From the Department of Rehabilitation Medicine, University of
Occupational and Environmental Health, Fukuoka, Japan (T.M., F.T., M.Y.,
H.O.); and the Department of Rehabilitation Medicine, State University of New
York at Buffalo (K.-H.L.).
Correspondence to Fumihiro Tajima, MD, Department of Rehabilitation Medicine, University of Occupational and Environmental Health, 1–1 Iseigaoka Yahatanishi-ku Kitakyushu-shi, Fukuoka 807, Japan. E-mail ftajima{at}med.uoeh-u.ac.jp
Methods—In eight male patients with a history of CVA with
damage of the cortical or subcortical structures, we measured the cold
pressor response during recording of muscle sympathetic nerve
activity (MSNA) from the peroneal nerve on the hemiplegic side. We also
studied 10 age-matched male control subjects. Tests were performed
before, during, and after immersion of the nonhemiplegic hand in ice
water for a period of 3 minutes in each phase. We also recorded
changes in heart rate (HR), arterial blood pressure, skin
temperature of the middle finger, and perception of pain using the
Borg's score.
Results—During the control period, the mean burst count of MSNA
in CVA (57.2±3.9 beats/100 HR) was higher than in control subjects
(36.3±3.2 beats/100 HR) (P<.05). Total MSNA (the mean
burst amplitude per minute times burst rate) increased significantly in
CVA and control during the immersion period by 79.9±18.4% and
133.1±25.6%, respectively. The percent change in total MSNA in CVA
was attenuated during immersion compared with control subjects. The HR
and skin temperature responses as well as the Borg's score were
similar in both groups during control, hand immersion, and recovery
periods.
Conclusions—The present results suggest that increased MSNA
in CVA may be due to damage of cortical or subcortical structures or
stroke-related changes in other areas or nonspecific changes that cause
continuous increase in basal MSNA.
Autonomic dysfunction, eg, shoulder-hand
syndrome,9 supraventricular
tachycardia,10 and other
cardiovascular diseases,11 12 13 is
frequently encountered in cerebrovascular disease. BP is controlled by
a group of neurons in the medulla oblongata collectively termed the
vasomotor area or vasomotor center.14 Descending
tracts from the cerebral cortex (particularly the limbic cortex)
connect to the vasomotor center and relay in the hypothalamus and
possibly in the mesencephalon.14 Consequently,
central lesions that lead to autonomic dysfunction may result in
myocardial damage, cardiac arrhythmia, and disturbances
of the mechanisms regulating arterial BP.
Clinically, the cold pressor test has been used to detect
autonomic disorders and measures the response of arterial
BP and HR to hand immersion in cold water.15 A
marked increase in MSNA during the cold pressor test has been described
during microelectrode recordings from the peroneal nerve in
healthy subjects.16 17 Thus, one could gain
insight into the regulatory mechanisms that control MSNA during
localized cooling of the skin.1
In the present study we recorded MSNA in the lower leg
(peroneal microneurography) during cold pressor tests in patients who
had subcortical or cortical lesions after more than 3 months of CVA. We
measured simultaneously HR, BP, skin temperature of the
third finger, and pain rating in eight male poststroke patients and 10
sex- and age-matched control subjects before, during, and after 3
minutes of hand immersion in ice water. The purpose of this study was
to characterize the response of MSNA in poststroke patients during
localized cooling of the skin and to assess quantitatively the effects
of CVA on the autonomic nervous system.
