Heart Nerve Anatomy

Updated: Jun 28, 2016
Author: Ramin Assadi, MD; Chief Editor: Richard A Lange, MD, MBA 


The heart is innervated by parasympathetic and sympathetic fibers. The medulla is the primary site in the brain for regulating sympathetic and parasympathetic outflow to the heart and blood vessels. The hypothalamus and higher centers modify the activity of the medullary centers and are particularly important in regulating cardiovascular responses to emotion and stress (eg, exercise, thermal stress).

The vagus nerve has 3 nuclei in the central nervous system (CNS) associated with cardiovascular control: (1) the dorsal motor nucleus, (2) the nucleus ambiguus, and (3) the solitary nucleus. The parasympathetic output to the heart comes mainly from neurons in the nucleus ambiguus and to a lesser extent from the dorsal motor nucleus (see the image below).[1] The solitary nucleus, being an integrating hub for the baroreflex, receives sensory input about the state of the cardiovascular system.

Schematic illustration of arterial baroreceptor re Schematic illustration of arterial baroreceptor reflex. SNS = sympathetic nervous system.

The afferent fibers of the autonomic nervous system of the heart share the same pathway with gastrointestinal, genitourinary, baroreceptors, and chemoreceptors and transmit signals to the medulla by cranial nerves X and IX. The nucleus tractus solitarius (NTS) of the medulla receives sensory input from baroreceptors and chemoreceptors (see the image above).

Autonomic outflow from the medulla is divided principally into sympathetic and parasympathetic branches (see the image below). All the fibers forming the different cardiac plexus present synapse with the cervical plexus, brachial plexus, and intercostal nerves through communicating branches. These synapses have a great importance in the presence of pain in certain cardiac pathologies.[1]

Sympathetic and parasympathetic efferents. Sympathetic and parasympathetic efferents.

See also Heart Anatomy, Aortic Valve Anatomy, Mitral Valve Anatomy, Pulmonic Valve Anatomy, and Tricuspid Valve Anatomy.


Gross and Microscopic Anatomy

Gross anatomy

Sympathetic nervous system

Sympathetic nerves travel along arteries and nerves and are found in the adventitia (eg, outer wall) of blood vessels. Varicosities, which are small enlargements along the nerve fibers, are the site of neurotransmitter release. Sympathetic efferent nerves are present throughout the atria, ventricles (including the conduction system), and myocytes in the heart and also the sinoatrial (SA) and atrioventricular (AV) nodes. These adrenergic nerves release norepinephrine (NE). The preganglionic sympathetic fibers are located in the lateral column of the spinal cord. These fibers give origin to the 3 cervical ganglia and to the first 3 or 4 thoracic ganglia.[2, 3]

The cardiac branches of the superior ganglion or cardiac superior nerve (located in front of the C2 and C3 vertebrae) originate on the inferior sector of the mentioned ganglion. Existing branches shunt it with the fillets originating in the other cervical ganglia. These cervical ganglia go down the primitive carotid and in front of the large muscles of the neck.

The middle cervical ganglion is tiny and can be absent (it is located on the same level as the C6, near the inferior thyroid artery). Its cardiac branch, the middle cardiac nerve, arises independently or emerges after the synapse with the inferior cervical ganglion. On the right side, it descends behind the primitive carotid to constitute the dorsal part of the cardiac plexus. On its way, it receives numerous branches from the principal pneumogastric and the recurrent nerves. On the left side, the nerve enters the thorax between the left primitive carotid and the subclavian, and it converges at the deep part of the cardiac plexus.

The inferior cervical ganglion is located between the base of the transverse process of the last cervical vertebra and the first rib, on the medial side of the costocervical artery. Its cardiac branch, the inferior cardiac nerve, descends behind the subclavian artery (here, it converges with the recurrent nerve and with a branch of the medium cervical nerve) and all along the anterior surface of the trachea, finally joining to the deep part of the cardiac plexus.[2, 4]

Parasympathetic nervous system (vagus nerve)

The name vagus comes from Latin and means "wandering." The vagus is a mixed nerve that has a role in sensory, motor, and secretory functions, and it contains approximately 80% sensory fibers.[5] Both the right and left vagus nerves descend from the brain in the carotid sheath, lateral to the carotid artery. The nerve runs from the lower brain stem through the base of the skull to travel in the neck with the carotid artery and jugular vein. It then penetrates the chest to travel to the heart and lungs.

