Upsala J Med Sci 81: 79-83, 1976

Changes of Reactive Hyperaemia after Clinical Bed Rest
for Seven Days

GORAN FRIMAN and ELISABETH HAMRIN

From the Departments of Infectious Diseases and Clinical Physiology,
University Hospital, Uppsala, Sweden

ABSTRACT
As an indication of peripheral circulatory function reactive
hyperaemh was studied in the forearm and calf muscle in 14
healthy young men before and after clinical bed rest for one
week. Blood flow was measured after different arterial occlu-
sion times with venous occlusion plethysmography. After bed
rest peak flow values in the calf after arterial occlusion for 3
or 5 minutes decreased moderately (by about 20-23 %) and
significantly. Peak flow in the forearm decreased as well
although not significantly.

INTRODUCTION

Immobilization and bed rest are known t o influence
central circulatory function (5,20) and blood volume
(13, but the effect on peripheral circulation seems to
have been less well investigated. The aim of the
present investigation was to establish the possible
influence of the bed rest regimen used on a modern
acute ward on peripheral circulation studied as reac-
tive hyperaemia in the forearm and calf muscles. The
investigation is part of a more extensive study of the
effect of clinical bed rest on a number of variables
related to physical fitness (9).

MATERIAL AND METHODS
Subjects
Fourteen healthy men aged 21-32 years, took part in the
investigation. They were confined to bed for 7 days in a
special room on a ward for infectious diseases. The aim was
to achieve the same degree of physical activity and caloric
intake as encountered by hospitalized patients. Thus, the
subjects were allowed to leave bed for personal hygiene. In
addition, they sat in an armchair for a short period twice
daily starting on the fifth day. Apart from this no physical
activity was permitted. Eight of the subjects were on a
standard hospital diet, while the other 6 had a starvation
diet for the first 4 days, thereafter the standard diet. Fluid
intake was unrestricted.

Procedure
Measurements were made on three occasions: one week
before the start of the bed rest period, a t the end of the bed
rest period, and one month later during which time the
subjects had maintained normal activity.

Measurements
B l o o d f l o w . Reactive hyperaemia in the forearm and calf
muscles was measured by venous occlusion plethysmo-
graphy and expressed in terms of ml/min. 100 ml tissue. A
more detailed description of the technique and procedure
used for blood flow measurements with venous occlusion
plethysmography has been given previously by Graf t
Westersten (13) and Graf (12). The forearm and calf
plethysmograph, an air-filled rubber cuff, enclosed a 5 cm
long segment of the muscular part of the extremity. A
proximal occlusion cuff was applied to the upper arm or to
the thigh, and a second occlusion cuff distal to the rubber
cuff. The air-filled plethysmograph cuff was always in-
flated to 40-50 mm HzO.

During ischaemia the proximal occlusion cuff was in-
flated to 100 mmHg above the systolic arterial blood pres-
sure in the brachial artery, while the distal occlusion cuff
was inflated to 90 mmHg. Reactive hyperaemia was rneas-
ured after different arterial occlusion times: 1 , 3 and 5 min.
During blood flow measurements the proximal cuff was
inflated to 60 mmHg (during reactive hyperaemia, this
value was initially somewhat higher) and the distal cuff was
simultaneously inflated to arterial occlusion pressure. The
blood flow was recorded on a conventional amplifier and a
direct-writing Mingograph (Siemens-Elema, Stockholm)
for 2 min with measurements made every 10 seconds during
the first minute.

The recommendations given by Graf (12) in order to
avoid errors of measurements connected with the method
were followed. Two models of venous occlusion
plethysmographs were used, the difference being the way
the pressure was applied to the proximal and distal occlu-
sion cuffs on the extremities. Mean values for the blood
flow for subjects using the two different models were
statistically tested, and no significant differences were
found.

Blood volume. Blood volume measurements were made
by determination of the total amount of haemoglobin (THb)
using the alveolar CO method, as described by Sjostrand

Upsala J Med Sci 81

80 G. Friman and E . Hamrin

Table I . Mean values M . E . M . ofbloodflow at rest andpeakjlow during reactive hyperaemia in forearm and
calf muscle after arterial occlusion f o r I , 3 and 5 rnin ( A . O . ) , and certain circulatory and anthropometric
data, in 14 healthy men subjected t o clinical bed rest f o r one week

A B C
(before (end of (one month
bed rest) bed rest) bed rest)

Forearm blood flow
(ml/min . 100 ml tissue)
Rest
1 min A.O.
3 rnin A . O .

5 min A.O.

Calf blood flow
(ml/min . 100 ml tissue)
Rest
1 min A.O.

3 rnin A . O .
5 rnin A.O.

