Cardiovascular physiology Week-4

Cardiac output (CO)

It is the amount of blood pumped by each ventricle in one minute. It can be calculated by
multiplying the heart rate (HR) by the stroke volume (SV):

CO (Cardiac output in mL/min) = HR (Heart rate in beats/min) X SV (Stroke volume in

mL/beat)

Factors affecting cardiac output

Cardiac output can be adjusted by changes in either:
A. Heart rate.
B. Stroke volume.
A. Factors affecting the heart rate
Normocardia: is when heart rate ranges between 60 and 100 beat per minute.
Tachycardia: is the increase in heart rate above 100 beats/minute.
Bradycardia: is the decrease in heart rate below 60/minute.
Heart rate can be regulated by the following mechanisms:
1. Autonomic regulation.
2. Chemical regulation.
Autonomic regulation of heart rate
Nervous system regulation of the heart originates in the cardiac center in the medulla
oblongata. The cardiac center is functionally divided into:
1. Sensory area: This area receives inputs from
- Higher brain centers: for example, just before the start of physical activity, especially in
competitive situations, heart rate may rise, this increase occurs because the limbic system
sends impulses to the cardiac center in the medulla.
- Proprioceptors: After the start of the physical activity, proprioceptors that monitor the
position of joints and muscles send nerve impulses to the cardiovascular center.
Proprioceptor input is a major stimulus for the quick rise in heart rate that occurs at the
onset of physical activity.
- Chemoreceptors: these monitor chemical changes in the blood.
- Baroreceptors: these monitor the stretching of major arteries caused by the pressure of the
blood flowing through them. Important baroreceptors located in the arch of the aorta and
in the carotid arteries detect changes in blood pressure and provide input to the
cardiovascular center.

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The cardiovascular center receives signals from the sensory area then directs appropriate output
by increasing or decreasing the frequency of nerve impulses in both the sympathetic and
parasympathetic branches of the ANS.
2. Cardiac excitatory center (CEC): this center sends sympathetic fibers to the SA node,
AV node, and most portions of the myocardium (atria and ventricles). Impulses in the
cardiac accelerator nerves trigger the release of norepinephrine, which binds to beta-1
receptors on cardiac muscle fibers. This interaction has two separate effects:
A. In nodal fibers, norepinephrine speeds the rate of spontaneous depolarization so that
these pacemakers fire impulses more rapidly and heart rate increases (i.e., positive
chronotropy).
B. In contractile fibers, norepinephrine enhances Ca+2 entry thereby increasing
contractility (positive inotropy). As a result, a greater volume of blood is ejected
during systole.
Sympathetic tone of the heart
Sympathetic tone is the continuous stream of impulses produced by the cardiac excitatory
center (CEC). Impulses pass through sympathetic nerves and accelerate the heart rate. Under
normal conditions, the vagal tone is dominant over sympathetic tone. Whenever vagal tone is
reduced or abolished, the sympathetic tone becomes powerful.

3. Cardiac inhibitory center (CIC): this center sends parasympathetic nerve impulses to
reach the heart via the right and left vagi. Vagal axons terminate in the SA node, AV node,
and atrial myocardium (the ventricles receive a very little parasympathetic innervation).
They release acetylcholine, which decreases heart rate by slowing the rate of spontaneous
depolarization in nodal fibers. As only a few vagal fibers innervate ventricular muscle,
changes in parasympathetic activity have little effect on contractility of the ventricles.
Vagal tone of the heart
Vagal tone is the continuous stream of inhibitory impulses from cardiac inhibitory center (CIC)
to heart via vagus nerve. Heart rate is kept under control mainly because of this vagal tone and
heart rate is inversely proportional to it. The removal of vagal input increases the heart rate.
Under resting conditions, vagal tone dominates sympathetic tone. Impulses from different parts
of the body regulate the heart rate through CIC, by altering the vagal tone.
A balance exists between sympathetic and parasympathetic tones of the heart. At rest,
parasympathetic tone predominates. The resting heart rate (about 75 beats/min) is usually lower
than the autorhythmic rate of the SA node (about 100 beats/min). With maximal stimulation

