blood circulation in the skeletal muscles and the skin of the cat under halothane anaesthesia
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Acta anaesth. Scandinav. 1969, 13, 209-227.
BLO 0 D C I RC U LATI 0 N IN THE SKELETAL MUSCLES AND THE SKIN OF THE CAT UNDER HALOTHANE ANAESTHESIA
BY
LARS WESTERMARK
Two of the most frequently observed features during halothane anaesthesia in man are a considerable arterial hypotension and a warm, well-perfused skin with prominent superficial veins suggesting considerable vasodilatation (JOHN-
STONE ( 1956)e). Vasodilatation in the skin and skeletal muscles has often been interpreted as an indicator of a reduction in total peripheral vascular resistance which has been held mainly responsible for the arterial hypotension (PAYNE ( 1963)18). Therefore, the finding of a decrease in skin vascular resistance in cat experiments (LINDGREN, WESTERMARK and WRHLIN (1965b)lS) was not sur- prising. Somewhat more puzzling was the finding of an unchanged or increased vascular resistance in skeletal muscles in other cat experiments (LINDGREN WESTERMARK and WAHLIN ( 1965a)18). Vasoconstriction in skeletal muscles under the influence of halothane has also been reported by CRISTOPORO and BRODY (1968)'. Different changes in vascular resistance in the skin and the skeletal muscles together with the results of blood-flow measurements in the kidney (WESTERMARK and WAHLIN (1969)ZO) and in the intestine (WESTER- MARK and WAHLIN ( 1969)21) of the cat make it doubtful whether the change in total peripheral resistance is of such a size that it could be responsible to more than a rather small extent for the pronounced arterial hypotension observed during the halothane exposures.
Of the investigated vascular beds, those of the skin and the skeletal muscles showed the widest difference in response to halothane. To confirm this finding it was considered convenient to investigate the simultaneous vascular responses in these two tissue regions in the same animal under the influence of halothane. Such an investigation would make the possibility of divergent although simul- taneous vasomotor responses in different tissues more apparent and the hypothesis of a reduction in total peripheral resistance as a main cause of arterial hypotension during halothane anaesthesia more questionable.
From the Central Department of Anaesthesiology (Head: T. GORDH), Karolinska Sjuk- huset, and the King Gustaf V Research Institute (Head: G. BIRKE), Stockholm, Sweden. Received February 14, 1969.
2 10 LARS WESTERMARK
CENTRAL VENOUS PRESSURE
BLOW FLOW muscle - skin _ _ _ _ _
mussle - shin _ _ _ _ _
TIME: 5 w ExPosuE t 4
Fro. la. 1% 1.5% 4
MATERIALS AND METHODS
Five cats weighing 2.9-4.2 kg were used for the experiments. Basal anaesthe- sia, artificial respiration, heparinization, measurements of arterial and central venous pressures and of heart rate, as well as the technique of halothane and -for purposes of comparison-of ether administration, are described in other reports (LINDGREN, WESTERMARK and WAHLIN (1965a, b)12J3 and WESTERMARK and WAHLIN ( 1969) 20).
One hind-leg paw was prepared for measurement of the venous outtlow from the great sephenous vein representing skin blood flow; the other hind-leg was skinned, the paw was ligated just above the malleoli, and the femoral vein was prepared for measurement of venous outflow representing skeletal muscle flow. The measurements were assessed by photo-electric counting in a drop chamber as described by LINDCREN (1958)" and as reported in previous papers (LINDCREN, WESTERMARK and WAHLIN (1965a, b)12* 13). The recordings were made on a Grass Polygraph Model 7 (Grass Instrument Co., Quincy, Mass., USA).
BLOOD FLOW IN MUSCLES AND SKIN UNDER HALOTHANE
CENTRM VENOUS PRESWRE
BUKK, FLOW murcle - skin .....
PERIPHERAL RESISTANCE
muscle - skin _ _ _ _ _
TIME: 5 MIN
EXPOSURE
140 A
211
FIG. lb.
FIGS. l a and 1b.-Circulatory variables under the influence of halothane or ether.
Arterial blood pressure, blood flows and calculated vascular resistances in per cent of control level. Central venous pressure in cm of water.
1. Start of exposure of the anaesthetic. 2. Disappearance of the corneal reflex. 3. Withdrawal of the anaesthetic.
Note increases in vascular resistance in the skeletal muscles together with decreases in vascular resistance in the skin.
a. Halothane 1-1.5y0 (exposure No. 6 in tabels la and 2a). Cat 3.3 kg. Control 1evels:-
Muscle blood flow = 9.4 ml/min = 100~o Arterial blood pressure = 150 mm Hg
Skin blood flow = 8.2 ml/min I I
b. Ether 2-3 Boyle “units” (exposure No. 1 in tables Ib and 2b). Cat 3.7 kg. Control levels:-
Muscle blood flow = 3.1 ml/min = lOOyo Arterial blood pressure = 145 mm Hg
Skin blood flow = 1.2 ml/min
2 12 LARS WESTERMARK
The five animals were exposed 10 times in all to different halothane con- centrations and-for comparison-four of them were exposed seven times to different ether concentrations. Between the exposures the animals were allowed to return to about the initial light state of basal anaesthesia. Previous experi- ments had shown that the degree of vascular response to the anaesthetics is largely dependent on depth of anaesthesia, which was therefore kept as light as possible at the start of each exposure to either of the two anaesthetics. The corneal reflex, tail movements, etc. were observed as indicators of anaesthetic depth.
