Dr Manish Ruhela

CARDIAC INNERVATION

The nerve supply of the heart is derived from –

1. The cardiac plexus formed by the sympathetic and parasympathetic(vagal) fibers and

2. Baroreceptors and chemoreceptors ( cardiac reflexes)

SYMPATHETIC CONTRIBUTION The preganglionic sympathetic fibres innervating the heart

are the axons of cells located in the lateral grey columns ofT1-T5 segments of the spinal cord.

They are myelinated preganglionic fibres and they leave thecord in the ventral roots of the corresponding spinal nervesand enter to adjacent ganglia in the paravertebralsympathetic trunk.

The postganglionic axons are unmyelinated or thinlymyelinated, and those for the heart run in the variouscardiac branches of the sympathetic trunks.

Thus in the sympathetic component of the autonomicnervous system the synapses between pre- and post-ganglionic neurons are often at considerable distances fromthe structure innervated, e.g. some of the cardiacpostganglionic fibres arise in the superior cervical gangliaand are lengthy.

By contrast parasympathetic postganglionic fibres areshort.

PARASYMPATHETIC CONTRIBUTION

The parasympathetic innervation arrives to the heart bymeans of branches of the vagus nerve.

The preganglionic vagal fibers flow from the brain stem,particularly from the bulbus (nucleus ambiguus, reticularnucleus and dorsal nucleus of vagus).

These nuclei are elongated columns of cells lying in themedulla oblongata.

The cardiac fibres are conveyed to their terminations in thevagus nerves and their branches, and they end by formingsynapses with postganglionic neurons in ganglia in thecardiac plexus or in the wall of the heart.

Synaptic relays close to or within the viscus supplied arecharacteristic of parasympathetic innervation and inconsequence parasympathetic postganglionic fibres arerelatively short compared with their sympatheticcounterparts, and more circumscribed in theirdistribution.

This is one reason why parasympathetic effects are morelocalized than sympathetic effects.

Anatomical Differences in Sympatheticand Parasympathetic Divisions

Length of postganglionic fibers Sympathetic – long postganglionic fibers

Parasympathetic – short postganglionic fibers

Branching of axons

Sympathetic axons – highly branched

Influences many organs

Parasympathetic axons – few branches

Localized effect

Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings

Anatomical Differences in Sympatheticand Parasympathetic Divisions

Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings

Anatomical Differences in Sympatheticand Parasympathetic Divisions

Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings

Basic pathways involved in the medullary control of heart by the vagus nerves

Neurotransmitters of Autonomic Nervous System

Neurotransmitter released by preganglionic axons Acetylcholine for both branches (cholinergic)

Neurotransmitter released by postganglionic axons Sympathetic – most release norepinephrine (adrenergic)

Parasympathetic – release acetylcholine

Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings

Cardiac Plexuses

Both the parasympathetic and sympathetic nerves form thesuperficial and deep cardiac plexuses

Superficial cardiac plexus - situated below the archof aorta in front of the right pulmonary artery, it is formedby – The superior cardiac branch of superior cervical ganglion of the left

sympathetic chain and

The cardiac branches from inferior cervical region ( inferior cervicalnerves ) of the left vagus nerve.

It gives branches to The deep cardiac plexus

The right coronary artery ( coronary plexus ) and

The left anterior pulmonary plexus.

Deep cardiac plexus - situated in front of the bifurcation of

trachea and behind the arch of aorta, it is formed by –

The cardiac branches of superior,middle & inferior cervical ganglia

& T 1 to T4/T5 ganglia of Rt & Lt sympathetic chain.

The inferior cervical ganglion & 1st thoracic ganglion are fused to

form a stellate ganglion.

Superior cardiac branches of vagus and recurrent laryngeal nerves of

both sides except inferior cardiac branches of Lt vagus (those which

form the superficial plexus).

Rt & Lt halves of plexus supplies branches to the corresponding

coronary and pulmonary plexus. Separate branches are given to

atria.

