every heart beat is under neural command: an hypothesis relating to the cardiac rhythm

Cardiovascular Hypothesis

Every Heart Beat is Under Neural Command: An Hypothesis Relating to the Cardiac Rhythm

Solomon Victor, FRCS, FRCP and Vijaya M. Nayak, MS

In the human heart there is a sequential contraction of the systemic veins, systemic venous sinusand the pectinated right atrium, ‘the systemic waltz’, and sequential contraction of the pulmon-ary veins, pulmonary venous sinus and pectinated left atrium, ‘the pulmonary waltz’. Thesystemic veins contract earlier than the pulmonary veins creating a ‘duet’. We hypothesise thatthis waltz and duet point to a complex extracardiac control of the cardiac rhythm on a beat-to-beat neural basis. (Heart, Lung and Circulation 2003; 12: 11–17)

Key words: evolution, heart rhythm, neural control.

n humans, notions regarding discrete centres, suchas the vasomotor, cardiac and respiratory centres inthe medulla in the brain, are being substituted by an

awareness of a complex interplay of pathways betweenthe cortex, subcortex, brain stem and spinal cord control-ling the heart.1–3 Separate pathways for beat-to-beatcentral control of chronotropic, dromotropic and ino-tropic properties of the heart, as well as coronary bloodflow, have been identified.2 This communication relatesto observations pointing to a neurogenic triggering ofevery heart beat.

Phylogenic BackgroundThere is an abundance of evidence about the increasinglycomplex autonomic innervation of the hearts in inverte-brates and vertebrates as they move up the evolutionaryscale.1–4

In the earthworm, there is a sequential contraction ofthe valved dorsal vessel and valved vascular arches(lateral hearts) connecting the dorsal and ventral vessels5–7

(Fig. 1).In the prawn, lobster (Fig. 2a) and crab (Fig. 2b), body

fluid pours into the pericardial cavity and then enters aventricle through valved openings.8 The ventricle exhibitsa solo performance. In the snail, a common atrium isattached as a booster pump that contracts in synchrony

with the ventricle (Fig. 3). In the cartilaginous fish, theshark, a sinus venosus is attached to the common atriumand functions as a reservoir.8,9 It is thin-walled andpossibly noncontractile. A sinoatrial valve preventsreflux when the pectinated common atrium contracts. Inthe air-breathing fresh-water fish, Channa striata, a dorso-caudal infolding of the wall of the sinus venosus dividesthe externally symmetrical heart (Fig. 4) into two sym-metrical halves.8–10 A primitive pulmonary vein entersone half of the sinus venosus.8–10 In the air-breathingIndian catfish, the heart is looped to the right (Fig. 5). Thedivision of the sinus venosus becomes asymmetrical.8–10

The sinoatrial orifice is shifted to the right.8–10 We haveobserved that in Channa striata and the Indian catfish thesinus venosus is not contractile. In the lungfish, there is amore complex separation of the systemic and pulmonarycirculations.6,9

In the frog, the sinus venosus is divided into systemicand pulmonary venous sinuses by a complete sinusvenosus septum.8–10 The two precaval and one postcavalsystemic veins drain into the smooth-walled systemicvenous sinus that empties through the sinoatrial valveinto the pectinated right atrium.8,10 A common pulmo-nary vein drains through a smooth pulmonary venouschamber into the pectinated left atrium.8,10 There is anincomplete interatrial septum. The smooth and pecti-nated parts of the atria are demarcated by crista termi-nalis on the systemic side, and a similar muscle band onthe pulmonary side.11 The three systemic veins contractin unison.10,12 There is sequential contraction of thesystemic veins, the systemic venous sinus (Fig. 6a) and

Correspondence: Solomon Victor, The Heart Institute, 34, East Street, Kilpauk Garden Colony, Chennai 600 010, India.Email: [email protected]

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12 S. Victor and V. M. Nayak Heart, Lung and Circulation 2003; 12Hypothesis relating to cardiac rhythm

the pectinated right atrium (Fig. 6b).10 Likewise, thereis sequential contraction of the pulmonary vein, thepulmonary venous sinus and the pectinated left atrium.10

Furthermore, the contraction of the common pulmonaryvein follows that of the synchronous contractions of thethree systemic veins.10

The reptiles, turtle, snake (Fig. 7a,b) and crocodile,with a complete interatrial septum, exhibit systemic andpulmonary waltz and duet.10 In birds, we have observedthe systemic and pulmonary waltz.10 The duet is noteasily discernible because of tachycardia.