Calculations.--The spikes on the recording paper representing the drops occurring in the counting chambers during the experiments were totalled for each minute, thus yielding the bloodflows in ml/min ( 1 ml = 16 drops). Peripherul resistance was calculated for each minute as the ratio of mean arterial pressure to blood flow, disregarding venous pressure.
Control levels.-The recordings of the flows and the arterial pressure on the Polygraph were converted into percentage diagrams, on which percentage curves of the calculated peripheral resistance were also plotted.
The values at the start of each exposure were taken as 100 per cent. In this way, comparison of the variables was facilitated. Heart rate and central venous pressure are presented in absolute values.
RESULTS
Figures la and lb show percentage diagrams of the variables during the influence of halothane and ether, respectively. Even though the changes were rather irregular and also differed between the various exposures, these illustra- tions are representative of the type of response pattern. Tables l a and l b show the percentage values of blood pressure, and tables 2a and 2b those of skin vascular resistance during each of the first 14 minutes of each exposure to halothane and ether, respectively. The percentage values of vascular resistance in skeletal muscles showed a pronounced skewness of distribution, and since mean values will therefore be irrelevant, this variable is presented in the form of percentage diagrams, in which each exposure to halothane and to ether is represented by a curve (figs. 4a and 4b, respectively). Diagrams of the mean percentage values of tables la, l b and 2a, 2b are illustrated in figures 2 (blood pressure) and 3 (skin vascular resistance).
In table 3, halothane and ether are compared as regards their influence upon blood pressure, skin vascular resistance and heart rate at an anaesthetic depth characterized by loss of the corneal reflex.
Blood pressure.-Statistically, there was a slightly to highly significiant decrease in blood pressure throughout the exposures both to halothane and to ether (tables l a and lb). Figures la, l b and 2 suggest that the blood-pressure
Ani
- m
al
No. I
1
2
I1
3 4
I11
5 6
IV
7 8
v9
10
Ref
lex
dis
ap
pearance
11
2 1
3 1
4 1
5 1
6 1
7 1
8 1
9 1
10
1 II 11
2
11
3
11
4
”;?
Fin
t 14 minutes of
halo
than
e exp
osur
e Ex-
Fluotec
sure
Po-
sett
lllg
di
al
No.
%
1-1.
542)
....
....
96
1-
1.5.
. ..
....
...
100
1 ...
....
....
....
94
1.
5.. ..
....
....
. 92
1-1.
5..
....
....
. 93
1-
1.5.
. ..
....
...
97
1-(1
.5).
....
....
. 96
1-
1.5
....
....
... 1
00
1.5.
. ...
....
....
89
1.5 .
....
....
....
94
83
89
86
74
75
88
86
95
70
68
80
82
83
68
72
84
83
89
63
55
77
78
81
60
70
79
80
89
59
48
74
72
71
69
75
73
72
71
78
74
71
69
57
56
- -
69
69
67
64
77
76
74
72
78
77
74
73
86
86
85
84
53
53
52
49
48
47
47
46
67
62
66
59
64
70
84
50
47 -
67
66
56
51
64
62
44
34
55
48
69
67
81
75
51
48
47
46
- -
58
48
60
29
43
66
70
46
44 -
51
46
19
46
44
14
59
58
- 5
29
29
13
40
37
7
64
63
17
66
64
20
44
40
19
43
43
8
- -
M ..
....
....
....
95
.1
81.4
75
.9
72.1
69
.5
68.3
68
.1
66.3
63
.2
59.3
55
.2
51.6
49
.1
47.1
S
D..
....
....
...
3.4
9.0
10.9
12
.6
12.5
12
.3
11.8
12
.2
11.1
12
.1
13.1
12
.8
12.1
12
.1
SE ..
....
....
....
1.
1 2.
9 3.
5 4.
0 4.
0 3.
9 3.
9 4.
1 3.
7 4.
0 4.
4 4.
3 4.0
4.0
t.. ..
....
....
...
4.5
6.5
7.0
7.0
7.7
8.2
8.1
8.3
10.0
10
.1
10.3
11
.4
12.6
13
.1
Sign
ific
ance
.. **
**
* **
* **
* **
* **
* **
* **
* **
* **
* **
* **
* **
* **
* ...
. M
=
mea
n
Leve
ls of s
igni
fican
ce :
SD =
sta
ndar
d de
viat
ion
NS
= n
ot s
igni
fican
t, p>
0.05
SE
=
Sta
ndar
d er
ror o
f th
e m
ean
= s
light
ly s
igni
fican
t, 0.
01 <
p<0.
05
At
the
botto
m of
the
tabl
e th
e hy
poth
esis
of
“no
chan
ge in
blo
od
pres
sure
” is
test
ed b
y m
eans
of
Stud
ent’
s t-t
est.
