Chapter 13 - Cardiac Function

Path of Blood Flow (Fig. 13.2)

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Anatomy of the Heart (Fig. 13.5)
Review anatomy on your own. Heart Anatomy Tutorial
Electrical Activity of the Heart
The contractions of the heart originate within muscle cells themselves and are myogenic. Hence, the heart
has its own autorhythmicity. This autorhythmicity is due to a small percentage of muscle cells that are
specialized to generate and conduct action potentials. These cells are called autorhythmic cells and they make
up the conduction system of the heart. The cells that generate the contractile force are called contractile cells.
The two types of autorhythmic cells are:

1. Pacemaker cells
The contractions are triggered by pacemaker cells concentrated primarily in the sinoatrial node and the
atrioventricular node.
2. Conduction fibers
These fibers are larger in diameter than other cardiac muscle cells and are specialized for rapid
conduction of action potentials.

The conduction system is designed to depolarize the atria first and make them contract as a unit and then to
depolarize the ventricles and cause them to contract as a unit. Rapid communication of action potentials
between cardiac muscle cells is possible because of the gap junctions present at structures called intercalated

disks. Intercalated disks also have desmosomes that enable muscle cells to resist the mechanical stress
associated with the stretching and contraction of the cardiac cycle.
Initiation and Conduction of an Impulse during a Heartbeat

1. An action potential is initiated in the SA node and travels by way of conduction fibers to the AV node.
Action potential spreads throughout the cells of the atria.
2. Impulse arrives at the AV node where there is a momentary delay because action potentials are
transmitted more slowly in these cells than in other cells of the conduction system.
3. Impulse leaves the AV node and travels through the atrioventricular bundle (bundle of His) in the
interventricular septum.
4. Atrioventricular bundles only travels a short distance before splitting into right and left bundle
branches.
5. Impulse travels to the myocardial cells of the ventricle by means of an extensive network of conduction
fibers called Purkinje fibers.
Control of Heart Beat
Both the SA node and the AV node are capable of generating spontaneous action potentials. However, the SA
node usually sets the pace because:
1. It fires more frequently than the AV node (70 impulses/min compared to 50 impulses/min).
2. After cells in the AV node are stimulated by impulses coming from the SA node they go into a
refractory period.
If the SA node fails to fire or if impulses from it are blocked the AV node can take over.
Spread of Excitation

The action potential is initiated at the SA node and spreads as a wave through the atrial muscle. When the
impulse reaches the AV node there is a delay before the AV node fires. This gives the atria time to squeeze
blood into the ventricles before they fire. The impulse is then carried by way of the AV bundle and the right
and left bundle branches to the apex of the heart and then spread through the walls of the ventricles towards
the base of the heart. This enables the heart to pump more efficiently as the contraction starts at the apex and
travels towards the base where the blood is finally ejected from the ventricles.
Ionic Basis of Electrical Activity in Pacemaker Cells
Pacemaker cells exhibit pacemaker potentials. After an action potential occurs the cells do not return to a
"resting potential" but begin to depolarize slowly until it reaches threshold and an action potential is triggered.
The action potential itself can be divided into a rapid depolarization phase and a repolarization phase.

The gradual depolarization that occurs in the early stage of the pacemaker potential is due to the closing of
potassium channels and the opening of "funny" channels. The closing of potassium channels moves the
membrane away from the equilibrium (EK = -94mV). Funny channels allow both potassium and sodium to cross
the membrane with sodium having the greater effect and moving the membrane potential toward its
equilibrium potential (ENa = 60 mV).
The funny channels are so named because they remain open for only a brief period of time and close short
of the threshold that triggers an action potential. However, the early depolarization opens voltage-gated
calcium channels which start to move the membrane potential toward its equilibrium potential (ECa = 130
mV). There are two types of calcium channels:
T-type channels
The T in T-type channel stands for transient. T-type channels open for a brief time and then close. The
depolarization due to the opening of the T-type channels activates the opening of the second type of
calcium channels, the L-type channels.
L-type channel
The L stands for long-lasting. The L-type channel stays open longer. The rapid increase in calcium
permeability associated with the opening of this channel causes the rapid depolarization phase of the
action potential.

