Journal of the American College of Cardiology Vol. 42, No.

9, 2003
© 2003 by the American College of Cardiology Foundation ISSN 0735-1097/03/$30.00
Published by Elsevier Inc. doi:10.1016/S0735-1097(03)01119-7

Peripheral Sympathetic Control During

Dobutamine Infusion: Effects of Aging and Heart Failure
Sonia Velez-Roa, MD, Marc Renard, MD, PHD, Jean-Paul Degaute, MD, PHD,
Philippe van de Borne, MD, PHD
Brussels, Belgium
OBJECTIVES We assessed the effects of beta-adrenergic agonism on muscle sympathetic nerve activity
(MSNA) in patients with congestive heart failure (CHF) and young and matched controls.
BACKGROUND Myocardial response to beta-adrenergic stimulation decreases with aging and with CHF.
METHODS In CHF patients, we measured cardiac hemodynamics and MSNA (microneurography)
before, with short-term (n ⫽ 5), and after 48-h (n ⫽ 9) of dobutamine infusion (10
␮g/kg/min). In eight young controls and nine controls matched to the CHF patients, we
measured cardiac hemodynamics and MSNA during randomized short-term dobutamine (10
␮g/kg/min) and placebo infusions.
RESULTS In CHF patients, short-term dobutamine infusion did not modify mean blood pressure
(MBP), MSNA, or heart rate (HR). Moreover, 48-h dobutamine infusion increased cardiac
index (3.1 ⫾ 0.2 vs. 2.2 ⫾ 0.2 l/min/m2, p ⫽ 0.006), decreased mean pulmonary pressure (28
⫾ 7 vs. 38 ⫾ 7 mm Hg, p ⫽ 0.0001) and peripheral resistance (1,099 ⫾ 112 vs. 1,759 ⫾ 263,
p ⫽ 0.03), but did not change MBP, HR, or MSNA in the patients. In matched controls,
dobutamine increased HR (87 ⫾ 5 vs. 65 ⫾ 2 beats/min, p ⫽ 0.0009) but did not change
MBP or MSNA. In young controls, dobutamine increased MBP (102 ⫾ 2 vs. 90 ⫾ 2 mm
Hg, p ⫽ 0.0003) and decreased MSNA (28 ⫾ 5 vs. 35 ⫾ 3 bursts/min, p ⫽ 0.03) but did
not change HR (p ⫽ 0.054). In the controls, the largest increases in MBP with dobutamine
were associated with the most marked reductions in MSNA (r ⫽ ⫺0.49, p ⫽ 0.04) and the
smallest increases in HR (r ⫽ ⫺0.70, p ⫽ 0.001).
CONCLUSIONS Arterial baroreceptor activation during increases in MBP inhibits MSNA and limits the HR
response to dobutamine in controls. This mechanism, together with peripheral vasodilation,
probably contributes to the absence of peripheral sympathetic withdrawal despite substantial
hemodynamic improvements in CHF patients. (J Am Coll Cardiol 2003;42:1605–10)
© 2003 by the American College of Cardiology Foundation

Sympathetic activation is a key component of the physio-
pathology of chronic congestive heart failure (CHF) (1–10),
as it is present from the early stages of the disease and is
related to the severity of heart failure (HF) (2,8). Sympa-
thetic activity is greatest in patients with the worst func-
tional class status and in patients with the largest ventricular
filling pressures and pulmonary pressures (1,6,9); it is also
implicated in the progression of HF and has important
prognostic significance (4,5,10).
Sustained intravenous dobutamine (a primarily beta-
adrenergic agonist) is frequently administered to patients
with severe CHF in coronary care and intensive care units
(11–13). However, substantial attenuation of the beta-
adrenergic inotropic response is described in CHF due to
reductions in beta-adrenergic receptor density and abnormal
G-protein function (14).