Peculiarities of nerve supply to the heart

Nerve supply Features1. Sympathetic innervation More at the base than the apex

2. Vagal activity Greater in posterior and inferior wall

3. Rt sympath. and vagus Affect SA node > AV node

4. Lt sympath. and vagus Affect AV node > SA node

Cardiac innervation

Sympathetic nerve – noradrenergic fiber; Parasympathetic

nerve- cholinergic fiber

Noradrenergic sympathetic nerve

to the heart increase the cardiac rate (chronotropic effect)

the force of cardiac contraction (inotropic effect).

Cholinergic vagal cardiac fibers decrease the heart rate.

CARDIAC RECEPTORS

Most important adrenoreceptor is heart is B1

B2 adrenoreceptor in heart has similar cardiac effect B1

Prejunctional a2 adrenoreceptor inhibit NE release

Prejunctional b2 adrenoreceptor facilitate NE release

Prejunctional M2 adrenoreceptor inhibit NE release

Right atrium – 74% b1 and 26% b2

Ventricles – 86% b1 and 14% b2

Control of heart activity by vasomotor

center(medulla oblongata) Lateral portion of vasomotor center transmit excitatory signals through sympathetic

fibers to heart to increase its rate and contractility.

Medial portion of vasomotor center transmit inhibitory signals through

parasympathetic vagal fibers to heart to decrease its rate and contractility. Neurons,

which give impulses to the heart, have constant level of activity even at rest, which is

characterized as nervous tone.

Receives input from higher centers, monitoring blood pressure and dissolvedgas concentrations.

Autonomic Innervation of the Heart

Figure 20.21

Cardiac Reflex Fast acting reflex loops between the heart and CNS

Regulates cardiac function

Maintains physiologic homeostasis

Cardiac receptors are linked to CNS by myelinated / unmyelinated afferents of vagus nerve

Cardiac receptors are present in Atria

Ventricles

Carotid bodies

Aorta

Cardiac Reflex

Reflexes originating in cardiac sensory receptors canbe classified according to various characteristics :

1 ) location of the receptors. for example, atrial or ventricular,

2) types of afferent fibers. for example myelinated versus nonmyelinated,

3) pathways of the afferent fibers for example. in

vagal or sympathetic nerves.

4) natural stimuli to the reflex , for example mechanosensitiveversus chemosensitive. and

5) cardiovascular effects. for example inhibition or excitation.

Cardiac receptor

Myelinated / unmyelinated afferent of vagus nerve

Central processing of sympathetic and parasympathetic nerve input in the CNS

Efferent fibres

Heart or systemic circulation

Particular reaction

Cardiovascular Reflexes Baroreceptor reflex (pressure receptor reflex)

Chemoreceptor reflex

Bainbridge atrial reflex (volume reflex) (atrial stretch reflex)

Bezold-Jarisch reflex (cardiopulmonary reflex)

Oculocardiac reflex (trigeminovagal reflex)

Cushing’s reflex

Valsalva maneuver

Afferent fibres of cardiac receptors (in vagus nerve)

Myelinated fibres (25%) Unmyelinated fibres (75%)

Present in walls of atria and

atriocaval junction

Present in walls of all cardiac

chambers

Baroreceptor Reflex (carotid sinus reflex)

initiated by stretch receptors, called baroreceptors Baroreceptors are present in

Carotid sinus Aortic arch Walls of right atrium at the entrance of SVC and IVC Walls of left atria at the entrance of pulmonary vein

These receptors in low pressure part of the circulation are called as cardiopulmonary receptors

They are stimulated by distension of the structure in which they are located

pressure in these structures are associated with discharge rate

Baroreceptor areas in the carotid sinus and aortic arch

Carotid sinus

At the bifurcation of the common carotid arteries

the root of internal carotid artery shows a little bulge

has stretch receptors in the adventitia

are sensitive to arterial pressure fluctuations

Afferent nerves from these stretch receptors travel in the carotid sinus nerve which is a branch of the glossopharyngealnerve (IXth cranial nerve)

Aortic Arch baroreceptors are also

present in the adventitia of the arch of aorta

have functional characteristics similar to the carotid sinus receptors.

their afferent nerve fibers travel in the aortic nerve,

branch of the vagus nerve. (Xth cranial nerve)

Baroreceptor system for controlling BP

Baroreceptor- reflex mechanism

Triggering factor( increased pressure )

Stimulates baro receptors in carotid sinus and aortic arch

information carries through Glossophrayngeal nerve ,Vagal nerve

Processing in medullary vasomotor centre

Increases parasympathetic tone, inhibition of sympathetic tone

Decreases heart rate, Stroke volume and vasodialation

Buffer nerves activity

The carotid sinus nerves and vagal fibers from the aortic arch are commonly called the buffer nerves

At normal blood pressure levels, the fibers of the buffer nerve discharge at a low rate.