The depolarization associated with the increase in calcium permeability opens the potassium channels and
the increase in potassium permeability causes the membrane potential to come down and repolarize. At the
same time, the repolarization that is due to the increase in potassium permeability causes the calcium channels
to close which also contributes to the repolarization of the membrane.
Electrical Activity in Cardiac Contractile Cells
In the cardiac contractile cells:
1. Some voltage -gated potassium channels close in response to depolarization and this is associated with
a decrease in potassium permeability.
2. Depolarization opens voltage-gated calcium channels which not only contributes to further
depolarization but triggers the muscle contraction.
The ventricular muscle cells have stable resting potentials and have action potentials that can be divided
into five phases. These phases are associated with the following permeability changes:

Phase 0 (depolarization)
There is a rapid depolarization associated with the opening of sodium channels. This is similar to what
happens during a neuronal action potential.
Phase 1 (repolarization)
The sodium channels start to inactivate, decreasing sodium permeability but at the same time:
1. Voltage-gated potassium channels close. A specific kind of voltage-gated potassium channel called
the inward rectifier channel closes and decreases the outward flow of potassium ions.
2. L-type voltage-gated calcium channels open. Both of these counter the effect of sodium channel
inactivation.
Phase 2 (plateau phase)
Potassium channels remain closed and calcium channels remain open. This results in a lower PK and a
higher PCa that keeps the membrane potential in the depolarized state.
Phase 3 (repolarization)
Another type of potassium channel (delayed rectifier channels) slowly open in response to the
depolarization and increases PK. The resulting repolarization also opens the first type of potassium
channels that closed in response to depolarization. The fall in potential also acts to close the calcium
channels which also contributes to a rapid repolarization of the membrane.
Phase 4 (resting potential)
The permeabilities for sodium, potassium and calcium return to their resting levels. Because PK is the
highest. The membrane potential is about -90 mV.
Excitation-Contraction Coupling
The excitation-contraction is similar to that for skeletal muscle except that the calcium that comes into the
cell during the plateau phase prolongs the crossbridge cycling and stimulates release of more calcium from the
sarcoplasmic reticulum.

The following breaks down the steps involved:

1. An action potential spreads along plasma membrane and along the T- tubules.
2. Voltage-gated Ca++ channels in sarcoplasmic reticulum and the plasma membrane open.
3. The action potential also causes Ca++ channels in the plasma membrane to open allowing more calcium
to enter the cytosol.
4. Ca++ that comes from both sources (Step 3 and 4) binds to ligand-gated Ca++ channels on the
membrane of the sarcoplasmic reticulum and opens them in what is called calcium-induced calcium
release.
5. Ca++ binds to troponin shifting tropomyosin off the binding sites on actin.
6. Crossbridge cycling occurs and the muscle contracts.
7. Ca++ is removed from the cytosol by:
a. Ca++ATPase transports Ca++ back into the SR.
b. Ca++ATPase pumps Ca++ out of the cell.
c. Na+-Ca++ exchanger exchanges Na+ for Ca+ + across the cell membrane.
8. The muscle relaxes as the calcium level drops, calcium unbinds from the troponin, and tropomyosin
recovers the actin bindings sites.
Electrocardiograph ECG or EKG
EKG helps the clinician to diagnose problems associated with the electrical activity of the heart. EKG
reflects the overall spread of electrical activity during the cardiac cycle and is measurable because the electrical

activity of many of the cells are synchronized during the cycle.

The current technique of recording the EKG employs Einthoven's triangle which is an imaginary triangle
that surrounds the heart with its corners at the right and left arms and the left leg. These correspond to places
where electrodes are placed. Pairs of electrodes (leads) are compared and are given Roman numeral
designations with one designating a positive electrode and the other a negative electrode.
The recording with a standard lead II EKG is shown in below:

1. P wave
Upward deflection associated with atrial depolarization.
2. QRS complex
Upward and downward deflections associated with ventricular depolarization (corresponds with phase
0 of the ventricular contractile cells).
3. T wave
Upward deflection associated with ventricular repolarization (phase 3).
It is important to remember that the EKG represents the patterns of action potentials in populations of
contractile cells and not that of an individual cell.
Certain intervals and segments of the ECG can provide important information about the function of the heart:
P-Q interval - gives an estimate of the time of conduction through the AV node.

Q-T interval - gives an estimate of the time the ventricles are contracting.
T-Q interval - gives an estimate of the time the ventricles are relaxing.
R-R interval - is the time between heartbeats. Dividing 60 by this time gives the heart rate.
Examples of Abnormal Electrical Activity
Sinus Tachycardia - Abnormally fast resting heart rate. Greater than 100 beats/min.
Sinus Bradycardia - Abnormally slow resting heart rate. Less than 50 beats/min.
Altered conduction through the AV node:
1. 1st Degree Heart Block
Delay in AV node. Shows an increased P-Q interval.
2. 2nd Degree Heart Block
Conduction through the AV node does not always occur. This is indicated by the occasional
absence of QRS complex and T wave after P wave.
3. 3rd Degree Heart Block

