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(Circulation. 1996;93:1667-1676.)
© 1996 American Heart Association, Inc.
Articles |
Cardiac Sympathetic Nerve Function in Congestive Heart Failure
From the Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke (G.E., I.J.K., D.S.G.), Bethesda, Md; the Cardiology Branch, National Heart, Lung, and Blood Institute (A.A.Q.), National Institutes of Health, Bethesda, Md; the Departments of Cardiology and Clinical Physiology, University of Göteborg, Göteborg, Sweden (P.F., B.R.); and the Baker Medical Research Institute, Prahran, Victoria, Australia (G.L., D.M.K., M.D.E.).
Correspondence to Graeme Eisenhofer, Bldg 10, Room 5N-214, 10 Center Dr MSC 1424, National Institutes of Health, Bethesda, MD 20892-1424. E-mail ge@box-g.nih.gov.
Background Increased availability of norepinephrine (NE) for activation of cardiac adrenoceptors (increased cardiac adrenergic drive) and depletion of myocardial NE stores may contribute to the pathophysiology and progression of congestive heart failure. This study used a comprehensive neurochemical approach to examine the mechanisms responsible for these abnormalities.
Methods and Results Subjects with and without congestive heart failure received intravenous infusions of [3H]NE. Cardiac spillover, reuptake, vesicular-axoplasmic exchange, and tissue stores of NE were assessed from arterial and coronary venous plasma concentrations of endogenous and [3H]-labeled NE and dihydroxyphenylglycol. Tyrosine hydroxylase activity was assessed from plasma dopa, and NE turnover was assessed from measurements of NE metabolites. NE release and reuptake were both increased in the failing heart; however, the efficiency of NE reuptake was reduced such that cardiac spillover of NE was increased disproportionately more than neuronal release of NE. Cardiac NE stores were 47% lower and the rate of vesicular leakage of NE was 42% lower in the failing than in the normal heart. Cardiac spillover of dopa and NE turnover were increased similarly in congestive heart failure.
Conclusions Increased neuronal release of NE and decreased efficiency of NE reuptake both contribute to increased cardiac adrenergic drive in congestive heart failure. Decreased vesicular leakage of NE, secondary to decreased myocardial stores of NE, limits the increase in cardiac NE turnover in CHF. Decreased NE store size in the failing heart appears to result not from insufficient tyrosine hydroxylation but from chronically increased NE turnover and reduced efficiency of NE reuptake and storage.
Key Words: norepinephrine • heart failure • nervous system, autonomic • radioisotopes
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H. Senzaki, N. Paolocci, Y. A. Gluzband, M. L. Lindsey, J. S. Janicki, M. T. Crow, and D. A. Kass {beta}-Blockade Prevents Sustained Metalloproteinase Activation and Diastolic Stiffening Induced by Angiotensin II Combined With Evolving Cardiac Dysfunction Circ. Res., April 14, 2000; 86(7): 807 - 815. [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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A. Bottner, G. Eisenhofer, P. Friberg, B. Rundqvist, and S.R. Bornstein Serum leptin levels in heart failure patients may be altered differently according to clinical stage Eur. Heart J., February 2, 2000; 21(4): 334 - 335. [PDF]
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 C. A. Walker, F. A. Crawford Jr, and F. G. Spinale MYOCYTE CONTRACTILE DYSFUNCTION WITH HYPERTROPHY AND FAILURE: RELEVANCE TO CARDIAC SURGERY J. Thorac. Cardiovasc. Surg., February 1, 2000; 119(2): 388 - 400. [Full Text] [PDF]
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O.-E. Brodde and M. C. Michel Adrenergic and Muscarinic Receptors in the Human Heart Pharmacol. Rev., December 1, 1999; 51(4): 651 - 690. [Abstract] [Full Text] [PDF]
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L. Spinelli, M. Petretta, F. Marciano, G. Testa, M. A. E. Rao, M. Volpe, and D. Bonaduce Cardiac autonomic responses to volume overload in normal subjects and in patients with dilated cardiomyopathy Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1361 - H1368. [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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A. Cohen-Solal, Y. Esanu, D. Logeart, F. Pessione, C. Dubois, G. Dreyfus, R. Gourgon, and P. Merlet Cardiac metaiodobenzylguanidine uptake in patients with moderate chronic heart failure: relationship with peak oxygen uptake and prognosis J. Am. Coll. Cardiol., March 1, 1999; 33(3): 759 - 766. [Abstract] [Full Text] [PDF]
