Download Cardiovascular Responses to Sustained Handgrip

Clinical Science and Molecular Medicine (1974) 46,295-306.
CARDIOVASCULAR RESPONSES TO SUSTAINED
HANDGRIP I N NORMAL SUBJECTS A N D I N PATIENTS
WITH DIABETES MELLITUS: A TEST O F AUTONOMIC
FUNCTION
D. J. EWING, J. B. I R V I N G , F. KERR, J. A. W. W I L D S M I T H
B. F. C L A R K E
AND
University Department of Medicine and the Diabetic and Dietetic Department,
The Royal Injirmary, Edinburgh
(Received 5 July 1973)
SUMMARY
1. The blood pressure and heart rate responses to static muscular exercise were
measured in sixty normal subjects and 124 patients with diabetes mellitus, aged 25-54
years, during a standardized sustained handgrip test at 30% maximum voluntary
contraction (MVC).
2. The normal range of the response was established. Females had a smaller blood
pressure rise than males, and their MVC was lower. In the normal subjects there was a
significant correlation between the size of the MVC and the height of the blood
pressure response. The absolute muscle tension exerted should be taken into account
in addition to the percentage MVC, when comparing responses to sustained exercise
in different disease states.
3. The diabetic subjects showed a similar sex difference in their response. The mean
diastolic blood pressure rises were smaller than in the control groups, both in males
and females, but this was related to a smaller mean MVC.
4. Twenty-two of the diabetic subjects had an abnormally low response to sustained
handgrip, which was not related to age, duration of diabetes, treatment or control of
the disease. These diabetic subjects probably had damage of the autonomic fibres
mediating the response. The findings would suggest that sustained handgrip is a useful
and simple method of detecting involvement of the autonomic nervous system in
diabetes.
Key words : cardiovascular responses to static exercise; diabetes mellitus; autonomic
nervous system.
Static muscular exercise produces a significant rise in blood pressure and heart rate, a response
which can easily be elicited by using sustained handgrip (Donald, Lind, McNicol, Humphreys,
Taylor & Staunton, 1967). Detailed haemodynamic measurements during sustained handgrip
Correspondence: Dr D. J. Ewing, University Department of Medicine, The Royal Infirmary, Edinburgh
EH3 9YW.
295
296
D.J. Ewing
et
al.
have been made both in normal subjects (Lind, Taylor, Humphreys, Kennelly & Donald, 1964)
and in patients with hypertension (Ewing, Irving, Kerr & Kirby, 1973), and the concept that
the magnitude of the cardiovascular response is determined by the percentage of the maximum
voluntary contraction of a particular muscle group is widely accepted. In clinical cardiology
sustained handgrip has found a place as a stress test to distinguish normal and abnormal left
ventricular function during cardiac catheterization (Fisher, Nutter, Jacob & Schlant, 1973;
Helfant, devilla & Meister, 1971; Kivowitz, Parmley, Donoso, Marcus, Ganz & Swan, I971),
and has been used as an aid in assessing difficult heart murmurs (McGraw, Siegal, Stonecipher,
Nutter, Schlant & Hurst, 1972), but its application in other fields has not yet been developed.
The response, which is reflex in nature (Coote, Hilton & Perez-Gonzalez, 1971), is thought to
be initiated by stimuli from the exercising muscle (Donald et al., 1967). The blood pressure rise
is mediated partly by a heart rate-dependent increase in cardiac output (Lind et al., I964), and
partly by peripheral vasoconstriction mediated via the a-adrenergicreceptors of the peripheral
autonomic nervous system (Freyschuss, 1970). Any damage to the neurological pathways
involved could lead to a diminished or absent cardiovascular response to sustained handgrip.
The aim of this study was both to establish the normal range of response to a standardized
handgrip test, and to measure that response in a disease in which autonomic nerve damage is
well recognized, diabetes mellitus (Colby, 1965), to see whether static exercise could usefully be
used as a simple clinical indicator of autonomic nervous system involvement.
SUBJECTS A N D METHODS
The responses to sustained handgrip of sixty-one normal subjects aged 25-54 years, who were
blood donors, medical staff or ambulant patients recovering from either a peptic ulcer or renal
colic, were compared with 126 age-matched diabetic patients of more than 1 year’s duration
from the onset of symptoms, who had been randomly selected at their routine attendance at the
diabetic outpatient department. Patients with known cardiac disease, hypertension or respiratory disease were excluded. Three of the subjects (one normal and two diabetic) were unable to
complete the test satisfactorily, and are not included in the results.
