Download 2.1 Introduction

2.00 Review of literature :
2.1 Introduction
The muscle fibers of the human heart are excitable cells like other
muscles, but they have a unique property that each cell in the heart will
spontaneously contract at a regular rate because the electrical properties
of the cell membrane spontaneously alter with time and regularly
depolarize (kestin 1993).
The normal human heart acts as a strong muscular pump; a little larger
than a fist of the hand. It pumps blood continuously through the
circulatory system. Each day the average
heart expansions and
contractions is about 100,000 times, and pumps about 2,000 gallons of
blood. In a 70 years lifetime, an average human heart beats more than
2.500.000.000 beats/min (Levick 1998).
2.1.1 Conductive system of the heart
For the heart to function properly, the four chambers must beat in an
organized manner. A chamber contracts when an electrical impulse or
signal moves across it through specific anatomical structure fibers called
conductive system.
A signal starts in a small bundle of highly specialized cells located in
the right atrium at its junction with the superior vena cava, called the
sinoatrial node (SA node) or pacemaker of the heart. The SA node
generates and discharges electrical impulses at a given rate, but under
steady state of emotional reaction and hormonal factors.
Depolarization of the SA node triggers a wave front of depolarization,
which travels through the both atria causing them to contracts and
sending blood into ventricles.
Direct conduction to the ventricles is prevented by fibrous ring, which
separates the atria from the ventricles. The atrioventricular node is
situated beneath the right atrial endocardium at the lower end of the
interatrial septum. It conducts slowly and regulates the frequency of
conduction to the ventricles. From the atrioventricular (AV) node, the
bundle of His passes through the fibrous ring, and it is divided into right
and left bundle branches which pass down to the respective sides of the
ventricular septum. The bundle branches are subdivided into anterior and
posterior hemibundles, and all fibers of the bundle of His radiate out the
Purkinje network (Berne and Levy 1992).
2
2.1.2 Pacemaker of the heart
Pacemaker tissue is found in the SA node, the AV node and the
purkinje tissue, but because the rate of depolarization of the SA node is
faster than the other pacemaker tissues and depolarization impulses
spread via the conducting pathway to other pacemaker tissues before they
become spontaneously depolarized, so the SA node is the pacemaker of
human heart (Guyton and Hall 1996).
Pacemaker of the heart has unstable resting membrane potential, which
equals -55 to -60 mV. This negativity in the SA node is due to an inherent
leakage in Na+ channels. The high concentrated level of Na+ ion in
extracellular fluid and the negative electrical charge inside the SA fiber
lead to leakage of Na+ ions from outside to inside the membrane of the SA
node. Influx of Na+ ions helps for rising membrane potential until reaching
the threshold voltage (-40mV), and at that time (Ca – Na) channels
become activated. This activation leads to rapid entry of both Ca++ and Na+
ions, so that the action potential will occur in SA node (Ganong 1997).
The Ca – Na channel will stay open for about 100 to 150 ms, and at the
same time potassium (K+) channels will start to open. These two causes
help to prevent depolarization of the SA node all the time, K+ channels
remain open for another few tenths of a second carrying a great excess of
positive K+ charges out of the cells, which temporarily causes excess
negativity inside the cells, this is called hyperpolarization. K+ channels
start to be closed, and now the inward leaking Na+ ions once again become
over balance the outward flux of K+ ions, which cause the resting
membrane potential to start again. Then, reexcitation will occur in the SA
node to elicit another cycle (Levick 1998).
The frequency of pacemaker firing is controlled by the activity of both
divisions of autonomic
nervous system (sympathetic
and
parasympathetic). Changes in autonomic neural activity often induce a
pacemaker shift. Where the site on initiation of impulse may shift to a
different locus within the SA node or to a different component of the
atrial pacemaker complex (Hainsworth 1995).