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by the parasympathetic division, the heart can slow to 20 or 30 beats/min, or can even stop
momentarily.
Factors affecting cardiac centers through regulation of vagal tone
After receiving the impulses from different sources, the cardiac area alters the vagal tone and
modulates the activities of the heart:
1. impulses from higher centers:
Cardiac center is mainly controlled by the impulses from higher centers in cerebral cortex and
hypothalamus. For example, the cerebral cortex is concerned with emotional reactions of the
body. During emotional conditions, this area sends inhibitory impulses to the CIC. This causes
reduction in vagal tone, leading to increase in heart rate.
2. impulses from respiratory centers:
In forced breathing, heart rate increases during inspiration and decreases during expiration. As
you learned from previous lectures, this variation is called sinus arrhythmia and is due to the
alteration of vagal tone because of impulses arising from respiratory centers during inspiration
inhibit the CIC, resulting in decreased vagal tone and increased heart rate. During expiration,
the respiratory center stops sending inhibitory impulses to CIC. Now, vagal tone increases,
leading to decrease in heart rate.
3. impulses from baroreceptors (Marey`s reflex)
Baroreceptors are the stretch receptors which respond to changes in blood pressure. There are
two types of baroreceptors:
A. Carotid baroreceptors, situated in carotid sinus and are supplied by Hering`s nerve,
which is the branch of glossopharyngeal (IX cranial) nerve.
B. Aortic baroreceptors, situated in the wall of arch of aorta. Aortic baroreceptors are
supplied by aortic nerve, which is a branch of vagus (X cranial) nerve

Function of baroreceptors reflex – Marey’s reflex

Baroreceptors regulate the heart rate through Marey’s reflex. Stimulus for this reflex is
increase in blood pressure. Marey’s reflex is a cardioinhibitory reflex that decreases heart rate
when blood pressure increases, or simply it is a reflex bradycardia in response to high blood
pressure. Whenever blood pressure increases, the aortic and carotid baroreceptors are
stimulated and stimulatory impulses are sent to CIC via Hering’s nerve and aortic nerve
(afferent nerves). Now, the CIC in turn increases the vagal tone, leading to decrease in heart
rate.

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When pressure is decreased, the baroreceptors are not stimulated. So, no impulses go to CIC.
There are no inhibitory impulses to the heart and heart rate is not decreased. Thus, the heart
rate is inversely proportional to blood pressure.
4. impulses from chemoreceptors:
Chemoreceptors are receptors that respond to changes in chemical constituents of blood,
particularly oxygen, carbon dioxide and hydrogen ion concentration. Peripheral
chemoreceptors are situated in the carotid body and aortic body, adjacent to baroreceptors.
Chemoreceptors in the carotid body are supplied by Hering’s nerve. Chemoreceptors in the
aortic body are supplied by aortic nerve.
Whenever there is hypoxia, hypercapnia and increased hydrogen ions concentration in the
blood, the chemoreceptors are stimulated and inhibitory impulses are sent to CIC decreasing
vagal tone thus the heart rate increases. Therefore, it is a reflex tachycardia in response hypoxia,
hypercapnia, or acidosis.
5. impulses from right atrium – Bainbridge reflex
Bainbridge reflex is a cardioaccelerator reflex that increases the heart rate when venous return
is increased. Since this reflex arises from right atrium, it is also called (right atrial reflex).
Increase in venous return causes distention of right atrium and stimulation of stretch receptors
situated in the wall of right atrium. Stretch receptors, in turn, send inhibitory impulses through
inferior cervical sympathetic nerve to CIC resulting in decrease in vagal tone and increase in
sympathetic tone and hence the heart rate increases. Therefore, it is a reflex tachycardia in
response to increased venous return.
Chemical regulation of heart rate:
1. Hormones: Epinephrine and norepinephrine (from the adrenal medullae not from the
cardiac nerve) enhance the heart’s pumping effectiveness. These hormones increase both
heart rate and contractility. Exercise, stress, and excitement cause the adrenal medullae to
release more hormones. Thyroid hormones also enhance cardiac contractility and increase
heart rate that’s why one sign of hyperthyroidism is tachycardia.
2. Cations: Elevated blood levels of K+ or Na+ decrease heart rate and contractility. Excess
Na+ blocks Ca+2 inflow during cardiac action potentials, thereby decreasing the force of
contraction, whereas excess K+ blocks generation of action potentials. A moderate increase
in interstitial Ca+2 level speeds heart rate and strengthens the heartbeat.
Other factors in heart rate regulation
1. Age: A newborn baby is likely to have a resting heart rate over 120 beats/min; the rate then
gradually declines throughout life.

