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Clinical Science (2004) 106, 605–611 (Printed in Great Britain)
Sympathetic neural hyperactivity and its
normalization following unstable angina
and acute myocardial infarction
Lee N. GRAHAM, Paul A. SMITH, John B. STOKER, Alan F. MACKINTOSH
and David A. MARY
Department of Cardiology, St James’s University Hospital, Leeds LS9 7TF, U.K.
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Impaired autonomic function occurs after AMI (acute myocardial infarction) and UA (unstable
angina), which may be important prognostically. However, the pattern of sympathetic nerve
hyperactivity has been investigated only after AMI. We aimed to quantify central sympathetic
output to the periphery in patients with UA, investigate its progress over time relative to that
after uncomplicated AMI and to explore the mechanisms involved. Muscle sympathetic nerve
activity (MSNA) assessed from multiunit discharges and from single units (s-MSNA) was obtained
in matched patients with UA (n = 9), AMI (n = 14) and stable CAD (coronary artery disease,
n = 11), patients with chest pain in which AMI was excluded (NMI, n = 9) and normal controls
(NCs, n = 14). Measurements were obtained 2–4 days after UA or AMI, and repeated at 3 monthly
intervals until they returned to normal levels. The respective MSNA and s-MSNA early after UA
(72 +
− 4.0 bursts/100 beats and 78 +
− 4.2 impulses/100 beats respectively) were less than those
after AMI (83 +
4.4
bursts/100
beats
and 93 +
−
− 5.5 impulses/100 beats respectively). Relative to
the control groups of NCs (51 +
2.7
bursts/100
beats and 58 +
−
− 3.4 impulses/100 beats respectively) and patients with CAD (54 +
3.7
bursts/100
beats
and
58 +
−
− 3.9 impulses/100 beats
+
4.9
impulses/100
beats respectively),
respectively) and NMI (52 +
4.5
bursts/100
beats
and
59
−
−
values returned to normal after 6 months in UA (55 +
5.0
bursts/100
beats
and
62 +
−
− 5.5 impulses/
100 beats respectively) and 9 months after AMI (60 +
3.8
bursts/100
beats
and 66 +
−
− 4.2
impulses/100 beats respectively). In conclusion, both UA and AMI result in sympathetic hyperactivity, although this is of smaller magnitude in UA and is less protracted than in AMI. It is suggested
that this hyperactivity is related to the degree of left ventricular dysfunction and reflexes.
INTRODUCTION
Patients with AMI (acute myocardial infarction) and UA
(unstable angina) are known to have impaired autonomic
function [1–6], particularly in cases which have an
adverse outcome [1–4]. In a recent report [7], we used
microneurography to show that uncomplicated AMI was
associated with a protracted increase in sympathetic nerve
activity relative to three control groups: normal controls
(NCs), patients with stable CAD (coronary artery
disease), who had no prior AMI, and patients hospitalized
with chest pain in whom AMI was subsequently excluded
(NMI). In patients admitted to hospital with UA, there
has been virtually no information on the magnitude of
sympathetic nerve activity, particularly in comparison
with that seen following AMI. The only reported data
have involved levels of plasma norepinephrine measured
during admission for suspected AMI. These levels
Key words: action potential, myocardial infarction, sympathetic nervous system, unstable angina.
Abbreviations: ACE, angiotensin-converting enzyme; AMI, acute myocardial infarction; CAD, coronary artery disease;
CK, creatine; LVEF, left ventricular ejection fraction; MSNA, muscle sympathetic nerve activity; s-MSNA, MNSA from single
units; NC, normal control; NMI, AMI excluded; UA, unstable angina.
Correspondence: Dr Lee N. Graham ([email protected]).
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Table 1 Characteristics of the five study groups
2
Data are expressed as means +
− S.E.M. Analyses were performed using ANOVA post-tests, except for sex difference in which χ test was
∗
∗∗
∗∗∗
P < 0.001 compared with AMI. †P < 0.05 and ††P < 0.01 compared with UA. impulses/100 b,
used. P < 0.05, P < 0.01 and
impulses/100 cardiac beats; bursts/100 b, bursts/100 cardiac beats.