(In
expo
sure
No.
3 th
e co
rnea
l ref
lex
still
rem
aine
d af
ter 2
0 m
inut
es, w
hen
the
expo
sure
was
ter
min
ated
for
tech
nica
l reasons.)
** =
sig
nific
ant,
0.00
1 <p<
O.O
l **
* =
hig
hly
sign
ifica
nt, p
<O.0
01
B
0
U s t E a U
N
w c
TA
BL
E
Ib.
Infl
uenc
e of
eth
er o
n bl
ood
pres
sure
dur
ing
the
firs
t 14
min
utes
of e
xpos
ure.
Pe
rcen
tage
of
cont
rol l
evel
.
Reflex
Dia
l set
ting
d
isap
pe
ar an
c e
Fir
st 1
4 m
inut
es o
f ha
loth
ane
expo
sure
11
2 1
3 1
4 1
5 1
61
71
8 1
9 !
lO
~l
l~
I~
~I
3~
~(
Ex-
of B
oyle
hi-
ma1
sure
po-
vapo
rize
r No.
No.
I 1
2-3
....
....
....
. 10
0 97
97
98
10
0 10
0 88
77
72
68
-
- -
- 9
s
2 3 .
....
....
....
..
92
71
61
60
63
65
65
63
57
51
44
39
- -
6z
11
1 3
2-3.
. ..
....
....
. 98
86
84
89
95
99
10
1 10
0 89
78
71
64
55
47
11
..
l;
3 4
2-2
113-
2 1/
2..
96
93
93
92
88
86
80
74
68
63
57
55
52
51
IV
5 2
112
- -
....
....
....
97
90
83
80
79
78
77
75
74
72
70
- V
6
2%
89
74
54
53
51
54
55
56
55
54
- -
- E c
....
....
....
. -
6 7
234 ..
....
....
...
97
77
65
63
60
59
59
60
65
67
66
65
62
58
16
M..
....
....
....
95
.6
84.0
76
.7
76.4
76
.6
77.3
75
.0
72.1
68
.6
64.7
61
.6
55.7
56
.3
52.0
S
D..
....
....
...
3.8
10.1
16
.7
17.7
18
.9
18.7
16
.5
14.8
11
.5
9.6
11.3
12
.0
5.2
5.6
SE ..
....
....
....
1.
4 3.
8 6.
3 6.
7 7.
1 7.
0 6.
2 5.
6 4.
3 3.
6 5.
0 6.
0 3.
0 3.
2 t.
....
....
....
..
3.1
4.2
3.7
3.5
3.3
3.2
4.0
5.0
7.3
9.7
7.6
7.4
14.6
14
.9
Sign
ific
ance
. ...
. *
**
*
* *
**
**
***
***
**
**
**
**
M =
mea
n SD
= s
tand
ard
devi
atio
n SE
=
sta
ndar
d er
ror
of t
he m
ean
At
the
botto
m o
f th
e ta
ble
the
hypo
thes
is o
f “n
o ch
ange
in
bloo
d pr
essu
re”
is te
sted
by means
of S
tude
nt’s
t-te
st.
Leve
ls o
f sig
nifi
canc
e as
in t
able
1 a.
BLOOD FLOW IN MUSCLES AND SKIN UNDER HALOTHANE 215
80
60
40
2 4 6 8 10 12 14 rnin
FIG. 2.-Arterial blood pressure during the first 14 minutes of exposure. -~ Halothane (mean percentage values f SE from table la). _ - _ _ _ _ _ _ _ _ _ Ether (mean percentage values & SE from table Ib).
fall, minute by minute, is less under the influence of ether than under that of halothane. It would be more appropriate, however, to compare the hypotension at about the same depth of anaesthesia, for example, at the disappearance of the corneal reflex, which does not occur at the same point of time during the course of the exposures. Such a comparison is made in table 3, showing that at this depth of anaesthesia the blood pressure was 45.9 f 4.5 per cent and 63.0 f 4.1 per cent of control level for halothane and ether, respectively. These changes were statistically highly significant, and the difference between them was statisti- cally slightly significant, thus corfirming the impression obtained from the illustrations.
Bloodj7ows.-The skin blood flow increased more or less initially during all exposures except in two halothane and two ether exposures, which showed a decrease in skin blood flow. With only one exception (ether) th is decrease was less than that of the blood flow in the skeletal muscles, which was gradually reduced to a varying extent during all exposures to halothane as well as to ether. The initially increased skin blood flow was gradually reduced during the course of the exposures, and finally it usually fell to below 100 per cent, apparently owing to a decreasing perfusion pressure. However, with the above- mentioned exception, the skin blood flow did not decrease to the same extent as the muscle blood flow.
Perifiheral resistance.-Qualitatively, the responses to halothane and ether present about the same pattern even though they were quantitatively different.
In the skin, the vascular resistance showed a reduction during all the exposures, both those to halothane (table 2a, on an average, a highly significant reduction) and those to ether (table 2b, on an average, a significant or slightly
!2 T
AB
LE
2a
. 0-
I In
fluen
ce of
hal
otha
ne o
n skin v
ascu
lar
resi
stan
ce d
urin
g th
e fir
st 14
min
utes
of e
xpos
ure.
