Transcript 04 Nerve and humeral regulation of heart activity

Nerve and humeral regulation of
heart activity.
Nerve and humoral regulation of heart
activity. Physiology of systemic
circulation regulation
Mechanisms of heart regulation
 The
aim of the circulatory regulation is to
regulate the blood flow of organs to fit their
metabolic requirement in different condition.
 The regulation of blood flow are of three
major types:
Neural
Humoral
Local
Cardiac innervation


Sympathetic nerve – noradrenergic fiber;
Parasympathetic nerve – cholinergic fiber
Noradrenergic sympathetic nerve
 to the heart increase the cardiac rate
(chronotropy effect)
 the force of cardiac contraction (inotropy effect).

Cholinergic vagal cardiac fibers
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 intracellular concentration of cAMPh
causes activation of cAMPhdependent proteinkinase, which
catalyzes the phosphorylation
of proteins. It leads to an
increase in entrance of sodium
and calcium into the cell.
noradrenalin
adrenoreceptor
adenylate
cyclase
cytoplasm
ATPh
Not active
proteinkinase
cAMPH
Activeted proteinkinase
sarcoplasmic
reticulum
Increasisng of strength
of heart contractions
troponin
Catecholamines
The action of acetylcholine on the activity of the heart
(Effects of n. vagus on the heart)
In the external membrane of cardiomyocytes
muscarinic (M)-cholinergic receptors are
dominated. Similarly as β-adrenoceptors, density
of muscarinic receptors in the myocardium
depends on the concentration of their
antagonists.
During interaction with muscarinic receptors
Acetylcholine primarily couses inhibition of
Adenylate-cyclase activity and secondary –
activates Guanylate-cyclase (GC).
The GC converts Huanozyn-tryfosfat into the
Cyclic Guanosine-monophosphate (cGMP).
Increase of intracellular concentration
of cGMP causes activation of Acetylcholine
dependent potassium channels. It leads to
increase the of potassium ions out of
the cardiomyocytes. Due to increased release of
potassium occurs hyperpolarization of cell
membranes.
Efects:
1. negative inotropy
2. negative chronotropy
3. negative dromotropy
4. negative batmotropy
acethylholine
M-cholinergic
receptors
Hyperpolarizatin
of membrane
inhibition
GC
cytoplasm
ATP
cGMP
cAMP
proteincinase
Effect of thyroid hormones on the heart
Thyroxine and triiodothyronine
Regulate
isozyme
composition
myosin
Increase the number of
þ-adrenergic receptors
and their sensitivity
to catecholamines
Reduce the number of
M-holinorenoretseptoriv
Positive effects: chronotropy,
batmotropy, dromotropy, inotropy
Effect of corticosteroids on the heart
Glucocorticoids
Increase þ-adrenergic sensitivity
to catecholamines
Positive effects: chronotropy,
batmotropy, dromotropy, inotropy
Effect of changes of extracellular concentration of
potassium ions on the heart activity



When the concentration of potassium
1) 4 to 8 mmol/L is small depolarization, the
membrane potential decreases from -90 mV
to -80 mV. Condition of Na+ channels of
sarcolemma does not change significantly,
excitability of muscle fibers and the speed
of pulses increase;
2) from 8 to 35 mmol/L – membrane
potential decreases from -80 mV to -40 mV.
Significantly reduces conductance of fast
potential-dependent Na+ - channels
(relative refractory period). The result is a
reduction of excitability and conductivity,
and changing of nature of the action
potential
Reducing of the potassium extracellular concentration - hypokalemia,
causing hyperpolarization of the membrane. If hypokalemia up to the
level of 2,3 mmol/L, the threshold depolarization significantly increase,
the anxiety decrease, the duration of action potentials and force of heart
contractions increase.
Effect of changes in extracellular calcium
concentration on the heart activity

