CLINICAL RESEARCH
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* and
Philippe van de Borne, MD, PhD*
* Department of Cardiology, Erasme Hospital, Brussels, Belgium
Manuscript received November 25, 2002;
revised manuscript received May 16, 2003,
accepted July 7, 2003.
* Reprint requests and correspondence: Dr. Sonia Velez-Roa, Department of Cardiology, Erasme Hospital, 808 Lennik Road, 1070 Brussel, Belgium.
pvandebo{at}ulb.ac.be
 |
Abstract
|
|---|
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 µg/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 µg/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.
|
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 |
|
Sympathetic activation is a key component of the physiopathology 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). Sympathetic activity is greatest in patients with the worst functional 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 understood and is probably complex, as it is related to altered receptor sensitivity, decreased beta-adrenergic receptor density, and intrinsic alteration of the contractile response to catecholamines by the aged myocardium (17,18).
The differential effects of aging and HF on the sympathetic nerve response to beta-adrenergic agonism are unknown. Short-term administration of low doses of dobutamine (3 µg/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 (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 supporting clinical, chest roentgengraphic, and echocardiographic evidence of impaired left ventricular function. The effects of dobutamine were studied only in patients who were suffering 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 percutaneously under local anesthesia into an internal jugular or subclavian vein to allow measurements of resting right atrial pressure, pulmonary artery and capillary pulmonary pressures, 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 with a Physiocontrol Colin BP-880 sphygmomanometer (Colin press Mate, Colin Corp., Japan) as well as electrocardiogram (Siemens Medical, ECG Monitoring, Germany), 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·s·cm–5) was calculated from CO (l/min) and mean BP (MBP) using the following formula: TPR = 80 x 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 µm, tapering to an noninsulated tip of 1 to 5 µm). A subcutaneous 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 sympathetic nerve activity.
Protocol and intervention in HF patients.
After the baseline hemodynamic and MSNA measurements, dobutamine was infused at successive doses of 3, 6, and 10 µg/kg/min. The doses were increased every 5 min. Measurements were repeated 10 min after the beginning of an infusion rate of 10 µg/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 prolonged dobutamine therapy (10 µg/kg/min). A placebo-controlled design was not adopted in the patients because of severe clinical instability.
Protocol and intervention in control subjects.
The administration of dobutamine and placebo was performed after a randomized cross-over double-blind protocol. Dobutamine or placebo (5% glucose solution) was infused in identical volumes corresponding to successive doses of 3, 6, and 10 µg/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 µg/kg/min of dobutamine 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-tailed) Student t tests. A linear regression analysis determined if dobutamine-induced changes in arterial BP affected modifications in heart rate (HR) and MSNA in the controls. Significance was assumed at p < 0.05.
|
Results
|
|---|
Parameters in the absence of dobutamine infusion.
Mean arterial BP was lower in the patients with CHF (n = 12) (81 ± 2 mm Hg) than in the matched controls (95 ± 1 mm Hg, p = 0.0002) and the young controls (90 ± 2 mm Hg, p = 0.03). Sympathetic activity was markedly elevated in the patients with CHF (77 ± 4 bursts/min) as compared with the matched controls (47 ± 3 bursts/min, p < 0.0001) and the young controls (35 ± 3 bursts/min, p < 0.0001). Moreover, HR was higher in the HF patients (91 ± 5 beats/min) than in the matched (65 ± 2 beats/min, p = 0.0007) and the young (69 ± 4 beats/min, p = 0.006) controls. Sympathetic activity was higher in the matched controls as compared with the young controls (p = 0.02).
Effects of dobutamine in CHF patients.
1) Short-term effects of dobutamine (n = 5): Ten minutes of 10 µg/kg/min dobutamine infusion did not modify BP (Table 1), sympathetic activity (74 ± 8 bursts/min under dobutamine vs. 79 ± 8 bursts/min at baseline, p = 0.14) or HR (102 ± 7 beats/min under dobutamine vs. 103 ± 7 beats/min at baseline, p = 0.52) in the patients with CHF.