Study groups
Parameters
n (males)
Age (years)
Body weight (kg)
Body mass index (kg/m2 )
Heart rate (beats/min)
Blood pressure (mmHg)
Mean
Systolic
Diastolic
LVEF (%)
s-MSNA (impulses/min)
s-MSNA (impulses/100 b)
MSNA (bursts/min)
MSNA (bursts/100 b)
AMI
14 (11)
59 +
− 2.4
78 +
− 3.4
26 +
− 0.9
55 +
− 1.6
89 +
− 2.4
114 +
− 3.8
76 +
− 2.0
49 +
− 1.7
50 +
− 2.6
93 +
− 5.5
45 +
− 2.3
83 +
− 4.4
UA
9 (6)
54 +
− 3.0
82 +
− 5.1
28 +
− 1.8
57 +
− 2.5
95 +
− 5.2
∗∗
131 +
− 8.2
77 +
− 4.0
∗∗∗
58 +
− 1.5
44 +
− 3.6
∗
78 +
− 4.2
41 +
− 3.0
∗
72 +
− 4.0
were raised in patients with UA [8], and were either
mildly raised [9] or within normal limits [10] in patients
who did not have evidence of AMI. Also, using the
technique of norepinephrine spillover rate in patients
with UA, an increase in cardiac sympathetic output without a significant change in whole body
sympathetic output was reported [11].
The present investigation was, therefore, designed to
quantify the magnitude of central sympathetic vasoconstrictor output to the peripheral vascular bed in
patients admitted to a coronary care unit with UA and to
investigate its pattern of normalization over time, relative
to that found in matched patients with uncomplicated
AMI, in order to explore the mechanisms involved. For
this purpose, the mean frequency of sympathetic nerve
activity was directly measured by microneurography
between days 2–4 and then at 3-monthly intervals until
normalization with reference to three matched control
groups consisting of NCs and patients with CAD and
NMI.
METHODS
Subjects
A total of 63 white subjects were examined. They
included 20 patients who had uncomplicated AMI
between January 2000 and March 2002, nine patients
who had UA, 14 NCs, 11 patients with stable CAD, who
had no prior history of AMI, and nine patients with NMI,
who had angiographically normal coronary arteries.
Of the 20 patients who had AMI, two developed
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NC
14 (9)
57 +
− 1.6
79 +
− 3.1
26 +
− 0.8
63 +
− 2.3
∗∗∗
100 +
− 1.3
∗∗∗
134 +
− 2.0
83 +
− 1.1
∗∗∗
62 +
− 1.3
∗∗∗
36 +
− 1.7 †
∗∗∗
58 +
− 3.4 †
∗∗∗
31 +
− 1.0
∗
51 +
− 2.7 ††
CAD
11 (8)
55 +
− 3.3
82 +
− 3.3
26 +
− 0.9
58 +
− 2.4
96 +
− 1.6
∗∗
131 +
− 3.1
78 +
− 1.3
∗∗∗
60 +
− 1.4
∗∗∗
34 +
− 2.8 †
∗∗∗
58 +
− 3.9 †
∗∗∗
31 +
− 2.6
∗∗∗
54 +
− 3.7 †
NMI
9 (7)
55 +
− 2.2
79 +
− 3.3
26 +
− 1.3
63 +
− 4.7
98 +
− 1.2
∗∗
130 +
− 1.4
82 +
− 1.3
∗∗∗
61 +
− 1.5
∗∗
37 +
− 3.3
∗∗∗
59 +
− 4.9 †
∗∗∗
33 +
− 3.0
∗∗∗
52 +
− 4.5 †
clinical complications (re-infarction and heart failure
respectively), and stable microneurographic data could
not be obtained in a further four. Complete data were,
therefore, obtained from 14 patients with uncomplicated
AMI, nine patients with UA, 14 NCs, 11 patients with
stable CAD and nine patients with NMI, who were all
matched in terms of age and body mass index (Table 1).