The diabetic patients were grouped according to the duration of the disorder: 1-4 years,
forty patients (32%); 5-9 years, twenty-seven patients (22%); 10 or more years, fifty-seven
patients (46%). Seventy-ninepatients (67%) were being treated with insulin, and the other forty
patients (33%) were on oral hypoglycaemic agents, or diet alone. The degree of control of
diabetes was assessed by the blood glucose measurements at previous clinic attendances.
Forty-four patients (37%) were ‘well controlled‘ (blood glucose under 160 mg/100 ml), fortyfive patients (38%) were ‘fairly well controlled’ (blood glucose 160-200 mg/100 ml) and thirty
patients (25%) were ‘badly controlled‘ (blood glucose over 200 mg/100ml). Diabetic retinopathy of varying severity was present in thirty-one patients (26%). Incomplete data were
available on five patients.
After instruction in the use of the handgrip dynamometer, the details of which have been
described elsewhere (Ewing et al., 1973), the subjects gripped maximally with their dominant
arm for a few seconds, and this was repeated twice. The highest value of the three contractions
was taken as the maximum voluntary contraction (MVC). Handgrip was then maintained
steadily at 30% MVC for as long as possible up to a maximum of 5 min. The test was standardized at 30% MVC, since at this level most subjects are able to sustain handgrip for approxi-
Sustained handgrip in normals and diabetics
297
mately 4 min, thus allowing time for repeated measurements of blood pressure and heart rate.
Heart rate was recorded with an electrocardiograph and the rate calculated from the average of
five successive beats. Blood pressure was measured with a sphygmomanometer on the nonexercising arm, and the diastolic blood pressure was taken as the point of muffling of the sound.
These observations were recorded three times at rest, at 1 min intervals during handgrip and
twice more immediately after release. The subjects remained seated throughout. The changes
in blood pressure and heart rate were taken as the difference between the mean of the three
resting readings, and the last reading before release of handgrip. Although it was known to the
observer which subjects were normal and which were diabetic, subconscious bias in the recording of blood pressure was minimized by not analysing the responses in the two groups until
after the study had been completed.
RESULTS
Resting bloodpressure and heart rate, MVC and duration of handgrip (Tables 1-3)
The resting blood pressure was higher in the diabetic than in the normal subjects and the
heart rate was faster. Both male and female diabetics had a smaller mean MVC than the
controls. There was a highly significant difference between the MVC of males and females
(P<0+001) both in diabetic and normal subjects, but there were no significant differences in the
duration that handgrip was maintained, except in male diabetics aged 25-34 years, whose
endurance time was significantly shorter.
Response lo sustained handgrip (Tables 1-3)
The blood pressure rose markedly in all normal subjects and in most diabetic subjects during
sustained handgrip. The mean rise in systolic pressure was similar in both groups, but the mean
diastolic rise was less in all diabetic age groups, except males aged 45-54 years. The overall
mean values of diastolic pressure rise were significantly different from the controls, both in
males (P<0.05) and in females (P<0.005). The differences between the blood pressure responses
of males and females, both in the normal and in the diabetic group, were highly significant.
Because of the wide variation in individual heart-rate response, there were no statistically
significant differences between the normal and diabetic subjects. The mean rise in heart rate
was greater in the males than the females, but this was only significant in the diabetic group
(P<O.O2). Further analysis of the diabetic subjects showed that the duration of the disorder,
method of treatment, control, and the presence or absence of retinopathy had no significant
effect on the response to handgrip. In the normal subjects there was no correlation between the
resting blood pressure and rise in blood pressure, or resting heart rate and rise in heart rate.
Recovery after handgrip
There was no significant difference between the resting blood pressure and heart-rate values
before handgrip, and those measured after release, either in the diabetic subjects or in the normal
controls.
Abnormal response to handgrip
Twenty-two of the diabetics (nine male and thirteen female) showed a clearly abnormal
B
Group
No.