Unlike the sympathetic innervation, which must first synapse within chain ganglia to supply the heart with postsynaptic fibers, the parasympathetic fibers synapse at ganglia located directly on the heart and short postsynaptic fibers then supply the target organ. The parasympathetic nervous system mainly innervates the SA and AV nodes in the heart. Atrial muscle is also innervated by vagal efferents, whereas the ventricular myocardium is only sparsely innervated by vagal efferents.

Natural variants

The right vagus nerve primarily innervates the SA node, whereas the left vagus innervates the AV node; however, significant overlap can exist in the anatomic distribution.

Microscopic anatomy

The alpha-1 (α1) receptors are located postsynaptically on the membrane of the effector cells, whereas the alpha-2 (α2) receptors are located presynaptically on the cell membrane of the sympathetic nerve innervating the effector cells.

The following image demonstrates autonomic stimulation of the heart rate.[6]

Autonomic stimulation of the heart rate acts throu Autonomic stimulation of the heart rate acts through G-protein coupled receptors (GPCR). Parasympathetic activation (vagus nerve) exerts an inhibitory action on the heart: it slows conduction from the sinus node, leading to bradycardia, and reduces conduction via the atrioventricular node. Activation by the sympathetic nervous system exerts an excitatory action on the heart: it stimulates sinus node and atrioventricular conduction, leading to faster heart rate. One pattern of signal transduction linking the autonomic nervous system to the intracellular effector is mediated through the cyclic adenosine monophosphate (cAMP) pathway. The muscarinic (M2) receptor, which is stimulated by the vagus nerve, binds acetylcholine and is coupled to the inhibitory G protein (Gi). The beta-adrenergic (B1) receptor, which is stimulated by the sympathetic nervous system, binds catecholamines and is coupled to the stimulatory G protein (Gs). When ligands bind to their respective GPCR, activated heterotrimeric G protein complexes dissociate from the GPCR and split into activated Gi and Gs subunits, which act on adenylyl cyclase. Gs stimulates adenyl cyclase to enhance cAMP production, whereas Gi proteins prevent cAMP production. The cAMP signaling cascade leads to an increased heart rate. Manipulation of this signaling pathway by gene therapy may be useful in treating cardiac arrhythmias.

Sympathetic and parasympathetic receptors are shown in the image below.

Sympathetic and parasympathetic neurotransmitters Sympathetic and parasympathetic neurotransmitters and receptors.

Pathophysiologic Variants

Sympathetic activation

Activation of sympathetic nerves during exercise, emotional stress, dehydration, or hemorrhage causes vasoconstriction of arteries and veins mediated by alpha-adrenoceptors and increased heart rate (positive chronotropy), contractility (positive inotropy), rate of relaxation (increased lusitropy), and conduction velocity (positive dromotropy) by the beta-1 (β1) adrenoceptor.

Parasympathetic activation

The parasympathetic system effects are mediated by muscarinic receptors. The sinoatrial (SA) and atrioventricular (AV) nodes have a large amount of vagal innervation. Parasympathetic effects on inotropy are weak in the ventricle but relatively strong in the atria. This produces negative chronotropy and dromotropy in the heart, as well as negative inotropy and lusitropy in the atria (the negative inotropic and lusitropic effects of vagal stimulation are relatively weak in the ventricles).

Chest pain and myocardial ischemia

The heart does not ache. However, chest pain is one of the most important symptoms of heart disease. A probable explanation is that metabolic changes suffered by the myocardial cells produce "irritation" of nerve fibers. The painful stimulation on the cardiac plexus (C fibers) through afferent vagal nerve corresponding dermatomes (C7-T4), goes through the communicating boughs to the cervical, brachial (internal cutaneous brachial), and the intercostal nerves. Therefore, heart pain is a "referred" type of pain and is known as angina pectoris.

