Neural mechanism of Neural mechanism of heart’ regulationheart’ regulation

Nerve and humeral regulation of heart Nerve and humeral regulation of heart activityactivity.. Physiology of systemic Physiology of systemic

circulation regulationcirculation regulation

Mechanisms of heart regulation

The aim of the circulatory regulation is to The aim of the circulatory regulation is to regulate the blood flow of organs to fit their regulate the blood flow of organs to fit their metabolic requirement in different metabolic requirement in different condition. condition.

The regulation of blood flow are of three The regulation of blood flow are of three major types:major types:NeuralNeuralHumoral Humoral

LocalLocal

Cardiac innervationCardiac innervation

Sympathetic nerve Sympathetic nerve –– noradrenergic fiber; noradrenergic fiber; Parasympathetic nerveParasympathetic nerve – – cholinergic fibercholinergic fiber

Noradrenergic sympathetic nerveNoradrenergic sympathetic nerve to the heart increase the cardiac rate to the heart increase the cardiac rate

(chronotropy effect) (chronotropy effect) the force of cardiac contraction (inotropy the force of cardiac contraction (inotropy

effect). effect). CCholinergic vagal cardiac fibersholinergic vagal cardiac fibers

decrease the heart rate.decrease the heart rate.

The mechanism of catecholamines action on the heart

Catecholamines, interacting with   β-adrenoceptors of heart, cause activation of enzyme adenylatecyclase, which converts adenosinetryfosforic acid in cyclic adenosinemonophosphate (cAMP). Increasing of intra-cellular concentration of cAMPhcauses activation of cAMPh-dependent proteinkinase, whichcatalyzes the phosphorylationof proteins. It leads to an increase in entrance of sodium and calcium into the cell.

noradrenalin

adenylatecyclase

Activeted proteinkinaseNot active proteinkinase

Increasisng of strength of heart contractions

sarcoplasmic

reticulum

troponin

cAMPH

cytoplasm

adrenoreceptor

ATPh

CatecholaminesCatecholamines

The action of acetylcholine on the activity of the heart (Effects of n. vagus on the heart)

In the external membrane of cardiomyocytesmuscarinic (M)-cholinergic receptors aredominated. Similarly as β-adrenoceptors, densityof muscarinic receptors in the myocardiumdepends on the concentration of theirantagonists. During interaction with muscarinic receptorsAcetylcholine primarily couses inhibition ofAdenylate-cyclase activity and secondary –activates Guanylate-cyclase (GC). The GC converts Huanozyn-tryfosfat into theCyclic Guanosine-monophosphate (cGMP). Increase of intracellular concentrationof cGMP causes activation of Acetylcholinedependent potassium channels. It leads toincrease the of potassium ions out ofthe cardiomyocytes. Due to increased release ofpotassium occurs hyperpolarization of cellmembranes.

Efects:1. negative inotropy 2. negative chronotropy 3. negative dromotropy4. negative batmotropy

acethylholine

M-cholinergic receptors Hyperpolarizatin

of membrane

inhibition

cytoplasm

GC

cGMP

cAMPproteincinase

ATP

Frank experiments on frog heart has found that ventricular output increases with the increase of saline pressure, which stretches the ventricular cavity. Starling showed on isolated dog hearts that the more ventricles are stretched by blood during diastole, the more their reduction in the next systole.

Frank-Starling lawFrank-Starling law

Lung

Scheme of heart-lung aparate by Starling

Ventriculus volume

Compression in aorta

Venois reservoir

Compresion camera

Resistance regulation

ce

filling pressure

As a result the "law of the heart" (Frank-Starling law or heterometryc mechanism of regulation) was derived: the force of myocardial contraction fibers depends on their end-diastolic length. From the heart of the law implies that increased filling of the heart with blood leads to increased force of heart contractions. Reducing of the force of myocardial contraction observed when it stretched more than 25% of the initial length. Such stretching is absent in the healthy heart (only 20%). So, this act, means that the number of bridges of aktynomioze is the maximal during strain of each sarcomere to 2.2 microns. And force of cardiac contraction will depend on the number of formed bridges.

The essence of the Frank-Starling law

the Frank-Starling law

stretching of the sarcomere

FORCE

time

STREIN

Actine – Act

Myosine – My

Act

My

Anrep's effectAnrep's effect Increase of blood flow in aorta and so coronary Increase of blood flow in aorta and so coronary

arteries leads to excessive stretching surrounding arteries leads to excessive stretching surrounding myocardial cells. myocardial cells.

According to Frank Starling low cardiac contraction is According to Frank Starling low cardiac contraction is directly proportional to initial length of its fibers. So directly proportional to initial length of its fibers. So increase of coronary blood flow leads to stimulation increase of coronary blood flow leads to stimulation heartbeat.heartbeat.

Boudichi phenomenonBoudichi phenomenon

In evaluation heart beat rate increase of In evaluation heart beat rate increase of every next heart contraction is observed. every next heart contraction is observed.

It caused by rising of Ca2+ influx into It caused by rising of Ca2+ influx into myocardial cells without perfect outflow, myocardial cells without perfect outflow, because of shortening of cardio cycle because of shortening of cardio cycle duration. duration.

