Clinical and hemodynamic correlates of sympathetic nerve activity in normal humans and patients with heart failure: evidence from direct microneurographic recordings

Department of Internal Medicine, University of Iowa Hospitals, Iowa City 52247.

To characterize the neural excitatory state of heart failure, simultaneous measurements of efferent sympathetic nerve activity to muscle (by microneurography) and rest hemodynamics were obtained in 10 normal subjects (age 25 +/- 2 years, mean +/- SEM) and 29 patients with heart failure (age 49 +/- 2 years; New York Heart Association functional class II to IV; left ventricular ejection fraction 21 +/- 1%; cardiac index = 2.16 +/- 0.13 liters/min per m2; pulmonary capillary wedge pressure 23 +/- 2 mm Hg). Sympathetic nerve activity was significantly higher in the patients with heart failure (54.7 +/- 4.5 bursts/min) than in normal subjects (16.7 +/- 2.2 bursts/min, p less than 0.001). Multiple linear regression analyses indicated that sympathetic activity in these human subjects was most strongly and inversely correlated with left ventricular stroke work index (r = -0.86, p less than 0.0001) and stroke volume index (r = -0.85, p less than 0.0001). There was a strong positive correlation between sympathetic nerve activity and pulmonary artery diastolic (r = 0.82, p less than 0.0001) and mean (r = 0.81, p less than 0.0001) pressures. Similar correlations were seen when patients with heart failure were analyzed separately. There was no significant correlation between sympathetic nerve activity and mean arterial pressure, left ventricular ejection fraction (by radionuclide ventriculography), cardiac chamber size (by echocardiography) or arterial oxygen tension in the patients with heart failure. Direct measurements of sympathetic nerve activity correlated closely with plasma norepinephrine (r = 0.72, p less than 0.0001) in patients with heart failure. Thus, sympathetic nerve activity at rest parallels impairment of cardiac performance in patients with heart failure.

This article has been cited by other articles:

				W.-Z. Wang, L. Gao, H.-J. Wang, I. H. Zucker, and W. Wang Interaction between cardiac sympathetic afferent reflex and chemoreflex is mediated by the NTS AT1 receptors in heart failure Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1216 - H1226. [Abstract] [Full Text] [PDF]

				I. H. Zucker, J. F. Hackley, K. G. Cornish, B. A. Hiser, N. R. Anderson, R. Kieval, E. D. Irwin, D. J. Serdar, J. D. Peuler, and M. A. Rossing Chronic Baroreceptor Activation Enhances Survival in Dogs With Pacing-Induced Heart Failure Hypertension, November 1, 2007; 50(5): 904 - 910. [Abstract] [Full Text] [PDF]

				M. D. Womack, R. Morris, T. C. Gent, and R. Barrett-Jolley Substance P Targets Sympathetic Control Neurons in the Paraventricular Nucleus Circ. Res., June 8, 2007; 100(11): 1650 - 1658. [Abstract] [Full Text] [PDF]

				A. Ciarka, J.-L. Vachiery, A. Houssiere, M. Gujic, E. Stoupel, S. Velez-Roa, R. Naeije, and P. van de Borne Atrial Septostomy Decreases Sympathetic Overactivity in Pulmonary Arterial Hypertension Chest, June 1, 2007; 131(6): 1831 - 1837. [Abstract] [Full Text] [PDF]

				M. K. Stickland, J. D. Miller, C. A. Smith, and J. A. Dempsey Carotid Chemoreceptor Modulation of Regional Blood Flow Distribution During Exercise in Health and Chronic Heart Failure Circ. Res., May 11, 2007; 100(9): 1371 - 1378. [Abstract] [Full Text] [PDF]

				D. H. J. Thijssen, P. de Groot, M. Kooijman, P. Smits, and M. T. E. Hopman Sympathetic nervous system contributes to the age-related impairment of flow-mediated dilation of the superficial femoral artery Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H3122 - H3129. [Abstract] [Full Text] [PDF]

				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]

				M. R. Bristow Cardiac resynchronization therapy and adrenergic mechanisms Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2590 - H2591. [Full Text] [PDF]

				I. H. Zucker Novel Mechanisms of Sympathetic Regulation in Chronic Heart Failure Hypertension, December 1, 2006; 48(6): 1005 - 1011. [Full Text] [PDF]