2.1.3 Cardiac innervations centers
The autonomic nerve supply to the heart has the important function of
rapid adjustment of the heart rate and vasomotor tone according to
different conditions in the body. There are higher centers in the medulla
oblongata which control the sympathetic and parasympathetic discharge
to cardiovascular system. These centers are called the cardiovascular
centers. The cardiovascular centers have no sharp boundaries. They are
3
found as diffuse areas in the medullary reticular formation with a great
deal of anatomical and functional overlap (Abusitta et al 1995).
2.1.3.1 The pressor or vasoconstrictor area
This area is also called the vasomotor area or vasomotor center (VMC).
It is located bilaterally in the anterolateral portions of the upper medulla
oblongata and it is connected with preganglionic sympathetic nerves in
the spinal cord. However, this area contains two centers; cardiac
acceleratory center (CAC), which is also known as cardiac stimulatory
center (CSC) and the vasoconstrictor center (VCC). Stimulation of the
pressor area leads to circulatory sympathetic effects; which result in
generalized vasoconstriction of the arterioles, acceleration of the heart
rate and increasing in myocardial contractility force. On the other hand,
under normal resting conditions, the VCC discharges impulses
continuously at a certain rate. This is called vasomotor tone which leads
to partial vasoconstriction of the arterioles and venules (Guyton and Hall
2000).
2.1.3.2The depressor or vasodilator area
It is found bilaterally in the anterolateral portions of the lower of the
medulla oblongata and it contains a cardio inhibitory center (CIC) which
is an inhibitory area. It is present in the dorsal motor nucleus of the vagus
nerve or nucleus ambiguus. Stimulation of this area produces
parasympathetic (vagal) effects on the heart which will lead to a decrease
in the heart rate and atrial contractility force. This area is equally
discharges a continuous inhibitory impulses along the vagus nerve to the
heart. This is called vagal tone which checks the high inherent rhythm of
the S.A node (Guyton and Hall 2000).
2.1.3.3 The medullary sensory area
This area located bilaterally in the tractus solitarius in the posterolateral
portions of the medulla and lower pons. The neurons of this area receive
sensory nerve signals mainly through the vagus and glossopharyngeal
nerves, and the output signals from this sensory area then help to control
the activities of both the vasoconstrictor and vasodilator areas of the
vasomotor center, thus providing "reflex" control of many circulatory
functions. (Guyton and Hall 2000).
4
2.1.4 Innervation of the Heart
The major controlling influence on reflex cardiac activity is the
autonomic nervous system. In terms of it's regulation, the autonomic
nervous system exerts it's functions via two counter balancing influences
provided by the sympathetic and parasympathetic systems.
2.1.4.1 The sympathetic innervation of the heart
The preganglionic sympathetic fibers originated from the lateral horne
of the upper four thoracic segments of the spinal cord (T1-T4). These
preganglionic fibers relay in the cervical ganglia (superior, middle &
inferior) and the upper four thoracic ganglia of the sympathetic chain.
However, these fibers arise from these ganglia to supply the atria and
the ventricles of the heart including the specialized tissues of the cardiac
conducting pathway as well the coronary vessels. The main results of
stimulation of these fibers are activation of all properties of the cardiac
muscle, vasodilatation of the coronary arteries and increasing of the
oxygen consumption of the cardiac muscles (Guyton and Hall 2000 and
Sukker et al. 2000).
Under resting normal conditions, the sympathetic nervous system
discharges impulses continuously to the heart. The effect of this impulses
has an positive inotrophic tone which increase the pumping capacity of
the heart by 20-25% as well, it also increase the heart rate up to 120
beats/min. However, this positive inotrophic tone is abolished by more
dominant negative chronotrophic vagal tone (Guyton and Hall 2000).
2.1.4.2 The parasympathetic innervations of the heart
The parasympathetic supply to the heart is take place via two vagi: the
preganglionic vagal fibers arise from the dorsal vagal nucleus (CIC) in
the medulla oblongata and the preganglionic fibers relay in terminal
ganglia located in the atria. However, the postganglionic fibers are short,
they arise from the terminal ganglia to supply the atrial muscle, S A node,
AV node, main stem of the AV bundle. Stimulation of these fibers will
lead to inhibition of all cardiac muscle properties, vasoconstriction of
coronary arteries and decrease the oxygen consumption of the heart
(Guyton and Hall 2000 and Sukker et al. 2000).
