Donate Help Contact The AHA Sign In Home
American Heart Association
Hypertension
Search: search_blue_button Advanced Search
« Previous Article | Table of Contents | Next Article »
Hypertension. 2004;44:727-731
Published online before print September 20, 2004, doi: 10.1161/01.HYP.0000144271.59333.a7
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
44/5/727    most recent
01.HYP.0000144271.59333.a7v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Grassi, G.
Right arrow Articles by Mancia, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Grassi, G.
Right arrow Articles by Mancia, G.
Related Collections
Right arrow Congestive
Right arrow Pacemaker
Right arrow Ablation/ICD/surgery
Right arrow Other Treatment

(Hypertension. 2004;44:727.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Sustained Sympathoinhibitory Effects of Cardiac Resynchronization Therapy in Severe Heart Failure

Guido Grassi; Antonio Vincenti; Roberta Brambilla; Fosca Quarti Trevano; Raffaella Dell’Oro; Antonio Cirò; Giuseppe Trocino; Antonella Vincenzi; Giuseppe Mancia

From the Clinica Medica (G.G., F.Q.T., R.D.’O., G.M.), Dipartimento di Medicina Clinica, Prevenzione e Biotecnologie Sanitarie, Università Milano-Bicocca; and Centro Interuniversitario di Fisiologia Clinica e Ipertensione (G.G., R.D.’O., G.M.), Centro Auxologico Italiano (G.G., G.M.), and Divisione di Cardiologia (A.V., R.B., A.C., G.T., A.V.), Ospedale San Gerardo, Milan, Italy.

Correspondence to Prof Giuseppe Mancia, Clinica Medica, Ospedale S. Gerardo, Via Donizetti 106, 20052 Monza (Milano), Italy. E-mail giuseppe.mancia{at}unimib.it


*    Abstract
up arrowTop
 *Abstract
down arrowIntroduction
 down arrowMethods
 down arrowResults
 down arrowDiscussion
 down arrowReferences
 
Evidence is available that in heart failure, cardiac resynchronization therapy by biventricular pacing improves myocardial function and exercise capacity. Whether this is accompanied by a sustained inhibition of heart failure–dependent sympathoexcitation is uncertain. In 11 heart failure patients (mean±SEM age, 68.4±1.5 years) in New York Heart Association (NYHA) class III and IV under medical treatment with an intraventricular conduction delay (QRS duration ≥130 ms), with a markedly depressed left ventricular ejection fraction, and undergoing implantation of a biventricular pacemaker, we measured beat-to-beat blood pressure and muscle sympathetic nerve traffic. Measurements, which also included echocardiographic and clinical variables, were performed before and {approx}10 weeks after successful resynchronization therapy. Ten age- and NYHA class–matched heart failure patients who were under medical treatment for the same time period served as controls. Long-term resynchronization therapy improved cardiac function and caused a significant increase in systolic blood pressure coupled with an improvement in maximal oxygen consumption and exercise capacity. These effects were coupled with a significant and marked reduction in sympathetic nerve traffic when expressed both as burst frequency over time (44.1±3.6 vs 30.7±3.0 bs/min, –30.5%, P<0.02) and as burst frequency corrected for heart rate (68.3±5.9 vs 47.3±4.3 bs/100 beats, –32.1%, P<0.02). No significant change in the aforementioned parameters was seen in the control group. These data provide the first direct evidence that in severe heart failure, resynchronization therapy exerts a marked and sustained sympathoinhibition. Because in heart failure sympathetic overactivity adversely affects prognosis, this may have important clinical implications.


Key Words: electrical stimulation • heart failure • sympathetic nervous system • autonomic nervous system


*    Introduction
up arrowTop
 up arrowAbstract
 *Introduction
down arrowMethods
 down arrowResults
 down arrowDiscussion
 down arrowReferences
 
Cardiac resynchronization therapy (CRT) by biventricular pacing exerts favorable effects in patients with congestive heart failure (CHF) and intraventricular conduction delay in whom it improves symptoms, functional class, and quality of life with an increase in exercise tolerance.1–3 Whether the favorable effects include a reduction in the enhanced sympathetic cardiovascular drive characterizing CHF4–6 is uncertain, however, because the studies that have addressed this issue so far had either methodological or design limitations. That is, they assessed adrenergic function only indirectly by plasma norepinephrine assay3,7 or used direct measurement of muscle sympathetic nerve activity (MSNA) that was confined, however, to the acute phase of biventricular pacing.8,9