When the pressure in the sinus and aortic arch rises, the discharge rate increases;

when the pressure falls, the rate declines.

Importance of the baroreceptor reflex

To keep the arterial pressure relatively constant

Short term regulation of blood pressure in the range of 70 mmHg to 150 mmHg, maintain the mean blood pressure at about 100 mmHg

Pressure buffer system – reduce the BP fluctuation during the daily events, such as changing of the posture, respiration and excitement

Baroreceptors are compromised by autonomic neuropathy and denervated heart ( Transplanted heart ).

Baroreceptor Resetting

Baroreceptor will adapt to the long term change of blood

pressure.

That is, if the blood pressure is elevated for a longer time, as in

chronic HTN, the set point will transfer to the elevated mean blood

pressure

So there is decrease baroreceptor response in pts with chronic HTN

This makes the baroreceptor system unimportant for long-

term regulation of arterial pressure

Baroreflex failure

Baroreflex failure lead to loss of response to arterial baroreceptorstimulation and failure of neural regulation of BP.

Damage to afferent neuronal input ( vagus and glossophrayngealnerves) or from damage to brainstem nuclei due to variouscauses( surgery, radiation therapy, CVA).

Clinical presentation can vary over time, and acute episodesduring waking hours may mimic a pheochromocytoma; severehypotension and bradycardia may occur during sleep.

Chemoreceptor Reflex Chemoreceptors are sensitive to the changes in blood chemistry.

main function is to keep the alveolar pCO2 at a normal level of40mmHg and also maintains arterial pO2,pCO2 and pH.

Mediated by two types chemoreceptors

Peripheral chemoreceptors

Carotid bodies

Aortic bodies

Central chemoreceptors

Medulla (associated with cardiovascular control “centers”)

Sinus nerve of Hering (branch of 9th cranial nerve) and vagus nerve

Peripheral Chemoreceptors

Present in carotid & aortic bodies

2 mm in size

Supplied with abundant blood flow through a small nutrient artery (senses changes in BP)

Rich sensory innveration

Rate of response is fast

Chemoreceptor areas in carotid and aortic bodiesCAROTID

BODY

AORTIC

BODY

Carotid bodies

2 in number

2 mg weight

Highest blood flow – 2000 ml/100 g/min

Present at bifurcation of each common carotid artery

Innervated by sinus nerve (branch of 9th nerve)

Aortic bodies

1-3 in numbers

Adjacent to aorta

Near the aortic arch

Near root of subclavian artery

Innervated by 10th nerve

Respiratory control by peripheral chemoreceptors in the carotid and aortic bodies

Central chemoreceptoprs – medulla (slow response)

Cardiac control centres in medulla oblongeta

Cardioaccelerator stimulatory

centre (VMC)

Cardioaccelerator inhibitory

centre (CIC)

Sympathetic stimulation Parasympathetic stimulation

Central & peripheral chemoreceptors respond to changes in chemical composition of blood or surrounding fluid

Central chemoreceptors respond only to acidosis (H⁺)

Peripheral chemoreceptors are sensitive to changes in arterial O2 and CO2 tension and to pH

Increasingly important when mean arterial pressure falls below 60 mmHg (i.e. when arterial baroreceptor firing rate is at minimum)

PaO2 < 50 mmHg / acidosis / PaCO2

Stimulate chemoreceptor in carotid & aortic bodies

Sinus nerve of Hering & vagus nerve

Medullary vasomotor centres

Stimulate respiratory centres

Directly stimulates sympathetic system

pulm ventilation(rate & depth)

BP

Indirectly catecholamine secretion from the adrenal medulla

BP

BAIN BRIDGE ATRIAL REFLEX

Receptors- Cardiac baroreceptors located in the walls of heart (

subendocardial distribution)

Anatomy

Primarily mediated through vagal myelinated afferent fibres;

activation of sympathetic afferent fibers may also occur. Increased

right atrial pressure directly stretches the SA node and enhances

its automaticity, increasing the heart rate.