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2. Gender: Adult females often have slightly higher resting heart rates than adult males,
although regular exercise tends to bring resting heart rate down in both sexes.
3. Physical fitness: A physically fit person may even exhibit bradycardia, a resting heart rate
under 50 beats/min. This is a beneficial effect of endurance-type training because a slowly
beating heart is more energy efficient than one that beats more rapidly.
4. Body temperature: Increased body temperature, as occurs during a fever (Every 1F rise in
body temperature increase HR by 10 beats /min) or strenuous exercise, causes the SA node
to discharge impulses more quickly, thereby increasing heart rate. Decreased body
temperature decreases heart rate and strength of contraction.
Factors affecting the stroke volume
Since the stroke volume = EDV – ESV, therefore any factor that alters either the EDV or the
ESV will change SV. For example, an increase in EDV increases SV, whereas an increase in
ESV decreases SV. Three factors regulate stroke volume:
1. Preload.
2. Afterload.
3. Contractility.
Preload.
The degree of stretching in ventricular muscle cells at the end of ventricular diastole is called
the preload. The preload is directly proportional to the EDV: The greater the EDV, the larger
the preload. When the EDV increases, the myocardium stretches further and as the sarcomeres
approach optimal lengths, the ventricular muscle cells can contract more efficiently and
produce more forceful contractions and they also shorten more thus more blood is pumped out
of the heart. In general, the greater the EDV, the larger the stroke volume.
The relationship between the amount of ventricular stretching and the contractile force means
that, within normal physiological limits, increasing the EDV results in a corresponding increase
in the stroke volume, or simply “the more in = the more out”. This is known as the Frank–
Starling principle or Frank–Starling law of the heart.
The Frank–Starling law of the heart equalizes the output of the right and left ventricles and
keeps the same volume of blood flowing to both the systemic and pulmonary circulations. If
the left side of the heart pumps a little more blood than the right side, the volume of blood
returning to the right ventricle (venous return) increases. The increased EDV causes the right
ventricle to contract more forcefully on the next beat, bringing the two sides back into balance.

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The EDV:
Two factors affect this volume:
1. The filling time: Filling time is the duration of ventricular diastole, the more the filling
time the more the EDV. It depends entirely on the heart rate: The faster the heart rate,
the shorter is the time available for filling.
2. The venous return: the more the venous return the more the EDV and hence the more
stroke volume. Venous return is influenced by several factors.
− Muscle contraction (muscle pump): Contraction of limb muscles as occurs during
normal locomotory activity (walking, running, swimming) promotes venous return
by the muscle pump mechanism.
− Venous constriction (venoconstriction): Sympathetic activation of smooth muscles
in the veins causes them to constrict, increasing venous pressure and promoting
venous return (since the pressure gradient between the veins and atria increases).
− Respiratory pump (abdomino-thoracic pump): During inspiration, the venous
return increases because the pressure in the thoracic cavity is reduced in all areas
within the chest particularly around the venae cavae and increased in the abdomen,
this means that the blood moves from a high-pressure area outside the thoracic
cavity to a low-pressure area inside the cavity. Basically, sucking the blood in and
back to the heart
− Gravity: Veins in the upper body are aided by gravity in order to return blood to the
heart.
Afterload:
The pressure that must be overcome before a semilunar valve can open is termed the afterload.
The greater the afterload, the longer the period of isovolumetric contraction, the shorter the
duration of ventricular ejection, and the larger the ESV. In other words, as the afterload
increases, the stroke volume decreases and more blood remains in the ventricles at the end of
systole (ESV). Conditions that can increase afterload include hypertension and narrowing of
semilunar valves. The afterload is directly proportional to ESV and inversely proportional to
SV, for example, an increase in afterload (e.g., in aortic valve stenosis) decreases SV, and
causes ESV to increase. Conversely, a decrease in afterload augments SV and decreases ESV.
Contractility (Inotropy)
Contractility is the amount of force produced during a contraction. Changes in ventricular
inotropy (contractility) alter the rate of ventricular pressure development, thereby affecting