The present study was designed to determine the long-term sympathetic effects of CRT in CHF patients with an intraventricular conduction delay by using a design similar to the 1 used in the MIRACLE trial, which had shown CRT to be accompanied by a sustained improvement in patient clinical status.3 Sympathetic activity was quantified both indirectly by measurement of plasma norepinephrine levels and directly by microneurographic recording of MSNA. We thought this information to be of clinical relevance because the prognosis in CHF is linked to the level of activation of the sympathetic nervous system.6,10,11


*    Methods
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 *Methods
down arrowResults
 down arrowDiscussion
 down arrowReferences
 
Population
The study population consisted of 21 male patients with stable CHF in New York Heart Association (NYHA) class III or IV because of ischemic or idiopathic cardiomyopathy. Eleven patients (mean±SEM age, 68.4±1.5 years; range, 58 to 74 years) had an intraventricular conduction delay (QRS complex duration ≥130 ms; range, 150 to 220 ms) and underwent an electrophysiological study and implantation of a device for biventricular pacing without (Medtronic InSync model 8040 [n=2], Medtronic InSync III Model 8042 [n=3]) or with (InSync ICD 7272 [n=2], InSync III Marquis 7279 [n=3], InSync III Marquis 7277 [n=1]) defibrillator capabilities. The remaining 10 patients (mean±SEM age, 68.2±1.7 years; range, 56 to 75 years) had no significant intraventricular conduction delays (QRS complex duration <130 ms) and thus did not undergo implantation of the biventricular pacemaker; these patients served as controls. All patients were in sinus rhythm and under optimized pharmacological treatment with diuretics, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and ß-blockers, according to current therapeutic guidelines. The drug treatment schedule and daily dosage were left unchanged throughout the study period. All subjects gave their written consent to the study after being informed of its nature and purpose. The study protocol was approved by the Ethics Committee of our institution.

Measurements
Measurements consisted of an ECG, the NYHA functional classification, Minnesota Living Heart Failure questionnaire, the distance expressed in meters walked by the patients during a 6-minute corridor test, peak maximal oxygen consumption during a cardiopulmonary exercise test, and left ventricular end-diastolic diameter, end-systolic diameter, and calculated ejection fraction by M-mode and B-mode echocardiography. Echocardiographic data were collected by a single operator. The within-operator coefficients of variation (ie, the assessment of within-operator reproducibility of the measurements) of left ventricular diameter data were 5.9%.

Blood pressure (BP) was measured by (1) a mercury sphygmomanometer, taking the first and fifth Korotkoff sounds to identify systolic and diastolic values, respectively, and (2) a finger photoplethysmographic device (Finapres 2300, Ohmeda) capable of providing accurate and reproducible beat-to-beat systolic and diastolic values.5 Heart rate (HR) was monitored continuously by a cardiotachometer triggered by the R wave of an ECG lead. Respiration rate was monitored by a strain-gauge pneumograph positioned at midchest level. Multiunit recording of efferent postganglionic MSNA was obtained from a microelectrode inserted in the right or left peroneal nerve posterior to the fibular head, as previously described.5,8,9 The microelectrode was made of tungsten and had a diameter of 200 µm in the shaft, tapering to 1 to 5 µm at the level of the uninsulated tip. A reference electrode positioned subcutaneously 10 to 30 mm from the recording electrode served as the ground. The nerve signal was amplified 70|000x, fed through a bandpass filter (700 to 2000 Hz), and integrated with a custom nerve traffic analysis system (Bioengineering Department, University of Iowa, Iowa City). Integrated nerve activity was monitored by a loudspeaker, displayed on a storage oscilloscope (model 511A,Tektronix), and recorded with BP, HR, and respiratory movements on an ink polygraph. The muscle nature of MSNA was assessed according to published criteria,5,8,9 and the recording was accepted only if the signal-to-noise ratio was >3. MSNA was quantified as bursts per minute and bursts per 100 heart beats. Plasma norepinephrine was measured by high-performance liquid chromatography12 on blood withdrawn from an antecubital vein of the arm opposite the one used for BP measurements.