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J. R. Henegar, D. D. Schwartz, and J. S. Janicki ANG II-related myocardial damage: role of cardiac sympathetic catecholamines and beta -receptor regulation Am J Physiol Heart Circ Physiol, August 1, 1998; 275(2): H534 - H541. [Abstract] [Full Text] [PDF]
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I. J. Kopin, B. Rundqvist, P. Friberg, J. Lenders, D. S. Goldstein, and G. Eisenhofer Different relationships of spillover to release of norepinephrine in human heart, kidneys, and forearm Am J Physiol Regulatory Integrative Comp Physiol, July 1, 1998; 275(1): R165 - R173. [Abstract] [Full Text] [PDF]
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T. Nozawa, A. Igawa, N. Yoshida, M. Maeda, M. Inoue, Y. Yamamura, H. Asanoi, and H. Inoue Dual-Tracer Assessment of Coupling Between Cardiac Sympathetic Neuronal Function and Downregulation of ß-Receptors During Development of Hypertensive Heart Failure of Rats Circulation, June 16, 1998; 97(23): 2359 - 2367. [Abstract] [Full Text] [PDF]
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 G. Eisenhofer, H. Keiser, P. Friberg, E. Mezey, T.-T. Huynh, B. Hiremagalur, T. Ellingson, S. Duddempudi, A. Eijsbouts, and J. W. M. Lenders Plasma Metanephrines Are Markers of Pheochromocytoma Produced by Catechol-O-Methyltransferase Within Tumors J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 2175 - 2185. [Abstract] [Full Text]
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G. Eisenhofer, B. Rundqvist, and P. Friberg Determinants of cardiac tyrosine hydroxylase activity during exercise-induced sympathetic activation in humans Am J Physiol Regulatory Integrative Comp Physiol, March 1, 1998; 274(3): R626 - R634. [Abstract] [Full Text] [PDF]
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M. Ungerer, F. Hartmann, M. Karoglan, A. Chlistalla, S. Ziegler, G. Richardt, M. Overbeck, H. Meisner, A. Schomig, and M. Schwaiger Regional In Vivo and In Vitro Characterization of Autonomic Innervation in Cardiomyopathic Human Heart Circulation, January 20, 1998; 97(2): 174 - 180. [Abstract] [Full Text] [PDF]
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G. Grassi, M. Colombo, G. Seravalle, D. Spaziani, and G. Mancia Dissociation Between Muscle and Skin Sympathetic Nerve Activity in Essential Hypertension, Obesity, and Congestive Heart Failure Hypertension, January 1, 1998; 31(1): 64 - 67. [Abstract] [Full Text] [PDF]
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G. Eisenhofer, A. Aneman, P. Friberg, D. Hooper, L. Fandriks, H. Lonroth, B. Hunyady, and E. Mezey Substantial Production of Dopamine in the Human Gastrointestinal Tract J. Clin. Endocrinol. Metab., November 1, 1997; 82(11): 3864 - 3871. [Abstract] [Full Text] [PDF]
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 D. S. Goldstein, C. Holmes, R. O. Cannon, G. Eisenhofer, and I. J. Kopin Sympathetic Cardioneuropathy in Dysautonomias N. Engl. J. Med., March 6, 1997; 336(10): 696 - 702. [Abstract] [Full Text] [PDF]
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B. Rundqvist, G. Eisenhofer, M. Elam, and P. Friberg Attenuated Cardiac Sympathetic Responsiveness During Dynamic Exercise in Patients With Heart Failure Circulation, February 18, 1997; 95(4): 940 - 945. [Abstract] [Full Text]
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B. Rundqvist, M. Elam, Y. Bergmann-Sverrisdottir, G. Eisenhofer, and P. Friberg Increased Cardiac Adrenergic Drive Precedes Generalized Sympathetic Activation in Human Heart Failure Circulation, January 7, 1997; 95(1): 169 - 175. [Abstract] [Full Text]
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G. Bru-Mercier, E. Deroubaix, D. Rousseau, A. Coulombe, and J.-F. Renaud Depressed transient outward potassium current density in catecholamine-depleted rat ventricular myocytes Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1237 - H1247. [Abstract] [Full Text] [PDF]
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