Clinical Science (1986)10, 249-255
249
Evaluation of an isotope washout technique to measure skin
vascular resistance and skin perfusion pressure: influence of
age, site and arterial surgery
HENRY J . DUNCAN
AND
IRWIN B . F A R I S
Department of Surgery, University of Adelaide, Adelaide, Australia
(Received 31 May11 9 September 1985; accepted 20 September 1985)
Summary
1. A simplified isotope washout technique has
been devised to calculate the skin perfusion
pressure (SPP) and skin vascular resistance (SVR).
This test is simple, requires inexpensive equipment
and is well tolerated by patients.
2. SPP and SVR were calculated in 20 patients
<30 years of age, 13 patients >30 years of age
and in 15 patients with peripheral vascular disease
(PVD). With increasing age the SPP and SVR were
increased. The SPP was similar to the mean arterial
pressure in normal individuals but was decreased
in patients with PVD. The SPP is a useful indicator
of the severity of the PVD.
3 . The SPP and SVR were higher in the calf than
in the foot. This is probably related to the
decrease in pressure in the distal arterial tree.
4. SPP was increased by 110% and skin blood
flow by 190% by arterial reconstructive surgery.
This test may be of use in assessing the effectiveness of arterial surgery.
Key words: age, perfusion pressure, peripheral
vascular disease, skin, vascular resistance.
Abbreviations: PVD, peripheral vascular disease;
SPP, skin perfusion pressure; SVR, skin vascular
resistance.
especially important in diabetic patients with
distal gangrene and ulceration. There have been
many methods developed to assess lower limb
perfusion. These include segmental blood pressures
[ 1, 21, skin blood flow [3], transcutaneous oxygen
tension estimation [4-61, laser Doppler [7, 81,
Doppler ultrasound [9] and photoplethysmography
[lo]. All these methods have been used to predict
ulcer and amputation healing but none has yet
been adopted for widespread use. One of the
more reliable predictors of healing has been the
measurement of skin perfusion pressure by means
of an isotope washout technique Ell]. However,
this method has not received wide acceptance
because it is considered to require expensive equipment, highly trained staff and is time consuming.
We have been using a modification of this technique which not only overcomes these problems
but also allows us to estimate the skin vascular
resistance. This modified technique is being used
to investigate diabetic and hypertensive microvascular disease and in the prediction of healing
of lower limb ischaemia [12, 131. The aim of this
study was to examine this technique critically in
a normal population and in patients undergoing
arterial surgery.
Methods and materials
Introduction
Technique
The assessment of arterial perfusion of the foot
and lower limb is important when managing a
patient with peripheral vascular disease. This is
The method used to measure skin perfusion
pressure (SPP) and skin vascular resistance (SVR)
is based on an isotope washout technique
described by Faris & Lassen 1141. This method
involves an intradermal injection (via a 26 g
needle) of 0.05 ml (approx. 250-500 PCi or 10-20
MBq) of 9 9 m T(in
~ the sodium pertechnetate form)
Correspondence: Dr Henry Duncan, Department of Surgery, Royal Adelaide Hospital, Adelaide
S.A. 5000, Australia.
H. J . Duncan and I. B. Faris
250
and 0.1-0.15 ml of sodium nitroprusside (250400 p g ) into either the anteromedial aspect of the
calf, mid-way between the medial malleous and
the patella, or the dorsum of the foot. The nitroprusside maximally dilates the vascular bed [ 151,
thus eliminating any local or systemic factors
which may influence local blood flow. The leg
was placed in a foam cushion to reduce any unwanted movements which may alter counting
geometry.
The gamma emission was measured by a NaI
scintillation detector placed 10-20 cm directly
above the depot. The impulses were recorded by a
scaler ratemeter (SR7, Nuclear Enterprises Ltd,
U.K.) set around the 141 kV peak for 99mTc.
The number of counts each 10 s period was
determined and relayed to an on-line Apple I1
microcomputer, which gave a visual display of the
counts against time. After sufficient points were
obtained (90-180 s) the computer calculated the
washout rate (k min-') by the least squares
method. This washout rate is proportional to the
blood flow through the vascular bed [16].
To estimate the SPP, external counter pressure
was applied over the isotope depot by means of
an air-filled plastic bag (1 2 cm x 10 cm) held in
position by a standard sphygmomanometer cuff.
The plastic bag ensured that the pressure was
applied evenly over the depot [17]. The pressure
was measured by a mercury manometer connected
directly to the bag. The external pressure (PmmHg)
was increased in a stepwise fashion by 20 mmHg
and the washout rate was determined at each
pressure. The pressure was increased until k
approximated to zero, and the procedure was then
repeated. Depending on the external pressure
required to stop clearance from the skin, the
procedure lasted 15-25 min.