Sympathetic activity also increases with age in normal
humans (15,16), and a diminished inotropic response of the
aged myocardium to catecholamines is described as well
(17,18). The underlying mechanism is, however, not well
From the Department of Cardiology, Erasme Hospital, Brussels, Belgium.Sup-
ported by the Erasme Foundation, Belgium (S.V-R.), the National Belgian Fund for
Research, the Foundation for Cardiac Surgery, the Jacqueline Bernheim Award, and
the Marc Hurard Foundation, Belgium (P.v.d.B.), and an Astra-Zeneca Grant,
Belgium (J.-P.D.).
Manuscript received November 25, 2002; revised manuscript received May 16,
2003, accepted July 7, 2003.
understood and is probably complex, as it is related to
altered receptor sensitivity, decreased beta-adrenergic recep-
tor density, and intrinsic alteration of the contractile re-
sponse to catecholamines by the aged myocardium (17,18).
The differential effects of aging and HF on the sympa-
thetic nerve response to beta-adrenergic agonism are un-
known. Short-term administration of low doses of dobut-
amine (3 ␮g/kg/min) increases blood pressure (BP) and
decreases muscle sympathetic nerve activity (MSNA) in
normal young subjects (19) but changes neither BP nor
MSNA in patients with HF (20). Peripheral sympathetic
activity is primarily under baroreflex control (20 –22). We
therefore tested the hypothesis that the largest arterial
baroreflex activation through marked changes in BP in
subjects with the highest beta-adrenergic sensitivity would
result in the most marked sympatho-inhibition.
We assessed the effects of beta-adrenergic stimulation
with dobutamine on peripheral sympathetic activity in 12
patients with CHF, in eight young subjects, and in nine
subjects matched for age, gender, and body mass index
(BMI) to the CHF patients.
METHODS
HF patients. Twelve patients (11 male, age 54 ⫾ 3 years
[mean ⫾ SEM], with left ventricular ejection fraction of 21
⫾ 2%, BMI 27 ⫾ 1 kg/m2, in class III (n ⫽ 7) and IV
1606 Velez-Roa et al.
Beta-Adrenergic Agonism and Sympathetic Tone
Abbreviations and Acronyms
BMI ⫽ body mass index
BP ⫽ blood pressure
CHF ⫽ congestive heart failure
CO ⫽ cardiac output
DBP ⫽ diastolic arterial blood pressure
HF ⫽ heart failure
HR ⫽ heart rate
MBP ⫽ mean arterial blood pressure
MSNA ⫽ muscle sympathetic nerve activity
SBP ⫽ systolic arterial blood pressure
TPR ⫽ total peripheral resistance
(n ⫽ 5) of the New York Heart Association classification)
admitted to the coronary care unit with decompensated
CHF were included in the study. All patients had support-
ing clinical, chest roentgengraphic, and echocardiographic
evidence of impaired left ventricular function. The effects of
dobutamine were studied only in patients who were suffer-
ing from chronic CHF and were experiencing an acute
episode of decompensation in this context. None of these
episodes was due to an acute coronary syndrome or acute
myocarditis. Atrial fibrillation converted to sinus rhythm
24 h after intravenous dobutamine therapy in one patient.
All other patients remained in normal sinus rhythm during
the study. Patients were treated with angiotensin-converting
enzyme inhibitor or angiotensin II receptor antagonists
(n ⫽ 12), furosemide (n ⫽ 12), spironolactone (n ⫽ 11),
and digoxin (n ⫽ 9). The doses of these medications were
kept constant during the study, except in three patients for
whom furosemide was changed from oral to intravenous
administration. Beta-blockers were not prescribed to any of
the patients because of hemodynamic instability.
Controls. We studied eight young male subjects (26 ⫾ 3
years) and nine subjects matched for age (50 ⫾ 1 year),
gender (eight men), and BMI (26 ⫾ 0.9 kg/m2) to the
group of patients with CHF. All were healthy volunteers
based on medical history and physical examination. They
were not taking any medications including cardiac
medications.