(kg)
MVC
Duration
of
handgrip
(min)
Systolic
30% grip
After release
Increase in blood
Increase
Blood pressure
Heart
pressure (mmHg)
in heart
(rnmHg)
Heart
rate
rate
___
rate
Diastolic (beats/min) Systolic Diastolic (beats/min) Systolic Diastolic (beatslmin)
Blood pressure
(mmHg)
Rest
TABLE
I. Response to sustained handgrip at 30% MVC in normal subjects (rnean+SD)
b
No.
11
24
31
66
13
19
26
58
Group
Males
25-34years
35-44YWS
45-54years
All males
Females
25-34YearS
354years
45-54YeaS
All females
26f6.2
26f5.2
253~4.5
25f5.1
43f6.4
40k9.2
37f6.8
39.5f7.9
MVC
(kg)
3.6+1-1
3.7k1.0
3-9-1-1.1
3.8k1.1
2.9c0.5
3.7+1-0
3.8k1.0
3-6+1-0
Duration
of
handgrip
(min)
121f15
135f25
156217
141f24
127k16
127f16
139f20
133f19
88+11
93f11
86f16
89f14
95+9
89+12
79213
87f13
82f12
83+13
77+11
89f13
88f15
85+9
89f12
87+11
Blood pressure
(mmHg)
Systolic
30% Grip
After release
27f15
25f15
25+13
23f15
43f15
32f16
41211
38f14
17+11
17+11
21-1-10
16-1-13
34+14
25-1-12
28-1-9
28-1-11
829
929
12f12
727
18212
12f8
12f10
13210
159+21
142+27
121+14
134-1-28
130415
129&17
143f22
136+20
86t-15
89+14
89+13
893~13
94f12
82+11
883~12
83+13
843~12
95+8
78f11
89f14
87&16
86+9
92f13
89+12
Increase in blood
Increase
Blood pressure
Heart
pressure (mmHg)
in heart
(mmHg)
Heart
rate
rate
rate
Diastolic (beatslmin) Systolic Diastolic (beats/min) Systolic Diastolic (beatslmin)
Rest
TABLE
2. Response to sustained handgrip at 30% MVC in diabetic subjects (mean+ SD)
n
g.
~
!2
a
2
a
3
3
2
G*
3
&
Q
s.
3
Normal males
and normal females
Diabetic males
and diabetic females
Normal males
and diabetic males
Normal females
and diabetic females
Groups
NS
NS
NS
NS
P< 0.001
P< 0.02
P< 0.05
Duration
of
handgr ip
P< 0.001
MVC
P< 0.001
P< 0.01
P< 0 0 2
P< 0001
P< 0.10
NS
P< 0.05
NS
NS
NS
Diastolic
Heart
rate
P< 005
NS
Systolic
Blood pressure
Rest
NS
NS
P< 0~001
P< 0.05
Systolic
P< 0.005
P< 0.05
P< 0.001
P< 0.001
Diastolic
Rise in blood pressure
30% Grip
TABLE
3. Response to sustained handgrip at 30% MVC: differences between groups. NS, not significant
P< 0.10
NS
P<0.02
NS
Rise in
heart
rate
%
-..
2
-b5
301
Sustained handgrip in normals and diabetics
response to handgrip. This was defined as a rise in diastolic blood pressure that was two standard deviations below the mean value for normal subjects of the same sex (Fig. 1). In these
subjects, the mean MVC, resting blood pressure and heart-rate values did not differ significantly from the other diabetic subjects studied (Table 4). There was no correlation of the
abnormal response with the age of the patient, duration of diabetes, method of treatment
or control, and although there was a higher incidence of retinopathy (38%) when compared
with the incidence among the rest of the diabetics (23%), this difference was not statistically
significant.
Males
Normal
-
50
Females
Diabetic
Normal
Diabetic
- _ - - - - --0
0
9
a
lo
0
I
I
88
,.
-
I
0
0
- l o t
-20
FIG.1. Increase in diastolic blood pressure in normal and diabetic subjects during sustained handgrip at 30% MVC.Broken lines (- - -) represent 2 standard deviations from the mean values for
the normal subjects.
Relation between MVC and the magnitude of the cardiovascular response
There was a significant correlation between the MVC and the rise in blood pressure both in
normal and in diabetic subjects. In normal subjects it was possible to construct confidence
intervals from the data of the diastolic blood pressure rise (Fig. 2). The correlation with systolic
blood pressure in normal subjects was not as close (r = 0.4265; P<O-OOI). There was no significant relationship between MVC and heart rate rise in normal subjects (r = 0.2395; P<O.lO).