Stimulus

Increased vagal tone and distention of the right atrium or central

veins.

Bainbridge Atrial Reflex(atrial stretch reflex, volume reflex)

right sided filling pressure

Stimulates stretch receptors present in right atrial wall & cavoatrial junction

Vagal myelinated afferent fibres

Cardiovascular center of medulla

Inhibit parasympathetic activity

HR

Directly stimulates SA node

HR

Stretching of atria

Efferents of vagus nerve

Reflex depends upon the preexisting heart rate

With slow heart rate, it causes progressive tachycardia

With pre-existing tachycardia, there is no effect

Denervation of vagi to heart eliminate this reflex

Clinical significance-

It helps prevent collection of blood in veins, atria andpulmonary circulation

It inhibits ADH release and promote secretion of ANP

When blood volume is increased, the Bainbridge reflex isdominant, when it is decreased, baroreceptor reflex isdominant

Bezold-Jarisch reflex(cardiopulmonary reflex)

Reflex triggered by

Intracoronary injection of serotonin, nicotine, capsaicin

Coronary ischemia (MI)

Bradykinin, PGI2, Arachidonic acid

Ventricular distension

Thrombolysis

Revascularization

BEZOLD-JARISCH REFLEX

Anatomy

Ventricular chemoreceptor and mechano-receptors withafferent pathway in unmyelinated vagal C fibres

Stimulus

Noxius stimuli to either ventricle, associated withmyocardial ischaemia, profound hypovolemia, coronaryreperfusion

Bezold-Jarisch reflex(cardiopulmonary reflex)

Triggering factors

Stimulates cardiopulmonary chemoreceptors and mechanoreceptors of LV wall

Unmyelinated vagal afferent type C fibres

Inhibit medullary vasomotor centre

parasympathetic tone

Triad of – bradycardia, hypotension, peripheral vasodilatation

Response

Hypotension, bradycardia, parasympathetically inducedcoronary vasodilatation and inhibition of sympatheticoutflow from vasomotor centres

Clinical significance

Reperfusion of previously ischemic tissue elicits reflex

Thus, Bezold Jarisch reflex may be less pronounced inpatients with cardiac hypertrophy

Bezold-Jarisch reflex

MI / Coronary reperfusionMolecules generated during ischemia and reperfusion such as free

radicals and PG

Stimulate cardiac inhibitory receptors(present in inferior & posterior walls of heart)

Hypotension Bradycardia and renal

vasodilatation

Sudden cardiac death Decreases myocardial oxygen

demand and augments renal

perfusion (protective reflex)

Oculocardiac Reflex(Trigemino-vagal Reflex, Aschner Phenomenon, Aschner Reflex, Aschner Dagini Reflex)

Reflex triggered by Pressure on globe Traction on the extraocular muscle (esp. medial rectus

muscle) as in strabismus surgery Ocular trauma Severe pain Orbital compression due to hematoma or edema Procedures under topical anaesthesia Orbital injections Hypercapnia or hypoxemia Fentanyl

Pressure on the globe of the eye or traction on the extraocular muscles

Stimulates stretch receptors of extraocular muscle

Afferents of short and long ciliary nerves

Ciliary ganglion

Ophthalmic division of trigeminal nerve

Gasserian ganglion

Sensory nucleus of trigeminal in the floor of 4th ventricle

Efferents of vagus nerves (vagal cardiac depressor nerve)

Parasympathetic stimulation

Bradycardia / hypotension / asystole / AV block / ventricular ectopy

Oculocardiac reflex

Treatment

Immediate

Cessation of manipulation

IV atropine

Lignocaine infiltration – near extrinsic muscles in case of recurrence

IV epinephrine 6-12 mg for hypotension

Prevention

Indicated in patients with h/o conduction block, vaso-vagal responses or b-blocker therapy

Premedication with anti-cholinergics (atropine or glycopyrrolate) (block efferent pathway)