The Mammalian and Human SituationIn mammals, the intrapericardial segment of the inferiorvena cava is thin-walled and macroscopically devoid of

muscle, except at its junction with the right atrium. Theintrapericardial superior vena cava and terminal seg-ments of all the pulmonary veins are muscularised.

Observation of the human hearts exposed for surgeryreveals sequential contraction of the muscularised intra-pericardial segment of the superior vena cava, the sys-temic venous sinus and the pectinated right atrium.10

Likewise, we have observed at surgery a ‘waltz’ of thepulmonary veins, the pulmonary venous sinus and thepectinated left atrium.10

During induction of, or recovery from, cardioplegia,we have observed a ‘duet’ between the superior venacava and the right pulmonary veins.10 Although theintrapericardial inferior vena cava does not contract,there is contraction of its junction with the atrium. In thecoronary angiogram we have also seen contraction ofthe coronary sinus during ventricular diastole.

Present Concept of Cardiac RhythmWhat is the mechanism sustaining waltz and duet in thehearts of frogs, reptiles, birds, mammals and humans? Thecardiac rhythm is naively attributed to the inherent rhyth-micity of the sinoatrial node. There is no explanation ofhow this rhythmic activity is initiated and sustained.What governs the rhythmic influx and efflux of potas-sium, sodium and other ions? The autonomic nervoussystem is given credit only for modulating the rate of thisinherent rhythmicity.

Cardiac InnervationIn humans there is a rich autonomic innervation beside,and inside, the heart.2–4 Numerous autonomic ganglia

Figure 2. Single ventricle shown in the lobster (a) and crab (b) suspended inside the dorsally-located pericardial cavity. Observethe solo ventricular complex (R) in the electrocardiogram of the lobster (a, inset).

Figure 1. The lateral hearts (arrowheads) connecting thedorsal (DV) and ventral vessels (VV) in the earthworm.

Heart, Lung and Circulation 2003; 12 S. Victor and V. M. Nayak 13Hypothesis relating to cardiac rhythm

have been identified close to, and in, the superior venacava, pulmonary veins, sinoatrial node, atria, atrioven-tricular node and ventricles.2–4

Virtually every myocardial cell is innervated.3,4 Suchrich innervation suggests that their physiological func-tion is more complex than what has been acknowl-edged. The human cardiac plexuses of nerves areclassified as superficial and deep,3 and interlinked witheach other. Licata4 divides the autonomic innervationinto venous and arterial plexuses, connected to theposterior mediastinum through sinoatrial andconotruncal mesocardia. Perhaps the names, inlet andoutlet plexuses, are more appropriate. Licata has identi-fied right and left precaval, atrial and postcaval nervesemerging from the inlet plexuses and carrying bothsympathetic and parasympathetic fibres.4 The left atrialnerve is related to the vein of Marshall. If the leftsuperior vena cava is persistent, this nerve is as promi-nent as its right counterpart.4 Among the numerousganglia in the inlet plexus, Licata describes a largesinoatrial ganglion close to, and linked, by nerves withthe sinoatrial node. This is named as ganglion ofAschoff,4 and is connected to smaller ganglia in the inletplexus. It is large and encapsulated, with multipolarcells. The right precaval nerve has a sinoatrial branch,which enters this ganglion.

It is of interest that in the limulus, a crustacean, thereare right and left cardiac nerves linked to a median row ofganglia.7 With lateralisation of venous circulation to theright and arterial circulation to the left, the symmetry inautonomic innervation to the heart is lost in the humanbody, being replaced by staggered inlet and outlet plex-uses, with interlinked right and left components.