				J. Spaak, Z. J. Egri, T. Kubo, E. Yu, S.-I. Ando, Y. Kaneko, K. Usui, T. D. Bradley, and J. S. Floras Muscle Sympathetic Nerve Activity During Wakefulness in Heart Failure Patients With and Without Sleep Apnea Hypertension, December 1, 2005; 46(6): 1327 - 1332. [Abstract] [Full Text] [PDF]

				C. K. Ganta, N. Lu, B. G. Helwig, F. Blecha, R. R. Ganta, L. Zheng, C. R. Ross, T. I. Musch, R. J. Fels, and M. J. Kenney Central angiotensin II-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1683 - H1691. [Abstract] [Full Text] [PDF]

				S. Motte, M. Mathieu, S. Brimioulle, A. Pensis, L. Ray, J.-M. Ketelslegers, N. Montano, R. Naeije, P. van de Borne, and K. M. Entee Respiratory-related heart rate variability in progressive experimental heart failure Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1729 - H1735. [Abstract] [Full Text] [PDF]

				M U Braun, T Rauwolf, T Zerm, M Schulze, A Schnabel, and R H Strasser Long term biventricular resynchronisation therapy in advanced heart failure: effect on neurohormones Heart, May 1, 2005; 91(5): 601 - 605. [Abstract] [Full Text] [PDF]

				D. Kaye and M. Esler Sympathetic neuronal regulation of the heart in aging and heart failure Cardiovasc Res, May 1, 2005; 66(2): 256 - 264. [Abstract] [Full Text] [PDF]

				O. Ozdemir, O. Alyan, M. Soylu, F. Metin, F. Kacmaz, A. D. Demir, B. Geyik, D. Aras, H. Sasmaz, and S. Korkmaz Improvement in sympatho-vagal imbalance and heart rate variability in patients with mitral stenosis after percutaneous balloon commissurotomy Europace, January 1, 2005; 7(3): 204 - 210. [Abstract] [Full Text] [PDF]

				N. Lu, B. G. Helwig, R. J. Fels, S. Parimi, and M. J. Kenney Central Tempol alters basal sympathetic nerve discharge and attenuates sympathetic excitation to central ANG II Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2626 - H2633. [Abstract] [Full Text] [PDF]

				Y. Oda, H. Asanoi, H. Ueno, K. Yamada, S. Joho, T. Kameyama, T. Hirai, T. Nozawa, S. Takashima, and H. Inoue Pulse-synchronous sympathetic burst power as a new index of sympathoexcitation in patients with heart failure Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1821 - H1827. [Abstract] [Full Text] [PDF]

				P A Modesti, G Polidori, I Bertolozzi, S Vanni, and I Cecioni Impairment of cardiopulmonary receptor sensitivity in the early phase of heart failure Heart, January 1, 2004; 90(1): 30 - 36. [Abstract] [Full Text] [PDF]

				S. Velez-Roa, M. Renard, J.-P. Degaute, and P. van de Borne Peripheral sympathetic control during dobutamine infusion: effects of aging and heart failure J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1605 - 1610. [Abstract] [Full Text] [PDF]

				R. S. T. Leung, J. S. Floras, G. Lorenzi-Filho, F. Rankin, P. Picton, and T. D. Bradley Influence of Cheyne-Stokes Respiration on Cardiovascular Oscillations in Heart Failure Am. J. Respir. Crit. Care Med., June 1, 2003; 167(11): 1534 - 1539. [Abstract] [Full Text] [PDF]

				R. U. Pliquett, K. G. Cornish, J. D. Peuler, and I. H. Zucker Simvastatin Normalizes Autonomic Neural Control in Experimental Heart Failure Circulation, May 20, 2003; 107(19): 2493 - 2498. [Abstract] [Full Text] [PDF]

				S. Andreas, C. Bingeli, P. Mohacsi, T. F. Luscher, and G. Noll Nasal Oxygen and Muscle Sympathetic Nerve Activity in Heart Failure Chest, February 1, 2003; 123(2): 366 - 371. [Abstract] [Full Text] [PDF]

				C.F. Notarius, E.R. Azevedo, J.D. Parker, and J.S. Floras Peak oxygen uptake is not determined by cardiac noradrenaline spillover in heart failure Eur. Heart J., May 2, 2002; 23(10): 800 - 805. [Abstract] [Full Text] [PDF]

				K. Zhang, Y.-F. Li, and K. P. Patel Reduced endogenous GABA-mediated inhibition in the PVN on renal nerve discharge in rats with heart failure Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2002; 282(4): R1006 - R1015. [Abstract] [Full Text] [PDF]