Pe
rcen
tage
of c
ontr
ol le
vel.
hi-
mal
No.
Ref
lu
dm
p
-8pc
e l
l 2
13
14
15
16
17
18
19
110
1 ll I12 1131 14
rn”
Firs
t 14 m
inut
es of halothane e
xpos
ure
Ex-
Fluotec
po-
dial
sure
No.
sett
ing
%
I 1
1-1.5-(2)..
....
.. 89
63
65
59
56
55
58
53
54
54
57
54
55
54
19
2 1-1.5.. ..
....
... 122
89
65
66
64
57
61
56
57
51
56
53
51
60
14
I1
3 1 .
....
....
....
.. 9
4 52
44
43
51
46
38
34
32
25
26
26
26
24
-F
4
1.5.. ...
......
.. 108
46
42
46
62
66
- -
- -
- -
- -
5E
7;
;1
I1
1 5
1-1.5. ..
....
....
101
74
64
62
60
51
55
53
51
48
43
42
42
42
13
2 F ..
....
....
. 6
1-1.5
101
88
85
84
80
78
75
74
71
67
65
61
60
56
IV
7 1-(1.5)
90
45
36
32
30
28
27
26
26
26
26
26
27
29
17
8 1-1.5 ...
......
.. 92
52
41
36
35
31
31
30
31
31
29
29
29
31
20
V
9 1.5.. ..
....
....
. 68
42
37
35
33
33
33
33
34
34
34
35
36
39
19
10
1.5 .
....
....
....
94
47
47
49
51
49
49
51
49
47
51
51
56
63
8
......
....
R
M.. ...
......
... 95
.9
59.8
52.6
51.2
52.2
SD.. ....
....
...
14.0
17.9
16.2
16.4
15.8
SE.. ..
....
....
..
4.4
5.6
5.1
5.2
5.0
t.. .
....
....
....
0.9
7.1
9.3
9.4
9.6
Sign
ifica
nce ..
....
NS
***
***
***
***
w =
mea
n SD =
sta
ndar
ddev
iati
on
SE =
sta
ndar
d er
ror o
f the
mea
n
49.4
47.4
45.6 45.0 42.6
43.0
41.9
42.4
44.2
15.9
16.3
15.6
15.0
14.2
14.9
13.4
13.5
14.6
5.0
5.4
5.2
5.0
4.7
5.0
4.5
4.5
4.9
10.1
9.6
10.5
11.0
12.2
11.5
13.0
12.8
11.5
I**
***
***
***
***
***
***
***
***
At t
he b
otto
m o
f the
tab
le th
e hy
poth
esis
of “
no c
hang
e in
vasc
ular
re
sist
ance
” is
test
ed b
y m
eans
of S
tude
nt’s
t-te
st.
Lev
els
of si
gnifi
canc
e as in t
able
1 a
.
(In
expo
sure
No.
3, th
e cor
neal
refle
x sti
ll re
mai
ned
afte
r 20
min
utes
, whe
n th
e ex
posu
re w
as t
erm
inat
ed fo
r te
chni
cal r
easo
ns.)
TABLE
2 b.
Infl
uenc
e of
eth
er o
n skin v
ascu
lar r
esis
tanc
e du
ring
the
firs
t 14
min
utes
of e
xpos
ure.
Pe
rcen
tage
of c
ontr
ol le
vel.
Dia
l set
tin
g
of B
oyle
Ex-
hi
-
mal
m
e
po-
vapo
rize
r No.
No.
FLst
14
min
utes
of e
ther
ex
pa
ure
R
dC
X
dis
ap
pear
ance
1
12
13
14
15
16
17
18
19
I1
0
I ll I12 I13 I14
in&. No.
M..
....
....
....
97.
4 76
.0 68
.7
64.0
62
.4
60.4
57
.9
64.9
59
.3
60.6
61
.6
70.5
68
.3
69.3
S
D..
....
....
...
15.8
18
.7 27
.5 26
.0
26.9
28
.3
27.9
24
.2
26.9
29
.2 35
.0
36.6
42
.2 43
.0 SE ..
....
....
....
6.0
7.1
10
.4
9.8
10.2
10.7
10
.5
9.1
10.2
11
.1 15
.7 18
.3
24.4
24
.8
t.. ..
....
....
...
0.4
3.4
3.0
3.7
3.7
3.7
4.0
3.9
4.0
3.6
2.5
1.6
1.3
1.2
Sign
ific
ance
....
..
NS
* *
* *
**
**
**
* NS
NS
NS
NS
M =
mea
n SD
= s
tand
ard
devi
atio
n SE =
sta
ndar
d er
ror
of t
he m
ean
At
the
botto
m o
f th
e ta
ble
the
hypo
thes
is “
no c
hang
e in
vas
cula
r re
sist
ance
” is
test
ed b
y m
eans
of
Stud
ent’
s t-t
est.