Numerous neurochemicals playing a role in auto-nomic control of the heart add to the complexity. Apartfrom catecholamines and acetylcholine, adenosine 5′-triphosphate, neuropeptide Y, histamine, 5-hydroxy-tryptamine, galamin, substance P, nitric oxide, calcitoninand gene-related peptide have been identified aschemical neurotransmitters controlled by incompletelyunderstood release and neutralising mechanisms.2

Furthermore, there is a close liaison between para-sympathetic and sympathetic efferent and afferent path-ways.2,3 Sensory motor neurones that link the afferentand efferent channels have been identified.2,3

The neural crest has been linked with the embryonicdevelopment of the outflow tract and innervation of theproximal main coronary arteries. The embryology of theinnervation of the inflow tract is yet to be elucidated. It isof interest that the right and left hearts are alreadylateralised and separate in the primitive embryonicplate.13 It is likely that neural networking for systemicand pulmonary waltz is established at this stage. Inde-pendent beating of the right and left hearts have beenobserved in the heart of the chick embryo, suggestingseparate right and left networking.13 A duet possibly getsestablished later, when the right and left networks arelinked.

Figure 4. The externally-symmetrical heart in Channa stri-ata, with the midline ventricle (V) anterior to the atrium (A).Electrocardiogram (inset) shows P and QRS complexes relatedto atrial and ventricular contractions.

Figure 3. Single atrium and single ventricle in a snail.


Evolution of Neurogenic Control of Cardiac RhythmIn this scenario of elaborate organised autonomic inner-vation, the terms ‘myogenic’ and ‘neurogenic’5,6 are mis-leading. There is no evidence that any vertebrate heart ispurely myogenic, devoid of nervous control. Even ininvertebrates, synchronous contractions of the dorsalvessel and the lateral hearts in the worms have beenattributed to neural coordination.5 The neurogeniccontrol is simple to comprehend in the lobster whose

ventricle is triggered by extracardiac autonomousganglia interposed between higher centres and the uni-ventricular heart.5 In the snail, a common atrium iscoordinated with a single ventricle through a morecomplex innervation. As evolution progresses with theappearance of systemic and pulmonary venous sinusesattached to pectinated atria, the autonomic controlbecomes increasingly intricate.

In the hearts of frogs, reptiles, birds, mammals andhumans we need to explain the genesis of the waltz and

Figure 6. Systemic side of a frog’s heart showing systole of the systemic venous sinus following SV complex in the electrocardio-gram (a, inset), and systole of the pectinated right atrium related to the P wave in the electrocardiogram (b, inset). Lt. PCV, leftprecaval vein; Pect. RA, pectinated right atrium; Post CV, post caval vein; Rt. PCV, right precaval vein; Syst. VS, systemic venoussinus; V, ventricle. Arrowheads indicate the location of the sinoatrial junction.

Figure 5. Asymmetrical heart looped to the right in the Indian catfish. (a) Heart in situ. (b) Angiocardiogram. A, common atriumlateralised to the right; ACV, anterior cardinal vein; PCV, posterior cardinal vein; PPV, primitive pulmonary vein; SV, sinusvenosus with lateral venous sinuses; V, ventricle lateralised to the left.


duet. Is the sinoatrial node activating the veins by retro-grade passage of the depolarising current? This cannotexplain an antegrade contraction. How would thesinoatrial node be responsible for simultaneous contrac-tion of three systemic and four pulmonary veins in thehuman heart, which are not equidistant from thesinoatrial node? If the sinoatrial node controls all of theseveins, the conduction velocities of the triggering path-ways, if existent, must vary. If each vein has an unidenti-fied pacemaker, how are the venous pacemakersactivated at the same time?

In the frog (Fig. 6) and the reptiles (Fig. 7) there is acomplex in the electrocardiogram preceding the P wave,preferably designated as O wave. Contraction of theveins and corresponding venous sinuses follows theO wave. The OP interval is fairly long, which is consist-ent with the observation that the hearts of frogs andreptiles function as six chambered hearts. The systole ofthe venous sinuses commencing after the O wave isprolonged and distinct. There is no correspondingcomplex in the surface electrocardiograms of the mam-malian and human hearts.

