Clinical Science (1992) 82, 47-54 (Printed in Great Britain)
I
47
Nocturnal variations in lower-leg subcutaneous blood flow
in paraplegic men
J. H. SINDRUP*, H. WROBLEWSKlt, J. KASTRUPt and F. BIERING40RENSENt
*Department of Clinical PhysiologylNuclear Medicine, Bispebjerg Hospital, Copenhagen, Denmark,
and Cardiovascular laboratory of Medical Department B and +Centre for Spinal Cord Injured,
Department TH, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
t
(Received 6 March17 June 1991; accepted 27 August 1991)
1. Lower-leg subcutaneous adipose tissue blood flow
rates were measured over 12-20 h under ambulatory
conditions by means of the '33Xe-washout technique in
nine paraplegic men, all with complete spinal cord lesions
at or below the Th 6 level, and in nine age-matched
healthy men. Portable CdTe(C1) detectors and datastorage units were used.
2. The central and local sympathetic vasoconstrictive
activity at the lower leg was measured under laboratory
conditions by means of the '33Xe-washout technique and
a stationary NaI(TI) detector system.
3. The paraplegic men were found to have intact central
and local sympathetic vasoconstrictive activity in their
lower legs. Moreover, they all had a nocturnal
hyperaemic blood flow phase of the same magnitude and
duration as the control subjects.
4. The possibility that the somaesthetic nerves play a role
in the hyperaemic response could be excluded, as all the
paraplegic men suffered from complete lower-leg somaesthetic denervation.
5. A significant correlation was found between the time of
going to bed and the nightly hyperaemic response in the
right and left lower legs ( P < 0.01).
6. It is concluded that the present data are in accordance
with the concept of a central nervous or humoral elicitation of nocturnal hyperaemia, although local metabolic
and other factors might participate as well. Paraplegic
men have an intact regulation of the postural and
nocturnal changes in peripheral blood flow whether of
central sympathetic or humoral origin.
With the change from the upright to the supine position
at the beginning of the night period, an instantaneous
blood flow rate increment of 30-40% was observed in
accordance with a decrease in central and local postural
sympathetic vasoconstrictive activity [9-111. Approximately 90 min after the subjects went to bed, a hyperaemic blood flow phase lasting 100 min was observed [7].
An increase in blood flow rate of as much as 244% (mean
84%) was measured. Studies of regional variations in the
lower-leg subcutaneous blood flow pointed to a central
nervous or humoral elicitation of the nightly hyperaemia,
although a role for local metabolic factors as well could
not be excluded [ 121. Simultaneous recording of nocturnal lower-leg subcutaneous blood flow levels and sleepstages in normal human subjects revealed a significant
correlation of the hyperaemic phase with deep sleep (J. H.
Sindrup et al., unpublished work). These results are in
accordance with current theories of the interrelationship
between the thermoregulatory and the arousal state
control systems [ 141. Therefore the nocturnal subcutaneous hyperaemic blood flow phase might represent a
thermoregulatory effector mechanism. The purpose of the
present investigation was to study the local and central
sympathetic vasoconstrictive activity and the nocturnal
blood flow patterns in the lower-leg subcutaneous tissue
of patients with low-thoracic or upper-lumbar complete
spinal cord injury (i.e. paraplegic patients) to elucidate the
role of somaesthetic and autonomic nervous control in
the nocturnal hyperaemic response.
MATERIALS AND METHODS
INTRODUCTION
Local blood flow rates in the human subcutaneous
adipose tissue can be measured by means of the L33Xewashout technique [l, 21, and by applying a portable
cadmium telluride [CdTe(CI)] detector system [3, 41 the
measurements can be performed under ambulatory conditions over prolonged periods of time [ 5 , 61. In recent
studies, measurements of subcutaneous blood flow rates
over 12-20 h under ambulatory conditions were performed in the lower legs of normal human subjects [7,8].
Subjects
Nine men with spinal cord injury took part in the study
(age 40.7 f8.7 years, mean fSD). They were injured at the
age of 10-44 years (27.7 f 11.7 years, mean fSD) and the
study was carried out 5-28 years (12.9k8.8 years,
mean k SD) after injury. The cause of injury was a traffic
accident in three, a fall in three, two were hit by a moving
object, and one contracted spinal cord injury during
spinal surgery.