Informed consent was obtained from each patient and
control subject. The institutional Human Subjects Review
Committee approved the study protocol.
Measurements. All measurements were performed under
quiet resting conditions by the same investigators. In nine
patients with HF, a 7.5F flow-directed thermodilution
Swan-Ganz catheter (Baxter, California) was inserted per-
cutaneously under local anesthesia into an internal jugular or
subclavian vein to allow measurements of resting right atrial
pressure, pulmonary artery and capillary pulmonary pres-
sures, and cardiac output (CO) by the thermodilution
method. Measurements were taken at least four times and
averaged. In the controls, a venous catheter was inserted
into a basilic vein for infusion of dobutamine and placebo
after a double-blind randomized protocol. All patients and
controls underwent arterial BP measurements every 3 min
JACC Vol. 42, No. 9, 2003
November 5, 2003:1605–10
with a Physiocontrol Colin BP-880 sphygmomanometer
(Colin press Mate, Colin Corp., Japan) as well as electro-
cardiogram (Siemens Medical, ECG Monitoring, Ger-
many), respiration (Respitrace, Studely data system, model
1150, Oxford, England), and MSNA recordings that were
acquired on a MacLab 8/s data acquisition system. Total
peripheral resistance (TPR) (dyne䡠s䡠cm⫺5) was calculated
from CO (l/min) and mean BP (MBP) using the following
formula: TPR ⫽ 80 ⫻ MBP/CO.
Sympathetic nerve activity to the muscle circulation was
recorded continuously by obtaining multiunit recordings of
postganglionic sympathetic activity, measured from a nerve
fascicle in the peroneal nerve posterior to the fibular head
(23). Electrical activity in the nerve fascicle was measured
using tungsten microelectrodes (shaft diameter 200 ␮m,
tapering to an noninsulated tip of 1 to 5 ␮m). A subcuta-
neous reference electrode was inserted 2 to 3 cm away from
the recording electrode, which was inserted into the nerve
fascicle. The neural signals were amplified, filtered, rectified,
and integrated to obtain a mean voltage display of sympa-
thetic nerve activity.
Protocol and intervention in HF patients. After the
baseline hemodynamic and MSNA measurements, dobut-
amine was infused at successive doses of 3, 6, and 10
␮g/kg/min. The doses were increased every 5 min. Mea-
surements were repeated 10 min after the beginning of an
infusion rate of 10 ␮g/kg/min of dobutamine in five
patients, in order to assess the effects of short-term beta-
adrenergic therapy on hemodynamics and sympathetic
nerve activity. In nine patients (two among them also
participated in the assessment of the effects of short-term
dobutamine infusion), measurements were repeated 48 h
after the initiation of dobutamine therapy in order to
examine the hemodynamic and sympathetic effects of pro-
longed dobutamine therapy (10 ␮g/kg/min). A placebo-
controlled design was not adopted in the patients because of
severe clinical instability.
Protocol and intervention in control subjects. The ad-
ministration of dobutamine and placebo was performed
after a randomized cross-over double-blind protocol. Do-
butamine or placebo (5% glucose solution) was infused in
identical volumes corresponding to successive doses of 3, 6,
and 10 ␮g/kg/min of dobutamine. The doses were increased
every 5 min. Measurements were taken 10 min after the
initiation of an infusion rate of 10 ␮g/kg/min of dobut-
amine and placebo. A recovery period of 20 min was allowed
between the two infusions.
Data analysis. Technically excellent studies examining the
effects of dobutamine on cardiac hemodynamics and
MSNA were obtained in all patients with HF and controls.
A random code was attributed to the recordings so that all
data analyses were performed completely blinded to the
session during which the recording had been performed
(24).
Statistical analysis. Results are expressed as mean ⫾ SEM.