Angina often radiates to other parts of the body, including the upper abdomen, shoulders, arms, wrist, fingers, neck and throat, lower jaw and teeth (but not upper jaw), and, rarely, to the back (specifically the interscapular region). Radiation to both arms is a stronger predictor of acute myocardial infarction.[7, 8]

Valsalva maneuver

The Valsalva maneuver provides a measure of sympathetic, vagal, and baroreceptor function. This maneuver has the following 4 phases:

  • Phase 1 - Transient rise in arterial pressure and an associated decrease in heart rate

  • Phase 2 - Gradual fall in blood pressure, followed by recovery (An increase in heart rate accompanies this phase [during the expiratory phase of the maneuver].)

  • Phase 3 - Brief fall in blood pressure with an accompanying increase in heart rate occurring with the cessation of straining

  • Phase 4 - Increase in blood pressure above the resting value (the "overshoot") and bradycardia

Phases 1 and 3 most likely reflect mechanical factors (eg, intrathoracic pressure changes), whereas phases 2 and 4 are a consequence of sympathetic, vagal, and baroreflex interactions.[9, 10]

Neurocardiogenic (vasovagal) syncope

Neurocardiogenic syncope, also known as vasovagal reaction, is a common cause of syncope.[11] Neurally mediated (reflex) syncope refers to a reflex response causing vasodilatation and/or bradycardia (rarely tachycardia), leading to systemic hypotension and cerebral hypoperfusion.[12] Types of neurally mediated syncope include neurocardiogenic (vasovagal) syncope, carotid sinus syncope, situational syncope, and glossopharyngeal neuralgia.

The following 3 types of responses are seen: (1) cardioinhibitory response, (2) vasodepressor response, and (3) mixed response with both features.[13] It is likely that sensory inputs through vagal afferents, pain pathways, and central pathways (visual, temporal lobe, and other inputs) affect the nucleus tractus solitarius to cause sympathoinhibition and vagal efferent activation. Bezold-Jarisch and carotid sinus reflexes may be involved. Patients may have increased muscle sympathetic nerve activity at rest and a blunted response to orthostatic stress.[14, 15]

Bezold-Jarisch reflex

The Bezold-Jarisch reflex is an eponym for a triad of responses (apnea, bradycardia, and hypotension) following intravenous injection of Veratrum alkaloids in experimental animals. This observation was first reported in 1867 by von Bezold and Hirt and confirmed in 1938-1940 by Jarisch.[16]

The reflex originates in cardiac sensory receptors with nonmyelinated vagal afferent pathways (C fibers). The left ventricle, particularly the inferoposterior wall, is a principal location for these sensory receptors. Stimulation of these inhibitory cardiac receptors by stretch, chemical substances, or drugs increases parasympathetic activity and inhibits sympathetic activity. These effects promote reflex bradycardia, vasodilation, and hypotension, as well as modulate renin release and vasopressin secretion.[17]

Carotid sinus reflex

Blood pressure and heart rate are normally controlled in part by input from baroreceptors located within the carotid sinus and aortic arch. An increase in blood pressure or pressure applied to the carotid sinus enhances the baroreceptor firing rate and activates vagal efferents, thereby slowing the heart rate and reducing the blood pressure.

Oculocardiac and trigeminocardiac reflexes

The oculocardiac reflex involves a decrease in heart rate and/or blood pressure in response to eyeball pressure. The reflex is thought to originate from the ophthalmic portion of the trigeminal nerve. Afferent stimuli move through the reticular formation and nuclei of the vagus nerve output and proceed via an efferent link through the vagus nerve to cardiovascular structures.

The trigeminocardiac reflex (TCR) is defined as the sudden onset of parasympathetic dysrhythmia, sympathetic hypotension, apnea, or gastric hypermotility during stimulation of any of the sensory branches of the trigeminal nerve. Clinically, this could occur during craniofacial surgery, orbital fracture, balloon-compression rhizolysis of the trigeminal ganglion, and tumor resection in the cerebellopontine angle.