~~~
Key words: adipose tissue blood flow rate, centralllocal sympathetic vasoconstrictiveactivity, isotope-washout technique, lower leg, microcirculation, nocturnal fluctuations, paraplegia, spinal cord injury, subcutaneous blood flow rate, thermoregulation, "'Xe-washout technique.
Abbreviation: CTVR, cutaneous thermoregulatory vasomotor response.
Correspondence: D r lens Hein Sindrup, Frederiksberg Alle 32, 4. th., DK-1820 Frederiksberg C, Denmark.
48
J. H. Sindrup et al.
Two had complete spinal cord lesions at the T h 6-Th
10 level and three at the T h 11 level and T h 12 level,
respectively; the last participant had a complete motor
lesion at the T h 12 level, whilst the sensory lesion was
complete from the L 2 level, but incomplete from the T h
11 level. Thus all the paraplegic men suffered from a
complete lower-leg somaesthetic denervation. Only
patients with lesions at or below the T h 6 level were
included in order to exclude patients suffering from
hyperhidrosis or other signs of autonomic hyperreflexia.
Nine age-matched, lean, healthy men served as control
subjects (age 38.1 & 14.3 years, mean ~ s D ) .
None of the subjects was receiving calcium antagonists,
/?-adrenoceptor blocking agents or angiotensin-converting enzyme inhibitors. None of the subjects had chronic
heart failure, diabetes mellitus, hypertension or any
symptoms or signs indicating atherosclerosis or insufficiency of the lower-limb veins. Their feet were without
clinically severe oedema or skin lesions.
The study was approved by the local ethical committee,
and informed consent was obtained from all participants
before the investigation.
Procedure for the nocturnal measurements
‘33Xe-washout measurement. The blood flow
measurements were performed on the medial aspect of
the right and left lower legs 10 cm proximal to the malleolar level. The depots of the tracer I”Xe were applied by
means of the atraumatic, epicutaneous labelling technique
as described previously [7]. Portable CdTe(CI) detectors
were mounted over the central area of the depots. The
detectors were fixed directly on to the skin surface with a
single layer of Mylar membrane interposed between the
detector and the skin surface [8]. Counts were accumulated in 1, 2 or 4 min intervals and were stored in a portable data storage unit (Memolog system 600; B.
Simonsen Medical A/S, Randers, Denmark).
The measurements started 90 min after the labelling
procedure between 15.00 and 16.00 hours and ended at
approximately 09.00 hours the next day. During this
period, which took place under ambulatory conditions,
the subjects recorded their physical activities, time of
meals and sleeping periods. The subjects performed their
normal activities during the daytime (paraplegics: sitting/
moving in wheel chair; control subjects: standing, walking
and sitting) and slept in the supine position during the
night. The subjects were not allowed to drink alcohol.
Measurements of systemic arterial blood pressure and
heart rate. In the paraplegic men, the systemic arterial
diastolic and systolic blood pressures together with the
heart rate were measured every 15 min during the
ambulatory period. An automatic, portable blood pressure recorder and processor unit was used (TM-2420,
TM-2020; Takedo Medical, A. and D. Company Ltd,
Japan). Determination of the blood pressure was effected
by means of two microphones that eliminate noise and
recognize Korotkoff sounds. Cuff pressurization was
effected by means of a low-noise rotary micropump. U p
to 600 measured values of diastolic blood pressure,
systolic blood pressure and heart rate as well as
measurement times may be stored in the internal 8 KB
semi-conductor memory.
Procedure for the laboratory measurements
Measurements of central and local sympathetic vasoconstrictive activity. The local veno-arteriolar and the
centrally elicited reflexes were investigated in both the
healthy control subjects and the paraplegic men. Central
and peripheral haemodynamic studies were performed in
the forenoon. Subcutaneous blood flow was measured 10
cm proximal to the lateral malleolus by the local isotopewashout technique as described previously [ 1, 21 using
0.1-0.3 ml of I”Xe dissolved in 150 mmol/l NaCl (10.0
mCi/ml = 370 MBq/ml; Amersham International, Amersham, Bucks, U.K.). The y-emission of the isotope was
registered by a NaI scintillation detector with a symmetric
20% window set around the 82 keV photopeak of ‘33Xe.