				C. F. Notarius, D. J. Atchison, G. A. Rongen, and J. S. Floras Effect of adenosine receptor blockade with caffeine on sympathetic response to handgrip exercise in heart failure Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1312 - H1318. [Abstract] [Full Text] [PDF]

				M. J. Kenney, T. I. Musch, and M. L. Weiss Renal sympathetic nerve regulation to heating is altered in rats with heart failure Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2868 - H2875. [Abstract] [Full Text] [PDF]

				C. F. Notarius, D. J. Atchison, and J. S. Floras Impact of heart failure and exercise capacity on sympathetic response to handgrip exercise Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H969 - H976. [Abstract] [Full Text] [PDF]

				S Heindl, C Dodt, M Krahwinkel, G Hasenfuss, and S Andreas Short term effect of continuous positive airway pressure on muscle sympathetic nerve activity in patients with chronic heart failure Heart, February 1, 2001; 85(2): 185 - 190. [Abstract] [Full Text]

				C. F. Notarius and J. S. Floras Limitations of the use of spectral analysis of heart rate variability for the estimation of cardiac sympathetic activity in heart failure Europace, January 1, 2001; 3(1): 29 - 38. [Abstract] [PDF]

				B. G. Phillips, M. Kato, C. A. Pesek, M. Winnicki, K. Narkiewicz, D. Davison, and V. K. Somers Sympathetic Activation by Sildenafil Circulation, December 19, 2000; 102(25): 3068 - 3073. [Abstract] [Full Text] [PDF]

				Y. B. Sverrisdottir, B. Rundqvist, G. Johannsson, and M. Elam Sympathetic Neural Burst Amplitude Distribution : A More Specific Indicator of Sympathoexcitation in Human Heart Failure Circulation, October 24, 2000; 102(17): 2076 - 2081. [Abstract] [Full Text] [PDF]

				M. Petretta, L. Spinelli, F. Marciano, C. Apicella, M. L. E. Vicario, G. Testa, M. Volpe, and D. Bonaduce Effects of losartan treatment on cardiac autonomic control during volume loading in patients with DCM Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H86 - H92. [Abstract] [Full Text] [PDF]

				R. Corti, C. Binggeli, I. Sudano, L. E. Spieker, R. R. Wenzel, T. F. Luscher, and G. Noll The Beauty and the Beast: Aspects of the Autonomic Nervous System Physiology, June 1, 2000; 15(3): 125 - 129. [Abstract] [Full Text] [PDF]

				E. R. Azevedo, G. E. Newton, J. S. Floras, and J. D. Parker Reducing Cardiac Filling Pressure Lowers Norepinephrine Spillover in Patients With Chronic Heart Failure Circulation, May 2, 2000; 101(17): 2053 - 2059. [Abstract] [Full Text] [PDF]

				K. P. Patel, K. Zhang, and P. K. Carmines Norepinephrine turnover in peripheral tissues of rats with heart failure Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2000; 278(3): R556 - R562. [Abstract] [Full Text] [PDF]

				J. Cinca and A. Rodriguez-Sinovas Cardiovascular reflex responses induced by epicardial chemoreceptor stimulation Cardiovasc Res, January 1, 2000; 45(1): 163 - 171. [Abstract] [Full Text] [PDF]

				V. G. Macefield, B. Rundqvist, Y. B. Sverrisdottir, B. G. Wallin, and M. Elam Firing Properties of Single Muscle Vasoconstrictor Neurons in the Sympathoexcitation Associated With Congestive Heart Failure Circulation, October 19, 1999; 100(16): 1708 - 1713. [Abstract] [Full Text] [PDF]

				V. K. Somers To Sleep, Perchance to Breathe . Implications for the Failing Heart Am. J. Respir. Crit. Care Med., October 1, 1999; 160(4): 1077 - 1078. [Full Text] [PDF]

				C. Rostagno, M. Felici, S. Caciolli, G. Olivo, M. Comeglio, G. Galanti, and G. G. N. Serneri Decreased Baroreflex Sensitivity Assessed from Phase IV of Valsalva Maneuver in Mild Congestive Heart Failure Angiology, August 1, 1999; 50(8): 655 - 664. [Abstract] [PDF]

				W. Wang, H. D. Schultz, and R. Ma Cardiac sympathetic afferent sensitivity is enhanced in heart failure Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H812 - H817. [Abstract] [Full Text] [PDF]

