q
U-
M II 13 z v N pv
ro S-I
a
a~ U
a 0
a0
N
z_
O~ H r
O " rl
" .i 01 r-I OO A " ~I
N
sr lD
0o 1 +i
MM M r-I + +I
~(1 M 00 + +I
O rl 0o
Mv ul r rl M vi~
MM 1 rl ü
o+ao
10 ri 01 O
rN 01 O~
+ +I
MM OO
~o r
in v r rl ON
Mv rl +I
rao ~O N I +i
00 1 +1
+ +1
er ~
00 1 ++
I +1
NO + +~
+ rol m
E
~ r-I
Ó U
ro~ " rl ,l~ f-I N
a~ +~
a
M
q 1-i
a O -~ r
H
zz o -U
rl M O~ rl O" O" +i
r-I
rl O" +I
~n v
rl M 00 O +I
Ol b~ O ro
U
0
0v
a w
w~ ro~ ".i N f-i
r-I
U
â~
"ro~ ~I N fa ri
v Ú ~~
roo o " .~
N r-I
ó~
m~ " ~I N
vi
G1
r-I
â~
rov
q
Vol . 17, No . 12
Metabolic Changea in Anaphylactic Shock
~o
â
I r~ n z M~~ r-I z
0o N 10
+ +1
r~r~ OO
rrn
N V~ O O OO
.-1 V~ NO OO
ui ~o
00 I ++
OO
ó0 + +,
W
-O~
a
a_ OA~,10 W ri ~ II Ixz C7 ~o mU
z
z
U-
a
~+
n
13z
b
N~v
a a
a o âó ~ca
ââ 0 0
U " .i U
óó + +i
I
++
++~
0
x a
O 01 N f+1 NN
- °
~w~
N
z
r o ~ ~o
ON
0o OO
ao v rl o
o~r rao
a~o ~o
Na, No
0 o + +1
No
0o I +i
I +i
00 I ++
OO + +i
00 ++a
O ~ O U N wE
~a ww H H W Gl a ro x U
ao -. pd r E II zz ~ `r U
a~ o ~orl ~D rl 00
ri ~o vo 00 +i
o ~
ro 00 ++
0 O v a ~i 0 0 v a
â .~ a~ w~ w } w --
óx ++ . aa a a~ o~ U ~ N 7. o --
w v~ O x
q ro
1859
1860
Metabolic Changes in Anaphylactic Shock
Vol . 17, No . 12
rate, decreased cardiac output) . The major change in metabolism appears to be an elevated RQ indicating increased reliance by the body on carbohydrate metabolism . The changes in FFA flux in the present study were similar to those found by Paul, et al (B) . It is of interest to point out that conscious dogs subjected to anaphylactic shock behave similarly to anesthetized ones in showing a decreased cardiac output, decreased FFA flux, and increased lactate concentration (9) . The major hemodynamic difference between the two groups of animals is shown in changes of heart rate . The latter variable increases during anaphylactic shock in the conscious dogs while it decreases 1n the anesthetized animals . In conclusion, our studies indicate that the metabolic alterations that characterize anaphylactic shock in the conscious state consist of a shift in metabolism towards an increased utilization of carbohydrates and a decreased turnover of FFA. Acknowledgement These studies were supported by Grant HL 16850 from the National Institutes of Health . References 1.
J. J . Spitzer and J . A. Spitzer, Am . J . Physiol . 222
101 (1972) .
2.
J . J . Spitzer, A. A. Bechtel, L . T . Archer, M. R. Black, and L . B. Hinshaw, Am . J. Ph~iol . 227 132 (1974) .
3.
N. Back, H . Wilkins, and R. Steqer, An . of N. Y . Aced . Sc . 146
4.
J. M. Kinsman, J. W . Moore, and W. F . Hamilton, Am . J. Physiol . 89 (1929) .
5.
D. T . Armstrong, R. Steele, N. Altszuler, A . Dune, J . S. Bishop, and R . C . DeBodo, Am . J . Phys iol . 201 9 (1961) .
6.
R. ::iener and J . J. Spitzer, Am . J . Physiol . 227
7.
J. J . Spitzer, R. Wiener, and E. H . Wolf, in Neuroh injury, (P . 221) Plenum Press, New York (1973) .
8.
P. Paul and W. L. Holmes, Lipid s 8
9.
J . J . Spitzer, Proc . Soc. Exper . Biol . Med . 15 1 in press (1976) .
491 (1968) .
5 (1975) . oral Aspects of
142 (1973) .
322