The detector was placed at a distance of about 20 cm
above the isotope depot, and the accumulated counts
were registered every 20 s. The subjects were lightly
dressed and were placed in a supine position on a tilt
table, with the feet immobilized by a vacuum pillow in
order to avoid changes in counting geometry due to
movements. The room temperature was about 23°C and
was consistent during the investigations. To avoid the
influence of the injection trauma [ 151, measurements were
not started until at least 30 min after the injection of
133Xe.
A
single investigation
consisted
of seven
measurements, each lasting 6-10 min, with the labelled
area on the lower leg in the following positions: (1)supine
position, leg at heart level (reference level); (2) leg lowered
50 cm below reference level; (3)leg at reference level; (4)
passive head-up tilt (45”), the labelled area on the leg
lowered about 50 cm below heart level; (5) leg at reference level; (6)passsive head-up tilt (45”),a cuff placed over
the labelled area and inflated to a pressure of 40 mmHg;
(7)leg at reference level. All measurements were initiated
2-4 min after the subject was brought to the described
position.
Calculations
Nocturnal measurements. The collected counts from
the 133Xe-disappearance measurements during the
ambulatory period were computed and the logarithmically transformed clearance curves from relevant time
periods were plotted. Linear regression analysis was performed and only rate constants ( k )from curve sections
with a correlation coefficient ( r ) >0.80 were taken into
consideration. A few minor curve sections were rejected
on the basis of this criterion; however, in no case was all
data from a subject omitted. Irregularities on the curves
were typically due to either geometrical disturbances
between the detector and the isotope depot or temporary
detector circuit noise.
The curves were analysed for goodness of fit and
linearity by linear regression analysis, and the distribution
of the residuals was inspected [7]. According to the
49
Peripheral blood flow regulation in paraplegic men
former, the majority of the curves could be divided into
five phases as follows: phase 1=day 1, phases 2, 3 and
4=night; phase 5 =day 2. Phase 2 was the initial supine
period in bed after standinglsitting. This period was without any central and local sympathetic or hurnoral orthostatic vasoconstrictive activity. Therefore the blood flow
rate during this phase was chosen as the reference level
(index= 1.00), and the changes in blood flow rate during
the period of measurement were calculated relative to
phase 2.
During the night period, three distinct phases were
detected with highly significant different isotope-washout
rates (phases 2, 3 and 4). The two break points between
the three nocturnal phases were not associated with any
known events. The determination of these two break
points was not based solely on visual inspection. First, the
logarithmically transformed washout curve for the night
period was inspected. Then the residuals were generated
and inspected on a plot [7]. The approximate location of
the points on the washout curves where the washout rate
constant changed, the break points, corresponded to the
inflexions on the residual plot. T h e accurate location of
the break points (time/count number on the x axis) was
subsequently determined by computerized multi-regression analysis by the least sum of squares method [7].
The absolute subcutaneous blood flow rate (ml min100 g - I ) = 1 x k x 100, where 1 ( = 10 ml/g of subcutaneous tissue) is the tissue-to-blood partition coefficient.
Assuming 1 to be a constant throughout the period of
measurement, relative changes in the washout rate constant ( k ) reflect relative changes in the subcutaneous
adipose tissue blood flow rate.
Laboratory measurements. The slope ( k )of the regression line was calculated by the least-squares method with
logarithmically transformed count rates corrected for
background activity. As the studies on a particular day
were performed using the same radioactive depot, 1 was
assumed to remain constant during the various experimental conditions. Relative blood flow was then calculated as f;eSl/frer=
kl,,r/krcfr
where k,,,, is the washout rate
constant obtained during the various hydrostatic stress
situations and krefis the average of the washout rate constants obtained just before and after the test.
As the level of significance, a P value of <0.05 was
chosen.
