(Circulation. 1999;100:274-279.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Parasympathetic Control of Cardiac Sympathetic Activity
Normal Ventricular Function Versus Congestive Heart Failure
From the Department of Medicine, Division of Cardiology, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
Correspondence to John D. Parker, MD, Mount Sinai Hospital, University of Toronto, Department of Medicine, Division of Cardiology, 600 University Avenue, Suite 1609, Toronto, Ontario M5G-1X5, Canada. E-mail jdp{at}inforamp.net
Background—Muscarinic receptors on adrenergic nerve terminals attenuate norepinephrine release. The role of these receptors in the modulation of cardiac norepinephrine release in humans remains uncertain.
Methods and Results—Twelve patients with normal left ventricular (LV) function and 18 with congestive heart failure (CHF) were studied. A radiotracer technique was used to measure cardiac norepinephrine spillover (CANESP) in response to intracoronary acetylcholine (ACh, 5x10-5 Mol), and in response to intracoronary atropine (12 µg/min). ACh did not affect CANESP in the group of subjects with normal LV function, but it caused a significant reduction in those with CHF [197 (150 to 302) versus 168 (87 to 288) pmol/min, P<0.05]. Atropine caused a significant increase in CANESP in those with normal LV function [47 (27 to 51) versus 64 (38 to 139) pmol/min, P<0.05], but no change was observed in the CHF group.
Conclusions—Therefore, in the setting of heart failure and sympathetic activation, muscarinic receptor stimulation decreases CANESP, an effect not observed in patients with preserved LV function. Blockade of muscarinic receptors with atropine increased CANESP in patients with normal LV function, suggesting that cardiac parasympathetic tone has inhibitory effects on cardiac sympathetic activity. This basal inhibition was not observed in CHF patients in response to atropine. The lack of basal parasympathetic inhibition of cardiac sympathetic activity may play a role in the pathogenesis of cardiac sympathetic activation in heart failure.
Key Words: nervous system, autonomic • acetylcholine • norepinephrine • receptors
This article has been cited by other articles:
 |
|
 |
|
  F. Triposkiadis, G. Karayannis, G. Giamouzis, J. Skoularigis, G. Louridas, and J. Butler The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications. J. Am. Coll. Cardiol., November 3, 2009; 54(19): 1747 - 1762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Hardwick, C. N. Baran, E. M. Southerland, and J. L. Ardell Remodeling of the guinea pig intrinsic cardiac plexus with chronic pressure overload Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2009; 297(3): R859 - R866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Floras Sympathetic nervous system activation in human heart failure: clinical implications of an updated model. J. Am. Coll. Cardiol., July 28, 2009; 54(5): 375 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Olshansky, H. N. Sabbah, P. J. Hauptman, and W. S. Colucci Parasympathetic Nervous System and Heart Failure: Pathophysiology and Potential Implications for Therapy Circulation, August 19, 2008; 118(8): 863 - 871. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tsutsumi, T. Ide, M. Yamato, W. Kudou, M. Andou, Y. Hirooka, H. Utsumi, H. Tsutsui, and K. Sunagawa Modulation of the myocardial redox state by vagal nerve stimulation after experimental myocardial infarction Cardiovasc Res, March 1, 2008; 77(4): 713 - 721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Vecoli and N. Paolocci When the heart sleeps... Is the vagus resetting the myocardial 'redox clock'? Cardiovasc Res, March 1, 2008; 77(4): 609 - 611. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Freeling, K. Wattier, C. LaCroix, and Y.-F. Li Neostigmine and pilocarpine attenuated tumour necrosis factor {alpha} expression and cardiac hypertrophy in the heart with pressure overload Exp Physiol, January 1, 2008; 93(1): 75 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. U. Muller Increased eNOS expression as a compensatory mechanism reducing {beta}-adrenergic responsiveness? Cardiovasc Res, September 1, 2005; 67(4): 575 - 577. [Full Text] [PDF]
|
|
|
|
|
|
D. J. Duncker, D. B. Haitsma, D. A. Liem, P. D. Verdouw, and D. Merkus Exercise unmasks autonomic dysfunction in swine with a recent myocardial infarction Cardiovasc Res, March 1, 2005; 65(4): 889 - 896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. S. Akers and L. A. Cassis Presynaptic modulation of evoked NE release contributes to sympathetic activation after pressure overload Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2151 - H2158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Arora, R. Cardinal, F. M. Smith, J. L. Ardell, L. J. Dell'Italia, and J. A. Armour Intrinsic cardiac nervous system in tachycardia induced heart failure Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2003; 285(5): R1212 - R1223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Schlaich, D. M. Kaye, E. Lambert, M. Sommerville, F. Socratous, and M. D. Esler Relation Between Cardiac Sympathetic Activity and Hypertensive Left Ventricular Hypertrophy Circulation, August 5, 2003; 108(5): 560 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Al-Hesayen, E. R. Azevedo, G. E. Newton, and J. D. Parker The effects of dobutamine on cardiac sympathetic activity in patients with congestive heart failure J. Am. Coll. Cardiol., April 17, 2002; 39(8): 1269 - 1274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Rabelo, K. De Angelis, P. Bock, T. Gatelli Fernandes, F. Cervo, A. Bello Klein, N. Clausell, and M. Claudia Irigoyen Baroreflex Sensitivity and Oxidative Stress in Adriamycin-Induced Heart Failure Hypertension, September 1, 2001; 38(3): 576 - 580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Oberhauser, E. Schwertfeger, T. Rutz, F. Beyersdorf, and L. C. Rump Acetylcholine Release in Human Heart Atrium : Influence of Muscarinic Autoreceptors, Diabetes, and Age Circulation, March 27, 2001; 103(12): 1638 - 1643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|