In a solution without calcium ions, isolated
heart stops quickly. The reason for this is a
complete rift between excitation and contraction.
Normally, during phase "plateau" calcium ions,
which enter from the extracellular space into
sarkoplazma of cardiomyocytes, “start" Ca 2+
release from the sarcoplasmic reticulum and
replenish its reserves in these structures of
muscle fibers.
Reserves of Ca2 in the sarcoplasmic reticulum rapidly depleted during
redusing of their extracellular concentration. Also Ca2 concentration in the
sarcoplasm decreases and thus reduces the strength of heart rate.
Increasing of the calcium ions concentration in the plasma leads to
reduction of myocardium ’excitability and contractility. As an extreme
expression of this positive inotropic action of calcium ions cardiac arrest in
systole arise. Rison is the is the binding of calcium ions with troponin, that
allow actin and miozyn threads to interact and provide myocardial contraction .
If calcium level decrease, the decrease of excitability and contractility of the
heart observed.
Effect of changes in extracellular calcium ion
concentration on the strength of heart contractions
In a solution with no calcium ions, isolated heart
stops quickly. The reason for this is a complete rift
betweenexcitation and contraction. Normally calcium
ions,which are received during the phase "plateau"
from the extracellular environment into sarkoplazma of
cardiomyocytes - "trigger" the release of Ca2 + from
the sarcoplasmic reticulum and replenish its reserves in
these structures of muscle fibers.
As the concentration of extracellular Ca2 + decreased its holdings in the sarcoplasmic
reticulum rapidly depleted , the concentration of Ca2 + in the sarcoplasma decreases and
thus the force of heart contractions reduces.
Increasing of the concentration of calcium ions in the plasma leads to increased
excitability and contractility of the myocardium. An extreme expression of this positive
inotropic action of calcium ions is cardiac arrest in systole . Its cause is the binding of
calcium ions from the troponin , which enables actin and miozyn threads to interact
and provide a reduction in infarction. If blood calcium lower then a decrease excitability
and contractility of the heart.
Frank-Starling law

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.
Resistance
regulation
Compresion
camera
ce
Lung
Venois
reservoir
Compression
in aorta
filling
pressure
Ventriculus volume
Scheme of heart-lung
aparate by Starling
The essence of the Frank-Starling law
As a result the "law of the heart" (FrankStarling 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 Frank-Starling law
Actine – Act
Myosine – My
stretching of the sarcomere
Act
S
T
R
E
I
N
My
FO
R
CE
time
Anrep's effect

Increase of blood flow in aorta and so coronary
arteries leads to excessive stretching surrounding
myocardial cells.

According to Frank Starling low cardiac contraction is
directly proportional to initial length of its fibers. So
increase of coronary blood flow leads to stimulation
heartbeat.
Boudichi phenomenon
 In
evaluation heart beat rate increase of
every next heart contraction is observed.
 It caused by rising of Ca2+ influx into
myocardial cells without perfect outflow,
because of shortening of cardio cycle
duration.
Bainbridge Reflex
Increased Intravascular Volume
Atrial Stretch Receptors
Medullary Activation (via Vagus
Nerve)
Increased Sympathetic
Activity to SA Node
Direct Stretching
of SA Node
Increased
Heart Rate
Mechanisms of heart autoregulation

Greater rate of metabolism or less blood flow causes
decreasing O² supply and other nutrients. Therefore
rate of formation vasodilator substances (CO², lactic
acid, adenosine, histamine, K+ and H+) rises. When
decreasing both blood flow and oxygen supply smooth
muscle in precapillary sphincter dilate, and blood flow
increases.
 Moderate increasing temperature increases contractile
strength of heart. Prolonged increase of temperature
exhausts metabolic system of heart and causes
cardiac weakness. Anoxia increases heart rate.
Moderate increase CO² stimulates heart rate. Greater
increase CO² decreases heart rate.
Effect of the cerebral cortex on heart
activity
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
Hypothalamus
AVnode
Medulla
SAnode
Cord
Symphatic
cardiac nerves
paravertebral symphatic ganglia
Effects of the hypothalamus on heart activity
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.
Cortex
Hypothalamus
AVnode
Medulla
SAnode
Cord
Symphatic
cardiac nerves
paravertebral symphatic ganglia
Cardiovascular centers of the brainstem
Medulla
oblongata is
essential to
Cardiovascuar
centers.
Peculiaritiesof the vagal innervation of the heart
In the medulla oblongata the nucleus of
vagus 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 metasympatyc
neurons.
Medulla
Right vagus nerve fibers are distributed
mainly in the right atrium. The associated
neurons inervate myocardium, coronary vessels
and sinus-atrial node. As a result of the
structural features of the right vagus nerve
stimulation of it shows its influence on heart
rate.
AVnode
N. vagus
SAnode
Efects:
1. negative inotropy
2. negative chronotropy
3. negative dromotropy
4. negative batmotropy
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).
Effects of n. vagus