The computer was programmed to display a
plot of the k values at each pressure (Fig. 1). A
line of best fit was then determined by the least
squares method. The equation of this line was
k = b .P+a where a represents Ic at zero external
pressures. This is the maximum washout rate
(kmax.). The intercept of this line with the
pressure axis, given by a/b, is the calculated
pressure required to stop washout of the isotope.
This is the skin perfusion pressure. The slope of
the line, b , is the ratio of flow to pressure, therefore l / b represents the skin vascular resistance
(SVR). Because the vessels are maximally dilated
by the nitroprusside this represents the minimum
resistance.
Subjects
The main group investigated consisted of 33
normal subjects and 15 patients with peripheral
vascular disease. The normal subjects were divided
into two groups depending on age. Group 1 were
subjects less than 30 years of age. This group
consisted of 20 individuals with a mean age of
20.4 (18-27) years. There were 11 men and nine
women. Group 2 consisted of 1 3 subjects with
ages greater than 30 years. The mean age of this
group was 58.3 (33-86) years and consisted of six
men and seven women. No subject in either group
had a history of diabetes niellitus, hypertension
or peripheral vascular disease, which was excluded
by normal ankle pressures and palpable foot pulses.
0.081
h
.-K
E
v
.x
0.04
0.02
0
20
40
60
80
Pressure (mmHg)
FIG. 1 . Relationship between washout rate ( k inin-') and external pressure. The line
represents the line of best fit and is given by the equation k = b . P + a (see the
Methods and materials section).
Skin vascular resistance
All subjects gave informed consent to the study,
which was approved by the Research Review
Committee of The Royal Adelaide Hospital. The
median age of the 15 patients with peripheral
vascular diseases (group 3) was 67.9 (46-87)
years. There were eight men and seven women,
none of whom had a history of hypertension or
diabetes. All patients had peripheral vascular
disease (severe claudication or rest pain) requiring
arterial reconstructive surgery and were studied
after surgery.
The ausculatory arm blood pressure was
measured in the left arm of all patients, by using a
12 cm x 26 cm cuff. The diastolic pressure was
taken at the cessation of the Korotkoff sounds
and the mean arterial pressure (MAP) was calculated as the diastolic pressure plus one-third of the
pulse pressure. Ankle pressure was determined in
each patient by placement of a photoplethysmography probe on the toe as a pulse detector.
The SPP, SVR and k,,,. were determined on the
anteromedial aspect of the calf as described above.
Vascular resistance was also estimated (EVR) in
groups 1 and 2 by dividing the pressure gradient
by the washout rate calculated with no external
pressure [18]. The pressure gradient is the difference between the arterial and venous pressures.
The venous pressure in the leg of a supine patient
is very low and for simplification was taken as
0 mmHg. Therefore, the pressure gradient was
assumed to be equivalent to the mean arterial
pressure.
influence o,f location
The SPP, SVR and k,,,,
were determined on
the dorsum of the foot and on the anteromedial
aspect of the calf in 12 patients to determine
whether location influenced any of these variables.
The mean age was 65.6 (18-86) years and there
were seven men and five women. Three patients
were free of peripheral vascular disease. The remaining seven patients had peripheral vascular
disease and were studied postoperatively. No
patients had diabetes mellitus but two patients
had a history of hypertension.
25 1
24-48 h before surgery and repeated 7-10 days
after surgery.
Data analysis
All results are expressed as means& 1 SEM and
were analysed by the Student’s t-test for paired
and unpaired samples.
Results
MAP,SPP and ankle pressure
The mean arterial pressure (MAP), skin perfusion pressure (SPP) and ankle pressure for
groups 1, 2 and 3 are shown in Fig. 2. The MAP in
group 1 was 9 0 5 2 m m H g . This was lower than
group 2 (100 f 2 mmHg, P < 0.001) and group 3
(101 rt: 2 mmHg, P < 0.001). There was no difference between groups 2 and 3.
The SPP in group 1 was 9 3 f 2 m m H g . This
was lower than group 2 (100 f 3 mmHg, P < 0.05)
and higher than group 3 (82k 4 mmHg, P < 0.02).
Group 2 had a higher SPP than group 3 (P< 0.01).
The MAP and the SPP were similar in both groups
1 and 2 (P< 0.20 for both groups) but the MAP
was higher than the SPP in group 3 (P< 0.001).
The ankle pressure in group 1 (1 30 f 3 mmHg)
was slightly higher than the systolic pressure
(1 25 rt: 3 mmHg, P < 0.05). In group 2 the ankle
pressure ( 1 3 7 f 4 mmHg) was similar to the
systolic blood pressure (137 f 4 mmHg, P < 0.20).
In group 3 the ankle pressure (105 f 10 mmHg)
was lower than the systolic pressure (143 + 4
mmHg, P < 0.01).