Vagal tone is the continuous inhibitory impulses carried by the vagus
nerve from the CIC to the heart to inhibit the high inherent rhythm of the
S.A. node. This is equally occurs under resting condition and produces a
5
basal heart rate (about 70 beats/min). At rest, the vagal tone to the heart is
dominant over the weak sympathetic tone. However, during muscular
exercise heart rate is increased due to a decrease in vagal tone and an
increase in sympathetic activity (Guyton and Hall 2000).
2.1.5 Regulation of Heart Rate
Heart rate is normally determined by the rate of depolarization cardiac
pacemaker (Hainsworth 1995).
Rhythmical beating of the heart at a rate of approximately 100
beats/min. will occur in complete absence of any nervous and hormonal
influences, but under normal resting the heart rate is about 72 beats/min.
The resting heart rate can vary widely in different individuals during
different physiological and physical conditions (Vander et al. 1994).
The heart rate indirectly affects the force of the contraction. As the
heart rate is increased, the duration of diastole becomes shorter and the
end diastolic volume (EDV) becomes smaller, the stroke volume
according to Starling's low is decreased. The diastolic filling will be
affected when heart rate exceeds 120 beats/min. But during exercise there
is compensation for any increase in sympathetic stimulation with increase
in strength of cardiac contraction (Guyton and Hall 1996).
2.1.5.1 Autoregulation of the heart rate (intrinsic control)
Cardiac muscle has myogenic rhythm, that has ability to contract
Rhythmically without nervous input (Ganong 1997).
The heart will continue to beat even when it is completely removed
from the body. At least some cells in the walls of all four cardiac
chambers are capable for initiating beats, such as nodal tissues or
specialized conducting fibers of the heart. When the SA node and other
components of atrial pacemaker complex are excised or destroyed,
pacemaker cells in the A V node usually are the next most rhythmic and
they become the pacemaker for the entire heart. When the AV Junction is
unable to conduct the cardiac impulses from the atria to ventricles,
idioventricular pacemakers in the Purkinje fiber network initiate the
ventricular contractions at frequency 30 to 40 beats per minute. Other
regions of the heart that initiate beats under special circumstances are
called ectopic foci or ectopic pacemaker. Ectopic foci may become
pacemaker when their own rhythmicity become enhanced, or the
rhythmicity of the higher order pacemakers becomes depressed, or all
6
conduction pathways between the ectopic focus and these regions with
greater rhythmicity become blocked (Berne and Levy 1992).
2.1.5.2 Nervous regulation of the heart rate(extrinsic control)
The S.A node is usually under the tonic influence of both divisions of
the autonomic nervous system. The sympathetic system enhances
automaticity where as the parasympathetic system inhibits it. Changes in
the heart rate usually involves a reciprocal action of the two divisions of
autonomic nervous system (Berne and Levy 1992).
2.1.5.2.1 Action of cardiac sympathetic fibers
Increased activity in the sympathetic nerves results in increases
both heart rate and the force of contraction. In addition, the rate
conduction through the heart of cardiac impulse is increased due
shorting in the AV nodal delay and the duration of the contraction
shortened (Hainsworth 1995).
in
of
to
is
Most of the norepinephrine released during sympathetic stimulation is
taken up again by the nerve terminals and much of remainder is carried
away by the blood stream, these processes are relatively slow. Therefore,
at the beginning of sympathetic stimulation, the facilitatory effects on the
heart attain steady state values much more slowly due to the inhibitory
effects of vagal stimulation (Berne and Levy 1992).
Increase in the heart rate leads to decrease of the time available for
diastolic filling, but the quicker contraction and relaxation induced
simultaneously by sympathetic nerve partially compensate for this
problem by permitting a large traction of cardiac cycle to be available for
filling. In other words, increasing in heart rate above critical level, the
heart strength itself will decrease due to overuse of metabolic substance
in cardiac muscles, at the same time decrease the duration of systolic
contraction and allows more time for filling during diastole (Vander et al.