However, we have observed a complex in the electro-cardiogram obtained from the human superior vena cava,preceding and close to the P wave. This is consistent withthe amalgamation of venous sinuses and pectinated atriaresulting in the four-chambered avian, mammalian andhuman hearts, and the need for very close coordinationbetween the venous sinuses and the pectinated atria topromote unidirectinal flow, especially in the absence of a

sinoatrial valve. We have observed that when the heart isrecovering from cardioplegia, the systemic venous sinusmay contract while the pectinated right atrium is quies-cent. At this stage, the surface electrocardiogram exhibitsno P wave. Is the electrical activity too weak to berecorded in the surface leads? P waves appear when thepectinated atrium starts contracting.

We hypothesise that an extracardiac network ofganglia in the right side of the inlet plexus subservient toa complex central command triggers the three systemicveins simultaneously. The left side of the inlet plexussubsequently triggers the four pulmonary veins simulta-neously (Fig. 8). The interlinks between the right and leftsides of the inlet plexus delay the contraction of thepulmonary veins, creating a duet, akin to electroniccontrol of appropriate sets of traffic lights. This trigger-ing of the veins is followed by the contraction of theveins and the corresponding venous sinus. It is likelythat the nervous mechanism triggering the systemicveins is linked to neural triggering of the sinoatrial nodethrough the sinoatrial ganglion (Fig. 8), leading to thecontraction of the right and left pectinated atria. This isfollowed by currently conceived concepts about thecardiac cycle.

At present, there is no satisfactory explanation for theorderly spread of atrial and ventricular activation. Con-sidering the rich innervation of the atria, atrioventricularnode and ventricles, it is necessary to explore the possi-ble role of the nerves playing a key role in this orderlyactivation. It is interesting that the autonomic nerves end

Figure 7. The right view of the heart of a snake shows systole of the systemic venous sinus (a) and systole of the pectinated rightatrium (b). Pect RA, pectinated right atrium; Post CV, post caval vein; Rt. PCV, right precaval vein; RV: right ventricle; Syst. VS,systemic venous sinus. Complexes related to contraction of the veins and venous sinuses (SV), atria (P) and ventricles (QRS) areseen in the electrocardiogram (below). Arrowheads indicate the location of the sinoatrial junction.


in filaments that intertwine with sarcomeres, pierce thesarcolemma and enter the cytoplasm.4 Not only impulseformation but also impulse conduction is perhapsdependent on nerves. The orderly contractions of theveins and venous sinuses are also likely to be controlledby a neural network. We need to explain why the depo-larisation of the venous sinuses does not jump over to thepectinated atria that are controlled by the sinoatrial node.Perhaps there is discontinuity of the neural network atthe sino atrial junction; or a functional block due toactivation of the band at the junction of venous sinusesand the pectinated atria, represented by the right and leftcrista terminalis and their common link.11

There are many other pointers to a neurogenic basisfor waltz and duet. Centres in the brain, anterolateralcolumn of the cord and local ganglia in the heart exhibitrhythmic oscillations, suggesting existence of central andsubcentral command posts.2 Nature, however, has pro-vided escape mechanisms for lower command units totake over. Even a denervated heart may be undercommand of local ganglia that do not degenerate afterdenervation.3 It is of interest that a tridecapeptide, neuro-tensin, which possibly has a physiological role inimpulse generation and conduction, has been isolatednot only in the sinoatrial and atrioventricular nodes butalso in the hypothalamus.2

The respiratory rhythm is preceded by a neuralrhythm. Impulses have been identified in the phrenicnerves synchronous with the respiratory cycle.2 It islikely that closely allied cardiac rhythm is also underneurogenic control. Techniques to identify and pick upthe signals triggering the veins leading to the heartwould be more demanding than studying neural pulsesin the phrenic nerves. The complexity of neurochemicalsinvolved will add to the difficulty. An indirect evidenceof possible beat-to-beat control is the provision for rapidclearance of the chemical transmitters involved.2 Thedefinitive proof of beat-to-beat control of the heart wouldbe to identify neural impulses preceding contraction ofthe veins. Such proof may be difficult to obtain becauseof elaborate central and peripheral networking forcardiac pacing. We need to study the equivalent of theextracardiac ganglia pacing the lobster heart in thehuman heart. This could prove to be a difficult taskbecause the neural command conducting the waltz andduet would be logically more complex than that respon-sible for the solo performance of the single ventricle ofthe lobster!