150
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100
a
Influence of surgery
80
The effect of arterial surgery on the SPP,
SVR and k,,.
of the calf was determined in eight
patients undergoing femoropopliteal bypass
surgery. The median age of the group was 68
(46-82) years and there were five men and three
women. Two patients were diabetic and two had
hypertension. One patient had both diabetes and
hypertension. The pre-operative test was taken
10
1
2 3
MAP
1
2
SPP
3
1
2
AP
3
FIG. 2. Results (meansf 1 SEM) for mean arterial
pressure (MAP), skin perfusion pressure (SPP) and
ankle pressure ( A P ) for groups 1 (n = 20), 2 ( n =
13) and 3 ( n = 15).
H. J . Durican and I. B. Faris
252
1500
,/'
0
0
1100
,/'
0
T
,*'
,/' oo
T
0
'
1000
h
c
m
.d
h
.-3
G
900
v
3
v
d
2i
0
G
c
,s
500
700
0
500
0
100
500
1000
1500
SVR (units)
0
2
1
3
FIG. 3. Skin vascular resistance (means+ 1 SEM)
for groups 1 ( n = 2 0 ) , 2 ( n = 13) and 3 (12 = 15).
FIG. 5 . Comparison between estimated vascular
rcsistance (EVR) and skin vascular resistance
(SVR) for groups 1 ( 0 ) and 2 (9).The broken line
( y = 0 . 9 2 ~-t 43, r = 0.88) is the line of best fit.
group 3 (995 + 4 5 units, P < 0.001). There was no
difference between groups 2 and 3 (P > 0.20).
kn,,,.
The results for k,,,,
for the three groups are
shown in Fig. 4. k,,,. in group 1 (0.130f0.005
min-') was higher than in group 2 (0.095 +0.005
min-', P < 0.001). k,,,.
in group 3 (0.084?0.006
min-') was lower than group 2 (P> 0.1 0).
T
1
FIG. 4. k,,,,
(n = 20), 2
(12
T
SVR vs EVR
2
The relationship between the SVR and the
estimated vascular resistance EVR is shown in Fig.
5. The EVR for group 1 was 71 8 f 37 units and for
group 2 was 1021 + 4 7 units. From Fig. 5 it can be
seen that there is a very good correlation between
SVR and EVR for both groups (r=O.88, P <
0.000 1).
3
(min-'; means + 1 SEM) for groups 1
= 13) and 3 ( n = 15).
S VR
The results for the skin vascular resistance
(SVK) in the three groups are shown in Fig. 3. The
SRV in group 1 (739 f 28 units) was lower than in
both group 2 ( 1 0 4 0 k 5 7 units, P<O.OOl) and
Location
The influence of location is shown in Fig. 6.
The SVR was higher in the calf (1082+70 units)
than the foot (870 +65 units, P < 0.05). Similarly, the SPP was higher in the calf (86 f 6 mmHg)
than in the foot (69 f 7 mmHg, P < 0.01).k,,,.
was similar in the calf (0.087 0.01 min-') and
foot (0.087 C 0.01 min-', P > 0.20).
*
Skin vascular resistance
1500
253
120
0.1!
h
.G IOOC
CI
d
z
50(
0.0
*Ot
FIG. 6. Influences of location on SVR, SPP and kmax.:
1
0 , foot; 0 , calf.
0.20
h
h
2&
I
-i
3
E
a
v
3
b
0.1c
E
Y
+
(
FIG. 7 SVR, SPP and k,,.
before
( 0 ) and
Surgery
The effect of surgery is shown in Fig. 7. The
postoperative SVR (907 f 113 units) was lower
than the pre-operative value (1 145 f 73 units, P >
0.20). The postoperative SPP (77 f 7 mmHg) was
higher than pre-operatively (37 rt 9 mmHg, P <
0.01), as was k,,,.
(0.096+0.015 min-' compared with 0.033 fO.01 min-', P<O.Ol).
Discussion
The estimation of skin perfusion pressure (SPP)
by the isotope washout method has proved useful
after ( 0 ) femoropopliteal surgery.
in clinical practice in predicting healing of major
amputations of the leg [ l l ] . The measured
pressure is close to the mean arterial pressure (Fig.
1). Holstein et al. [17, 191, who also showed this
relationship, postulated that the SPP was an indirect measure of the wedge pressure, that is, the
pressure in the main artery supplying the tissue
being studied. Thus the SPP may be useful in
assessing the severity of ischaemia of the foot,
particularly in patients with diabetes mellitus in
whom arterial calcification may prevent accurate
measurement of ankle pressure. It has also proved
useful in prediction of healing of ischaemic lesions
of the foot in diabetic subjects [13].
