Parasympathetic control of cardiac sympathetic activity: normal ventricular function versus congestive heart failure.
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.


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 micrograms/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.
Department of Medicine, Division of Cardiology, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
E R
ER
Azevedo
J D
JD
Parker
D000109:Acetylcholine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000294:innervation; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000378:metabolism; D016276:Ventricular Function / Q000502:physiology
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D001285:Atropine; D000109:Acetylcholine; D009638:Norepinephrine