				K. Narkiewicz, C. A. Pesek, P. J. H. van de Borne, M. Kato, and V. K. Somers Enhanced Sympathetic and Ventilatory Responses to Central Chemoreflex Activation in Heart Failure Circulation, July 20, 1999; 100(3): 262 - 267. [Abstract] [Full Text] [PDF]

				C.F. Notarius, S. Ando, G.A. Rongen, and J.S. Floras Resting muscle sympathetic nerve activity and peak oxygen uptake in heart failure and normal subjects Eur. Heart J., June 2, 1999; 20(12): 880 - 887. [Abstract] [PDF]

				D. M. Kaye, A. M. Dart, G. L. Jennings, and M. D. Esler Antiadrenergic effect of chronic amiodarone therapy in human heart failure J. Am. Coll. Cardiol., May 1, 1999; 33(6): 1553 - 1559. [Abstract] [Full Text] [PDF]

				B. L. Abramson, S.-i. Ando, C. F. Notarius, G. A. Rongen, and J. S. Floras Effect of Atrial Natriuretic Peptide on Muscle Sympathetic Activity and Its Reflex Control in Human Heart Failure Circulation, April 13, 1999; 99(14): 1810 - 1815. [Abstract] [Full Text] [PDF]

				P. van de Borne, N. Montano, K. Narkiewicz, J. P. Degaute, R. Oren, M. Pagani, and V. K. Somers Sympathetic Rhythmicity in Cardiac Transplant Recipients Circulation, March 30, 1999; 99(12): 1606 - 1610. [Abstract] [Full Text] [PDF]

				R. Ma, I. H. Zucker, and W. Wang Central gain of the cardiac sympathetic afferent reflex in dogs with heart failure Am J Physiol Heart Circ Physiol, December 1, 1997; 273(6): H2664 - H2671. [Abstract] [Full Text] [PDF]

				K. Ashino, E. Gotoh, S.-i. Sumita, A. Moriya, and M. Ishii Percutaneous Transluminal Mitral Valvuloplasty Normalizes Baroreflex Sensitivity and Sympathetic Activity in Patients With Mitral Stenosis Circulation, November 18, 1997; 96(10): 3443 - 3449. [Abstract] [Full Text]

				P. Ponikowski, T. P. Chua, M. Piepoli, D. Ondusova, K. Webb-Peploe, D. Harrington, S. D. Anker, M. Volterrani, R. Colombo, G. Mazzuero, et al. Augmented Peripheral Chemosensitivity as a Potential Input to Baroreflex Impairment and Autonomic Imbalance in Chronic Heart Failure Circulation, October 21, 1997; 96(8): 2586 - 2594. [Abstract] [Full Text]

				P. van de Borne, N. Montano, M. Pagani, R. Oren, and V. K. Somers Absence of Low-Frequency Variability of Sympathetic Nerve Activity in Severe Heart Failure Circulation, March 18, 1997; 95(6): 1449 - 1454. [Abstract] [Full Text]

				H. Murakami, J.-L. Liu, and I. H. Zucker Angiotensin II Enhances Baroreflex Control of Sympathetic Outflow in Heart Failure Hypertension, February 1, 1997; 29(2): 564 - 569. [Abstract] [Full Text]

				P. van de Borne, R. Oren, E. A. Anderson, A. L. Mark, and V. K. Somers Tonic Chemoreflex Activation Does Not Contribute to Elevated Muscle Sympathetic Nerve Activity in Heart Failure Circulation, September 15, 1996; 94(6): 1325 - 1328. [Abstract] [Full Text]

				G. Grassi, G. Seravalle, B. M. Cattaneo, A. Lanfranchi, S. Vailati, C. Giannattasio, A. Del Bo, C. Sala, G. B. Bolla, M. Pozzi, et al. Sympathetic Activation and Loss of Reflex Sympathetic Control in Mild Congestive Heart Failure Circulation, December 1, 1995; 92(11): 3206 - 3211. [Abstract] [Full Text]

				F. H. H. Leenen, B. S. Huang, H. Yu, and B. Yuan Brain `Ouabain' Mediates Sympathetic Hyperactivity in Congestive Heart Failure Circ. Res., November 1, 1995; 77(5): 993 - 1000. [Abstract] [Full Text]

				H. P. Schobel, R. E. Schmieder, S. Hartmann, H. Schachinger, and F. C. Luft Effects of Bromocriptine on Cardiovascular Regulation in Healthy Humans Hypertension, May 1, 1995; 25(5): 1075 - 1082. [Abstract] [Full Text]