RESULTS
Fig. 1 depicts the 133Xe-clearancecurves of the right
lower leg ( a )and the left lower leg ( 6 )of a paraplegic man
during simultaneous measurements over 12 h. Immediately after the patient went to bed, there was a significant increase in blood flow. Approximately 1 h later, an
additional, highly significant increase in blood flow was
observed in both the right and left lower legs. This hyperaemic phase lasted 2 h, after which the blood flow in both
legs returned to the pre-hyperaemic level for the rest of
the night.
Fig. 2 illustrates an identical three-phasic nocturnal
subcutaneous blood flow pattern in the right lower leg of a
healthy control subject.
Table 1 shows the indices and durations of the different
subcutaneous adipose tissue blood flow rate phases of the
right and left lower legs of the nine paraplegic men. In two
of the paraplegic men, the clearance curves of the left
lower leg could not be evaluated for technical reasons,
leaving seven legs for data analysis. The blood flow
patterns of the right and left lower legs were identical.
Highly significant differences were found between the
blood flow rate indices of phases 2 and 3 as well as
between phases 3 and 4 in both legs ( P < O . O O O l ) . No
significant differences were found between the blood flow
105
-
104 101 -
Day 2
10’ -
Phase:
I
*2& 3
4
4
15
Statistics
The Pearson product-moment correlations for pairs of
variables were calculated by means of a statistical package
(Statistical Package for the Social Sciences) for the right
and left lower-leg absolute blood flow rate of all phases,
for the relative increase between phase 2 and phase 3, and
for the duration of phases 2 and 3.
Groups of mean blood flow rate indices and mean
values of the blood pressure and the heart rate of the different phases were compared by using Student’s t-test for
paired samples (Statistical Package for the Social
Sciences).
Groups of mean variables from the local veno-arteriolar and the centrally elicited reflex investigations were
compared by using Student’s t-test for unpaired data.
Day 2
5
17.00 19.00 21.00
23.00 01.00 03.00 05.00 07.00 09.00
Time of day (hours)
Fig. 1. logarithmically transformed ‘I]Xe-clearance curves
recorded over I2 h f r o m depots in the medial aspect of the right
lower leg ( a ) and left lower leg (6)of a paraplegic man. Identical
three-phasic isotope-washout rate patterns were observed during the
night period. The points of significant change in the washout rates
during the night period are indicated by small arrows on the curves. The
period of time in bed is indicated by vertical lines through the curve.
J. H. Sindrup et al.
50
rate indices of phase 1 (day 1) and phase 5 (day 2)
(P=O.12, right lower leg; P = 0.62 left lower leg).
Table 2 illustrates the indices and durations of the different phases of subcutaneous adipose tissue blood flow
rate in the right lower legs of the nine age-matched,
healthy control subjects. The blood flow rate pattern and
the duration of the different phases corresponded to those
of the paraplegic men (Table 1).
Table 3 lists the correlation coefficients ( r )between the
right and left lower-leg absolute blood flow rates, the
increase in relative blood flow rate from phase 2 to phase
3 and the durations of phases 2 and 3 for the seven paraplegic men in whom blood flow rate measurements were
available in both legs. A highly significant positive correlation was found between the absolute blood flow rates of
the right and left lower legs in phase 1 (day 1) ( P < 0.00 1).
Significant positive correlations were detected for the
104
-
10’
-
N
Y
“
I
2
8
Phase:
I
42 4
3
4
4 5
4
10‘
23.00
01.00
03.00
05.00
07.00
Time of day (hours)
11.00
09.00
Fig. 2. logarithmically transformed
‘”Xe-clearance
curve
recorded over 9 h from a depot in the medial aspect of the right
lower leg of a healthy control subject. A three-phasic isotopewashout rate pattern was observed during the night period. The points
of significant change in the washout rates during the night period are
indicated by small arrows on the curve. The period of time in bed is
indicated by vertical lines through the curve.
duration of both phase 2 and phase 3 ( P < O . O l ) . Good,
but non-significant, correlation was found for the relative
increase from phase 2 to phase 3 ( r = 0.82). No additional
significant correlations were found.
