Autonomic pathophysiology in heart failure patients. Sympathetic-cholinergic interrelations.

Abstract

We conducted this study in an effort to characterize and understand vagal abnormalities in heart failure patients whose sympathetic activity is known. We measured sympathetic (peroneal nerve muscle sympathetic recordings and antecubital vein plasma norepinephrine levels) and vagal (R-R intervals and their standard deviations) activities in eight heart failure patients and eight age-matched healthy volunteers, before and after parasympathomimetic and parasympatholytic intravenous doses of atropine sulfate. At rest, sympathetic and parasympathetic outflows were related reciprocally: heart failure patients had high sympathetic and low parasympathetic outflows, and healthy subjects had low sympathetic and high parasympathetic outflows. Low dose atropine, which is known to increase the activity of central vagal-cardiac motoneurons, significantly increased R-R intervals in healthy subjects, but did not alter R-R intervals in heart failure patients. Thus, our data document reciprocal supranormal sympathetic and subnormal parasympathetic outflows in heart failure patients and suggest that these abnormalities result in part from abnormalities within the central nervous system. (J. Clin. Invest. 1990.

Muscarinic receptor modulation of basal and beta-adrenergic stimulated function of the failing human left ventricle.

“…We hypothesize that the explanation for the lack of an atropine effect in the heart failure group is that there was little endogenous acetylcholine present within ventricular myocardium to antagonize, similar to our previous observation in patients post heart transplantation (9). This hypothesis is consistent with previous investigations that demonstrated reduced parasympathetic tone in heart failure based on heart rate and heart rate variability measurements (1,2).…”

“…First, the intracoronary concentration of atropine may have been insufficient to antagonize the stimulation of muscarinic receptors by endogenous acetylcholine. However, in the normal ventricular function group the same infusion of atropine augmented dobutamine responses, and the concentration of acetylcholine within ventricular myocardium is likely to have been higher in this group as compared to the heart failure group (1,2). Furthermore, atropine was able to antagonize the effects of exogenous acetylcholine in heart failure patients studied in Protocol 3.…”

“…Parasympathetic outflow to the heart is reduced in patients with heart failure (1,2). The importance of this abnormality in the pathogenesis of life-threatening rhythm disturbances has been observed (3), and the possible utility of pharmacological augmentation of parasympathetic tone in patients with heart failure has been suggested (4).…”

Reduced N‐Type Ca 2+ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis

“…In particular, a sustained increase of sympathetic activity and a marked decrease of parasympathetic tone are used as distinctive hallmarks of CHF 7, 8, 9. Thus far, most of the studies used the analysis of heart‐rate variability and arterial baroreflex sensitivity to evaluate cardiac sympathetic and parasympathetic autonomic activity in physiological and pathophysiological conditions 38.…”

“…Cardiac autonomic dysfunction is a major feature of CHF, characterized by a sustained increase of sympathetic tone and withdrawal of cardiac vagal activity 7, 8, 9. Much evidence has shown that this autonomic imbalance leads to arrhythmogenesis and is associated with the high mortality of CHF 2, 10, 11.…”