Of these 43 subjects, 10 patients with AMI, 13 NCs,
11 patients with CAD and nine patients with NMI,
were included in a previous publication with a different
objective [7]. All patients were screened by history,
physical and laboratory examination. Patients were excluded if there was a history of previous myocardial infarction, hypertension, diabetes or other chronic disease
that may influence the autonomic nervous system. Those
patients with evidence of arrhythmia, conduction abnormalities, heart failure or cardiogenic shock were also
excluded.
AMI was confirmed by the following criteria: (i) a
clinical history of ischaemic-type chest pain, (ii) changes
on serially obtained ECGs, (iii) a rise in serum CK
(creatine kinase) levels to > 400 international units/l
and its subsequent fall, and (iv) serum troponin-I levels
> 0.5 µg/l. All AMI patients were in Killip class I,
and were receiving conventional therapy in the form
of thrombolysis (n = 12), β-blockers (n = 14) and ACE
(angiotensin-converting enzyme) inhibitors (n = 10).
Seven of these patients were already receiving β-blockers
for at least 2 months before AMI. ACE inhibitors were
prescribed in these patients for secondary prevention.
None of the AMI patients were taking nitrates or had
received morphine on the day of examination.
Sympathetic activity in acute coronary syndromes
UA was diagnosed by the following criteria: (i) clinical
history of unstable ischaemic symptoms. Angina was
deemed to be unstable when it was either of newonset (of at least Canadian Cardiovascular Society
class III severity), becoming more frequent or longer
in duration, or occurring at rest (usually prolonged
pain > 20 min duration), (ii) no evidence of AMI by
the criteria above, including normal troponin-I levels
of < 0.03 µg/l, signifying no significant myocardial
cell necrosis. Subsequent exercise testing and coronary
angiography confirmed the presence of significant CAD
in these patients. None of the AMI or UA patients
had frequent ventricular ectopic beats or conduction
defects, chest rales or radiographic evidence of pulmonary
vascular congestion. Also, none had an LVEF (left
ventricular ejection fraction) of < 40 % as determined
by echocardiography. None had undergone any revascularization procedure, as all were asymptomatic and
clinically stable during follow-up. Seven of the AMI
patients had anterior and seven had inferior infarcts.
CAD was diagnosed both by exercise treadmill testing
and coronary angiography. A positive exercise test was
defined by horizontal ST depression of at least 2 mm
during exercise with associated chest pain. Coronary
angiography demonstrated significant CAD in these
patients (> 70 % stenosis of at least one major epicardial
coronary artery). In the AMI, UA and CAD patients,
the findings comprised single vessel disease (n = 8, 4 and
9 respectively), two-vessel disease (n = 5, 4 and 2 respectively) and three-vessel disease (n = 1, 1 and 0
respectively). Patients with UA were taking β-blockers
(n = 9) and ACE inhibitors (n = 8); the indication for the
latter was that these patients had significant CAD. In
six patients, β-blockers were started at least 2 months
before admission. In addition, all CAD patients and five
of the NMI group were taking β-blockers for at least
2 months.
The investigation was carried out in accordance with
the Declaration of Helsinki (2000) and with the approval
of St. James’s University Hospital Ethics Committee. All
subjects provided written informed consent.
General protocol
Sympathetic nerve activity was assessed in the AMI
and UA patients at 2–4 days following admission and
repeated at 3-monthly intervals until it returned to levels
similar to those found in the three control groups.
The details of the protocol and data analysis have
been published previously [7]. Briefly, all investigations
were performed under similar conditions between 09:00
and 12:00 hours to avoid circadian autonomic variation.
Subjects were asked to have had a light breakfast and
to empty their bladder before commencing the study.
The subjects maintained a normal dietary sodium intake
of approx. 400 mmol/day, and they were requested to
avoid nicotine and caffeine products for 12 h and alcohol
and strenuous exercise for 24 h prior to investigation.