Stroke occurred at least 3 months before the present study and was
confirmed by CT scan and classified according to the classification of
cerebrovascular disease III of the National Institute of Neurological
Disorders and Stroke.18 Patient characteristics
and type of CVA are shown in Table 3
Nerve Recordings
Physiological Measurements
Experimental Protocol
Data Analysis
Statistical Analysis
Immersion of the hand in cold water increased the total MSNA by
79.9±18.4% in poststroke patients (relative to the control period;
P<.05) (Fig 2
Changes in Cardiovascular Parameters
Changes in Skin Temperature
Changes in Perceived Pain
It is well known that immersion of the hand in ice water induces a high
pressor response, including a significant rise in BP and
HR.16 21 22 The test also induces a powerful
stimulation of MSNA.16 21 22 BP, HR, and MSNA
responses in the control subjects and poststroke patients in the
present study were consistent with those reported in the
above earlier studies. However, the percent increase of MSNA in
poststroke patients during the cold pressor test was attenuated
compared with the control subjects.
The medullary vasomotor area receives input from the cerebral cortex
(particularly the limbic cortex) that is relayed in the hypothalamus
and possibly also in the mesencephalon. These fibers are responsible
for the rise in BP and tachycardia during emotions such as
fear, sexual excitement, and anger.23 In the
present study, afferent stimuli to the cortex from thermoreceptors
in the hand and thermal information into the vasomotor area from the
hands were similar in both groups of subjects, since the skin
temperature of the third finger and the ratings of perceived pain in
poststroke patients were not different from those in control subjects.
These results suggest that stimuli from the finger to the cortex and
hypothalamus in poststroke patients were similar to those in control
subjects.
The mechanisms of augmented MSNA during the control period in
poststroke patients may be explained by the following mechanisms: (1)
impulses generated in the cerebral cortex might inhibit the tonic
discharge of sympathetic nerve activity,24 and
the loss of such tonic inhibitory influences after cortical
or subcortical lesions in poststroke patients might increase MSNA, and
(2) poststroke patients may be physically uncomfortable or stimulated
by nonspecific stimuli during the test, resulting in a continuous
augmentation of MSNA. It is possible that the augmented basal MSNA in
poststroke patients may directly or indirectly contribute to the
attenuated sympathetic response during the cold pressor test.
In contrast, the HR response in poststroke patients tended to be higher
than in control subjects during the experimental period, although the
difference was not statistically significant. Although the basal MSNA
in poststroke patients was augmented during the control period, the
difference in HR between the two groups was not statistically
significant. In this regard, previous studies by Victor et
al17 demonstrated that changes in MSNA do not
always parallel those of HR. The present study does not provide a
sufficient explanation for the difference between augmented MSNA and
lack of change in HR during the control period between control subjects
and poststroke patients. On the other hand, the mean BP during the
experimental period in poststroke patients was almost similar to that
of control subjects. The tendency for increased HR in poststroke
patients may result in a similar increase in mean BP despite the
presence of attenuated MSNA during the cold pressor test.
Previous studies reported that age,25 26
sex,27 28 and resting
BP25 29 could influence the behavior of MSNA.
Therefore, to eliminate the effect of these factors on our results, we
selected control subjects who were similar to poststroke patients with
regard to age, BP (systolic, diastolic, and mean
BP), and sex.
Clinical observation indicates that a proportion of patients with
hemispheric stroke may develop the shoulder-hand
syndrome,9 orthostatic
hypotension,30 ECG
abnormalities,10 or other
cardiovascular diseases.11 12 13
These disorders might be induced by damage of cortical and subcortical
structures. However, no reports have shown direct evidence of disorders
of regulation of MSNA in such patients. Most reports describing
sympathetic disorders in patients with CVA have used either indirect
measurements of sympathetic nerve activity or systemic measurement of
sympathetic nerve activity (such as blood catecholamines).
The present results demonstrating the presence of disorders of MSNA
regulation during the cold pressor test will help us to understand
these clinical aspects of poststroke patients.
In conclusion, the present study showed that total MSNA in supine
resting patients with a history of CVA was higher than in control
subjects and that the percent change in total MSNA (MSNA response)
during the cold pressor test was attenuated in these patients compared
with control subjects. This behavior of MSNA may be due to damage of
cortical or subcortical structures or other direct or indirect
stroke-related associated changes that produce tonic activation of
MSNA.
