Parasympathetic control of cardiac sympathetic activity - Normal ventricular function versus congestive heart failure

Background-Muscarinic receptors on adrenergic nerve terminals attenuate nor epinephrine release. The role of these receptors in the modulation of cardi ac norepinephrine release in humans remains uncertain. Methods and Results-Twelve patients with normal left ventricular (LV) funct ion 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 respons e to intracoronary atropine (12 mu g/min). ACh did not affect CANESP in the group of subjects with normal LV function, but it caused a significant red uction 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 no rmal LV function [47 (27 to 51) versus 64 (38 to 139) pmol/min, P<0.05], bu t no change was observed in the CHF group. Conclusions-Therefore, in the setting of heart failure and sympathetic acti vation, muscarinic receptor stimulation decreases CANESP, an effect not obs erved in patients with preserved LV function. Blockade of muscarinic recept ors with atropine increased CANESP in patients with normal LV function, sug gesting that cardiac parasympathetic tone has inhibitory effects on cardiac sympathetic activity. This basal inhibition was not observed in CHF patien ts in response to atropine. The lack of basal parasympathetic inhibition of cardiac sympathetic activity may play a role in the pathogenesis of cardia c sympathetic activation in heart failure.