Retrobulbar block with 1-3 ml of 1-2% lidocaine

Reponses ceases with repeated stimulation

Reflex is more sensitive in neonates and children, especially

during squint surgery

Clinical significance

Demonstrated in 30-90% of patients undergoing ophthalmic

surgery

Transient cardiac arrest may occur as 1 in 2200 strabismus

surgeries

Cushing ReflexReflex activated by

Cerebral edema

Hematoma – subdural, epidural, contusion, ICH

Depressed skull fracture

Hydrocephalus

Venous sinus thrombosis

IC-SOL: Tumor, hematoma, abscess

Brainstem compression

Acute traumatic brain injury

Neuroendoscopy

CSF pressure / ICT

Compression of cerebral arteries

Cerebral ischemia at the medullary VMC ( CO2 in blood, lactic acid in VMC)

Sympathetic stimulation

HR, BP, myocardial contractility improve cerebral perfusion

Stimulaes baroreceptors

Reflex bradycardia

Stimulates vasoconstrictor and cardioaccelerator neurons in VMC

Clinical significance:-

Triad of HTN, bradycardia and apnea

Seen in 33% of patients with ICT

Occurrence of bradycardia & HTN is used as warning sign

of ICT during neuroendoscopy

Treatment

Treated by measures to reduce ICP rather than pharmacological treatment of HTN

Elevate head to 30-45°

Avoid hypoxia (pO2 <60 mmHg)

Ventilate to normocarbia (pCO2 35-40 mmHg)

Sedation

Drain 3-5 ml CSF if ventriculostomy present

Hyperosmolar agents – mannitol, urea, glycerol

3% NaCl infusion

Barbiturates – thiopentone

Systemic diuretics – furosemide, ethacrynic acid

steroids – dexamethasone

Forced expiration against a closed glottis (after full inspiration)

Valsalva Maneuver

Intrathoracic pressure ( BP initially)

VR, CO

BP

Inhibit baroreceptors

Sympathetic stimulation

HR

myocardial contractility

Compression of veins ( CVP)

Opening of glottis (return of intrathoracic pressure to normal)

VR

myocardial contractility

BP

Stimulates baroreceptors

Stimulates parasympathetic efferent pathways to the heart

BP, HR

Phase I

Transient rise in BP due to increased intra-thoracic and intra-abdominal pressure

Phase II

Fall of BP followed by recovery

Increased HR due to sympathetic activation

Phase III

Fall in BP due to release of intrathoracic pressure

Phase IV

Increase in BP due to “overshoot” of cardiac output into a vasoconstricted peripheral circulation

Fall in HR with transient bradycardia, in the normal state, until after the BP overshoot

Valsalva ratio

Stimulus Expiration of 40 mmHg for 15 sec

Afferent Baroreceptors, glossopharyngeal, vagus nerves

Central Nucleus tactus solitarus

Efferent Vagus and sympathetic nervous system

Response HR & BP changes

• VR=Max HR/min HR

• A normal VR indicates an intact baroreceptor mediated increase and

decrease in HR

• A decreased VR reflects baroreceptror and cardiovagal dysfunction

• Normal value is a ratio of >1.21

In sympathectomized patients, HR changes occur since

baroreceptors and vagi are intact.

In autonomic insufficiency HR changes does not occur.

Transplanted heart (Denervated heart)

In cardiac transplantation, the vagus nerve and the cervical and thoracic sympathetic cardiac nerves are severed when the donor heart is removed.

These nerves will not generate, and they will not be reanastomosedwith the same nerves in the recipient.

Functional changes in transplanted heart occur both at rest and with activity and exercise. At the same time, some areas of cardiac physiology remain unchanged or minimally altered.

Normal Cardiac function in the Denervated heart The basic contractility of myocardium and intrinsic control

system remains intact. Starling effect remains intact (with increased venous

return, contractile force of myocardium will increase,causing increase in the stroke volume and cardiac output).

Anrep effect retained (with a rise in aortic pressure –afterload, the contractile force of myocardium willincrease, causing an increase in stroke volume and cardiacoutput).