During each session, the subjects were studied in the semisupine position. Measurements were made in a darkened
laboratory in which the temperature was constant at 22–
24 ◦ C. Resting blood pressure was measured from the arm
using a standard mercury sphygmomanometer. Heart rate
and arterial blood pressure were monitored and recorded
using a standard ECG and a Finapres device, and blood
flow to the muscle of the left calf was obtained using
standard strain-gauge plethysmography.
Microneurography
Post-ganglionic MSNA (muscle sympathetic nerve
activity) was recorded from the right peroneal nerve for
5 min after subjects had attained steady state for at least
30 min regarding measured variables as described previously [7]. Briefly, the neural signal was amplified
(× 50 000) and, for the purpose of generating bursts representing multiunit discharge, the signal was filtered
(bandwidth of 700–2000 Hz) and integrated (time constant 0.1 s). The output of action potentials and
bursts from this assembly were passed to a dataacquisition system, which digitized the action potentials at 12 000 samples/s and other data channels at
2000 samples/s (8 bits).
MSNA was differentiated from skin sympathetic
activity and afferent activity by previously accepted
criteria [7]. Single units (s-MSNA) in the raw action
potential neurogram were obtained by adjusting the
electrode position whilst using fast monitor sweep and
on-line storage oscilloscope to confirm the presence of
a consistent action potential morphology, as described
previously [7]. Only vasoconstrictor units were accepted
and examined, the criteria of acceptance being appropriate
responses to spontaneous changes in arterial blood
pressure, the Valsalva manoeuvre and isometric handgrip exercise. Simultaneous measurement of calf vascular
resistance confirmed the vasoconstrictor function of the
observed neural activity. During the Valsalva manoeuvre,
sympathetic activity increased during the latter part of
phase-II and/or phase-III and decreased during phaseIV (increase and overshoot of blood pressure). Isometric
hand-grip exercise, performed using a dynamometer,
produced a late increase in arterial blood pressure and
sympathetic neural activity.
An electronic discriminator was used objectively to
count the spikes of s-MSNA, and was quantified as
mean frequency of impulses/min and also as impulses/100
cardiac beats to avoid any interference by the length
of the cardiac cycle [12]. The bursts of MSNA were
identified by inspection when the signal-to-noise ratio
was > 3, and they were quantified in a similar manner.
The variability of measuring both s-MSNA and MSNA
in this laboratory did not exceed 10 % [7]. Furthermore, in 11 subjects who were re-examined after the lapse
of 8 +
− 2.7 months, no statistically significant differences
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Table 2 Changes over time in the measured parameters of the 14 AMI patients
∗
∗∗
Data are expressed as means +
− S.E.M. Analyses were performed using ANOVA post-tests. P < 0.05, P < 0.01 and
∗∗∗
P < 0.001 compared with data at 2–4 days. †P < 0.05, ††P < 0.01 and †††P < 0.001 compared with data at
3 months. ‡P < 0.05 and ‡‡P < 0.01 compared with data at 6 months. impulses/100 b, impulses/100 cardiac beats;
bursts/100 b, bursts/100 cardiac beats.
Time after admission
Parameters
Body weight (kg)
Body mass index (kg/m2 )
Heart rate (beats/min)
Arterial pressure (mmHg)
Mean
Systolic
Diastolic
LVEF (%)
s-MSNA (impulses/min)
s-MSNA (impulses/100 b)
MSNA (bursts/min)
MSNA (bursts/100 b)
2–4 days
3 months
78 +
− 3.4
26 +
− 0.9
55 +
− 1.6
80 +
− 3.7
27 +
− 1.1
53 +
− 2.4
89 +
− 2.4
114 +
− 3.8
76 +
− 2.0
49 +
− 1.7
50 +
− 2.6
93 +
− 5.5
45 +
− 2.3
83 +
− 4.4
92 +
− 1.8
∗
123 +
− 2.9
77 +
− 2.0
∗∗
53 +
− 1.2
∗
44 +
− 2.7
∗∗
85 +
− 5.4
∗∗
40 +
− 2.5
77 +
− 5.0
occurred in sympathetic nerve activity and the variability
of measurement was a maximum of 12 %.