Received October 8, 1997;
revision received December 12, 1997;
accepted December 12, 1997.
© 1998 American Heart Association, Inc.
Original Contributions
Muscle Sympathetic Nerve Activity During Cold Pressor Test in Patients With Cerebrovascular Accidents
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and
Purpose—Autonomic dysfunction is frequently present in
patients with cerebrovascular accidents (CVA). However, the
pathophysiological mechanisms of these disorders
are not clear. The purpose of the study was to assess the effects of
CVA on the autonomic nervous system.
Key Words: autonomic nervous system • blood pressure • cerebrovascular disorders • microneurography
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
The technique of
microneurography has enabled researchers to record efferent MSNA in
humans by direct intraneural recording of postganglionic
sympathetic efferent fibers.1 2 3 MSNA consists of
sympathetic vasoconstrictor nerve impulses that innervate
skeletal blood vessels and thus plays an important role in the
regulation of regional blood flow and systemic
BP.4 5 Microneurography has contributed to our
understanding of normal and abnormal function of the autonomic nervous
system in several clinical disorders, such as diabetic
polyneuropathy,6 congestive heart
failure,7 and
hypertension.8
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Subjects
Peroneal nerve recordings were performed in eight male
patients with a history of CVA and 10 age- and resting BP–matched male
subjects aged 48 to 67 years (mean±SEM age, 57.5±2.5 years) and 43 to
68 years (mean±SEM age, 57.8±2.4 years), respectively.
Systolic BP, diastolic BP, and mean BP of the
control subjects were similar to those in poststroke patients (Tables 1
and 2).
None of the control subjects was on any medication.
View this table:
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Table 1. Resting Arterial BP in Poststroke
Patients
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Table 2. Resting Arterial BP in Control Subjects .
Patients and control subjects were free of diabetes and neurological
and cardiovascular disorders with the exception of
hypertension and CVA. In addition, patients were not on medications
that may affect the cardiovascular system at least 36
hours before the study. Other medications are shown in Table 4. A number of patients were on
purgatives to prevent constipation that may potentially alter
sympathetic nerve activity. Each patient gave signed informed consent,
and the experimental protocol was approved by the Human Investigation
Committee of the University of Occupational and Environmental Health,
Fukuoka, Japan.
View this table:
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Table 3. Patient Characteristics and Type of Cerebrovascular
Lesion
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Table 4. Medications Used by Poststroke Patients
Previous studies have demonstrated that the burst rate of MSNA
on the hemiplegic side in hemiplegic stroke patients is similar to that
on the normal side.19 We confirmed this
observation in a series of preliminary studies in six poststroke
patients which demonstrated that the mean burst count of MSNA on the
hemiplegic side (63.1±3.8 beats/100 HR) was similar to that
recorded on the normal side (61.5±3.1 beats/100 HR), and we
accordingly recorded MSNA from the peroneal nerve on the hemiplegic
side in all subjects. A tungsten microelectrode (Iowa Doppler
Products) with a noninsulated tip approximately 5 µm in
diameter was inserted at the location of the head of the fibula through
intact skin into the underlying peroneal nerve. A reference surface
electrode was attached 15 mm from the recording electrode.
The nerve was localized by means of electrical stimulation delivered
through the recording electrode. The position within a
muscle-nerve fascicle was identified by muscle twitches after
electrical stimulation. After identification of the fascicle, the
electrode was carefully adjusted until the characteristic multiunit
bursts of MSNA were encountered. The nerve signal was amplified in two
steps, with a total gain of 50 000, and fed through a 500- to 1700-Hz
band-pass filter. A resistance-capacitance integrating network with a
time constant of 100 milliseconds allowed the recording of the
mean voltage neurogram, which was displayed and recorded for later
analysis of the nerve activity. The recorded signals were
displayed on a storage oscilloscope, a chart recorder, and a
loudspeaker throughout the experiment.