Effects of n. vagus on the
heart activity.
Parasympathetic stimulation
causes decrease in heart rate
and contractility, causing
blood flow to decrease.
 It is known as negative
inotropic, dromotropic,
bathmotropic and
chronotropic effect.
Influence of sympathetic nervous system
activity 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 dromotropic
4. positive batmotropnyy
Cortex
AVnode
Hypothalamus
Medulla
Cord
SAnode
Symphatic
cardiac nerves
paravertebral symphatic ganglia
Sympathetic effects

Sympathetic nerves from Th1-5 control
activity of the heart and large vessels.
First neuron lays in lateral horns of spinal
cord. Second neuron locates in
sympathetic ganglions. Sympathetic
nerve system gives to the heart
vasoconstrictor and vasodilator fibers.
Vasoconstrictor impulses are transmitted
through alfa-adrenoreceptors, which are
most spread in major coronary vessels.
Transmission impulses through betaadrenergic receptors lead to dilation of
small coronary vessels.

Sympathetic influence produces positive
inotropic, chronotropic, dromotropic,
bathmotropic effects, which is increase of
strength, rate of heartbeat and stimulating
excitability and conductibility also.
Adrenergic receptors
Epinephrine
Norepinephrine
α1 receptor on vessels
Vasoconstriction
β1 receptor on heart
Positive effect
β2 receptor on vessels
(skeletal muscle and liver)
Vasodilation
Control of heart activity by
vasomotor center

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.
Location and innervation of arterial baroreceptors
Intravenous Infusion
Atrial Stretch
Decreased Sympathetic
Activity to Kidney
Decreased
Vasopressin
(ADH)
Increased
Atrial Natriuretic
Peptide
Increased
Urine Output
Increased
Urine Output
Increased
Natriuresis
Urine Output
Decreased
Water Reabsorption
BP
Decreased
BP
Irritation of visceroreceptors

Irritation of visceroreceptors results in stimulation
of vagal nuclei, which cause decreasing blood
pressure and heartbeat. Parasympathetic
stimulation causes decrease in heart rate and
contractility, causing blood flow to decrease. It is
known as negative inotropic, dromotropic,
bathmotropic and chronotropic effect.
 This mechanism is important for doctor in
performing diagnostic procedures, when probes
from apparatuses are attached into visceral organs.
This may cause excessive irritation of visceral
Reflexes from proprio-, termo- and interoreceptors
Contraction of skeletal muscle during exercise
compress blood vessels, translocate blood from
peripheral vessels into heart, increase cardiac
output and increase arterial pressure.
 Stimulation of termoreceptors cause spreading
impulses from somatic sensory neurons to
autonomic nerve centers and so leads to
changing tissue blood supply. Irritation of
visceroreceptors results in stimulation of vagal
nuclei, which cause decreasing blood

pressure and heartbeat.
Regulation of blood flow in physical exercises
 Proprioreceptor
activation spread
impulses through interneurons to
sympathetic nerve centers. So,
contraction of skeletal muscle during
exercise compress blood vessels,
translocate blood from peripheral
vessels into heart, increase cardiac
output and increase arterial pressure

In physical exercises
impulses from pyramidal
neurons of motor zone in
cerebral cortex passes both
to skeletal muscles and
vasomotor center.
 Than through sympathetic
influences heart activity and
vasoconstriction are
promoted. Adrenal glands
also produce adrenalin and
release it to the blood flow.
Regulation of blood
flow in physical
exercises
Cardiovascular Adjustments
to Exercise
Respiratory arrhythmia
Respiratory arrhythmia
Inspiration
Expiration
In case of respiratory arrhythmia significant role belongs to impulses
from lung receptors, mechanoreceptors of atriums, that responsiveble
to increase of flow of venous blood to the heart.
Effects of Hypoxia on Cardiac Activity
Hypoxia
Moderate
Severe
Indirect Effects
Direct Effects
Sympathetic
Nervous System
Activation
Depressed
Myocardial
Contractility
Increased HR
Increased CO
Increased Contractility
Effects of Hypercarbia on Cardiac Activity
Hypercarbia
Indirect Effects
Direct Effects
Sympathetic
Nervous System
Activation
Depressed
Myocardial
Contractility
Increased HR
Increased CO
Increased Contractility
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