Other assessments were carried out independently
and without knowledge of the results from the
microneurography data. LVEF was determined using
two-dimensional echocardiography (Toshiba SSA-380A;
Toshiba Corp, Tokyo, Japan), as described previously [7].
Briefly, left ventricular wall motion was assessed visually
using a nine-segment model and graded as described
previously in patients with myocardial infarction [13,14].
The following scores were used: 3 for hyperkinaesia, 2
for normokinesia, 1 for hypokinesia, 0 for akinesia and
− 1 for dyskinaesia. Wall motion index was calculated by
dividing the sum of the scores in each individual segment
by 9; when multiplied by 0.3, this index gave the estimate
of LVEF.
Statistics
ANOVA with Newman–Keuls post-tests were used to
compare data between patients and subjects and to test
changes of data during follow-up in patients (repeated
measures). The least-square technique was used for
assessing the linear relationship between variables. Values
of P < 0.05 were considered statistically significant. Data
are presented as means +
− S.E.M.
RESULTS
There were no significant differences between the AMI,
UA, NC, CAD and NMI groups (Table 1) with respect
to age, body weight, body mass index or heart rate.
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6 months
∗
81 +
− 4.0
∗
27 +
− 1.2
55 +
− 1.7
94 +
− 1.8
∗∗
128 +
− 2.6
77 +
− 1.8
∗∗∗
55 +
− 0.9
∗∗∗
41 +
− 2.1
∗∗∗
76 +
− 4.4 ††
∗∗∗
38 +
− 2.9
∗∗∗
70 +
− 4.0 †
9 months
∗
81 +
− 3.8
∗
27 +
− 1.2
57 +
− 1.4
92 +
− 1.6
∗∗
126 +
− 2.8
76 +
− 1.6
∗∗∗
56 +
− 1.3 †
∗∗∗
37 +
− 2.0 †††‡
∗∗∗
66 +
− 4.2 †††‡‡
∗∗∗
35 +
− 1.8 ††‡
∗
60 +
− 3.8 †††‡‡
Also, there were no significant differences in the gender
ratio between the five groups (χ 2 = 0.99; P > 0.9), or
in the number of significantly diseased coronary arteries
between UA, AMI and CAD groups. Mean arterial
pressure in AMI was similar to UA, CAD and NMI, but
lower than in NCs. Systolic pressure was significantly
lower in AMI than in the other four groups. The mean
LVEF in the AMI group was significantly lower than that
in the other four groups (Table 1).
During follow-up, there were no changes in the therapeutic agents given to AMI and UA patients. In the
AMI group, no significant changes occurred in indices of
body weight or heart rate. There was also no significant
change in either mean or diastolic blood pressure,
but systolic blood pressure increased significantly at
3 months (P < 0.05; Table 2). Also, a progressive increase
occurred in LVEF during the 9 months of follow-up. In
the UA group, there were no significant changes in heart
rate, arterial pressure or LVEF, but indices of body weight
were significantly greater at 3 and 6 months than at 2–
4 days. At 6 months, LVEF was significantly greater in
the UA group compared with the AMI group (P < 0.05).
All indices of sympathetic neural discharge showed a
progressive decrease (at least P < 0.05) relative to baseline
values obtained 2–4 days after AMI or UA, although
the decreases in the AMI group did not attain statistical
significance for indices/min between 3 and 6 months
(Tables 2 and 3). At 2–4 days, indices of sympathetic
neural discharge were lower in UA than AMI (Table 1
and Figure 1). These indices remained greater than in
NC, CAD and NMI groups until 9 months following
AMI and 6 months following UA when there were no
Sympathetic activity in acute coronary syndromes
Table 3 Changes over time in the measured parameters of
the nine UA patients
Data are expressed as means +
− S.E.M. Analyses were performed using ANOVA
post-tests. ∗ P < 0.05, ∗∗ P < 0.01 and ∗∗∗ P < 0.001 compared with data
at 2–4 days. †P < 0.05 and ††P < 0.01 compared with data at 3 months.
impulses/100 b, impulses/100 cardiac beats; bursts/100 b, bursts/100 cardiac
beats.