Statistical analysis consisted of paired and unpaired (two-
JACC Vol. 42, No. 9, 2003 Velez-Roa et al. 1607
November 5, 2003:1605–10 Beta-Adrenergic Agonism and Sympathetic Tone

Table 1. BP Responses to Acute Dobutamine Infusion in CHF Table 2. Effects of 48 Hours of Dobutamine Infusion
Patients, in Matched Controls, and in Young Controls (10 ␮g/kg/min) on Hemodynamic Parameters and on
Sympathetic Nerve Traffic in Nine Patients With Severe
Matched Young Congestive Heart Failure
CHF Controls Controls
Baseline or Placebo (n ⴝ 5) (n ⴝ 9) (n ⴝ 8) Parameters Baseline Dobutamine
SABP (mm Hg) 102 ⫾ 7†‡ 131 ⫾ 2 130 ⫾ 3 HR (beats/min) 86 ⫾ 5 89 ⫾ 5
MABP (mm Hg) 79 ⫾ 4†‡ 95 ⫾ 1‡ 90 ⫾ 2† SABP (mm Hg) 106 ⫾ 7 105 ⫾ 7
DABP (mm Hg) 65 ⫾ 1† 74 ⫾ 1 68 ⫾ 3 MABP (mm Hg) 82 ⫾ 3 76 ⫾ 4
DABP (mm Hg) 66 ⫾ 4 60 ⫾ 3
Matched Young
CHF Controls Controls CO (l/min) 4.1 ⫾ 0.4 5.8 ⫾ 0.5*
Dobutamine (n ⴝ 5) (n ⴝ 9) (n ⴝ 8) CI (l/min/m2) 2.2 ⫾ 0.2 3.1 ⫾ 0.2*
MPBP (mm Hg) 38 ⫾ 7 28 ⫾ 7*
SABP (mm Hg) 107 ⫾ 12†‡ 150 ⫾ 4*‡ 165 ⫾ 5*† PCP (mm Hg) 25 ⫾ 1 17 ⫾ 1*
MABP (mm Hg) 79 ⫾ 7†‡ 98 ⫾ 2 102 ⫾ 2* RAP (mm Hg) 10 ⫾ 2 5 ⫾ 1*
DABP (mm Hg) 66 ⫾ 5†‡ 75 ⫾ 1 75 ⫾ 2* MSNA (burst/min) 77 ⫾ 3 78 ⫾ 5
*p ⬍ 0.05 dobutamine vs. baseline or placebo; †p ⬍ 0.05 vs. matched controls; ‡p ⬍ TPR (dyne·s·cm⫺5) 1,759 ⫾ 263 1,099 ⫾ 112†
0.05 vs. young controls.
*p ⬍ 0.01; †p ⬍ 0.05.
BP ⫽ blood pressure; CHF ⫽ congestive heart failure; DABP ⫽ diastolic arterial
CO ⫽ cardiac output; CI ⫽ cardiac index; DABP ⫽ diastolic arterial blood
blood pressure; MABP ⫽ mean arterial blood pressure; SABP ⫽ systolic arterial
pressure; HR ⫽ heart rate; MABP ⫽ mean arterial blood pressure; MPBP ⫽ mean
blood pressure
pulmonary blood pressure; MSNA ⫽ muscle sympathetic nerve activity; PCP ⫽
pulmonary capillary pressure; RAP ⫽ right atrial pressure; SABP ⫽ systolic arterial
blood pressure; TPR ⫽ total peripheral resistance.
tailed) Student t tests. A linear regression analysis deter-
mined if dobutamine-induced changes in arterial BP af- infusion remained markedly elevated in the HF patients as
fected modifications in heart rate (HR) and MSNA in the compared with the matched controls and the young controls
controls. Significance was assumed at p ⬍ 0.05. (both p ⬍ 0.05) (Fig. 1).
Removal of the patient who was in atrial fibrillation
RESULTS before dobutamine infusion did not affect any of these
results.