Blood volume (1)
Total hemoglobin (g)

Red cell volume (1)
Plasma volume (1)
Body weight (kg)
Extremity circumference (cm)

Hb (g%)

Forearm
Calf

Handgrip

Knee extension

Plantar flexion

Isometric muscle strength (kp)

1 . 9 f 0 . 3
14.6f2.1
24.6f2.6

28.4f3.0
(n=13)

2.8k0.3
1 7 . l f 1.4
(n=13)
30.6f 1.4
36.52 1.7
(n= 13)
5.24f0.14
702k 20

14.65f0.28
2.08f 0.06
3.17f0.10
70.5k2.2

2 6 . 2 f 0 . 3
*35.8+0.5

*51.6k 2.5

69.6f 1.6

163.7f 6.3

2 . 0 f 0 . 4
11.72 1.3
22.4f2.6
(n = 13)
25.8k2.4
(n=13)

2.3-10.3
14.6f 1.0

***24.5f1.1
**28.2k 1.5

(n=13)
* * 4.96f0.12

* *664f 22
14.6950.23

* * 1.975 0.07
*2.99f 0.06

**69.4f2.0

26.1 f 0.3
**35.4f0.5

49.3 k 2.5

66.5f2.7

152.4f7.4

1.820.4
12.8k 1.1
24.7f 1.8

30.3k 1.8

2 . 8 2 0 . 4
**19.9f 1.3

***32.1?1.3
***37.712.1

**5.23f0.13
*688120
14.46f0.25
*2.04f 0.06

**3.26?0.08
69.842.0

26.220.3
35.5k0.5

48.8k 2.5
(n = 13)
69.84 1.9
(n=13)

* 158.24 8.0
(n=13)

*, **, and *** denote statistically significant differences (p<0.05,0.01 and 0.001, respectively), and refer to the values of
the columns between which they are interposed; asterisks in column A refer to comparisons between values of column A
and C.

(21). The total blood volpume was then calculated from the
THb and the haemoglobin concentration (Hb) of blood
from a cubital vein, punctured without venous occlusion.
Duplicate determinations of THb were always made with
an interval of one day, the coefficient of variation for the
single determination being about 4 % during the period of
investigation. The determinations made at the end of the
bed rest period were performed on the seventh day of bed
rest and on the following day.

In addition, haematocrit was determined and the plasma
volume (PV) and red cell volume (RCV) were calculated.

Isometric muscle strength. The maximal isometric mus-
cle strength was tested under standardized conditions ac-
cording to BacMund & Nordgren (2). In this paper only the
values for handgrip, knee extension and plantar flexion are
presented.

Statistical methods
In order to reveal differences between the observations on
the three occasions Student’s t-test for paired observations
was used.

Upsala J Med Sci 81

RESULTS
All results are summarized in Table I .

Bloodjlow in forearm and calf(Fig. 1). In forearm
the resting blood flow did not change during bed rest.
The mean values for peak flow during reactive
hyperaemia decreased, although not significantly,
after arterial occlusion for 1, 3 as well as 5 min.

In calf the resting blood flow decreased during bed
rest, but the change was not statistically significant.
The peak flow values recorded at the end of bed rest
were significantly lower after arterial occlusion for 3
and 5 min ( P < O . O O l and 0.005, respectively), whilst
the decrease after occlusion for 1 minute did not
reach significance.

At the one month control peak flows in calf with
arterial occlusion for 1 , 3 and 5 rnin showed a signifi-
cant increase when compared with the values re-

Peripheral circulation after bed rest 81

corded at the end of bed rest (p<0.005, 0.001 and
0.001, respectively).

Blood volume. The total blood volume was signifi-
cantly lower at the end of bed rest than before
@<0.005) or one month later (p<O.Ol).

THb, PV and RCV showed the same pattern of
response.

Body weight and extremity circumference. The
body weight fell significantly during bed rest
@<0.01) and had not returned to the initial level after
one month. The calf circumference decreased sig-
nificantly during bed rest (P<O.Ol), and the one
month control value was still significantly lower than
the initial value bC0.05).

Isometric muscle strength. The maximal strength
of isometric plantar flexion was lower at the end of
bed rest than when the subjects were ambulant;
however, the difference was significant (pcO.05)
only when compared with the one month control
value.

The strength of knee extension did not change
significantly.

Unexpectedly, the handgrip strength was signifi-
cantly lower at the one month control compared to
the initial value (p<0.05), while the value at the end
of bed rest attained an intermediate position.

DISCUSSION

In the present study we have found a significant
change of reactive hyperaemia in the calf but not in
the forearm of 14 healthy young men after bed rest

for one week. In order to avoid errors of measure-
ment connected with venous occlusion plethysmo-
graphy the recommendations given by Graf (12) have
been closely followed, both in connection with the
subjects and the evaluation of the inflow curves. The
pressure system in the plethysmograph has been
tested and some variation of the inflation pressures
of the cuffs have been accepted, as in earlier works
(3).