Conduction through AV node does not occur at all. Ventricular contraction occurs independent of
stimulation from the AV node. However, the rate is very slow (30-40 times per minute) because it is
determined by the rate of bundle of His fiber discharge.
Stimuli outside of normal conduction pathway may cause an extra contraction called extrasystole. In the
atrium it is called a premature atrial contraction (PAC). In the ventricle it is called a premature
ventricular contraction (PVC).
Fibrillation occurs when the cardiac muscle no longer displays synchronous depolarization.
Atrial fibrillation is lack of synchronized depolarization of atria and is not life threatening.
Ventricular fibrillation is lack of synchronized depolarization of ventricles and is incompatible with life.
Cardiac Cycle Heart Cycle Animation
Pump Cycle
Two major stages:
Systole - Period of ventricular contraction.
Diastole - Period of ventricular relaxation.
The cardiac cycle can be further divided into:

1. Ventricular Filling
During early-to-late diastole, the pressure of blood in the veins drives blood through the atria into the
ventricles. AV valves are opened and semilunar valves are closed. Late in diastole atria contract and
drive more blood into the ventricles.
2. Isovolumetric Contraction
At the beginning of systole, ventricles are contracting but the amount of blood in the ventricles
remains the same. This is due to the fact that pressure exerted on the blood closes the AV valves but is
not yet high enough to force the semilunar valves to open.
3. Ventricular Ejection
During the remainder of systole, the pressure of blood in the ventricles is strong enough to open the

semilunar valves and blood is ejected from the ventricles into the pulmonary trunk and aorta. When the
pressure in the ventricles declines to that below that of the aorta and pulmonary trunk the semilunar
valves close and systole ends.
4. Isovolumetric Relaxation
On the onset of diastole, the ventricular muscles begin to relax but pressure on the AV valves is still
enough to keep them closed. With the semilunar and AV valves closed at the same time, the volume of
blood in the ventricles remains the same as the pressure drops. Once the pressure has dropped low
enough the AV valves open and the cycle begins again.
Atrial and Ventricular Pressure

By convention pressure is measured in mm of mercury and is relative to atmospheric pressure (760 mm Hg)
which is taken as zero (e.g. 100 mm Hg pressure is 860 mm Hg). Atrial contraction is associated with a small
and short-lived rise in pressure associated with atrial contraction.
Ventricular pressure stays low in early diastole but there is a small abrupt rise in late diastole due to atrial
contraction forcing blood into the ventricles. A much larger increase in pressure occurs as systole begins with
ventricular contraction. During early diastolic, pressure falls to near zero. During the remainder of diastole the
pressure slowly rises as the ventricles fill with blood.
Aortic Pressure

During diastole aortic pressure shows a gradual decline. The minimum pressure is diastolic pressure.
During phase 2 with the onset of systole, aortic pressure continues to fall. During phase 3 with ventricular
ejection, aortic pressure rises rapidly. The maximum pressure reached during phase 3 is called systolic
pressure. At the end of systole the aortic valve closes and there is a sudden increase followed by a sudden
decrease in pressure that is referred to as the dicrotic notch. The average aortic pressure during the cardiac
cycle is called mean arterial pressure.
Aortic systolic and diastolic pressures are estimated by measuring pressure in the brachial artery.
Although the blood exits the heart in spurts blood flows through the vasculature continuously. This is
because the elastic walls of the aorta stretches while blood is being ejected into the aorta during systole and
returns this energy during diastole. In this way the aorta acts as a pressure reservoir that stores some of the
energy generated by the heart during ventricular contraction and releases it during ventricular relaxation.
Ventricular Volume

During diastole blood volume in the ventricle rises rapidly but then rises less rapidly until the end of diastole when
there is a small but abrupt rise in pressure associated with atrial contraction. The volume reached at the end of diastole
is called end-diastolic volume. During isovolumetric contraction volume remains the same but rapidly declines during
ventricular ejection. The volume of blood in the ventricles at the end of systole is end-systolic volume.
The difference between the end-diastolic volume and the end-systolic volume is the stroke volume.
Not all the blood in the ventricles is ejected during systole. The fraction of the diastolic volume ejected during
systole is called the ejection fraction. This amount can be increased during stress.
Heart Sounds Heart Sounds Tutorial

The first heart sound, a low-pitched "lub" occurs at the start of systole when the AV valve closes. The second
sound, a high pitched "dub" occurs at the beginning of diastole when the semilunar valve closes.
Cardiac Output and Its Control
Cardiac output is the rate at which the ventricle pumps blood. It is equal to the heart rate times the stroke
volume or:
CO
=
HR
x
SV

The left and right ventricles have the same cardiac output over the long run and average about the same
stroke volume. Nervous input to the heart exerts a significant effect on cardiac output by regulating the rate and
force of muscle contraction. Hormones also have an effect on cardiac output.
The heart is under extrinsic control such as neural input and hormones, and intrinsic control from factors
originating within the organ itself.
Autonomic Input to the Heart