2) Prolonged administration of dobutamine (n = 9): The effects of 48 h of dobutamine infusion (10 µg/kg/min) on the hemodynamic parameters and sympathetic activity in HF patients (n = 9) are shown in Table 2. A 48-h infusion of dobutamine increased cardiac index (p = 0.006) and decreased mean pulmonary artery pressure (p = 0.0001), pulmonary capillary pressure (p = 0.0002), right atrial pressure (p = 0.0003), and TPR (p = 0.03). Prolonged dobutamine infusion, however, did not change arterial pressure (p > 0.10), MSNA (p = 0.79), or HR (p = 0.33).
View this table:
[in this window]
[in a new window]
|
Table 2 Effects of 48 Hours of Dobutamine Infusion (10 µg/kg/min) on Hemodynamic Parameters and on Sympathetic Nerve Traffic in Nine Patients With Severe Congestive Heart Failure
|
|
Muscle sympathetic nerve activity during dobutamine infusion remained markedly elevated in the HF patients as compared with the matched controls and the young controls (both p < 0.05) (Fig. 1).
View larger version (29K):
[in this window]
[in a new window]
|
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.
|
|
Removal of the patient who was in atrial fibrillation before dobutamine infusion did not affect any of these results.
Control subjects.
In the matched controls, dobutamine increased systolic arterial BP (SBP) (p < 0.05) but did not modify MBP and diastolic arterial BP (DBP) (Table 1). Dobutamine did not affect MSNA (47 ± 3 bursts/min under placebo vs. 44 ± 7 bursts/min under dobutamine, p = 0.68) but increased HR (from 65 ± 2 to 87 ± 5 beats/min, p = 0.0009).
These changes contrast with those observed in the young controls, where dobutamine increased SBP, MBP, and DBP (Table 1), decreased MSNA (from 35 ± 3 to 28 ± 5 bursts/min, p = 0.03), while the increase in HR was less marked than in the matched controls and was of borderline significance (69 ± 4 beats/min under placebo vs. 76 ± 5 beats/min under dobutamine, p = 0.054).
In the control subjects, the largest increases in MBP with dobutamine were associated with the most marked reductions in MSNA (r = –0.49, p = 0.04) and the lowest increases in HR (r = –0.70, p = 0.001) (Fig. 2). Similar correlations were found for SBP (r = –0.69 with HR, r = –0.51 with MSNA, p < 0.05) and for the HR response to changes in DBP (r = –0.50, p < 0.05).
View larger version (9K):
[in this window]
[in a new window]
|
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.
|
|
|
Discussion
|
|---|
The major new finding of this study is the evidence that systemic BP changes are important determinants of peripheral sympathetic nerve control and HR response during dobutamine infusion. In young controls, dobutamine infusion markedly increased BP, which activated the arterial baroreceptors leading to subsequent inhibition of MSNA, as well as to limitation in the increase in HR. In contrast, the BP response to dobutamine was much less marked in the matched controls and, in the absence of arterial baroreceptor 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 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 sensitivity, decreased beta-adrenergic receptor density, and intrinsic alteration of the contractile response to catecholamines 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 adrenergic 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 elevated 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 sympathetic activity in CHF patients is unaffected when MSNA is expressed as bursts/100 hb. This procedure, however, suppresses 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 sympathetic activation during dobutamine infusion in patients with CHF are: 1) evidence that beta-2 adrenergic stimulation may increase sympathetic traffic through an excitatory prejunctional mechanism (25); 2) enhanced peripheral vasodilation 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 between 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.