Protocol and Data Analysis
Patients underwent a 3-day screening period during which the ECG, the 6-minute corridor walking test, cardiopulmonary exercise test, and echocardiogram were obtained. The patients were then taken to the laboratory in the morning after an overnight fast, placed supinely, and fitted with the intravenous cannula, the microelectrodes for MSNA recording, and the other measuring devices. A venous blood sample for assessment of plasma norepinephrine was withdrawn, and BP was measured 3 times with a mercury sphygmomanometer. After a 30-minute interval, BP, HR, respiration rate, and MSNA were continuously measured over a 30-minute period. Patients were thereafter discharged from the laboratory and assigned, according to the presence or absence of the intraventricular conduction delay (see above), to either CRT or observation without intervention. The CRT implantation was done after 2.3±0.2 days (range, 1 to 3) from the end of the previously mentioned examinations. All measurements were repeated according to the same sequence after an interval of 10.2±0.3 weeks (range, 7.2 to 12.5). The CRT device was programmed in the biventricular atrial-triggered pacing mode, with a lower and an upper tracking rate amounting, respectively, to 50 and 130 bpm. The atrial-ventricular interval value was chosen on the basis of the best mitral Doppler spectrogram in terms of timing and amplitude of the E and A wave.13,14 In the CRT group, the second experimental session was performed in the spontaneous atrial-sensed sinus rhythm with the device left in the biventricular atrial-triggered pacing mode. No exercise training program was performed in the 2 groups of patients during the 2-month period of the study or in the 2 months preceding it.

Data were collected and analyzed by investigators unaware of the experimental design. Values from individual subjects were averaged for each group and each experimental session and expressed as mean±SEM. The significance of differences between the 2 sessions was assessed by 2-way ANOVA. Spearman analysis was used to determine the correlation between different variables. A value of P<0.05 was considered statistically significant.


*    Results
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 *Results
down arrowDiscussion
 down arrowReferences
 
As shown in the Table and in the Figure, the 2 groups of patients showed a similar average NYHA functional class as well as a similar marked abnormality in the maximal oxygen consumption during the cardiopulmonary exercise test, the score of the Minnesota questionnaire, the walking test, and left ventricular end-diastolic diameter and ejection fraction. BP, HR, and respiration rate were similar in the 2 groups, which also showed similar elevations in plasma norepinephrine and number of sympathetic neural bursts. In the group maintained on pharmacological therapy, no value showed a significant change. In contrast, in the group that had undergone CRT, there was, together with the expected reduction in the QRS duration, a significant increase in systolic but not in diastolic BP and a marked and significant improvement in left ventricular ejection fraction, NYHA functional class, and score of the Minnesota questionnaire. This was accompanied by no significant change in plasma norepinephrine but by a reduction in MSNA, which was significant and marked when expressed both as the number of bursts over time (–30.5%, P<0.02) and as burst number corrected for heart rate (–32.1%, P<0.02). There was no relation between (1) the initial QRS width and MSNA (r=0.29, P=NS), (2) the initial QRS width and the MSNA changes induced by CRT (r=0.41, P=NS), and (3) the changes in QRS width and MSNA induced by CRT (r=0.03, P=NS). No relation was also found between the change in MSNA and the change in left ventricular ejection fraction and systolic or diastolic BP induced by CRT (r=0.32, r=0.27, and r=0.18, respectively; P=NS for all).


View this table:
[in this window]
[in a new window]
  		Clinical, Hemodynamic, ECG, and Echocardiographic Variables in the Groups of Patients Undergoing and Not Undergoing CRT



View larger version (26K):
[in this window]
[in a new window]
  		Effects of CRT by biventricular pacing or observation without intervention (Control) on MSNA, expressed as burst frequency over time (upper panels) and as burst incidence corrected for HR (middle panels) and plasma norepinephrine (NE) values (lower panels). Individual and average data are shown. Asterisks (P<0.02) refer to the level of statistical significance between data obtained before and after CRT. B, Baseline; 2 months, after 2 months. All other abbreviations are as defined in text.


*    Discussion
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 *Discussion
down arrowReferences
 
In our patients with severe CHF, maintenance of a drug treatment (diuretic, an angiotensin-converting enzyme inhibitor [or an angiotensin II receptor blocker], and a ß-blocker) for 2 months did not affect MSNA values. This was not the case, however, in severe CHF patients in whom maintenance of the aforementioned treatment for 2 months was complemented by CRT with biventricular pacing. In this group, MSNA showed a reduction in most patients (9 of 11) and a significant and marked fall in the group as whole. This expands previous data obtained by assessing the acute sympathetic effect of biventricular pacing8,9 on 2 clinically relevant grounds. First, the sympathoinhibition caused by this therapeutic intervention is not transient but sustained under chronic conditions. Second, this occurs over and above pharmacological treatment with drugs that already effectively oppose the CHF-related sympathoexcitation.15–17