Parameters in the absence of dobutamine infusion.
Control subjects. In the matched controls, dobutamine
Mean arterial BP was lower in the patients with CHF (n ⫽
increased systolic arterial BP (SBP) (p ⬍ 0.05) but did not
12) (81 ⫾ 2 mm Hg) than in the matched controls (95 ⫾ 1
modify MBP and diastolic arterial BP (DBP) (Table 1).
mm Hg, p ⫽ 0.0002) and the young controls (90 ⫾ 2 mm
Dobutamine did not affect MSNA (47 ⫾ 3 bursts/min
Hg, p ⫽ 0.03). Sympathetic activity was markedly elevated
under placebo vs. 44 ⫾ 7 bursts/min under dobutamine, p ⫽
in the patients with CHF (77 ⫾ 4 bursts/min) as compared
0.68) but increased HR (from 65 ⫾ 2 to 87 ⫾ 5 beats/min,
with the matched controls (47 ⫾ 3 bursts/min, p ⬍ 0.0001)
p ⫽ 0.0009).
and the young controls (35 ⫾ 3 bursts/min, p ⬍ 0.0001).
These changes contrast with those observed in the young
Moreover, HR was higher in the HF patients (91 ⫾ 5
controls, where dobutamine increased SBP, MBP, and
beats/min) than in the matched (65 ⫾ 2 beats/min, p ⫽
DBP (Table 1), decreased MSNA (from 35 ⫾ 3 to 28 ⫾ 5
0.0007) and the young (69 ⫾ 4 beats/min, p ⫽ 0.006)
bursts/min, p ⫽ 0.03), while the increase in HR was less
controls. Sympathetic activity was higher in the matched
marked than in the matched controls and was of borderline
controls as compared with the young controls (p ⫽ 0.02).
significance (69 ⫾ 4 beats/min under placebo vs. 76 ⫾ 5
Effects of dobutamine in CHF patients. 1) Short-term
beats/min under dobutamine, p ⫽ 0.054).
effects of dobutamine (n ⫽ 5): Ten minutes of 10 ␮g/kg/
In the control subjects, the largest increases in MBP with
min dobutamine infusion did not modify BP (Table 1),
dobutamine were associated with the most marked reduc-
sympathetic activity (74 ⫾ 8 bursts/min under dobutamine
tions in MSNA (r ⫽ ⫺0.49, p ⫽ 0.04) and the lowest
vs. 79 ⫾ 8 bursts/min at baseline, p ⫽ 0.14) or HR (102 ⫾
increases in HR (r ⫽ ⫺0.70, p ⫽ 0.001) (Fig. 2). Similar
7 beats/min under dobutamine vs. 103 ⫾ 7 beats/min at
correlations were found for SBP (r ⫽ ⫺0.69 with HR, r ⫽
baseline, p ⫽ 0.52) in the patients with CHF.
⫺0.51 with MSNA, p ⬍ 0.05) and for the HR response to
2) Prolonged administration of dobutamine (n ⫽ 9): The
changes in DBP (r ⫽ ⫺0.50, p ⬍ 0.05).