1994).
There is a greater effect on heart rate from stimulation of right
sympathetic nerve than left at low frequency of stimulation. The left
sympathetic nerve is more concerned with regulation of cardiac inotropic
state (Hainsworth 1995).
2.1.5.2.2 Action of cardiac parasympathetic fibers
The parasympathetic (vagal) nerves innervate the A.V conducting
pathways, and the atrial muscle. The question of whether the vagi provide
an efferent control of ventricular muscle remains controversial
(Hainsworth 1995).
7
The stimulation of vagus nerve slows the heart rate, reduces force of
contraction of atrial muscle, increases delay of A.V node, and prolongs
action potential. Minimum duration of atrial action potential has about
120 ms (Bary 1999).
The right vagus nerve has a greater effect than the left due to different
innervations in both sides and frequency of stimulation (Berne and Levy
1992).
Strong vagal stimulation can decrease the heart rate to zero or almost
zero, and then the heart after being stopped for few seconds, then start
to beat again at rate 20-40 beats/min due to Autoregulation in AV node
and the purkinje fibers. Also strong stimulation of vagus nerve to the
heart leads to decrease of the strength of the heart contraction by 20-30
percent. This decrease is not great because vagal fibers are distributed
mainly to the atria but not much to ventricles where the power of cardiac
contraction occurred. Greater decrease in the heart rate combined with
slight decrease in heart contraction can decrease ventricle pumping to
50% or more (Guyton and Hall 1996).
2.1.5.3 Reflexes influencing the heart rate
Heart rate, at any instant of time, represents the resultant of many
influences on the vagal and sympathetic centers. Some reflexes may
increase heart rate through a decease in vagal tone, an increase in
sympathetic activity, or both. Others exert the opposite effects.
2.1.5.3.1 Baroreceptors reflex
Baroreceptors or stretch receptors are found in the wall of each
internal carotid artery slightly above the carotid bifurcation in an area
known as carotid sinus, also in the wall of the aortic arch (Vander et al.
1994).
The Baroreceptors system opposes either increases or decreases in
arterial pressure, it is often called pressure buffer system and the nerves
from these receptors which send their afferent impulses called buffer
nerves Normally. the carotid sinus Baroreceptors are not stimulated at all
by pressure between 0 and 60 mmHg, but above 60 mmHg, they respond
progressively more rapidly and reach a maximum at about 180 mmHg.
The responses of the aortic Baroreceptors are similar to those of carotid
receptors except that they operate, in general, at pressure levels about 30
mmHg higher. Stimulation of Baroreceptors results in increase in efferent
8
cardiac vagal activity and decrease in sympathetic activity. After the
Baroreceptors signals have entered the tractus solitarius of the medulla,
secondary signals eventually inhibit the vasoconstrictor center of medulla
and excite of the vagal center. The net effects are vasodilatation of the
veins and arterioles throughout the peripheral circulatory system,
decreased heart rate and strengthen heart contraction. Therefore,
excitation of the Baroreceptors by increased pressure in the arteries
reflexly causes the arterial pressure to decrease because of both decrease
in peripheral resistance and in cardiac output. Conversely, low pressure
has opposite effects, reflexly causing the pressure to rise back towards
normal (Guyton and Hall 2000).
2.1.5.3.2 Atrial and pulmonary artery reflexes
Both the atria and the pulmonary arteries have stretch receptors,
called low pressure receptors, in their walls similar to the baroreceptor
stretch receptors of the large systemic arteries. These low pressure
receptors play an important role in minimizing arterial pressure changes
in response to changes in blood volume. With the arterial baroreceptors
denervated, the ptessure will rise 40 mm Hg. If the low pressure receptors
are also denervated, the pressure may rise 100 mm Hg(Guyton and Hall
1997).
Thus, one can see that even though the low pressure receptors in the
pulmonary artery and in the atria connot detect the systemic arterial
pressure, these receptors nevertheless do detect simultaneous increases in
pressure in the low pressure areas of the circulation caused by an increase
in volume, and they elicit reflexes parallel to the baroreceptor reflexes to
make the total reflex system much more potent for control of arterial
pressure (Guyton and Hall 1997).