Several other results of our study deserve to be mentioned. First, in patients under biventricular pacing, the reduction in MSNA was accompanied by a nonsignificant reduction in plasma norepinephrine. A similar discrepancy between these 2 markers of sympathetic activity has been reported in some studies on obesity, hypertension, and heart failure5,18–21 and interpreted as being dependent on, among other factors (eg, tissue norepinephrine clearance22), the more limited reproducibility of plasma norepinephrine,23 which can make statistical significance more difficult to be achieved, particularly when the number of subjects is not high. In the current study, however, the discrepancy may be more apparent than real because under CRT, plasma norepinephrine showed a reduction in 9 of 12 patients, the change not being statistically significant only because of a striking increase in 1. Incidentally, this was the patient in whom also MSNA increased, although to a lesser degree, and no improvement in clinical status was observed. It is thus likely that MSNA and plasma norepinephrine were affected in the same direction by CRT. This is clinically relevant because evidence that in CHF sympathetic activation adversely affects prognosis has been largely based on plasma norepinephrine rather than on MSNA.6,10–11 Second, biventricular pacing led to a marked (30% or more) reduction in sympathetic activity to a vascular region, the skeletal muscle, which accounts to a great extent for total vascular resistance,24 suggesting that this effect may play a major role in the overall hemodynamic improvement accompanying CRT. It remains to be seen, however, whether similar sympathoinhibition occurs in other vascular districts important for the outcome of heart failure patients, such as the heart and kidney. The finding that 3 months after implantation of a biventricular pacemaker HR variability showed a clear increase7 suggests that for the heart, this may be the case, although with the caveat that HR variability reflects not only sympathetic but also vagal cardiac drive.25,26 Third, our study was not designed to investigate the mechanisms responsible for the sympathoinhibitory effect of CRT. The results, however, allow several hypotheses to be advanced. The sympathoinhibition may, for example, originate from the activation of arterial baroreceptors27 brought about by systolic BP, which increased during CRT by {approx}10 mm Hg. However, the MSNA and the BP changes showed no significant relation, which suggests that, although probably involved, the baroreflex does not play an exclusive role, and its function is markedly depressed in severe CHF.5,20,27 It may also originate from an increased activity of vagally innervated receptors anatomically located in the left ventricle that (1) exert a powerful reflex inhibition on sympathetic drive28 and (2) respond not only to an increase in left ventricular pressure but also to an increase in left ventricular contractility,28 which was most likely improved by CRT. This is not incompatible with the observation that in animals, left ventricular receptors cause bradycardia,28–30 which was not evident in our patients because (1) the bradycardic effect has been described mostly after massive receptor stimulation28–30 and (2) in humans, physiologic (and more modest) alterations in cardiopulmonary receptor drive do not cause substantial HR changes.28 The sympathoinhibition may also originate from removal of reflex sympathoexcitatory influences originating from receptors located in the cardiac and central vascular structure30–32 after improvement of the hemodynamic status by CRT. It cannot be excluded, however that, at least in part, the MSNA reduction seen after prolonged CRT also results from (1) resumption of physical activity (due to the improvement in clinical status), because physical training exerts sympathoinhibitory effects,21,33 and/or (2) a CRT-related improvement in central sleep apnea ad thus, in chemoreflex function.34

Perspectives
The results of the current study show that the marked sympathetic overactivity characterizing advanced heart failure states may be favorably affected in the long-term period by CRT. This procedure in our patients was also accompanied by an improvement in left ventricular ejection fraction, a reduction in NYHA functional class, and an increase in exercise tolerance. This is in line with the results of the MIRACLE trial,3 to which our study adds the information on the long-term modulatory effects exerted by the procedure on sympathetic neural outflow.

Received July 14, 2004; first decision July 23, 2004; accepted August 26, 2004.