The proposed mechanism for the development of TCR is the sensory nerve endings of the trigeminal nerve send neuronal signals via the Gasserian ganglion to the sensory nucleus of the trigeminal nerve, forming the afferent pathway of the reflex arc. The reaction subsides with cessation of the stimulus. Some patients may develop severe bradycardia, asystole, and hypotension, which require intervention.[18]

Sudden cardiac death

Diseases of cardiac nerves have been postulated to have role in sudden cardiac death (SCD). Neural involvement may be the result of random damage to neural elements within the myocardium, or they may be primary, as in a selective viral neuropathy. Secondary involvement can be a consequence of ischemic neural injury and has been postulated to result in autonomic destabilization, enhancing the propensity to arrhythmias. Nerve sprouting may be important.[19]

Postural tachycardia syndrome

Postural tachycardia syndrome (POTS) is an exaggerated increase in heart rate on tilt table testing or standing. The etiology of POTS is not clear, but the disorder may be heterogeneous. Abnormalities in autonomic regulation that may either be genetic or acquired are described (see Anatomy of the Autonomic Nervous System). Proposed mechanisms include partial sympathetic denervation leading to discordant cardiac and vascular sympathetic control, hypovolemia and impairment of the renin-angiotensin-aldosterone system, venous abnormalities, and baroreflex dysfunction. There is additional evidence of an attenuated vagal baroreflex response in POTS, as measured by changes in heart rate variability in response to Valsalva and lower body negative pressure.[20, 21]

Beat-to-beat variability

The beat-to-beat variability in heart rate accompanying respiration at normal respiratory rates is predominantly mediated by the vagus nerve and is reduced or abolished by vagotomy, vagus nerve cooling, and muscarinic blockade. The determinants of the respiratory fluctuations in heart rate include a stretch reflex from the lungs and thoracic wall, changes in cardiac filling, arterial baroreceptor responses to blood pressure changes, changes in baroreflex sensitivity with respiratory phase, and respiratory center activity overflow to medullary vasomotor neurons.

The amplitude of the beat-to-beat variation with respiration (ie, the maximum minus minimum heart rate difference, as measured in beats per minute [bpm]) and the E:I ratio (ratio of expiration to inspiration) are generally regarded as the simplest and most reliable measures of heart rate variability in response to deep respiration. The maximum heart rate variation in response to deep breathing is a sensitive and specific index of autonomic function. This test is the best noninvasive test to assess cardiac vagal innervation.

Apneic facial immersion

In humans, the diving reflex has been studied as a tool to assess the autonomic nervous system.[22] The expected response in normal subjects results from a combination of facial immersion and breath holding. The expected effect is parasympathetic-mediated bradycardia and sympathetic-mediated peripheral vasoconstriction.[23]

Heart transplant

Suturing the ventricular nervous fillets or reestablishing the intrinsic linking of the cardionector system is almost impossible. However, the rhythm is spontaneously reestablished, even when a cardiac pacemaker (in 10-20% of the cases) is eventually necessary. Because the vagus nerve is separated during the operation, the new heart beats at around 100 bpm until nerve regrowth occurs. This way, the heart rate maintains itself almost invariable, independent of the somatic activity, and patients do not perceive the ischemic pain.


Biofeedback is the process of becoming aware of various physiologic functions using instruments that provide information on the activity of those same systems, with a goal of being able to manipulate them at will. Behavioral neurocardiac training (BNT) with heart rate variability biofeedback modestly lowers ambulatory blood pressure during wakefulness, and it augments tonic vagal heart rate modulation. It is unknown whether efficacy of this treatment can be improved with biofeedback of baroreflex gain.[24] Reduced heart rate variability seems to indicate decreased cardiac vagal tone and elevated sympathetic activity in anxious and depressive patients and would reflect deficit in flexibility of emotional physiologic mechanisms.

A few studies have also revealed that biofeedback using respiratory control, relaxation, and meditation techniques can increase heart rate variability. For now, insufficient data exist to determine if paced respiration or subjective relaxation is necessary or sufficient for the efficacy of heart rate variability biofeedback.[25]

Carotid sinus hypersensitivity

Carotid sinus hypersensitivity is a common cause of syncope. The carotid sinus reflex arc is composed of an afferent limb arising from mechanoreceptors in the internal carotid artery that transmit impulses through cranial nerve IX to the medulla and terminate in the nucleus tractus solitarius (NTS) in the vagal nucleus and the vasomotor center. The efferent limb innervates the SA and AV nodes via the vagus nerve and the parasympathetic ganglia and also inhibits sympathetic nervous tone to the heart and blood vessels.

