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