Time after admission
Parameters
Body weight (kg)
Body mass index (kg/m2 )
Heart rate (beats/min)
Arterial pressure (mmHg)
Mean
Systolic
Diastolic
LVEF (%)
s-MSNA (impulses/min)
s-MSNA (impulses/100 b)
MSNA (bursts/min)
MSNA (bursts/100 b)
2–4 days
3 months
82 +
− 5.1
28 +
− 1.8
57 +
− 2.5
∗
85 +
− 5.0
∗
29 +
− 1.7
55 +
− 1.3
95 +
− 5.2
131 +
− 8.2
77 +
− 4.0
58 +
− 1.5
44 +
− 3.6
78 +
− 4.2
41 +
− 3.0
72 +
− 4.0
95 +
− 3.7
132 +
− 6.5
76 +
− 2.7
59 +
− 2.0
∗∗
38 +
− 2.4
∗∗
70 +
− 4.5
∗∗
35 +
− 2.2
∗∗
64 +
− 4.3
6 months
∗∗
86 +
− 5.1
∗∗
30 +
− 1.8
57 +
− 1.5
94 +
− 2.7
129 +
− 3.9
77 +
− 2.4
58 +
− 2.1
∗∗∗
35 +
− 3.1
∗∗∗
62 +
− 5.5 ††
∗∗∗
31 +
− 2.7 †
∗
55 +
− 5.0 ††
Figure 1 Values of s-MSNA (top) and MSNA (bottom) over
time in AMI and UA patients
MNSA and s-MNS in 14 patients with AMI and nine patients with UA during
the initial 2–4 days, at 3 (3m) and 6 months (6m) and also 9 months (9m)
in the AMI group after admission. Values are means +
− S.E.M. and illustrate the
normalization of sympathetic hyperactivity relative to the three control groups. Also
shown are the corresponding values obtained in the matched control groups of
14 NCs, 11 patients with stable CAD and nine hospitalized NMI patients.
significant differences (at least P > 0.05) between the five
groups (Figure 1).
The significant decrease in sympathetic activity during
follow-up in AMI and UA relative to baseline values did
not correlate significantly with any changes in indices
of arterial pressure or body mass index (for AMI, at
least r = 0.44, P > 0.11 and r = 0.36, P > 0.1 respectively;
and for UA, r = − 0.51, P > 0.15 and r = − 0.52, P > 0.15
respectively). However, the baseline values of all indices
of sympathetic activity, obtained 2–4 days following
AMI, showed an inverse correlation to LVEF (at least
r = − 0.58, P < 0.03). In both the patients and the controls
there was a positive correlation with age (at least r = 0.66,
P < 0.01).
DISCUSSION
The present study has confirmed our previous results [7],
that uncomplicated AMI is associated with a protracted
sympathetic nerve hyperactivity, and extended them to
show for the first time that this sympathetic activity took
9 months to return to levels similar to those found in
NC, CAD and NMI control groups. In addition, the
study shows for the first time that a matched group
of patients admitted to a coronary care unit with UA
also had sympathetic nerve hyperactivity, although this
was smaller in magnitude than that following AMI and
returned to normal levels at the earlier time of 6 months
after the event.
As in the previous study [7], we avoided the confounding effects of race [15], age, body weight, time of
day, dietary sodium intake, large meal and visceral distension, alcohol, nicotine and exercise [16–22]. Furthermore, the absence of sympathetic hyperactivity in the
NMI group and its lesser magnitude in UA than in
AMI suggest that admission to a coronary care unit
with chest pain did not significantly confound our results
regarding sympathetic activation. There were, however,
some differences regarding drug therapy between the
study groups. Patients with AMI, UA, CAD and NMI
were receiving β-blocker or ACE inhibitor therapy,
which resulted in a slightly lower mean arterial pressure
than NCs. Although the chronic effects of these drugs
on MSNA in AMI and UA are not known, they would
not unequivocally explain the sympathetic hyperactivity
observed in these patients. In hypertension and heart
failure, these drugs either have no effect on MSNA [23–
26] or decrease it [23,27]. Also, during follow-up all
patients received the same therapy.