Sympathetic activation is present in mild HF and is correlated with left ventricular filling pressures, mean diastolic 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, emphasizes the importance of arterial baroreflex activation on sympathetic nerve inhibition during pharmacologic interventions that do not improve arterial baroreflex function (19,22,31–33). Limited hemodynamic improvements during short-term dobutamine infusion did not improve sympathetic 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 hemodynamics 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 technique 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 highlights 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.
|
Footnotes
|
|---|
Supported 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.).
|
References
|
|---|
- Leimbach WN, Wallin BG, Victor RG, et al. Direct evidence from intraneural recordings for increased central sympathetic outflow in patients with heart failure. Circulation. 1986;73(5):913–919[Abstract/Free Full Text]
- Francis G, Benedict C, Johnestone D, et al. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure: a substudy of the Studies Of Left Ventricular Dysfunction (SOLVD). Circulation. 1990;82:1724–1730[Abstract/Free Full Text]
- Benedict CR, Weiner DH, Johnstone DE, et al. Comparative neurohormonal responses in patients with preserved and impaired left ventricular ejection fraction: results of the Studies Of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol. 1993;22(Suppl):A146–A153[Medline]
- Cohn JN, Levine TB, Olivari MT, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984;311:819–823[Abstract]
- CONSENSUS II Trial Study GroupSwedberg K, Eneroth P, Kjekshus J, et al. Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. Circulation. 1990;82:1730–1736[Abstract/Free Full Text]
- Ferguson DW, Berg WJ, Sanders JS, et al. Clinical and hemodynamic correlates of sympathetic nerve activity in normal humans and patients with heart failure: evidence from direct microneurographic recordings. J Am Coll Cardiol. 1990;16:1125–1134[Abstract]
- van de Borne P, Montano N, Pagani M, et al. Absence of low frequency variability of sympathetic nerve activity in severe heart failure. Circulation. 1997;95:1449–1454[Abstract/Free Full Text]
- Grassi G, Seravalle G, Cattaneo BM, et al. Sympathetic activation and loss of reflex sympathetic control in mild congestive heart failure. Circulation. 1995;92:3206–3211[Abstract/Free Full Text]
- Kaye DM, Lambert GW, Lefkovits J, et al. Neurochemical evidence of cardiac sympathetic activation and increased central nervous system norepinephrine turnover in severe congestive heart failure. J Am Coll Cardiol. 1994;23:570–578[Abstract]
- Cohn JN, Levine TB, Olivari MT, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984;311:819–823[Abstract]
- Hoffman BB, Lefkowitz RJ. Catecholamines and sympathomimetic drugs. In: Goodman Gilman A, editor. Goodman and Gilman’s the Pharmacological Basis of Therapeutics. 8th edition. New York, NY: Pergamon Press, 1990:202–3
- Lowes BD, Tsvetkova T, Eichhorn EJ, et al. Milrinone versus dobutamine in heart failure subjects treated chronically with carvedilol. Int J Cardiol. 2001;81:141–149[CrossRef][Medline]
- Yamani MH, Haji SA, Starling RC, et al. Comparison of dobutamine-based and milrinone-based therapy for advanced decompensated congestive heart failure: hemodynamic efficacy, clinical outcome, and economic impact. Am Heart J. 2001;142:998–1002[CrossRef][Medline]
- Parker JD, Landzberg JS, Bittl JA, et al. Effects of beta-adrenergic stimulation with dobutamine on isovolumic relaxation in the normal and failing human left ventricle. Circulation. 1991;84:1040–1048[Abstract/Free Full Text]
- Iwase S, Mano T, Watanabe T, et al. Age-related changes of sympathetic outflow to muscles in humans. J Gerontol. 1991;46:M1–M5[Medline]