In four of the nine paraplegic men, the blood pressure
and heart rate measurements were not available for either
technical reasons or because the patient stopped the
measurement during the night. The mean systemic
arterial blood pressures and the mean heart rates of the
different phases of subcutaneous adipose tissue blood
flow rate of the remaining five paraplegic men are shown
in Table 4. A significant decrease in mean arterial blood
pressure and heart rate was seen to occur from phase 1
(day 1) to phase 2 (start of night). An additional, but nonsignificant, fall was seen in mean arterial blood pressure
from phase 2 to phase 3 (hyperaemic phase). Increases
(non-significant) in mean arterial blood pressure and
mean heart rate occurred from phase 3 to 4 and from
phase 4 to 5 (day 2).
One paraplegic man reported a 2 h sleeping period in
the supine position during the late afternoon
(18.30-20.30 hours). During the first 50 min of this
period, the absolute blood flow rate was 7.3 ml min-l 100
g - l followed by an instantaneous increase in blood flow
rate to 16.7 ml min-l 100 g-l during the last 70 min (Fig.
3). During the nocturnal part of the measurement in this
patient, a hyperaemic phase (absolute blood flow rate 9.8
ml min-l 100 g-l) lasting 120 min was measured 136
min after the patient went to bed. The relative increase
from the pre-hyperaemic to the hyperaemic phase was
133%.
local veno-arteriolar reflex
Relative changes in subcutaneous blood flow during
lowering of the lower leg 50 cm below reference levels are
shown in Fig. 4 for eight of the nine paraplegic men and
their eight age-matched control subjects. In one of the
nine paraplegic men, the clearance curves of the lower leg
could not be evaluated for technical reasons, leaving eight
legs for data analysis. Lowering of the field corresponding
to an increase in local venous transmural pressure of
about 35 mmHg caused a relative decrease in the subcutaneous blood flow to identical levcls in the two investi-
Table I. Indices and durations of different phases of subcutaneous blood flow rate in the right (n=9) and left
(n=7) lower legs of nine paraplegic men. Values are meanskso. Statistical significance: * P <O.OOOI compared with the
previous phase. Phase I =day I (sittinglmoving in wheel chair), phase 2=start of night (supine rest in bed: reference level),
phase 3=hyperaemic phase (asleep in bed). phase 4=rest of night (asleep in bed). phase 5=day 2 (sittinglmoving in wheel
chair).
Phase I (day I)
Phase 2 (night)
Phase 3 (night)
Phase 4 (night)
Phase 5 (day 2)
Right lower leg
Index
Duration
(min)
0.48 f0. I 6
2 4 5 f I25
I .oo
63t23
2.09 f 0 . 8 2 *
I14t54
0.99 t0.42*
276 99
+
0.63 f0.22
61 f 2 6
Left lower leg
Index
Duration
(min)
0.66 f 0 . 2 0
219t II6
73 i 30
2.25 f I .25*
107k66
1.12t0.83*
275t121
0.75 t 0 . 5 8
59 f29
I .oo
Peripheral blood flow regulation in paraplegic men
gated groups compared with their reference levels (1.00)
(eight paraplegic men, mean 0.54, range 0.43-0.69; eight
control subjects, mean 0.53, range 0.34-0.68, P= 0.87).
51
jects. The measured blood flow rate indices and the durations of the different blood flow rate phases corresponded
to those described previously in normal human subjects
[7, 8, 12, 131. Thus, a nocturnal hyperaemic blood flow
Head-up tilt (45”) without and with local counterpressure (the central reflex with and without contribution of
the local nervous veno-arteriolar reflex)
Fig. 5 shows the relative changes in subcutaneous
blood flow in the lower leg during head-up tilt. Upright tilt
without local counterpressure (the central reflex with contribution of the local nervous veno-arteriolar reflex)
caused a relative decrease in the subcutaneous blood flow
to identical levels in the two investigated groups compared with their reference levels ( 1.OO) (nine paraplegic
men, mean 0.49, range 0.42-0.53; nine control subjects,
mean 0.47, range 0.30-0.66, P= 0.76).
In the nine paraplegic men, when applying a local
counterpressure during head-up tilt (the central reflex
without contribution of the local nervous veno-arteriolar
reflex), the relative decrease in the subcutaneous blood
flow (mean 0.33, range 0.35-0.82) compared with their
reference levels ( 1.00) was less than without counterpressure ( P= 0.002).