The new findings helped to explore possible mechanisms for the sympathetic hyperactivity seen in AMI
and UA. For example, this sympathetic hyperactivity was
found both in single unit activity and in multiunit bursts,
indicating the involvement of peripheral reflex effects [7].
However, this sympathetic hyperactivity and its change
over time could not be solely attributed to a reflex effect
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of arterial pressure, since this did not significantly change
during the follow-up period and there was no significant
correlation between arterial pressure and sympathetic
activity. Indeed, it has been found that the impairment
of the baroreceptor–heart rate reflex after AMI recovers
earlier than the impairment of the response of forearm
vascular resistance to changing the filling pressure of
the heart [28]. In addition, none of the patients had
angina for at least 24 h prior to the investigation, making
it likely that the sympathetic hyperactivity observed
was not influenced by pain. In contrast, we were not
able to exclude the operation of cardiac reflexes. For
instance, the magnitude of sympathetic hyperactivity was
greater in patients with lower values of LVEF. Also, the
sympathetic hyperactivity following AMI was greater in
magnitude than that following UA. It may be postulated
that AMI due to coronary artery occlusion would lead
to greater left ventricular dysfunction than that seen
in UA. Although our findings of increased calf muscle
sympathetic nerve activity may not be extrapolated to
other regions, a relationship between left ventricular
function and cardiac sympathetic output has been
reported previously [11,29,30]. In those reports, it was
shown that cardiac sympathetic output, as assessed by
norepinephrine spillover rate, is increased in patients who
suffered UA symptoms within the preceding 12 weeks,
in left ventricular dysfunction following ventricular
arrhythmias and during exercise-induced myocardial
ischaemia, but is normal in resting patients with stable
CAD. Furthermore, plasma norepinephrine levels are
known to be greatly raised in patients with AMI who
developed left ventricular failure [31].
Our present findings also help to define the nature
of the reflex mechanisms involved in the observed
sympathetic hyperactivity. In the experimental setting, at
least two receptor groups with contrasting reflex effects
on efferent sympathetic output have been postulated,
which respond to mechanical or chemical stimuli or both
[32,33]. The two groups are located in the left ventricle
and the coronary vessels and comprise a sympathoinhibitory group with mainly vagal afferents and a
sympatho-excitatory group with sympathetic afferent
fibres. Although both reflex effects may normally
interact, a predominant sympatho-excitation reflex is
proposed to emerge in acute pathological situations,
such as myocardial ischaemia and AMI, when chemicals
are released into the myocardium. In respect of left
ventricular dysfunction, an impairment of sympathoinhibitory reflexes from vagal afferents [34,35] has been
proposed to lead to efferent sympathetic hyperactivity.
As sympathetic hyperactivity persists for a relatively
shorter time in UA than in AMI, the above considerations
imply that the sympatho-excitation reflex operates
in the acute phases of UA and AMI, whereas
impairment of sympatho-inhibition reflex continues for
longer.
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2004 The Biochemical Society
In conclusion, it has been shown for the first time that
central sympathetic hyperactivity occurs following UA,
although it is smaller in magnitude and less protracted
than in AMI. It is suggested that the mechanism of this
sympathetic hyperactivity may at least in part involve
impairment of reflexes from cardiac receptors.
ACKNOWLEDGEMENTS
We would like to thank the British Heart Foundation for
sponsoring this work (grant no. FS/2000069), and Mr J.
Bannister, Mrs J. Corrigan and Mrs G. McGawley for
technical assistance.
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Received 17 November 2003/23 December 2003; accepted 3 February 2004
Published as Immediate Publication 3 February 2004, DOI 10.1042/CS20030376
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