Bainbridge ReflexBainbridge Reflex

Atrial Stretch Receptors

Medullary Activation (via Vagus Nerve)

Increased

Heart Rate

Increased Sympathetic Activity to SA Node

Increased Intravascular Volume

Direct Stretching of SA Node

Effect of the cerebral cortex on heart Effect of the cerebral cortex on heart activityactivity

Cortex is the organ of mental activity. It provides a holistic adaptive response. The work of the heart depends on the functional state of the cerebral cortex. Thus, in athletes observed pre-start condition manifesting with increasing of heart rate. Overpassing anxiety state reduction of it can be achieved. The effects of stimulation of the cerebral cortex occur during stimulation of motor and premotor zones, cingulate gyrus , orbital surface of the frontal lobe, the anterior region of the temporal lobe. Usually an increase of heart rate observed herewith.

Cortex

AV-node

Hypothalamus

Medulla

Cord

SA-node

paravertebral symphatic ganglia

Symphatic cardiac nerves

Effects of the hypothalamus on heart activity

Cortex

AV-node

Hypothalamus

Medulla

Cord

SA-node

paravertebral symphatic ganglia

Symphatic cardiac nerves

During stimulation of different areas of the hypothalamus in anesthetized animals special points were detected. Stimulation of them accompanied by changes of the frequency and force of heart contractions. Thus, in hypothalamus are structures that regulate the activity of the heart. Often, but not always, electrical stimulation of the anterior hypothalamus leads to decreased cardiac and rear – to increase heart rate.

Cardiovascular centers of the brainstem Cardiovascular centers of the brainstem

Medullaoblongata isessential toCardiovascuar

centers.

Peculiaritiesof the vagal innervation of the heart

In the medulla oblongata the nucleus ofvagus nerve located. The axons of the cells of the nucleus within the right and left nerve trunks sent directed to the heart and form synapses on motor metasympatycneurons.

Right vagus nerve fibers are distributedmainly in the right atrium. The associatedneurons inervate myocardium, coronary vesselsand sinus-atrial node. As a result of thestructural features of the right vagus nervestimulation of it shows its influence on heart rate.

Left vagus nerve fibers transmit their effects to atrioventricular node. As a result of the structural features of the left vagus nerve stimulation of it shows its influence on atrioventricular conduction and contractility of cardiomyocytes (heart rate effect).

AV-node

SA-node

Medulla

N. vagus

Efects:1. negative inotropy 2. negative chronotropy 3. negative dromotropy4. negative batmotropy

Effects of n. vagusEffects of n. vagus

Effects of n. vagus on the Effects of n. vagus on the heart activity. heart activity. Parasympathetic stimulation Parasympathetic stimulation causes decrease in heart rate causes decrease in heart rate and contractility, causing and contractility, causing blood flow to decrease. blood flow to decrease.

It is known as negative It is known as negative inotropic, dromotropic, inotropic, dromotropic, bathmotropic and bathmotropic and chronotropic effect. chronotropic effect.

Influence of sympathetic nervous system Influence of sympathetic nervous system activity of the heartactivity of the heart

The first neurons of the sympathetic nerves that transmit impulses to the heart, located in the lateral horns of the upper four or five thoracic segments of the spinal cord (Th1-Th5). Processes of these neurons terminate in the cervical and upper thoracic sympathetic nodes, where the latter neurons, processes which go to the heart.

Efects:1. positive inotropic 2. positive chronotropic 3. positive dromotropic4. positive batmotropnyy

Cortex

Hypothalamus

Medulla

Cord

Symphatic cardiac nerves

paravertebral symphatic ganglia

AV-node

SA-node

paravertebral symphatic ganglia

Sympathetic effectsSympathetic effects Sympathetic nerves from Th1-5 Sympathetic nerves from Th1-5

control activity of the heart and large control activity of the heart and large vessels. First neuron lays in lateral vessels. First neuron lays in lateral horns of spinal cord. Second neuron horns of spinal cord. Second neuron locates in sympathetic ganglions. locates in sympathetic ganglions. Sympathetic nerve system gives to Sympathetic nerve system gives to the heart vasoconstrictor and the heart vasoconstrictor and vasodilator fibers. Vasoconstrictor vasodilator fibers. Vasoconstrictor impulses are transmitted through impulses are transmitted through alfa-adrenoreceptors, which are most alfa-adrenoreceptors, which are most spread in major coronary vessels. spread in major coronary vessels. Transmission impulses through beta-Transmission impulses through beta-adrenergic receptors lead to dilation adrenergic receptors lead to dilation of small coronary vessels. of small coronary vessels.

Sympathetic influence produces Sympathetic influence produces positive inotropic, chronotropic, positive inotropic, chronotropic, dromotropic, bathmotropic effects, dromotropic, bathmotropic effects, which is increase of strength, rate of which is increase of strength, rate of heartbeat and stimulating excitability heartbeat and stimulating excitability and conductibility also.and conductibility also.

Epinephrine

Norepinephrine

α1 receptor on vessels

β1 receptor on heart

β2 receptor on vessels (skeletal muscle and liver)

Vasoconstriction

Positive effect

Vasodilation

Adrenergic receptorsAdrenergic receptors

Control of heart activity by Control of heart activity by vasomotor centervasomotor center

Lateral portion of vasomotor center transmit Lateral portion of vasomotor center transmit excitatory signals through sympathetic fibers to excitatory signals through sympathetic fibers to heart to increase its rate and contractility. heart to increase its rate and contractility.

Medial portion of vasomotor center transmit Medial portion of vasomotor center transmit inhibitory signals through parasympathetic vagal inhibitory signals through parasympathetic vagal fibers to heart to decrease its rate and contractility. fibers to heart to decrease its rate and contractility. Neurons, which give impulses to the heart, have Neurons, which give impulses to the heart, have constant level of activity even at rest, which is constant level of activity even at rest, which is characterized as nervous tone. characterized as nervous tone.

Location and innervation of arterial baroreceptors

Thank you!Thank you!