Leve
ls o
f sig
nifi
canc
e as
in ta
ble
1 a.
M 0
U s t U
(In
min
. 8
of
expo
sure
No. 7
, va
scul
ar r
esis
tanc
e w
as m
arke
dly
incr
ease
d in
con
nect
ion
with
refle
x te
stin
g.)
N
rl c
218 LARS WESTERMARK
100
80
60
40
2 4 6 8 10 12 14 min FIG. 3.-Skin vascular resistance during the first 14 minutes of exposure.
Halothane (mean percentage values f SE from table 2a). _ - _ _ _ _ _ _ _ _ _ _ Ether (mean percentage values f SE from table 2b).
significant reduction), except for a few irregularities in the first single minute of some exposures (table 2a, exposures Nos. 2 and 4; table 2b, exposures Nos. 1 and 7).
In tables 2a and 2b and in figure 3 the average decrease in skin vascular resistance seems to be more pronounced during halothane exposures than during ether exposures. Such a comparison, however, should correlate the changes to some indicator of anaesthetic depth, such as the corneal reflex, which is not indicated in figure 3 because the curves constructed of mean values in conse- cutive minutes of a number of exposures during which the corneal reflex was extinguished after periods of different length. A comparion between the influence of halothane and that of ether upon the skin vascular resistance at an anaesthetic depth corresponding to loss of the corneal reflex is made in table 3. At this depth of anaesthesia the skin vascular resistance was 52.8 f 4.0 per cent of control level when halothane was used, the change being highly significant, and it was 58.6 & 10.8 per cent when ether was used, which means a significant change. The difference between the changes, however, was not significant.
In the skeletal muscles, six of the 10 halothane exposures caused an increase in vascular resistance during a varying number of minutes (fig. 4a, exposures Nos. 2, 3, 5, 6, 9 and 10). The increases were extreme in two exposures (Nos.
FIGS. 4a and 4b.-Vascular resistance in the skeletal muscles under the influence of halothane or ether. Percentage of control level. -+
Triangles = Disappearance of the corneal reflex. Arrows = Withdrawal of the anaesthetic.
BLOOD FLOW IN MUSCLES AND SKIN UNDER HALOTHANE 2 19
7.
300
200
100
50
'1.
400
300
200
100
10 20 30 min
1 ' ' ' ~ I ~ ' ' ~ I 10 20 30 rnin
FIG. 4a.-Ten halothane exposures (Nos. as in tables la and 2a).
FIG. 4b.-Seven ether exposures (Nos. as in tables l b and 2b). In exposure No. 7 (discontinued curve), the resistance reached the value of 960 per cent.
TABLE
3.
Blo
od p
ress
ure
(BP)
, ski
n va
scul
ar r
esis
tanc
e (P
R) a
nd h
eart
rat
e (H
R) u
nder
the
infl
uenc
e of
hal
otha
ne o
r et
her
at a
n an
aest
hetic
de
pth
char
acte
rize
d by
loss
of c
orne
al re
flex.
BPE
- B
PH
HALOTHANE
I P
Rw
A
H-
PR
H
AE
hi
-
mal
No.
I11
5 1-
1.5.
. ..
..
6 1-
1.5.
. ..
..
8 1-
1.5.
. ..
..
V
9 1.
5 ...
....
. 10
1.
5.. ..
....
M
....
....
. SD
....
....
SE. .
....
...
t ...
....
...
Sign
ific
ance
IV
7 I-
(1.5
). ..
..
Ex-
Fluo
tcc
HR
PO
- di
al
No.
aw
e Je
ttin
g B
PH
P
RH
C
ontr
ol I
%
leve
l AH
29
42
74
75
4040
52
36
37
54
46
51
45.9
52
.8
13.6
12
.1
4.5
4.0
11.9
11
.7
***
***
(1)
(1)
Ex-
PO
- su
re
No.
170
50
166
27
207
22
192
38
230
55
214
46
203.
2 43
.6
23.2
13
.6
- 4.
5 -
9.6
***
- (1
)
HR
D
ialx
ttin
g Bq
Ylc
va
po
rize
r B
PE
PR
E
Con
trol
le
vel
A=
ET
HE
R
1 2-
3 ..
....
..
72
58
204
28
2 3 .
....
....
. 65
51
21
4 36
Ani
mal
not
exp
osed
to
eth
er
3 2-
3 ..
....
..
71
88
145
-17
4 2-
21/,-
24/,.
. 51
10
6 14
2 2
5 2%
. ...
....
77
33
18
6 6
6 2G
.. ..
....
54
47
20
0 3
Ani
mal
exp
osed
onl
y on
ce to
eth
er
7 2%
....
....
51
27
21
1 20
63.0
58
.6
186.
0 11
.1
10.9
28
.7
30.4
18
.1
4.1
10.8
-
6.8
9.0
3.8
-
1.6
***
**
NS
(2)
(2)
- (2
)
BP a
nd P
R as
perc
enta
ges of c
ontr
ol le
vel.
HR
in
beat
s/m
in.