4
7.3
4
16.7
4
1.3 ml min-’ IOOg”
DISCUSSION
In the present study, identical nocturnal subcutaneous
adipose tissue blood flow patterns were demonstrated in
the lower legs of paraplegic men and healthy control subTable 2. Indices and durations of different phases of subcutaneous blood flow rate in the right lower leg of nine
age-matched normal human subjects. Values are means fso. Statistical significance: *P <O.OOO I compared with the previous
phase. Phase I =day I (walking, standing and sitting), phase 2=start of night (supine rest in bed reference level), phase
3 =hyperaemic phase (asleep in bed), phase 4=rest of night (asleep in bed), phase 5=day 2 (walking, standing and sitting).
Index
Duration (min)
Phase I (day I )
Phase 2 (night)
Phase 3 (night)
Phase 4 (night)
Phase 5 (day 2)
0.77 f0.18
247 I25
I.oo
71 f 2 7
2.07 k0.66*
I l4f32
1.26k0.43*
267 f98
0.69 k0.22
160k28
+
Table 3. Correlation coefficient (r) between right and left lower-leg absolute blood flow rate and durations of
different phases in seven paraplegic men. Statistical significance: * P (0.01, **P <O.OOI.
Phase I
Phase 2
Phase 3
Phase 4
Phase 5
Phase 3lphase 2
Duration of
phase 2
Duration of
phase 3
0.99**
0.1 I
0.64
0.45
0.56
0.82
0.93*
0.88*
Table 4. Mean blood pressures and mean heart rates in the different phases of lower-leg subcutaneous adipose
tissue blood flow rate in five paraplegic men. Values are meanskso. Statistical significance: *P (0.05 compared with the
previous phase.
Phase I (day I)
Phase 2 (night)
Phase 3 (night)
Phase 4 (night)
Phase 5 (day 2)
Mean blood pressure
(mmHg)
96 f I0
84+5*
77f8
81 +8
9 4 f I3
Mean heart rate
(beatslmin)
88+5
72 ? 7’
70f6
73+8
83k12
~
~
J. H. Sindrup et al.
52
1.0
-
..
.
.
8 .
W
0
0 0
0
0
2 0.5 Y-
W
.w
W
0
0
0
0
0
0
w w
0
0
0
0
.:.
....
0
0
W
W
NS
0-
Control
subjects
NS
~~~~~
Control
subjects
Without
counterpressure
~
Paraplegic
patients
Fig. 4. Activation of the local nervous vasoconstrictor reflex. The
relative change in subcutaneous blood flow during lowering o f the lower
leg t o 50 cm below heart level (RLEF-,,) is shown. Each value was
calculated as blood flow during lowering divided by the mean value of
blood flow in the horizontal position before and after lowering. Abbreviation: NS, not significant.
rate phase could be demonstrated in all the paraplegic
men. Additionally, central as well as local sympathetic
vasoconstrictive activity was found to be intact in all the
paraplegic men.
In seven paraplegic men in whom simultaneous
measurements on identical locations at the right and left
lower legs were available, a significant positive correlation
was found between the latency periods (i.e. phase 2) until
the nocturnal hyperaemic phase (i.e. phase 3) in the two
legs. This is in accordance with the results of a previous
study [12] and supports the concept of a central nervous
or humoral elicitation of the nightly subcutaneous hyperaemia, although local metabolic and other factors might
participate as well.
The blood pressure and heart rate profiles of the paraplegic men in the present study corresponded to those
found previously in normal human subjects [ 161. They are
also in accordance with the results of previous studies,
where significant blood pressure rises have been reported
in patients with high thoracic and cervical cord lesions
associated with autonomic hyperreflexia [ 171. None of the
.