*    References
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 up arrowDiscussion
 *References
 

  1. Saxon LA, Ellenbogen KA. Resynchronization therapy for the treatment of heart failure. Circulation. 2003; 108: 1044–1048.[Free Full Text]
  2. Abraham WT, Hayes DL. Cardiac resynchronization therapy for heart failure. Circulation. 2003; 108: 2596–2603.[Free Full Text]
  3. Young JB, Abraham WT, Smith AL, Leon AR, Lieberman R, Wilkoff B, Canby RC, Schroeder JS, Liem LB, Hall S, Wheelan K; Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) Trial Investigators. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial. JAMA. 2003; 289: 2685–2694.[Abstract/Free Full Text]
  4. Eisenhofer G, Friberg P, Rundqvist B, Quyyumi AA, Lambert G, Kaye DM, Kopin IJ, Goldstein DS, Esler MD. Cardiac sympathetic nerve function in congestive heart failure. Circulation. 1996; 93: 1667–1676.[Abstract/Free Full Text]
  5. Grassi G, Seravalle G, Cattaneo BM, Lanfranchi A, Vailati S, Giannattasio C, Del Bo A, Sala C, Bolla GB, Pozzi M. Sympathetic activation and loss of reflex sympathetic control in mild congestive heart failure. Circulation. 1995; 92: 3206–3211.[Abstract/Free Full Text]
  6. Cohn JN. Sympathetic nervous system in heart failure. Circulation. 2002; 106: 2417–2418.[Free Full Text]
  7. Adamson PB, Kleckner KJ, VanHout WL, Srinivasan S, Abraham WT. Cardiac resynchronization therapy improves heart rate variability on patients with symptomatic heart failure. Circulation. 2003; 108: 266–269.[Abstract/Free Full Text]
  8. Hamdan MH, Zagrodzky JD, Joglar JA, Sheehan CJ, Ramaswamy K, Erdner JF, Page RL, Smith ML. Biventricular pacing decreases sympathetic activity compared with right ventricular pacing in patients with depressed ejection fraction. Circulation. 2000; 102: 1027–1032.[Abstract/Free Full Text]
  9. Hamdan MH, Barbera S, Kowal RC, Page RL, Ramaswamy K, Joglar JA, Karimkhani V, Smith ML. Effects of resynchronization therapy on sympathetic activity in patients with depressed ejection fraction and intraventricular conduction delay due to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2002; 89: 1047–1051.[CrossRef][Medline] [Order article via Infotrieve]
  10. Cohn JN, Levine TB, Olivari MT, Garberg B, Lura D, Francis GS, Simon AB, Rector T. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984; 311: 819–823.[Abstract]
  11. Swedberg K, Eneroth P, Kjekshus J, Wilhelmsen L. 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]
  12. Hjemdahl P, Daleskog M, Kahan T. Determination of plasma catecholamines by high-performance liquid chromatography with electrochemical detection: comparison with a radioenzymatic method. Life Sci. 1979; 25: 131–138.[CrossRef][Medline] [Order article via Infotrieve]
  13. Saxon LA, Hourigan L, Guerra P. Influence of programmed AV delay on left ventricular performance in biventricular pacing systems for treatment of heart failure. J Am Coll Cardiol. 2000; 35: 2A.–116A. Abstract.[CrossRef]
  14. Saxon LA, De Marco T. Resynchronization therapy for heart failure. www.naspe.org/professional_education 2003:24–25.
  15. Grassi G, Cattaneo BM, Seravalle G, Lanfranchi A, Pozzi M, Morganti A, Carugo S, Mancia G. Effects of chronic ACE inhibition on sympathetic nerve traffic and baroreflex control of circulation in heart failure. Circulation. 1997; 96: 1173–1179.[Abstract/Free Full Text]
  16. Azevedo ER, Kubo T, Mak S, Al-Hesayen A, Schofield A, Allan R, Kelly S, Newton GE, Floras JS, Parker JD. Nonselective vs selective ß-adrenergic receptor blockade in congestive heart failure. Circulation. 2001; 104: 2194–2199.[Abstract/Free Full Text]
  17. Esler M, Kaye D. Is very high sympathetic tone in heart failure a result of keeping bad company? Hypertension. 2003; 42: 870–872.[Free Full Text]
  18. Grassi G, Seravalle G, Cattaneo BM, Bolla GB, Lanfranchi A, Colombo M, Giannnattasio C, Brunani A, Cavagnini F, Mancia G. Sympathetic activation in obese normotensive subjects. Hypertension. 1995; 25: 560–563.[Abstract/Free Full Text]
  19. Grassi G, Seravalle G, Dell’Oro R, Turri C, Bolla GB, Mancia G. Adrenergic and reflex abnormalities in obesity-related hypertension. Hypertension. 2000; 36: 538–542.[Abstract/Free Full Text]