A =
dec
reas
e in
hea
rt r
ate.
m
eans
of S
tude
nt’s
t-te
st:-
M
=m
ean
(1
) N
o ch
ange
und
er t
he in
flue
nce
of h
alot
hane
. SD =
sta
ndar
ddev
iatio
n SE =
sta
ndar
d er
ror
of th
e m
ean
At
the
botto
m o
f th
e ta
ble
the
follo
win
g hy
poth
eses
are
tes
ted
by
(2) N
o ch
ange
und
er th
e in
flue
nce of e
ther
. (3
) No
diff
eren
ce b
etw
een
chan
ges u
nder
the
infl
uenc
e of e
ther
and
un
der
that
of
halo
than
e.
Leve
ls o
f sig
nifi
canc
e as
in table 1
a.
F E
17.1
5.
8 32
.4
6.3
11.6
7.9
2.7
0.
5 4.
1 *
NS
**
- -
-
(3)
(3)
(3)
BLOOD FLOW IN MUSCLES AND SKIN UNDER HALOTHANE 22 1
5 and 10). In four of these six exposures, the responses were enacted within the period preceding the disappearance of the corneal reflex (exposures Nos. 2, 5, 6 and 9) ; in one exposure it persisted beyond this period (exposure No. lo), and in one the vascular resistance was increased throughout the exposure, which, however, was discontinued for technical reasons before the time of disappearance of the corneal reflex was reached (exposure No. 3). The remaining four halothane exposures showed a slight decrease in vascular resistance of the skeletal muscles (exposures Nos. 1, 4, 7 and 8).
During five of the seven ether exposures, the vascular resistance in the skeletal muscles also increased (fig. 4b, exposures Nos. 1, 3, 5, 6 and 7). The increases were extreme in two of these exposures (Nos. 6 and 7). In each of the five exposures the response persisted for a longer period than the corneal reflex. During the remaining two ether exposures the muscle vascular resistance was more or less uninfluenced or slightly reduced (exposures Nos. 2 and 4).
Figures 4a and 4b suggest that the vascular resistance in skeletal muscles may be less pronounced during halothane exposures than during ether exposures, but a comparison between mean values would be irrelevant owing to the skewness of distribution of individual values. For the same reason a statistical comparison between the vascular resistance in the skeletal muscles and that in the skin was not performed, but it may be stated concerning both anaesthetics that the vascular resistance in skeletal muscles mostly increased, and that when it decreased, the reduction was never so great as the fall regularly occurring in skin vascular resistance.
Central venous pressure.-The central venous pressure rose by 1 4 cm water in six of the 10 halothane exposures simultaneously with the gradual fall in blood pressure. I t was more or less unchanged in two exposures and decreased by 1-2 cm water in the remaining two halothane exposures. In four of the seven ether exposures, there was an increase in central venous pressure by 1-2 cm water; in one there was no noteworthy change and in the remaining two there was a slight decrease by about 1 cm water. Thus, there seemed to be no appreciable difference between the two anaesthetics in this respect.
Heart rate.-During all exposures except ether exposure No. 3 there was a decrease in heart rate, as may be seen from table 3. At reflex disappearance, the average decrease of about 44 beatslmin during halothane exposures was statistically highly significant, but the average decrease of about 11 beats/min during ether exposures was not significant. These average reduction differed significantly from each other.
DISCUSSION
The results confirm the findings in previous investigations (LINDGREN, WESTERMARK and WKHLIN (1965a, b)l2I 9, viz. that the skeletal muscles and the skin present different vascular response patterns during anaesthesia, inde-
222 LARS WESTERMARK
pendently ofwhether halothane or ether is used. An increased vascular resistance in skeletal muscles together with a decrease in the skin vascular resistance is a combination which probably cannot contribute much to the fall in blood pres- sure during the gradual deepening of the anaesthesia. It is true that the per- centage reduction in skin vascular resistance in this investigation was usually more pronounced than the simultaneous increase in muscle vascular resistance when halothane was used. However, in view of the fact that the fraction of cardiac output normally distributed to the skin is much smaller than that to the skeletal muscles (cf., e.g., MELLANDER andJomssoN (1968)16) it is hardly probable that the two changes together will constitute any considerable reduction in vascular resistance. In other words, a small rise in the resistance to a relatively large fraction of the cardiac output (the skeletal muscles) might well compensate for a considerable reduction in the resistance to a rather small fraction of the cardiac output (the skin), and when there is a decreased vascular resistance in both regions the combined influence upon haemodynamics by the two re- gions will probably be dominated by the response in the larger one of them, i.e. the skeletal muscles, showing the lesser resistance decrease. Thus, in all probability, other factors must be responsible for the arterial hypotension during the initial period of the exposures. Later in the course of the exposures to halothane the muscle vascular response gradually weakened and in several exposures (fig. 4a) the muscle flow resistance fell slightly below control level, but it did not fall to such an extent as did the skin vascular resistance. The combined decrease in resistances in this phase of the exposures probably contributes to the hypotension. However, other factors must still be in action, since the hypotension was proportionately much more pronounced than any reduction in muscle vascular resistance, and since the hypotension continued to develop despite a more or less stabilized skin vascular resistance, which decreased mainly during the initial phase of the exposures (cf. figs. la, l b and 3).
