Circulation, Vol 73, 615-621, Copyright © 1986 by American Heart Association
GJ Hasking, MD Esler, GL Jennings, D Burton, JA Johns and PI Korner
The analysis of plasma kinetics of the sympathetic neurotransmitter
norepinephrine can be used to estimate sympathetic nervous "activity"
(integrated nerve firing rate) for the body as a whole and for individual
organs. In 12 patients with cardiac failure (left ventricular ejection
fraction 10% to 39%), the mean arterial plasma norepinephrine concentration
was 557 +/- 68 pg/ml (mean +/- SE) compared with 211 +/- 21 pg/ml in 15
subjects without heart failure (p less than .002). The difference was due
to both increased release of norepinephrine to plasma (indicating increased
"total" sympathetic activity) and reduced clearance of norepinephrine from
plasma. The increase in sympathetic activity did not involve all organs
equally. Cardiac (32 +/- 9 vs 5 +/- 1 ng/min; p less than .002) and renal
(202 +/- 45 vs 66 +/- 9 ng/min; p = .002) norepinephrine spillover were
increased by 540% and 206%, respectively, but norepinephrine spillover from
the lungs was normal. Adrenomedullary activity was also increased in the
patients with heart failure, whose mean arterial plasma epinephrine
concentration was 181 +/- 38 pg/ml compared with 71 +/- 12 pg/ml in control
subjects (p less than .02). There is marked regional variation, inapparent
from measurements of plasma norepinephrine concentration, in sympathetic
nerve activity in patients with congestive heart failure. The finding of
increased cardiorenal norepinephrine spillover has important
pathophysiologic and therapeutic implications.
ARTICLES
Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity
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B. L. Leonard, S. C. Malpas, K. M. Denton, A. C. Madden, and R. G. Evans Differential control of intrarenal blood flow during reflex increases in sympathetic nerve activity Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2001; 280(1): R62 - R68. [Abstract] [Full Text] [PDF]
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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]
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A. Gabrielsen, V. B. Sorensen, B. Pump, S. Galatius, R. Videbak, P. Bie, J. Warberg, N. J. Christensen, H. Wroblewski, J. Kastrup, et al. Cardiovascular and neuroendocrine responses to water immersion in compensated heart failure Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1931 - H1940. [Abstract] [Full Text] [PDF]
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J. Shite, E. Dong, H. Kawai, S. Y. Stevens, and C.-S. Liang Selegiline improves cardiac sympathetic terminal function and beta -adrenergic responsiveness in heart failure Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1283 - H1290. [Abstract] [Full Text] [PDF]
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G. Cice, E. Tagliamonte, L. Ferrara, and A. Iacono Efficacy of carvedilol on complex ventricular arrhythmias in dilated cardiomyopathy: double-blind, randomized, placebo-controlled study Eur. Heart J., August 1, 2000; 21(15): 1259 - 1264. [Abstract] [PDF]
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M. Zaugg, W. Xu, E. Lucchinetti, S. A. Shafiq, N. Z. Jamali, and M. A. Q. Siddiqui {beta}-Adrenergic Receptor Subtypes Differentially Affect Apoptosis in Adult Rat Ventricular Myocytes Circulation, July 18, 2000; 102(3): 344 - 350. [Abstract] [Full Text] [PDF]
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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]
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H. Kawai, A. Mohan, J. Hagen, E. Dong, J. Armstrong, S. Y. Stevens, and C.-S. Liang Alterations in cardiac adrenergic terminal function and beta -adrenoceptor density in pacing-induced heart failure Am J Physiol Heart Circ Physiol, May 1, 2000; 278(5): H1708 - H1716. [Abstract] [Full Text] [PDF]
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D. M. Kaye, G. Vaddadi, S. L. Gruskin, X.-J. Du, and M. D. Esler Reduced Myocardial Nerve Growth Factor Expression in Human and Experimental Heart Failure Circ. Res., April 14, 2000; 86 (7): e80 - e84. [Abstract] [Full Text] [PDF]
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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]
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M. R. Bristow {beta}-Adrenergic Receptor Blockade in Chronic Heart Failure Circulation, February 8, 2000; 101(5): 558 - 569. [Full Text] [PDF]
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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]
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R. W. Braith, M. A. Welsch, M. S. Feigenbaum, H. A. Kluess, and C. J. Pepine Neuroendocrine activation in heart failure is modified by endurance exercise training J. Am. Coll. Cardiol., October 1, 1999; 34(4): 1170 - 1175. [Abstract] [Full Text] [PDF]
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H. Kawai, T.-H. M. Fan, E. Dong, R. A. Siddiqui, A. Yatani, S. Y. Stevens, and C.-S. Liang ACE inhibition improves cardiac NE uptake and attenuates sympathetic nerve terminal abnormalities in heart failure Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1609 - H1617. [Abstract] [Full Text] [PDF]
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D. L. Mann Mechanisms and Models in Heart Failure : A Combinatorial Approach Circulation, August 31, 1999; 100(9): 999 - 1008. [Full Text] [PDF]
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 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]
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G Grassi and G Mancia Sympathetic overactivity and exercise intolerance in heart failure: a cause-effect relationship Eur. Heart J., June 2, 1999; 20(12): 854 - 855. [PDF]
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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]
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G. E. Newton, E. R. Azevedo, and J. D. Parker Inotropic and Sympathetic Responses to the Intracoronary Infusion of a ß2-Receptor Agonist : A Human In Vivo Study Circulation, May 11, 1999; 99(18): 2402 - 2407. [Abstract] [Full Text] [PDF]
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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]
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 S. C. Stanford, P. Salmon, G. Mikhail, D. Gettins, S. Zielinski, and J. R. Pepper Plasma catecholamines, pharmacotherapy and mood of subjects with cardiovascular disorder J Psychopharmacol, May 1, 1999; 13(3): 255 - 260. [Abstract] [PDF]
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L. Chen, A. L. Sica, and S. M. Scharf Mechanisms of acute cardiovascular response to periodic apneas in sedated pigs J Appl Physiol, April 1, 1999; 86(4): 1236 - 1246. [Abstract] [Full Text] [PDF]
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H. P. Brunner-La Rocca, G. Vaddadi, and M. D. Esler Recent insight into therapy of congestive heart failure: focus on ACE inhibition and angiotensin-II antagonism J. Am. Coll. Cardiol., April 1, 1999; 33(5): 1163 - 1173. [Abstract] [Full Text] [PDF]
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J. H. Traverse, P. Melchert, G. L. Pierpont, B. Jones, M. Crampton, and R. J. Bache Regulation of Myocardial Blood Flow by Oxygen Consumption Is Maintained in the Failing Heart During Exercise Circ. Res., March 5, 1999; 84(4): 401 - 408. [Abstract] [Full Text] [PDF]
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