Parasympathetic nervous system and heart failure: pathophysiology and potential implications for therapy.

Abundant evidence links sympathetic nervous system activation to outcomes of patients with heart failure (HF).1 In contrast, parasympathetic activation has complex cardiovascular effects that are only beginning to be recognized. In particular, the pathophysiological roles of normal and disordered parasympathetic innervation in patients with HF are not understood as comprehensively.2–5 In the present article, we review cardiovascular responses to parasympathetic activation, address the modulating factors that can affect parasympathetic function, discuss the role of the vagus nerve in ventricular dysfunction, and consider how activation of the parasympathetic nervous system may have important therapeutic implications for patients with congestive HF. The parasympathetic nervous system originates from medial medullary sites (nucleus ambiguous, nucleus tractus solitarius, and dorsal motor nucleus) and is modulated by the hypothalamus. Vagal efferents extend from the medulla to postganglionic nerves that innervate the atria via ganglia located in cardiac fat pads with neurotransmission that is modulated via nicotinic receptors. Postganglionic parasympathetic and sympathetic cholinergic nerves then affect cardiac muscarinic receptors (the Figure).6–8 Figure. Parasympathetic and sympathetic innervation of the heart: anatomy. Efferent fiber (vagus) comprises A-beta, A-delta, and unmyelinated C fibers. Reproduced from Martini FH. Fundamentals of Anatomy and Physiology . 8th ed. 2006. Chapter 20, by permission of Pearson Education, Inc Prentice Hall, copyright © 2006. Vagus nerve afferent activation, originating peripherally, can modulate efferent sympathetic and parasympathetic function centrally and at the level of the baroreceptor. Efferent vagus nerve activation can have tonic and basal effects that inhibit sympathetic activation and release of norepinephrine at the presynaptic level. Acetylcholine release from parasympathetic nerve terminals will activate ganglionic nicotinic receptors that in turn activate muscarinic receptors at the cellular level. Cardiovascular effects include heart rate reduction by inhibition of the sympathetic nervous system and by direct hyperpolarization of sinus nodal cells. Parasympathetic activation …