Neurohormonal adaptation in heart failure

Sympathetic nervous system activation is a compensatory mechanism in heart failure with inotropic and chronotropic activity. Sympathetic activation is associated with pathologic ventricular remodeling, increased arrhythmias, sudden death, and increased mortality in chronic heart failure. Preliminary human studies suggest a positive effect of statins on sympathovagal balance in patients with heart failure.[26]

Autonomic failure syndrome (orthostatic hypotension)

Orthostatic hypotension (OH) is a common cardiovascular disorder, with or without signs of underlying neurodegenerative disease. OH is defined as a decrease of ≥ 20 mm Hg in systolic blood pressure or ≥ 10 mm Hg in diastolic blood pressure within 2 minutes of standing. Its prevalence depends on age, ranging from 5% in patients younger than 50 years to 30% in those older than 70 years. OH may complicate treatment of hypertension, heart failure, and coronary artery disease; cause disabling symptoms, syncope, and traumatic injuries; and substantially reduce quality of life.

In healthy individuals, approximately 25-30% of circulating blood volume is found within the thoracic cavity while supine. Almost immediately, with the transition from the supine to the upright position, a gravity-mediated displacement of nearly 500 mL of blood away from the chest to the distensible venous capacitance system below the diaphragm (venous pooling) occurs. This results in a rapid decrease in central blood volume and a subsequent reduction of ventricular preload, stroke volume, and mean blood pressure. In the vascular system, a reference quantitative determinant of these changes is the venous hydrostatic indifference point (HIP), when pressure is independent of posture. In humans, the venous HIP is approximately at the diaphragmatic level, whereas the arterial HIP lies close to the level of the left ventricle. The venous HIP is dynamic and is significantly affected by venous compliance and muscular activity.

Upon standing, contractions of lower limb muscles, along with the presence of venous valves, provide an intermittent unidirectional flow, moving the venous HIP toward the right atrial level. Respiration may also increase venous return because deep inspiration results in both a decline in thoracic pressure and an increase in intra-abdominal pressure, which lowers retrograde flow due to compression of both the iliac and femoral veins. To provide an appropriate perfusion pressure to critical organs, an effective set of the neural regulatory system is promptly activated upon standing.

The sympathetic nervous system is fast-acting and primarily modulated by mechanoreceptors and, to a smaller degree, by chemoreceptors. Arterial baroreceptors (high-pressure receptors) are located in the carotid sinus and the aortic arch and—by conveying baroceptive impulses via carotid sinus and aortic depressor nerves to the brainstem, notably in the nucleus of the solitary tract—determine tonic inhibition of vasomotor centers. In contrast, cardiopulmonary baroreceptors (volume receptors) are located in the great veins and the cardiac chambers and detect changes in the filling of the central venous circulation but are not essential for orthostatic cardiovascular homeostasis. A sudden drop in blood pressure in the carotid sinus and the aortic arch triggers baroreceptor-mediated compensatory mechanisms within seconds, resulting in increased heart rate, myocardial contractility, and peripheral vasoconstriction. An additional local axon reflex, the veno-arteriolar axon reflex, results in constriction of arterial flow to the muscles, skin, and adipose tissue, leading to almost half of the increase in vascular resistance in the limbs upon standing. Ultimately, orthostatic stabilization is normally achieved in roughly 1 min or less.

During prolonged quiet standing, in addition to venous pooling, transcapillary filtration in the subdiaphragmatic space further reduces both central blood volume and cardiac output by approximately 15-20%. This transcapillary shift equilibrates after approximately 30 min of upright posture, which can result in a net fall in plasma volume of up to 10% over this time. Continued upright posture also results in activation of neuroendocrine mechanisms, such as the renin-angiotensin-aldosterone system, which may vary in intensity, depending on the volume status of the patient. Still, the most important homeostatic response to prolonged orthostatic stress appears to be the carotid baroreflex-mediated increase of peripheral vascular resistance. The inability of any one of these factors to perform adequately or coordinately may result in a failure of the system to compensate for an initial or sustained postural challenge. This may produce a transient or persistent state of hypotension, which, in turn, can lead to symptomatic cerebral hypoperfusion and loss of consciousness, either in the early or late phase of orthostatic challenge.[27, 28]