At the next level, the electrical response to possibleneural pacing may be relatively easier to identify, bysimultaneous recording of the electrical activity in eachof the systemic and pulmonary veins at varying dis-tances from the heart. This activity needs to be correlatedconcurrently in all these veins and the correspondingatria. Mechanical contraction of the veins, which followselectrical activity, could be studied during angiocardi-ography and echocardiography.

Need for Waltz and DuetThe waltz is necessary for the smooth milking effect onsystemic and pulmonary inflow, especially in theabsence of a sinoatrial valve in the human heart. Theorigin of cardiac contraction in the veins prevents back-flow during atrial systole. The duet is logical to enablethe pulmonary veins to drain the lungs after pulmonaryarterial inflow. Nature has provided for a duet betweenthe two atria and ventricles, attributed to the Bachman’sbundle and bundle of His, respectively.

Clinical ImplicationsThe neurogenic basis for cardiac arrhythmias deservesincreasing attention.14 Sinoatrial block has been attrib-uted to vagal overactivity.15 Disorders of the centralnervous system have been associated with cardiacarrhythmias.15 Many anti-arrhythmic drugs act throughreceptors for neurotransmission. A neurogenic cause forthe stunned myocardium has been identified.16 A role for

Figure 8. Rear view of a human heart showing diagrammaticrepresentation of the network of autonomic nerves with ganglia(circles 1, 2, 3 interlinked by white lines). Synchronised triggeringof systemic veins (1) followed by triggering of the four pulmonaryveins (2) is represented. Later (3) the sinoatrial node is pacedthrough the Aschoff’s ganglion. The dotted line represents thelocation of crista terminalis separating the pectinated right atrium(PRA) and the systemic venous sinus. The pectinated left atrium(PLA) is in front of the pulmonary venous sinus. IVC, inferiorvena cava; LV, left ventricle; SVC, superior vena cava.


neural pacing for control of arrhythmia is to be antici-pated. Perhaps cardioplegia could be achieved by neuralrather than chemical means, as neural control of thecontractility of the ventricles has been identified. Surgicaldissection should respect increasing knowledge aboutcardiac innervation. Interventional therapy may befocused on nerves rather than the myocardium. Long QTsyndrome has been attributed to imbalance betweenright and left cardiac sympathetic activity.17 Maze proce-dures possibly interrupt the neural networking. Diseasessuch as Chaga’s disease and diabetes affect the heartthrough autonomic denervation. Lignocaine acts, possi-bly, as an anti-arrhythmic through temporary chemicaldenervation. Increasing understanding of the influenceof the brain on the heart would explain the role ofcontrolling stress, promotion of positive emotions, medi-tation, prayer, yoga, faith-healing, acupuncture and reikiin the alleviation of cardiac symptoms.

SummaryKnowledge of the anatomy of the autonomic innervationof the heart2–4 has not been matched by an understand-ing of its function.2,10 Complex coordinated contractionof the veins, venous sinuses and pectinated atria sug-gests that orderly depolarisation resulting in impulseformation and conduction, leading to an amazing,precise and consistent veno-sino-atrio-ventricular rhythmis possibly controlled by an extracardiac network ofcardiac ganglions and plexus of nerves, subservient tocentral command.

AcknowledgementsDr Joy M. Thomas, electrophysiologist, provided evi-dence of electrical activity in the superior vena cava,preceding the P wave. Our thanks to Ms M. Radha forsecretarial assistance.

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every heart beat is under neural command: an hypothesis relating to the cardiac rhythm

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