HR was determined from the ECG. After we confirmed the absence
of laterality of BP in the upper extremities, a continuous
recording of BP was obtained with the use of
photoplethysmography (Finapres, NO2300). The sensor was placed on a
finger of the hand on the hemiplegic side. The skin temperature of the
third finger of the immersed hand was measured with a thermocouple
(AM-7001 ANRITSU). To assess the subjects' perception of pain during
skin cooling, a 15-point modified Borg's score was used, as described
previously.20 The score accommodated the full
range of cooling-associated human pain perception from nonpainful cold
discomfort to intensely painful sensation. Subjects identified the
descriptive phrase that best described their perception and gave the
most closely associated numerical value.
Subjects reported to the laboratory at 3 PM to 4
PM wearing short pants and T-shirts. They were studied in
the supine position in a quiet room (ambient temperature, 26°C to
27°C). Each test consisted of 9 minutes of recording. After
basal recording for 3 minutes (control period), the subject
immersed the unaffected hand to the wrist into a 0°C water bath for a
period of 3 minutes (immersion period), followed by removal of the hand
from the bath and continuation of recording for another 3
minutes (recovery period).
All signals were stored on tape and recorded on a chart
paper for subsequent analysis. The number of bursts of MSNA was
determined by visual inspection of the mean voltage neurogram; all
recordings were analyzed by the same investigator. The
total outflow of MSNA (total MSNA) was identified by inspection of the
mean voltage neurogram. The amplitude of individual bursts was
measured, and the total MSNA was calculated by multiplying the mean
burst amplitude per minute by burst rate and expressed as units per
minute. For analysis of the responses of MSNA in poststroke
patients and control subjects, the mean amplitude of the sympathetic
burst during immersion and recovery periods was expressed as a
percentage of the mean burst amplitude recorded during the control
period. MSNA was expressed as the total burst area per minute. Basal
levels of MSNA, BP, and HR were determined during the 3-minute control
period.
We determined the significant changes in each
parameter from the control to the immersion period within
the test and changes from control between different tests within a
given time period using repeated-measures ANOVA. Differences between
groups were examined for statistical significance with the use of
Fisher's protected least significant difference analysis. A
value of P<.05 was considered statistically significant.
Data were reported as mean±SEM.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Changes in MSNA
During the control period, the mean burst rate of MSNA in
poststroke patients (37.6±2.8 bpm) was significantly higher than in
control subjects (24.2±1.7 bpm) (P<.05). The mean burst
count of MSNA in poststroke patients (57.2±3.9 beats/100 HR) was also
higher (P<.05) than that in control subjects (36.3±3.2
beats/100 HR) during the control period. The mean burst count of MSNA
increased significantly during the immersion period in poststroke
patients and control subjects to 67.7±5.0 and 61.1±3.5 beats/100 HR
(P<.05), respectively (Fig 1). Surprisingly, the mean absolute value
of burst count of MSNA during immersion in the control subjects was
almost similar to that in poststroke patients.
View larger version (23K):
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Figure 1. Burst counts of MSNA in control (n=10) and
poststroke patients (n=8) during 3 minutes of the cold pressor test
(hand immersion in 0°C water). *P<.05 compared with
control period; #P<.05 control vs poststroke patients.
Data are mean±SEM. ) and by
133.1±25.6% in control subjects. During the recovery period, the
total MSNA immediately decreased in both groups; however, it remained
at a level significantly higher than the control period in control
subjects. The percent change in total MSNA during the immersion period
was significantly less in poststroke patients than in control subjects
(P<.05).
View larger version (20K):
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Figure 2. Percent change in total MSNA in control (n=10) and
poststroke patients (n=8) during 3 minutes of the cold pressor test
(hand immersion in 0°C water). *P<.05 compared with
control period; #P<.05 control vs poststroke patients.
Data are mean±SEM.