D.J. Ewing et al.
302
TABLE
4. Resting blood pressure and heart rate and change in values during sustained handgrip at 30% MVC in
those diabetic subjects whose response was defined as abnormal (mean fSD)
Rest
No.
Male
Female
MVC
(kg)
Duration
of
handgrip
(min)
Systolic
3.9k1.3
4.3k0.9
136+21
146k21
37k9
23+5
9
13
30% Grip
Blood pressure
(mmHg)
Increase in blood
Increase
Heart
pressure (mmHg)
in
rate
rate
Diastolic (beatslmin) Systolic Diastolic (beats/min)
90+13
92+8
91213
90k14
17+10
12+12
10+2
2-15
4+5
3k9
Normal 8ub:ects
60 -
y=10 604t0510.r
Confidence interval for
a predicted observation
50 -
.
-I"
-Ee -
0
.
40-
..
2
30-
.
....
u
.0
+
-
0
n
a 20-
/
95%
-
10 -
I
0
1
1
I
1
1
1
I
I
I
I
I
5
1
0
15
x)
25
33
35
40
45
50
55
I
60
I
65
FIG.2. Relation between maximum voluntary contraction and increase in diastolic blood pressure
during sustained handgrip at 30% MVC in sixty normal subjects.
303
Sustained handgrip in normals and diabetics
Although in diabetic subjects the mean values of both MVC and diastolic blood pressure rise
were lower than in normal subjects, the regression slope for the former ( y = 0.562x+4.422)
was not significantly different from that obtained in the normal subjects.
Magnitude of the blood pressure response in relation to time
Normal subjects who sustained handgrip for different lengths of time had similar mean rises
in diastolic blood pressure (Table 5). The rate of rise was therefore greatest in those who
released handgrip earliest.
TABLE
5. Diastolic blood pressure rise (mmHg) at minute intervals during sustained handgrip at 30% MVC in
normal subjects (mean fSD)
No.
Males
Held to 2 min
Held to 3 min
Held to 4 min
Held to 5 min
Ail males (no.)
1
15
11
6
Females
Held to 2 min
Held to 3 min
Held to 4 min
Held to 5 min
All females (no.)
10
8
8
1
1 min
14f7 (33)
30
2358
24f9
21 5 9
23+8 (33)
12
12f8
9+5
7k 5
1 0 k 6 (27)
17
18k9
16+5
13+7
1 6 f 7 (27)
15
13f7
15+6
15+9
3 min
2 min
31+8
305 10
2528
2 9 + 9 (32)
4 min
5 min
36+ 11
28+ 11
33+12 (17)
32f 10
32+10 (6)
25+8
2358
2 4 k 8 (16)
25+ 10
25f10 (8)
24k 8
19+6
17+7
20+8 (26)
Reproducibility
The individual variability of the response was measured in five normal subjects (all male
medical staff), who repeated the handgrip test five times within a 3 week period. Their results
are shown in Table 6. In order to determine the variability throughout the range of the response,
a further six normal subjects and nineteen diabetic subjects performed the handgrip test twice:
ten of the diabetic group had an abnormal response. In these twenty-five subjects, the mean
square of the deviation of the difference in diastolic blood pressure rise between subjects was
approximately seven times that within subjects ( F = 7-39; P <O.Ol), thus showing that the
response was reproducible.
DISCUSSION
Although the technique of sustained handgrip is not new, the normal range of the cardiovascular response has not previously been reported. The method used here has certain limitations, being dependent on the effort of the subject, and measurement of the blood pressure rise
is limited by the errors of sphygmomanometry. It has the advantage of simplicity, rapidity
(the total time to perform a test is about 10 min), safety (the cardiovascular changes revert to
normal within 1 min of releasing handgrip) and repeatability on an outpatient basis.