Mechanoreceptors have reflex effects on respiration and heart rate.
These receptors are found in upper respiratory airway, bronchi, alveoli
and pulmonary artery (Haslettetal1999).
In pulmonary blood vessels there are end unmyelinated ( C ) fibers
innervated an area called Juxtacapillary receptors. These receptors are
stimulated by hyperinflation of the lung and the response of the
stimulation is apnea followed by rapid breathing, bradycardia and
hypotension (Vander et al. 1994).
9
Stretch receptors exist in the wall of the pulmonary artery and they are
excited by increase in pulmonary arterial pressure, the reflex response is
an increase in pulmonary vascular resistance but it seems to have no
direct effect on the heart rate (Guyton and Hall 1997).
2.1.5.4 Chemical regulation of the heart
2.1.5.4.1 Arterial chemoreceptor
The chemoreceptor is the chemosensitive cells that respond to hypoxia,
hypercapnia and acidosis of arterial blood. Chemoreceptors include two
main types: peripheral and central chemoreceptors. The peripheral
chemoreceptors are situated mainly in carotid and aortic bodies. The most
obvious effects of peripheral chemoreceptor stimulation are increases in
rate and depth of respiration (Hainsworth 1995).
However, then- influence on the circulation is slight at normal gas
tensions. Peripheral chemoreceptor afferent fibers accompany the
baroreceptor afferent in Xth and IXth cranial nerves(Levick 1998).
Each carotid or aortic body is supplied with an abundant blood flow
through a small nutrient artery, so that chemoreceptors are always in
close contact with arterial blood. However, the chemoreceptor reflex is
not a powerful arterial pressure controller in the normal arterial pressure
range because the chemoreceptors themselves are not stimulated strongly
by pressure changes until arterial pressure falls below 80 mmHg. When
excitation of these chemoreceptors is increased by hypoxia and
hypercapnia, they elicit a sympathetically mediated constriction of
resistance vessels (except in the skin), constriction of splanchnic
capacitance vessels, bronchoconstriction, increase secretion of
antidiuretic hormone and release of adrenaline. The results of all of these
changes will help in increasing the arterial blood pressure, increase heart
rate, and by the short time return P02, PC02 and PH to normal level
(Guyton and Hall 2000).
Central chemoreceptors on the other hand, are located at near the
ventrolateral surface of medulla oblongata, this area is highly sensitive to
change in either blood PC02 or hydrogen ions concentrations which are
the only important direct stimulus of central chemoreceptors, that affect
mainly the respiratory center in the medulla and also have slight effect on
the adjacent vasomotor center (Guyton and Hall 2000).
10
2.1.5.5 Hormonal and acetylcholine regulation of the heart
2.1.5.5.1 The action of thyroid hormone of the heart rate
Cardiac activity is sluggish patients with inadequate thyroid function
(Hypothyroidism); that is the heart rate is slow and cardiac output is
diminished. The converse in true in-patient with over activity of thyroid
gland (Hyperthyroidism) (Berne and Levy 1992).
2.1.5.5.2 The action of adrenomedullary hormones on the heart
The adrenal medulla is essentially a component of the autonomic
nervous system. The principal hormone secreted by the adrenal medulla
is epinephrine, although some norepinephrine is also released (Berne and
Levy 1992).
Adrenaline and noradrenalin show both similarities and differences in
their effect on the circulation, but both adrenaline and noradrenalin have
stimulatory effects on the cardiac beta-adrenoceptors, so their action is to
increase heart rate and contractility (Hainsworth 1995).
2.1.5.5.3 The action of acetylcholine on the heart
Acetylcholine (Ach) is released by vagal stimulation and it reduces the
heart rate by increasing K+ ion conductance of pacemaker cells in the SA
node and also it interacts with muscarinic receptors in cardiac cell
membrane which lead to a decrease in myocardial contractility (Noma et
al. 1990).
11