HR increased significantly during the cold pressor test from a
mean control value of 64.0±2.8 and 65.8±2.4 bpm to 69.4±3.1 and
72.3±3.3 bpm in the control and poststroke patients, respectively, and
rapidly returned to control levels during the recovery period in both
groups (Fig 3). BP in both groups
increased significantly during the immersion period but returned to the
control level immediately after immersion (Fig 4). There were no differences in BP
between control and poststroke patients throughout the entire test.
View larger version (19K):
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Figure 3. Changes in HR in control (n=10) and poststroke
patients (n=8) during 3 minutes of the cold pressor test (hand
immersion in 0°C water). *P<.05 compared with control
period. Data are mean±SEM.
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Figure 4. Changes in mean arterial BP in control
(n=10) and poststroke patients (n=8) during 3 minutes of the cold
pressor test (hand immersion in 0°C water). *P<.05
compared with control period. Data are mean±SEM.
The skin temperature of the third finger abruptly fell to
19.3±0.8°C at 30 seconds of immersion and progressively decreased to
12.8±0.6°C at 3 minutes of immersion in control subjects. In
poststroke patients, the skin temperature of the third finger was
17.1±0.8°C at 30 seconds of immersion and 10.6±0.8°C at 3 minutes
of immersion. On removal from water, the skin temperature of the third
finger immediately rose toward the baseline level in both the control
and poststroke patients, although the temperature was lower in the
latter group at the end of the test compared with the control.
Interestingly, the decrease in the skin temperature of the third finger
in poststroke patients was greater than that in control subjects during
the period extending from 90 seconds after immersion in cold water to
90 seconds after removal of the hand (Fig 5). This finding suggests that the
magnitude of stimulation in poststroke patients was enhanced during
immersion.
View larger version (19K):
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Figure 5. Changes in skin temperature of the immersed finger
in control (n=10) and poststroke patients (n=8) during 3 minutes of the
cold pressor test (hand immersion in 0°C water).
*P<.05 compared with control period;
#P<.05 control vs poststroke patients. Data are
mean±SEM.
During ice water immersion, there was a sensation of intense pain
that was perceived almost immediately and persisted throughout
immersion in poststroke patients and control subjects. The Borg's
score during immersion in poststroke patients was not different from
that in control subjects (Fig 6).
View larger version (20K):
[in a new window]
Figure 6. Changes in the rating of perceived pain as
assessed by the Borg's score in control (n=10) and poststroke patients
(n=8) during 3 minutes of the cold pressor test (hand immersion in
0°C water). *P<.05 compared with control period;
#P<.05 control vs poststroke patients. Data are
mean±SEM.
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
The major findings of the present study were the following:
(1) total MSNA in the supine resting condition in poststroke patients
was higher than in control subjects; (2) the percent change in total
MSNA (MSNA response) during ice water immersion was attenuated in
poststroke patients compared with control subjects; and (3) there were
no differences between poststroke patients and control subjects in the
skin temperature of the third finger and ratings of perceived pain
during immersion. MSNA could probably be influenced by a variety of
nonspecific stimuli. However, since our control subjects were selected
so as to be closely similar to the poststroke patients, we could rule
out the possible effects of age, sex, hypertension, and the use of
medications. Accordingly, our results suggest that stroke is directly
associated with increased MSNA in poststroke patients compared with
control subjects at baseline resting conditions.
Selected Abbreviations and Acronyms
BP
=
blood pressure
bpm
=
beats per minute
CVA
=
cerebrovascular accident
HR
=
heart rate
MSNA
=
muscle sympathetic nerve activity
Acknowledgments
This study was supported by the Japanese National Foundation for
Scientific Research. The authors thank Satoko Aoki, Nozomi Noyama, and
Aya Katayama for their technical assistance in data acquisition, and
Hiroyuki Okawa and Shinichi Sato for their helpful advice. We also
thank Dr Keizou Shiraki, Professor of Physiology, University of
Occupational and Environmental Health, Japan, and Associate Professor
F. Issa for their careful reading and editing of our manuscript.
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
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