254
H. J . Duncan and I. B. Faris
The vascular resistance in the skin (SVR),
demonstrated in a pilot study [14], has not
previously been studied in this way. We have
shown that the SVR is equal to the vascular
resistance measured by more conventional
methods, thus validating this method. In patients
with peripheral vascular disease the mean arterial
pressure in the distal arterial tree is not known
and, therefore, the resistance can be calculated
only by the technique described in this paper.
The values for the SVR in the present study
were of the same order as those reported by Faris
& Lassen [14]. In the animal model [IS] nitroprusside used in the present study was a better
vasodilator than histamine, which was used by
Faris & Lassen. However, in patients, we have not
been able to demonstrate a systematic difference in
SVR when either vasodilating drug has been used.
We have shown in this study that the SVR
increases with age, is unaffected by atherosclerosis
and varies with different anatomical locations. The
increase with age supports histological studies
which have demonstrated thickening of the
arteriolar wall with age [20, 211. These age-related
changes significantly alter the physiology of the
microcirculation. There is a reduced reactive
hyperaemia in the human calf [22] and a decrease
in arterial distensibility with increasing age [23].
Despite a slightly higher SPP with age, the elevated
SVR significantly reduced k,,,, by approximately
27% (Fig. 4). This finding of a decrease in blood
flow with age may offer a partial explanation for
the observation that wound and ulcer healing in
the lower limbs of patients with peripheral
vascular disease is reduced with increasing age. The
determination of the SPP and SVR, therefore,
appears to be useful in the assessment of patients
with peripheral vascular disease with the SPP
reflecting large vessel disease and the SVR indicating disease of the microcirculation.
There appears to be regional variations in the
SPP and SVR as both these variables are 25%
higher in the calf compared with the foot. This
variation in SPP has been reported before, where it
has been found that there is a 12-48% reduction
in the SPP in the foot compared with calf [17,
241. These workers also measured the SPP at thigh
and ankle level and found no difference from the
calf. This is logical as the blood pressure is reduced
in the distal arterial tree, especially in the region
of the medium sized metatarsal arteries. The
elevated SVR could be an adaptation to the higher
SPP so that the skin blood flow is maintained
within normal limits. Indeed, the k,,,,, values
were identical in the foot and calf. Differences in
water content in the skin of foot and calf would
be another possible explanation for the increased
SVR in the foot. The different water content
would alter the partition coefficient between the
tissue and blood for 9mTc and thus alter with its
rate of washout. The SPP would not be affected
as the external pressure required to stop isotope
washout would be the same but the washout
rate, and thus the SVR, may vary.
Arterial reconstructive surgery resulted in a
1 10% increase in the SPP and 190% increase in the
k,,,, (and therefore blood flow) in the foot. This
demonstrates that with arterial surgery the distal
blood pressure increases, thus increasing the SPP
and skin blood flow. The k,,,,
increased to a
greater degree than the SPP, and this can be
explained by a 20% reduction in the SVR, which
did not reach statistical significance, possibly
because of the small numbers in the study. It is
proposed that the SVR decreases in these patients
because postoperatively there is an increased
distal blood pressure, which distends the arterioles
and increases their diameter and thus decreases
their resistance.
The concept of measuring tissue blood flow was
introduced by Kety in the late 1940s [16, 25j.
However, it has not received wide acceptance in
clinical medicine as it is believed to require
expensive equipment, highly trained staff and is
time consuming. We do not think that this is
valid. The equipment, including computer, cost
approximately $ASOOO. Apart from the injection,
which is given by a qualified medical practitioner,
the procedure is performed by our technical
assistant and requires 15-30 min for completion.
The injection involves a very small dose of a
readily available isotope which has been found to
give accurate estimates of blood flow [24, 261.
Sodium nitroprusside is also injected to
paralyse the vessels under study. This is important
for two reasons. The increased flow rates make it
easier to determine the influence of external
pressure on the isotope washout and thus assist
in the determination of the SPP. More importantly,
with the vessels paralysed and thus maximally
diluted the SVR can provide information concerning the structure of the microvessels. If they
were not paralysed differences in the SVR may be
due to alterations in vasomoter tone and not
structure. Other workers have used histamine
to dilate the vasculature [19, 24, 271, but we have
found in an animal model that nitroprusside is
more effective in dilating the blood vessels than
histamine [15]. The other disadvantage of
histamine is that intradermal injections are painful
for the patients.
The integrated effective whole body dose when
400 pCi (15 MBq) of sodium pertechnetate is
injected intraderinally is 11 pSv/MBq, which is
Skin vascular resistance
very small compared with most other procedures
used in nuclear medicine.
SPP and SVR can now be measured in a simple,
inexpensive washout technique and these variables
can provide useful information concerning the
severity of peripheral vascular disease and of
abnormalities of the microcirulation. This will be
of value when studying patients with diabetes
mellitus and hypertension. Changes with age,
location and the outcome of surgery can also be
determined.
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