39+2
38+ 3
43+3
48+6
45+ 5
1
3
4
5
2
MVC
(kg)
Subject
+
+
4.0+ 0.7
2.8 0.4
3.2k0.4
3.6e1.1
4.4 0.9
~~
Duration
of
handgrip
(min)
111+6
118+6
11924
132+8
117+1
Systolic
30% Grip
71+7
84+2
80+7
76+6
75+3
5924
71+6
63+5
67+7
61+5
129+5
159+17
165+12
166+8
153_+8
96+6
120+7
128+8
105+9
112k4
79+11
82+4
85+8
77+6
81+9
18+ 4
41f16
46+9
34+11
36+8
25+10
36f5
48210
29+10
37+4
18+4
1 4 26
16511
15+9
20+8
Blood pressure
Increase in blood
Heart
(mmHd
Heart
pressure (mmHg) Increase in
rate
rate
heart rate
Diastolic (beatshin) Systolic Diastolic (beatslmin) Systolic Diastolic (beatslmin)
Blood pressure
(mmHg)
Rest
(mean+ SD)
TABLE
6. Variability of the response to sustained handgrip at 30% MVC in five normal subjects who each performed the test five times
%
2
0s
2
9'
5
b
0
P
w
Sustained handgrip in normals and diabetics
305
The observations on reproducibility of the handgrip response confirm previous work. In four
normal subjects, Bruce, Lind, Franklin, Muir, Macdonald, McNicol & Donald (1968) found a
similar variation in blood pressure and heart rate. It might be expected that the MVC would not
necessarily be a true maximum contraction if there was poor subject co-operation, but Bowie &
Cumming (1971) showedthat the MVC and endurance times were reproducible,and that the first
value of MVC did not improve on training the subjects further in the use of the dynamometer.
The findings reported here extend these observations to diabetic subjects whose response was
also found to be reproducible. It is not possible to determine whether the handgrip was held to
the same level of fatigue in all subjects, but the similar mean values for duration of handgrip in
all except one of the different sub-groups suggests that variation in subject determination is
randomly scattered throughout the normal and diabetic population. That the response is continued throughout the sustained contraction can be seen by the steady rise in blood pressure
during the contraction.
The rise in diastolic blood pressure at the point just before release of handgrip was used as
the index of response to handgrip as it was the measurement with the smallest scatter among the
normal subjects. The marked sex difference in the normal response is probably explained by
the lower absolute muscle tension exerted by females. From these results it is clear that if
meaningful comparisons of static exercise in different disease states are to be made, the absolute
muscle tension exerted has to be taken into account, in addition to the percentage MVC. The
reason why a larger tension produces a greater response is not known, but the number and
frequency of the impulses travelling in the reflex pathway may be increased either because a
greater absolute pressure within the muscle bed releases a larger chemical stimulus to the
muscle afferents, or because a muscle exerting greater tension has greater muscle bulk, and
might therefore have more muscle af€erents to be stimulated.
The lower mean values of MVC in the diabetic subjects probably account for the overall
differences in response between the diabetic and normal subjects, but do not explain the
abnormally low response of some diabetic patients. Although the dividing line between diabetics with normal and abnormal responses is arbitrary, there are, nevertheless, a number of
diabetics whose response to handgrip is considerably diminished, and this diminished response
is reproducible.
The most likely explanation for the diminished response is that there is impairment of the
reflex arc due to damage of the autonomic nerve fibres mediating the response. None of the
diabetics was on a drug known to affect the autonomic nervous system. Other possible causes
for a reduced response do not apply in these subjects: the MVC was not lower in those diabetic
subjects whose response to handgrip fell below 2 standard deviations of the normal mean value
for the sex, suggesting that diminished muscular strength is not a factor in the genesis of the
abnormal response to handgrip; failure of the subjects to exert the true maximum voluntary
contraction is also unlikely as discussed above; there was no difference in the duration that
these diabetics sustained handgrip, suggesting that individual determination was not reduced
in this group, nor was there premature release of the handgrip; a recent report has suggested
that patients with marked left ventricular disease have a lower response than normal subjects
(Fisher et al., 1973), but no diabetic subjects with known heart disease, or symptoms suggestive
of heart disease, were included in this study. We conclude therefore that some diabetic subjects
have a defect of the autonomic pathways mediating the cardiovascular responses to sustained
exercise.
306
D.J. Ewing et al.
The failure of correlation of a reduced handgrip response in the diabetic subjects with age,
duration of diabetes, form of treatment and control of the blood glucose accords with previous
neurological studies including sensory perception thresholds (Chochinov, Ullyot & Moorhouse,
1972) and the Valsalva manoeuvre (Sharpey-Schafer & Taylor, 1960), but not with motor
nerve-conduction velocity (Gregerson, 1967). The higher percentage of patients with diabetic
retinopathy suggests that many of the abnormal responders had widespread microangiopathy.