effects of 48 h of dobutamine infusion (10 ␮g/kg/min) on
the hemodynamic parameters and sympathetic activity in
DISCUSSION
HF patients (n ⫽ 9) are shown in Table 2. A 48-h infusion
of dobutamine increased cardiac index (p ⫽ 0.006) and The major new finding of this study is the evidence that
decreased mean pulmonary artery pressure (p ⫽ 0.0001), systemic BP changes are important determinants of periph-
pulmonary capillary pressure (p ⫽ 0.0002), right atrial eral sympathetic nerve control and HR response during
pressure (p ⫽ 0.0003), and TPR (p ⫽ 0.03). Prolonged dobutamine infusion. In young controls, dobutamine infu-
dobutamine infusion, however, did not change arterial sion markedly increased BP, which activated the arterial
pressure (p ⬎ 0.10), MSNA (p ⫽ 0.79), or HR (p ⫽ 0.33). baroreceptors leading to subsequent inhibition of MSNA,
Muscle sympathetic nerve activity during dobutamine as well as to limitation in the increase in HR. In contrast,
1608 Velez-Roa et al. JACC Vol. 42, No. 9, 2003
Beta-Adrenergic Agonism and Sympathetic Tone November 5, 2003:1605–10

Figure 1. Individual recordings of the effects of dobutamine infusion on heart rate (HR), mean blood pressure (MBP), and sympathetic nerve activity
(MSNA). In a young control, arterial baroreceptor activation produced by marked increases in MBP with dobutamine inhibits MSNA and limits the rise
in HR. In a control subject matched to the congestive heart failure (CHF) patient, dobutamine does not increase MBP, and, in the absence of arterial
baroreflex activation, MSNA remains unchanged, and the chronotropic effect of dobutamine is preserved. In a CHF patient, dobutamine produces similar
effects to those seen in the matched control, except that HR does not increase.

the BP response to dobutamine was much less marked in
the matched controls and, in the absence of arterial barore-
ceptor activation, dobutamine infusion did not change
MSNA and did not limit the increase in HR. These
findings are important as they may account for variations in
the HR responses among subjects during dobutamine stress
testing.
The response in the patients with severe CHF was similar
to that observed in the matched controls, with no elevation
in MBP and no changes in MSNA. The lack of increase in

Figure 2. Regression analysis between changes in muscle sympathetic nerve activity (MSNA) (burst/min, left panel), heart rate (HR) (beats/min [bpm],
right panel), and mean arterial blood pressure (MBP) (mm Hg) during dobutamine infusion in the control subjects; the largest increases in MBP are
accompanied by the most pronounced inhibitions in MSNA as well as with the least increases in HR.
JACC Vol. 42, No. 9, 2003
November 5, 2003:1605–10
HR could be explained by the marked beta-adrenergic
downregulation in end-stage HF (14). Resting tachycardia
in the CHF patients may also have hampered any further
rises in HR.
Differences in the BP responses during dobutamine
infusion between the young controls, the matched controls,
and the CHF patients can be explained by a reduced
responsiveness to beta-adrenergic stimulation in the elderly
as well as in patients with HF. The exact mechanism of the
decreased response to adrenergic stimulation is not well
understood and is probably complex; altered receptor sen-
sitivity, decreased beta-adrenergic receptor density, and
intrinsic alteration of the contractile response to cat-
echolamines have been described in the aged myocardium
(17,18). In HF, the attenuated beta-adrenergic inotropic
response is attributed to reduced beta-adrenergic receptor
density and abnormal G-protein function (14). Deficient
cAMP production results in diminished left ventricular
contractility and systolic pump performance during adren-
ergic receptor stimulation in both conditions (14,17,18).
Sympathetic activity can also be expressed as bursts per
100 heart beats (bursts/100 hb) instead of in bursts/min.
When this is done in our study, the sympathetic responses
to dobutamine are similar between matched and young
controls (dobutamine decreases MSNA from 72 ⫾ 6 to
50 ⫾ 8 bursts/100 hb [p ⫽ 0.002] in matched controls and
decreases MSNA from 52 ⫾ 5 to 36 ⫾ 5 bursts/100 hb [p
⫽ 0.0007] in young controls). In contrast, in patients with
CHF, MSNA normalized for HR remains markedly ele-
vated after 48 h of dobutamine (92 ⫾ 5 bursts/100 hb at
baseline vs. 89 ⫾ 5 bursts/100 hb under dobutamine
infusion, p ⫽ 0.7). Muscle sympathetic nerve activity
normalized for HR was higher in the CHF patients than in
the young and older control subjects (p ⬍ 0.02). Thus, our
main conclusion that dobutamine does not decrease sympa-
thetic activity in CHF patients is unaffected when MSNA is
expressed as bursts/100 hb. This procedure, however, sup-
presses differences in the MSNA responses between the
young and older subjects, likely because it normalizes
baroreflex-mediated changes in MSNA for baroreflex-
mediated changes in HR.