Bowditch effect retained (an increased heart rate willaugment the contractile force of myocardium, againincreasing the cardiac output).

Altered Cardiac function in the Denervated heart

Does not experience anginal pain because the cervicalsympathetic cardiac efferent fibers are no longer intact.

Because the heart normally is more influenced by the PNS,the transplant recipient has a higher rate at rest comparedwith the normal heart( 90-110 bpm).

The denervated heart exhibits increased electrical stabilityand is much less susceptible to ventricular arrhythmias(VT/VF).

Ventricular fibrillation in denervated heart often is a signof significant rejection.

The valsalva maneuver and carotid sinus massage, both whichnormally decrease heart rate, have no effect on the heart rate of thedenervated heart.

Cardiac function with exercise:- With exercise, heart rate rises much more slowly because this

change is dependent on increased catecholamine levels rather thanneural system.

Hormonal system is much slower than the neural system and 5 – 10minutes warm-up period is essential for pt, without a gradualwarm-up cardiac output might not be able to deliver sufficientoxygen to exercising muscles , leading to exercise intolerance andultimately collapse of pt.

Pt with denervated heart never reaches normal peak HR withexercise.

Denervated heart is electrically stable and may be lessprone to ST segment deviation during exercise, even ifmyocardium becomes ischemic.

Recovery time after exercise is longer for the transplantedheart pt, HR decreases slowly because the re-uptake of thecatecholamines is a gradual process . A planned 5 – 10 minscool down period is important.

The absence of meaningful cardiac autonomic inputto the heart has imp implications forpharmacologic responses :-

Drugs with cardiac actions that depend on autonomicreflexes (e.g. atropine) are ineffective in altering HR.

for same reason, opioid induced bradycardia is absent.

Drugs that are direct agonist to beta adrenergic receptors(e.g. epinephrine ) are chosen when treating bradycardia.

Cardiac innervation may occur over time. Incomplete and unpredictable sympathetic reinnervation

Clinical determinants of reinnervation include time from transplant,

young age of the donor,

fast uncomplicated surgery, and

low rejection frequency.

The restoration of sympathetic innervation isassociated with improved contractility and HRresponse to exercise.

Sympathetic reinnervation may occur before, or inabsence of parasympathetic reinnervation. However, while parasympathetic reinnervation has been demonstrated in

animals, only sympathetic reinnervation has been demonstrated in humancardiac transplants.

THANKS

Cardiovascular Tests Used

Valsalva maneuver The subject sits quietly and then blows into a mouthpiece at a

pressure of 40 mmHg for 15 s.

The heart rate normally increases during the maneuver, followed by a rebound bradycardia after release.

The ratio of the longest R-R interval shortly after the maneuver to the shortest R-R interval during the maneuver is then measured.

We routinely express the result, the Valsalva ratio, as the mean ratio from three successive Valsalva maneuvers.

Normal ratio - ≥ 1.21

Heart rate response to standing up-

Subject lie quitely on couch and then stands –up.

Norm al response is immediate increase in HR maximal at about the

15th beat after starting to stand, followed by a relative bradycardia, max

around the 30th beat. This can be quantified as the 30:15 ratio, which

is the ratio of longest R-R interval around the 30th beat and shortest R-R interval around the 15th beat.

Normal ratio - ≥1.04

Blood pressure response to standing up

The blood pressure is measured using a standard sphygmomanometer

while the subject is lying down, and again after standing up.

The difference in systolic blood pressure is taken as the measure of postural blood pressure change.

Normal value of fall in SBP ≤ 10 mmHg

Blood pressure reponse to sustained handgrip –

Handgrip is maintained at 30% of the maximum voluntary contractionusing a handgrip dynamometer up to a maximum of 5 min, and theblood pressure measured each minute.

The difference between the diastolic blood pressure just before releaseof handgrip, and before starting, is taken as the measure or response.

Normal rise in diastolic BP - ≥ 16 mmHg

Heart rate response to deep breathing –

The subject sits quietly and then breathes deeply and evenly at 6 breaths/min.

The maximum and minimum heart rates during each breathing cycle are measured, and the mean of the differences during three successive breathing cycles are taken to give the max.-min. HR.

Normal value - ≥ 15