The blood pressure response to sustained handgrip at 30% MVC can easily be measured by
using a sphygmomanometer, and in diabetic subjects a rise of 10 mmHg or less in diastolic
blood pressure probably indicates damage to the autonomic nervous system. Further studies
are in progress in a selected group of diabetic patients with clinical autonomic neuropathy.
The handgrip test may also prove useful as a simple method of isolating those diabetic subjects
with involvement of their autonomic nerve fibres in the asymptomatic phase.
ACKNOWLEDGMENTS
We thank Professor K. W. Donald and Dr C. W. Vellani for their helpful advice; Dr D. A.
Williams for statistical help; Dr R. A. Cumming for allowing us to ask blood donors to act as
normal subjects, and Mr J. Walker and staff for technical assistance.
REFERENCES
BOWIE,W. & CUMMING,
G.R. (1971) Sustained handgrip-reproducibility ; effects of hypoxia. Medicine and
Science in Sports, 3, 2431.
BRUCE,R.A., LIND,A.R., FRANKLIN,
D., MUIR,A.L., MACDONALD,
H.R., MCNICOL,
G.W. & DONALD,
K.W.
(1968) The effects of digoxin on fatiguing static and dynamic exercise in man. Clinical Science, 34, 2942.
CHOCHINOV,
R.H., ULLYOT,
G.L.E. & MOORHOUSE,
J.A. (1972) Sensory perception thresholds in patients with
juvenile diabetes and their close relatives. New England Journal of Medicine, 286, 1233-1237.
A.O. (1965) Neurological disorders of diabetes mellitus. Diabetes, 14, 424-429.
COLBY,
COOTE,
J.H., HILTON,
S.M. & PEREZ-GONZALEZ,
J.F. (1971) The reflex nature of the pressor response to muscular exercise. Journal ofPhysiology, 215, 789-804.
DONALD,K.W., LIND,A.R., MCNICOL,G.W., HUMPHREYS,
P.W., TAYLOR,
S.H.& STAUNTON,
H.P. (1967)
Cardiovascular responses to sustained (static) contractions. Circulation Research, 20, Supplement 1, 15-30.
EWING,D.J., IRVING,J.B., KERR,F. & KIRBY,B.J. (1973) Static exercise in untreated systemic hypertension.
British Heart Journal, 35, 41 3-421.
FISHER,M.L., NUTTER,
D.O., JACOB,S.W. & SCHLANT,
R.C. (1973) Haemodynamic responses to isometric
exercise (handgrip) in patients with heart disease. British Heart Journal, 35, 422-432.
FREYSCHUSS,
U. (1970) Cardiovascular adjustment to somatomotor activation. Acta Physiologica Scandinauica,
Supplement 342.
GREGERSON,
G. (1967) Diabetic neuropathy: influence of age, sex, metabolic control and duration of diabetes
on motor wnduction velocity. Neurology (Minneapolis), 17,972-980.
HELFANT,
R.H., DEVILLA,
M.A. & MEISTER,
S.G. (1971) Effect of sustained isometric handgrip exercise on left
ventricular performance. Circulation, 44, 982-993.
KIVOWITZ,
C., PARMLEY,
W.W., DONOSO,
R., MARCUS,
H., GANZ,W. &SWAN,H.J.C. (1971) Effects of isometric
exercise on cardiac performance. Circulation, 44, 994-1002.
LIND, A.R., TAYLOR,
S.H., HUMFWREYS,
P.W., RENNELLY,
B.M. & DONALD,K.W. (1964) The circulatory
effects of sustained voluntary muscle contraction. Clinical Science, 27, 229-244.
MCGRAW,D.B., SIEGAL,W., STONECIPHER,
H.K., NUTTER,
D.O., SCHLANT,
R.C. & HURST,J.W. (1972)
Response of heart murmur intensity to isometric (handgrip) exercise. British Hearf Jozcrnal, 34, 605-610.
SHARPEY-SCHAFER,
E.P. &TAYLOR,
P.J. (1960) Absent circulatory reflexes in diabetic neuritis. Lancet, i, 559-562.