Without
counterpressure
P=O.O02
-
,
With
counterpressure
Paraplegic patients
Fig. 5. Activation of local andlor central nervous vasoconstrictor
reflex. The relative change in subcutaneous blood flow during head-up
tilt t o 4 5 O (REF) without and with local counterpressure is shown. Each
value was calculated as blood flow during head-up tilt divided by the
mean value o f blood flow in the horizontal position before and after
head-up tilt. Abbreviation: NS, not significant.
paraplegic men in the present study, who all had lesions
below the T h 6 level, suffered from hyperhidrosis (reflex
sweating) or other signs of autonomic hyperreflexia,
which are known to occur primarily in patients with spinal
cord lesions above the T h 6 level [ 17-22].
There is still controversy over the distribution of
impairment of the cutaneous thermoregulatory vasomotor response (CTVR) in spinal cord lesions at different
cord levels.
In his studies, Normell [23] demonstrated discrepancies between the loss of CTVR and somatic sensitivity in
the lower extremeties of paraplegic patients. Intact CTVR
was described in the feet of patients with lesions at T h 9
and below, and the area of loss of CTVR was generally
smaller than the area of loss of somatic sensibility, suggesting a sympathetic out-flow from the thoracic cord and
the sympathetic chain overbridging the spinal cord lesion.
Others have focused on the possibility of recovery of the
vasomotor response in man after complete spinal cord
lesions between T h 5 and T h 11 [24]. This was explained
by recovery from the spinal shock 4 months after the
trauma and suggested the spinal vasomotor reflex activity
to be a primitive and powerful mechanism for thermoregulation. Adaptation to a state of partial poikilothermia
as an adaptive thermoregulatory process after spinal cord
Peripheral blood flow regulation in paraplegic men
injury was proposed in another study [25]. The complexity of the matter is evidenced by the studies of
Downey et af. [26,27] of sudomotor activity in spinal man
and by the fact that the impairment of cutaneous vasomotor and sudomotor activity in spinal cord lesions at different levels are not necessarily congruent [23].
In the present study, the nocturnal lower-leg subcutaneous blood flow patterns of nine paraplegic men
were found to be identical with those of normal control
subjects. Head-up tilt (45") with local counterpressure
induced subcutaneous vasoconstriction in the lower leg of
the paraplegic patients. This might be explained by intact
central baroreceptor-mediated vasoconstrictive activity
or might be due to spinal sympathetic reflex activity, as
evidenced by previous studies of sympathetic reflex control of subcutaneous blood flow in tetraplegic patients
[28,29].
The local sympathetic vasoconstrictive activity was
found to be intact in all the paraplegic men. Since the local
vasoconstrictor reflex was abolished in chronically sympathectomized tissue (operatively denervated) [30, 3 11,
the present results strongly suggest an integrity of the
sympathetic connections between the hypothalamic
nuclei (thermoregulatory centre) and the efferent sympathetic nerve fibres originating from the spinal cord segments between T h 1 and L 2 and serving the lower leg
vasculature. The anatomical mechanism responsible
might be an overbridging of the spinal cord lesion by the
sympathetic chain.
All the paraplegic men in the present study suffered
from complete lower-leg somaesthetic denervation. The
studies of Henriksen [11, 321 ruled out the significance of
somaesthetic nerves in a local reflex regulating human
subcutaneous adipose tissue blood flow. Correspondingly,
a role for the somaesthetic nerves in the mechanism(s)
responsible for the nocturnal lower leg subcutaneous
hyperaemic phase is excluded in the present study. If
neurogenic factors play a major role, the autonomic (sympathetic) nervous system is most likely to be involved.
CONCLUSION
The present data are in accordance with the concept of
a central nervous or humoral elicitation of the nightly subcutaneous hyperaemia, although local metabolic or other
factors might participate as well. A role for the somaesthetic nerves was excluded by the present study. If a
neurogenic factor(s) plays a major role, the autonomic
(sympathetic) nervous system is most likely to be
involved.
ACKNOWLEDGMENTS
This work was supported by grants from the Danish
Medical Research Council (grant nos. 12-7357, 12-7888
and 12-7820), the Danish Heart Foundation, the Danish
Foundation for the Advancement of Medical Science, the
Novo Foundation, the Dagny and Harry West Jmgensen
Foundation, the August Wedell Erichsen Foundation, the
53
Jacob and Olga Madsen Foundation, Valdemar, and the
Thyra Foersom Foundation.
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