  20. Grassi G, Seravalle G, Quarti-Trevano F, Dell’Oro R, Bolla G, Mancia G. Effects of hypertension and obesity on sympathetic activation of heart failure patients. Hypertension. 2003; 42: 873–877.[Abstract/Free Full Text]
  21. Grassi G, Esler M. How to assess sympathetic activity in humans. J Hypertens. 1999; 17: 719–734.[CrossRef][Medline] [Order article via Infotrieve]
  22. Esler MD, Jennings G, Lambert G, Meredith I, Horne M, Eisenhofer G. Overflow of catecholamine neurotransmitter to the circulation: source, fate and functions. Physiol Rev. 1990; 70: 963–985.[Free Full Text]
  23. Grassi G, Bolla GB, Seravalle G, Turri C, Lanfranchi A, Mancia G. Comparison between reproducibility and sensitivity of muscle sympathetic nerve traffic and plasma noradrenaline in man. Clin Sci. 1997; 92: 285–289.[Medline] [Order article via Infotrieve]
  24. Shepherd JT. Circulation to skeletal muscle. In: Shepherd JT, Abboud FM, eds. Handbook of Physiology, Section 2: the Cardiovascular System. Bethesda, Md: American Physiological Society; 1983: 319–370.
  25. Eckberg DL. Sympathovagal balance: a critical appraisal. Circulation. 1997; 96: 3224–3232.[Free Full Text]
  26. Kingwell BA, Thompson JM, Kaye DM, McPherson GA, Jennings GL, Esler MD. Heart rate spectral analysis, cardiac norepinephrine spillover, and muscle sympathetic nerve activity during human sympathetic nervous activation and failure. Circulation. 1994; 90: 234–240.[Abstract/Free Full Text]
  27. Mancia G, Mark AL. Arterial baroreflex in humans. In: Shepherd JT, Abboud FM, eds. Handbook of Physiology, Section 2: the Cardiovascular System. Bethesda, Md: American Physiological Society; 1983: 755–793.
  28. Mark AL, Mancia G. Cardiopulmonary baroreflex in humans. In: Shepherd JT, Abboud FM, eds. Handbook of Physiology, Section 2: the Cardiovascular System. Bethesda, Md: American Physiological Society; 1983: 795–813.
  29. Vatner SF, Boettcher DH, Heyndrickx GR, McRitchie RJ. Reduced baroreflex sensitivity with volume loading in conscious dogs. Circ Res. 1975; 37: 236–242.[Abstract/Free Full Text]
  30. Thoren P. Characteristics of left ventricular receptors with nonmedullated vagal afferents in cats. Circ Res. 1977; 40: 415–421.[Abstract/Free Full Text]
  31. Mancia G, Donald DE. Demonstration that atria, ventricles and lungs each are responsible for a tonic inhibition of the vasomotor center in the dog. Circ Res. 1975; 36: 310–318.[Abstract/Free Full Text]
  32. Mark AL, Abboud FM, Schmid PG, Heistad DD. Reflex vascular responses to ventricular outflow obstruction and activation of ventricular baroreceptors in dogs. J Clin Invest. 1973; 52: 1147–1153.[Medline] [Order article via Infotrieve]
  33. Grassi G, Seravalle G, Calhoun DA, Mancia G. Physical training and baroreceptor control of sympathetic nerve activity in humans. Hypertension. 1994; 23: 294–301.[Abstract/Free Full Text]
  34. Sinha AM, Skobel EC, Breithard OA, Norra C, Markus KU, Breuer C, Hanrath P, Stellbrink C. Cardiac resynchronization therapy improves central sleep apnea and Cheyne-Stokes in patients with chronic heart failure. J Am Coll Cardiol. 2004; 44: 68–71.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 EuropaceHome page
P. A. Gould, G. Kong, V. Kalff, S. J. Duffy, A. J. Taylor, M. J. Kelly, and D. M. Kaye
Improvement in cardiac adrenergic function post biventricular pacing for heart failure
Europace, September 1, 2007; 9(9): 751 - 756.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
B. Najem, P. Unger, N. Preumont, J.-L. Jansens, A. Houssiere, A. Pathak, O. Xhaet, L. Gabriel, A. Friart, L. De Roy, et al.
Sympathetic control after cardiac resynchronization therapy: responders versus nonresponders
Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2647 - H2652.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
44/5/727    most recent
01.HYP.0000144271.59333.a7v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Grassi, G.
Right arrow Articles by Mancia, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Grassi, G.
Right arrow Articles by Mancia, G.
Related Collections
Right arrow Congestive
Right arrow Pacemaker
Right arrow Ablation/ICD/surgery
Right arrow Other Treatment

Hypertension Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 2004 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.