The same arguments against the changes in the two regional vascular resistances being a main cause of arterial hypotension seem also to be valid for ether. In fact, they would seem to be even more valid, since it appears that the reduction in skin vascular resistance was less pronounced and the increase in muscle vascular resistance was more pronounced and more persistent under the influence of ether than under that of halothane (figs. 3,4a and 4b), although these differences in response to the two anaesthetics were not shown to be signifi- cant.
It is striking that two anaesthetics with so different characteristics as halothane and ether exert such similar influences upon the vascular beds, as may be seen in figures la and lb, 4a and 4b, and 3. It is tempting to ascribe the qualitative similarity of these response patterns to some common feature in general anaesthesia which is present whatever anaesthetic is in use.
A depressive influence on the sympathetic ganglia (e.g. h V E N T 6 S ( 1956)i0, BISCOE and MILLAR (1966)a), on the transmission at the postganglionic nerve
BLOOD FLOW IN MUSCLES AND SKIN UNDER HALOTHANE 223
terminals or directly on the smooth vessel muscles (e.g. BEATON (1959)’, BURN and EPSTEIN ( 1959)3) could be partly responsible for the marked reduction of the skin vascular resistance.
Adrenergic nerve terminals have been demonstrated in abdominal sympa- thetic ganglia. They may be a morphological correlate to the known adrenergic inhibition of ganglionic synaptic transmission (NORBERG and SJOQVIST ( 1966)17) and may offer a possilibity of a differentiation of the influence exerted by anaesthetics upon ganglionic transmission. However, a difference in this respect has not so far been demonstrated in the ganglia of the vascular inner- vation to the skin and skeletal muscles (NORBERG (1968)la, NORBERG and SJOQVIST (1966)17) and probably cannot contribute to the explanation of the differentiation, observed in the present investigation, between these two tissue regions as regards the vascular response to the anaesthetics.
It has also been demonstrated that for every given nerve stimulation fre- quency the change obtained in vascular resistance in the skin is more pronounced than in the skeletal muscles, a phenomenon tentatively ascribed to an uneven distribution of constrictor fibres to the individual vascular beds (for references, see FOLKOW (1955)5, MELLANDER andJoHANssoN ( 1968)16). Such an anatomical difference between the vascular beds may be expected to contribute to a quantitative difference in vascular response to a reduction of sympathetic discharge rate owing to, e.g., a depression of the central nervous system by the anaesthetics. It does not, however, account for an increase in vascular resistance in skeletal muscles simultaneously with a decrease in skin vascular resistance.
A decrease in the level of circulating catecholamines would probably not result in the observed changes, since “it was found that the hormonal link of the sympatho-adrenal system was of fairly subordinate importance so far as it concerns the excitatory inhence on innervated cardiovascular effector units ; in most cases of physiological activations its eliminations will not usually significantly enfeeble the central cardiovascular control” (FOLKOW, JOHANSSON
and LOFVING (1961)7). Besides, even though the skin vessels are considered to be more influenced by noradrenaline than are the vessels of the skeletal muscles (FOLKOW ( 1960)6) it is hardly probable that a reduction of the level of circula- ting noradrenaline would result in an increase in muscle vascular resistance simultaneously with a decrease in skin vascular resistance. Furthermore, if a change in the level of circulating noradrenaline were the main cause of the observed haemodynamic adjustments, then the qualitative responses to the two anaesthetics would reasonably be more differentiated, since ether is known to have sympathicomimetic properties in contrast to halothane (for references, see, e.g., GREISHEIMER (1965) *). Admittedly, this difference may account for the quantitative differences in the observed responses to the two anaesthetics, i.e. a less decrease in blood pressure, skin vascular resistance and heart rate, and a seemingly more pronounced increase in muscle vascular resistance during ether exposures than during halothane exposures.
224 LARS WESTERMARK
Although it might be argued that the observed quantitative differences in vascular response could be partly accounted for by the above-mentioned peripheral mechanism, the latter does not offer a satisfactory explanation of the two most conspicuous features of this investigation, i.e. the qualitative similarity of the vascular responses despite the markedly different properties of the two anaesthetics on the one hand, and the divergence of the responses in the two simultaneously investigated tissue regions on the other.
However, the central nervous control of the blood vessels is a factor which is known to differ in separate tissue regions (FOLKOW (1960)8, FOLKOW, JOHANSSON and LOFVING (1961)'). A depressive influence of the anaesthetics on the sympathetic discharge from hypothalamic centres dominating the cutaneous vasoconstrictor fibres for temperature regulation would result in a reduced vascular resistance in the skin. At the same time the blood-pressure fall-whatever its main causes may be-would release the bulbar vasomotor centre from the normal inhibitory impulses from the baroreceptors. Since the vasoconstrictor fibres supplying the skin vessels are far less engaged in baro- receptor modulations than are those supplying the skeletal muscle vessels (LOFVING ( 1961)14) there is a possibility of vasodilatation in the skin and, at the same time, of a vasocontriction in the skeletal muscles as long as the anaesthesia is not deep enough to depress the bulbar vasomotor centre also. Such a bulbar differentiation makes a reflexly induced increase in the sympathetic discharge rate to the vascular bed of the skeletal muscles compatible with a virtually unopposed vasodilatation in the skin. Such an explanation would be in accord- ance with the present findings of divergent vascular responses in the skin and skeletal muscles under the influence of halothane or ether and it would also be in accordance with the fact that the response pattern was qualitatively fairly similar independently of which of the two anaesthetics was in use.