Additional possible mechanisms for persistent sympa-
thetic activation during dobutamine infusion in patients
with CHF are: 1) evidence that beta-2 adrenergic stimula-
tion may increase sympathetic traffic through an excitatory
prejunctional mechanism (25); 2) enhanced peripheral va-
sodilation during dobutamine due to beta-2 adrenergic
agonism (26,27) or to enhanced flow-mediated vasodilation
induced by the rise in CO (28,29). Subsequent baroreceptor
deactivation may have prevented a reduction in sympathetic
activity in the patients with HF.
Thus, although differences in sympathetic responses be-
tween CHF patients and young and matched controls were
a likely reflection of differences in the BP responses to the
administration of dobutamine, the exact mechanism of
these differing responses remains unclear.
Velez-Roa et al. 1609
Beta-Adrenergic Agonism and Sympathetic Tone
Sympathetic activation is present in mild HF and is
correlated with left ventricular filling pressures, mean dia-
stolic and capillary pulmonary pressures, and poor prognosis
(1–10). Marked hemodynamic improvement after mitral
valvuloplasty in mitral stenosis increases arterial baroreflex
sensitivity and normalizes sympathetic nerve activity (30).
These findings contrast with our study where large and
sustained hemodynamic improvements with dobutamine
did not modify the markedly elevated sympathetic activity in
patients with severe CHF. Dobutamine does not improve
baroreflex sensitivity (19,31). Our study, therefore, empha-
sizes the importance of arterial baroreflex activation on
sympathetic nerve inhibition during pharmacologic inter-
ventions that do not improve arterial baroreflex function
(19,22,31–33). Limited hemodynamic improvements dur-
ing short-term dobutamine infusion did not improve sym-
pathetic activity in CHF patients (20). We are, however,
not aware of a previous study on the effects of substantial
and sustained pharmacologic improvements in cardiac he-
modynamics on direct recordings of sympathetic outflow in
patients with CHF.
It has recently been reported that dobutamine reduces
cardiac sympathetic activity in CHF (34). Efferent cardiac
sympathetic activity was assessed using a radiotracer tech-
nique to measure cardiac norepinephrine spillover before
and during dobutamine infusion in 13 patients. Cardiac
sympathetic withdrawal during dobutamine infusion was
attributed to a reduction in left ventricular filling pressures
or ventricular mechanoreceptor activation. These findings
(34) are not in contradiction with our observation because
total body norepinephrine, which is contributed heavily by
norepinephrine spillover directed at skeletal muscle, did not
change in this previous study (34). Thus, our study high-
lights likely differential regional sympathetic regulation in
CHF.
In conclusion, our study reveals that arterial baroreflex
exerts a powerful control on peripheral sympathetic activity
and HR during dobutamine infusion. Arterial baroreceptor
activation during increases in MBP inhibits MSNA and
limits the HR response to dobutamine in normal subjects.
This mechanism, together with peripheral vasodilation,
likely contributes to the lack of peripheral sympathetic
withdrawal despite substantial hemodynamic improvements
in patients with CHF.
Acknowledgments
We are indebted to Dr. Pascal Godart for participation in
collecting data, to Dr. Karen Pickett for editorial assistance,
and to Mrs. Françoise Pignez for the drawing of the figures.
Reprint requests and correspondence: Dr. Sonia Velez-Roa,
Department of Cardiology, Erasme Hospital, 808 Lennik Road,
1070 Brussel, Belgium. E-mail: pvandebo@ulb.ac.be.
1610 Velez-Roa et al.
Beta-Adrenergic Agonism and Sympathetic Tone
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