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ESV and SV. For example, an increase in inotropy (e.g., produced by sympathetic activation
of the heart) increases SV and decreases ESV. Conversely, a decrease in inotropy (e.g., heart
failure) reduces SV and increases ESV. Factors that increase contractility are said to have a
positive inotropic action. Factors that decrease contractility have a negative inotropic action.
Positive inotropic agents typically stimulate Ca2+ entry into cardiac muscle cells, thus
increasing the force and duration of ventricular contractions. Negative inotropic agents may
block Ca2+ movement.
Circulatory shock
Circulatory shock is any state in which cardiac output is insufficient to meet the body’s
metabolic needs. All forms of circulatory shock fall into two categories:
1. Cardiogenic shock, caused by inadequate pumping by the heart usually as a result of
myocardial infarction,
2. Low venous return shock (LVR shock), in which cardiac output is low because too little
blood is returning to the heart. There are three principal forms of LVR shock:

A. Hypovolemic shock, is the most common form of LVR shock, is produced by a loss of
blood volume as a result of hemorrhage, trauma, bleeding ulcers, burns, or dehydration.
Dehydration is a major cause of death from heat exposure. In hot weather, the body
produces as much as 1.5 L of sweat per hour. Water transfers from the bloodstream to
replace lost tissue fluid, and blood volume may drop too low to maintain adequate
circulation.
B. Obstructed venous return shock, occurs when a growing tumor or aneurysm, for
example, compresses a nearby vein and impedes its blood flow.
C. Venous pooling shock (vascular shock), occurs when the body has a normal total blood
volume, but too much of it accumulates in the limbs. This can result from long periods
of standing or sitting or from widespread vasodilation. Vascular shock includes:
I. Neurogenic shock (vasovagal attack, fainting or syncope) is a form of venous
pooling shock that occurs when there is a sudden loss of vasomotor tone,
allowing the vessels to dilate. The causes include sudden acute pain, severe
emotional experience, spinal anesthesia and spinal cord damage.
Parasympathetic nerve impulses reduce the heart rate, and in turn, the cardiac
output. The venous return also reduced by the pooling of blood in dilated veins.
These changes effectively reduce the blood supply to the brain, causing fainting.
The period of unconsciousness is usually of short duration.

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II. Anaphylactic shock: caused by a systemic allergic reaction in which the massive
release of histamine triggers systemic vasodilation.
III. Septic shock: caused by a severe systemic bacterial infection (bacterial toxins
are notorious vasodilators).

Stages of shock:
1. Compensated shock (the responses by the body maintain cardiac output). Following a
small hemorrhage, for example, the heart rate increases, the blood vessels constrict, and
the kidneys decrease urinary output to conserve water. These responses help preserve
blood volume and maintain blood pressure, cardiac output, and blood flow to tissues.
2. Progressive shock (the state of shock leads to more shock).
Following a severe hemorrhage, cardiac output decreases and the myocardium itself is
deprived of blood. The heart weakens, which further decreases cardiac output. Arteries
that are deprived of their blood supply cannot remain constricted. As the arteries dilate,
venous return decreases, which in turn decreases cardiac output. Progressive shock is a
series of such vicious cycles, and medical intervention is required to restore cardiac
output to normal.
3. Irreversible shock: no amount of medical assistance can restore cardiac output to
normal. The usual cause of death is that the heart has been damaged too much to
recover. A severe myocardial infarction or massive hemorrhage may all be fatal despite
medical treatment.