Delius et al. (6) found the same changes of reactive
hyperaemia when measuring blood flow with venous
occlusion plethysmography in the forearm and calf
of 32 patients who had been operated upon for
acquired or congenital heart disease. The authors
drew the conclusion that the changes in blood flow
after the operation could have been caused by a
change in the sympathetic activity. Several authors
have reported alterations in reactive hyperaemia in
skeletal muscle after passive changes of body posi-
tion from horizontal to different degrees of tilting and
to the erect position. Paterson (19) found that reac-
tive hyperaemia in the forearm decreased signifi-
cantly during tilting, a finding which he believed
could be caused by increased sympathetic activity.
Mosley (17) found decreased reactive hyperaemia in
the forearm of healthy subjects when changing from
supine to erect position, a reaction which could be
abolished by intra-arterial infusion of sympathetic
adrenergic antagonists. Using microneurography
Delius et al. (7) recorded increased sympathetic
signals in human muscle nerves to forearm and calf
after tilting from horizontal to 30-45 degrees.

6-162852 Upsala J Med Sci 81

82 G. Friman and E . Hamrin

It is not clear from the literature whether an in-
crease in sympathetic tone occurs in healthy sub-
jects as a result of bed rest for one week. However,
Hyatt (15) studied haemodynamic and body fluid
alterations in healthy subjects during different
periods of bed rest (10, 14 and 28 days), and in all the
studies he found a decrease in plasma volume and
orthostatic tolerance and an increase of peripheral
vascular resistance. Hyatt considered increased
sympathetic tone to result from the decrease in
plasma volume. Since we have also found a signifi-
cant decrease in plasma volume, it seems reasonable
t o us that this decrease may exert an effect on the low
pressure baroreceptors and thus bring about a
change in the sympathetic tone. The role of the low
pressure baroreceptors during changes of blood vol-
ume have been clearly stated in different studies
using lower body negative pressure (LBNP). Thus,
Ardill et al. ( 1 ) found that LBNP significantly de-
creased the reactive hyperaemia in the forearm, and
that sympathetic adrenergic antagonists prevented
this effect. Johnson et al. (16) found that moderate
LBNP (to -20 mmHg) only reduced right atrial
pressure and forearm blood flow, while further low-
ering of the LBNP also changed aortic mean pres-
sure, aortic pulse pressure and heart rate. According
to this study the likely source of the stimulus for the
reduction of the muscular blood flow is the low
pressure baroreceptors. In recent experiments of
similar design Sundlof & Wallin (22) have come to
similar conclusions with recordings of sympathetic
signals by microenurography .

Apart from a change in the neurogenic component
regulating the vascular bed in skeletal muscle,
changes in the local components have to be consid-
ered. According to Folkow (8) myogenic activity is
especially important in muscles which are responsi-
ble for posture. The soleus muscle is a tonic muscle,
composed of mainly red (slow twitch) fibres (1 l ) , and
according t o EMG measurements (4) it plays a sig-
nificant role in the maintenance of balance and pos-
ture. During bed rest this muscle is not being used
as a posturq muscle, because of changes gravity
conditions. An alteration in rnyogenic activity as
the main cause of the observed change in reactive
hyperaemia might therefore explain the fact that the
change was significant in the calf but not in the
forearm.

Factors at the cellular and subcellular levels must
also be taken into consideration. It has been shown
in previous studies that immobilization may cause

Upsala J Med Sci 81

atrophy of skeletal muscle (14, 18). Disuse atrophy
(cf. denervation atrophy and atrophy after
tenotomy, for review see Goldspink (10)) is
characterized by a reduction of the myofibril protein
content, while the sarcoplasmic protein content
seems to be uninfluenced (14). The observed de-
crease of calf muscle strength and circumference
after bed rest in the present study is compatible
withe the hypothesis that a reduction of the amount
of contractile substance occurred despite the rather
short immobilization time. However, other explana-
tions of the strength reduction such as a decrease of
the ATP content are also possible. The finding of a
decreased calf circumference, on the other hand,
could be explained just as well by a reduction in
tissue water, a suggestion supported by the de-
creased plasma volume and body weight. A search of
the literature revealed no definite evidence of
whether the numbers or sizes of the blood vessels are
subjected to a reduction proportional to that of the
muscle cell in disuse atrophy. If such were the case a
reduction of reactive hyperaemia would be expected
with atrophy.

ACKNOWLEDGEMENTS
The work was supported by the Delegation for Applied
Medical Defence Research (grant no. U65/1973) and by the
County Council of Uppsala. Miss Margareta Torgen and
Mrs Ninni Rosen gave technical assistance and Miss Ingrid
Lundh secretarial aid.

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Received December 15, 1975

Address for reprints:

Elisabeth Hamnn, M.B.
Department of Clinical Physiology
University Hospital
S-750 14 Uppsala
Sweden

Upsala J M e d Sci 81