- Fagius J, Wallin BG. Long-term variability and reproductibility of resting human muscle nerve sympathetic activity at rest, as reassessed after a decade. Clin Auton Res. 1993;3:201–205[CrossRef][Medline]
- Weistfeldt ML. Aging of the cardiovascular system. N Engl J Med. 1980;303:1172–1174[Medline]
- Lakatta EG, Gerstenblith G, Angel CS, et al. Diminished inotropic response of aged myocardium to catecholamines. Circ Res. 1975;36:262–269[Abstract/Free Full Text]
- Schobel HP, Oren RM, Roach PJ, et al. Contrasting effects of digitalis and dobutamine on baroreflex sympathetic control in normal humans. Circulation. 1991;84:1118–1129[Abstract/Free Full Text]
- Ferguson DW, Berg WJ, Sanders JS, et al. Sympathoinhibitory responses to digitalis glycosides in heart failure patients. Circulation. 1989;80:65–77[Abstract/Free Full Text]
- Pagani M, Montano N, Porta A, et al. Relationship between spectral components of cardiovascular variabilities and direct measures of muscle sympathetic nerve activity in humans. Circulation. 1997;18:1441–1448
- Hamdam MH, Joglar JA, Page RL, et al. Baroreflex gain predicts blood pressure recovery during stimulated ventricular tachycardia in humans. Circulation. 1999;100:381–386[Abstract/Free Full Text]
- Delius W, Hagbarth KE, Hongell A, et al. General characteristics of sympathetic activity in human muscle nerves. Acta Physiol Scand. 1972;84:65–81[Medline]
- van de Borne P, Montano N, Zimmerman B, et al. Relationship between repeated measures of hemodynamics, muscle sympathetic nerve activity, and their spectral oscillations. Circulation. 1997;96:4326–4332[Abstract/Free Full Text]
- Newton GE, Azevedo ER, Parker JD. Inotropic and sympathetic responses to the intracoronary infusion of a beta 2-receptor agonist: a human in vivo study. Circulation. 1999;99:2402–2407[Abstract/Free Full Text]
- Bogaert MG, Fraeyman N. Receptor function in heart failure. Am J Med. 1991;29:10S–13S
- Altschuld RA, Starling RC, Hamlin RL, et al. Response of failing canine and human heart cells to beta 2-adrenergic stimulation. Circulation. 1995;92:1612–1618[Abstract/Free Full Text]
- Joanides R, Haefeli WE, Linder L, et al. Nitric oxide is responsible for flow-dependent dilation of human peripheral conduit arteries in vivo. Circulation. 1995;91:1314–1319[Abstract/Free Full Text]
- Järvisalo MJ, Rönnemaa T, Volanen I, et al. Brachial artery dilation responses in healthy children and adolescents. Am J Physiol Heart Circ Physiol. 2002;282:H87–H92[Abstract/Free Full Text]
- Ashino K, Gotoh E, Sumita S-I, et al. Percutaneous transluminal mitral valvuloplasty normalizes baroreflex sensitivity and sympathetic activity in patients with mitral stenosis. Circulation. 1997;96:3443–3449[Abstract/Free Full Text]
- van de Borne P, Heron S, Nguyen H, et al. Arterial baroreflex control during dobutamine exercise stress testing. Hypertension. 1999;33:987–991[Abstract/Free Full Text]
- Ferguson DW, Abboud FM, Mark AL. Selective impairment of baroreflex-mediated responses in patients with ventricular dysfunction. Circulation. 1984;69:451–460[Abstract/Free Full Text]
- Ferguson DW, Berg MJ, Roach PJ, et al. Effects of heart failure on baroreflex control of sympathetic neural activity. Am J Cardiol. 1992;69:523–531[CrossRef][Medline]
- Al-Hesayen A, Azevedo ER, Newton GE, et al. The effects of dobutamine on cardiac sympathetic activity in patients with congestive heart failure. J Am Coll Cardiol. 2002;39:1269–1274[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
S. Glaser, D. Alvaro, H. Francis, Y. Ueno, L. Marucci, A. Benedetti, S. D. Morrow, M. Marzioni, M. G. Mancino, J. L. Phinizy, et al.
Adrenergic receptor agonists prevent bile duct injury induced by adrenergic denervation by increased cAMP levels and activation of Akt
Am J Physiol Gastrointest Liver Physiol,
April 1, 2006;
290(4):
G813 - G826.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
Top
Abstract
Methods