Thus, it may be suggested that the reduction in skin vascular resistance contributes in some small measure to the observed arterial hypotension during halothane or ether anaesthesia, but that the vascular response in the skeletal muscles may rather be a consequence of the hypotension. The changes in heart rate point to a reduction in cardiac output as a contributory cause of arterial hypotension in the present experiments. This is in agreement with a report by KAIJSER, WESTERMARK and WKHLIN (1969)lO. Since central venous pressure was virtually uninfluenced or slightly increased, a reduction in circulating blood volume was probably not a primary cause of arterial hypotension in the present experiments. The less marked hypotension during the ether exposures may partly be due to a less marked reduction in heart rate, in so far as this indicates a less marked reduction in cardiac output.
BLOOD FLOW IN MUSCLES AND SKIN UNDER HALOTHANE 225
SUMMARY
In five cats the blood flows in the skeletal muscles and the skin were simulta- neously recorded with a drop-coun ting technique during exposures to halothane or ether. During both halothane and ether exposures, very similar qualitative response patterns were found, viz. arterial hypotension, increased or moderately decreased muscle vascular resistance, markedly decreased skin vascular resist- ance, decrease in heart rate and a more or less unchanged or slightly increased central venous pressure. The combination of the changes in peripheral resistances in the two tissue regions investigated is not considered to contribute greatly to the rather pronounced arterial hypotension, for which other causative factors are suggested, e.g. a reduction in cardiac output.
Even though depression anywhere in the sympathetic pathway may explain a skin vasodilatation, it is suggested that the divergence of the vascular responses in the two investigated tissue regions is caused mainly by a differentiation within the bulbar vasomotor centre when released from baroreceptor inhibition owing to the blood-pressure fall leading to a reflexly induced increase in vasocon- strictive discharge to the skeletal muscles but not to the dilated cutaneous vascular bed.
The quantitative differences between the responses to halothane and to ether, i.e. a less pronounced hypotension and a smaller decrease in skin vascular resistance and heart rate, as well as a seemingly more pronounced increase in muscle vascular resistance during the influence of ether, are, it is suggested, caused by the sympathicomimetic properties of this anaesthetic.
ZUSAMMENFASSUNG
Bei 5 Katzen wurde wahrend Halothan- oder Athernarkose die Blutdurch- stromung im Skelettmuskel und in der Haut mit einer Tropfenzahlmethode si- multan registriert. Die qualitativen Reaktionsmuster waren bei beiden Nar- koseagentien sehr ahnlich, das heisst arterielle Hypotension, erhohter oder schwach verminderter Gefasswiderstand im Muskel, deutlich verminderter Gefasswiderstand in der Haut, Abfall der Herzfrequenz und ein mehr oder weniger unveranderter oder schwach erhohter zentraler Venendruck. Die Kom- bination der Veranderungen im peripheren Widerstand dieser zwei unter- suchten Gewebsregionen kann wohl kaum besonders zu dem ziemlich aus- gepragten arteriellen Blutdruckabfall beitragen, fur den andere ursachliche Faktoren herangezogen werden miissen, z. B. eine Verminderung des Herz- minutenvolumens.
Obwohl eine Depression an irgendeiner Stelle der sympathischen Leitungs- bahnen die Gefasserweiterung in der Haut erklaren konnte, wird doch an- genommen, dass die Divergenz der vaskularen Reaktionen in den beiden unter-
226 LARS WESTERMARK
suchten Gewebsregionen hauptsachlich durch eine Unterschiedlichkeit im Bereich des bulbaren Vasomotorenzentrums bedingt ist, wenn dieses von der Barorezeptorenhemmung infolge des Blutdruckabfalls abgeschaltet ist, was zu einer reflexbedingten Erhohung der vasokonstriktiven Reize zur Skelettmusku- latur, aber nicht zu dem erweiterten Gefwbett der Haut fuhrt.
Was die quantitativen Untenchiede zwischen der Reaktion auf Halothan und auf Ather betrifft, das heisst die schwacher ausgepragte Hypotension und der geringere Abfall des Gefhwidentandes in der Haut, sowie der Herzfre- quenz, als auch die anscheinend ausgepragtere Erhohung des Gefiisswider- standes im Muskel unter dem Einfluss von Ather, wird angenommen, dass diese durch die sympathiko-mimetischen Eigenschaften dieses Narkotikums be- dingt sind.
A c k n o w l e d g e m e n t
This investigation was supported by a grant from the Swedish Medical Research Council (1 7X-750-01) and from Reservationsanslaget.
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BLOOD FLOW IN MUSCLES AND SKIN UNDER HALOTHANE 227
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