The heart is controlled by the autonomic nervous system. The sympathetic nervous system releases
norepinephrine and the parasympathetic nervous system releases acetylcholine. Sympathetic and
parasympathetic neurons exert opposite effects. Sympathetic preganglionic nerves emerge from the upper
thoracic regions of the spinal cord and synapse with postganglionic neurons in the sympathetic trunk.
Parasympathetic preganglionic fibers emerge from the medulla oblongata in the vagus nerve and synapse with
postganglionic neurons in the heart.
Factors Affecting CO: Changes in Heart Rate
The autonomic nervous system alters the heart rate through its two divisions:
Sympathetic Control

Sympathetic neurons to the SA node increases the frequency of action potentials. Postganglionic neurons
release norepinephrine which bind to 1 receptors on the SA nodal cells activating the cAMP second
messenger system. cAMP augments the opening of funny channels and T-type Ca++ channels which increases the
slope of spontaneous depolarization. The frequency of action potentials increase and increases the heart rate.
Parasympathetic Control

Parasympathetic neurons to the SA node decreases the frequency of action potentials. Postganglionic neurons
release acetylcholine which bind to muscarinic cholinergic receptors. The receptors open potassium channels
through stimulatory G proteins and close funny channels and T-type calcium channels through an inhibitory G
protein. The frequency of action potentials as a result decreases and decreases the heart rate.

Hormonal Control of Heart Rate

Epinephrine exerts effects similar to sympathetic stimulation, that is, increase in frequency and speed of
action potentials. Thyroid hormones, insulin and glucagon all increase the force of cardiac contraction.
Glucagon also increases the heart rate.
Integration of Heart Rate Control
The sympathetic and parasympathetic nervous systems act together to control the heart rate in a "push-pull"
manner, that is, when sympathetic activity increases parasympathetic decreases and vice versa. Without any
stimulation at all the natural heart rate would be higher than normal (about 100 beats/min.). This suggests that
under normal resting conditions the parasympathetic division dominates over the sympathetic division.
Factors Affecting Cardiac Output: Changes in Stroke Volume
There are three primary factors that affect stroke volume:
1. Ventricular contractility - The amount of force produced by the contracting ventricles.
2. End-diastolic volume - The amount of blood in the ventricles at the onset of ventricular contraction.
3. Afterload - The pressure that the ventricles have to work against as they contract.
We will now look at each factor in greater detail.
Ventricular contractility
Contractility refers to the ability of the muscle to generate force. An increase in contractility will increase
the stroke volume.
Autonomic control of ventricular contractility is exerted almost entirely by the sympathetic nervous system.
Sympathetic neurons increase ventricular contractility which increases cardiac output. Sympathetic activity also
causes the atria to contract with more force and increases the blood pumped into the ventricle.

Sympathetic neurons release norepinephrine which binds to 1 adrenergic receptors. These receptors
activate adenylate cyclase that catalyzes synthesis of cyclic AMP. Increased cyclic AMP has the following
effects:

1. Phosphorylation of calcium channels in the plasma membrane causes the calcium channels to remain
open longer during action potentials.
2. Phosphorylation of proteins in the sarcoplasmic reticulum enhances release of calcium from the
sarcoplasmic reticulum.
3. Phosphorylation of myosin increases the rate of myosin ATPase which increases the speed of
crossbridge cycling.
4. Phosphorylation of calcium pumps in the sarcoplasmic reticulum increases the speed of calcium reuptake which increases the rate of relaxation.

All the above effects increase the speed of ventricular contraction.

Hormonal Control
Insulin, glucagon, thyroid hormone and epinephrine enhance ventricular contractility. The effects of
epinephrine are similar to those of norepinephrine.
End-Diastolic Volume
End-diastolic volume influences stroke volume by stretching the ventricular myocardium. This effect is
intrinsic to the heart itself and is exemplified by Starling's law of the heart.
Starling's Law
According to Starling's law the heart automatically adjusts its output to match the end-diastolic volume. In
other words, as end-diastolic volume increases, the force of ventricular contraction increases, and as enddiastolic volume decreases, the force of ventricular contraction decreases.
The stretching of the myocardial fibers leads to an increase in the force of contraction by two mechanisms:
1. As the length of the muscle fiber is increased the muscle fiber comes closer to its optimum length for
contraction.
2. The stretching of the muscle fiber increases the affinity of troponin for calcium which increases the
crossbridge cycling.

The Starling effect is illustrated by the Starling curve, or cardiac function curve. This curve is basically a
length-tension curve with the length (x-axis) represented by the end-diastolic volume and the tension (y-axis)
represented by the stroke volume. Because in a healthy heart the cardiac muscle is always at lengths less than
optimal the slope of the curve is always positive.
The cardiac function curves assume a healthy heart and normal sympathetic input. In a person with a
chronically expanded heart, the heart's connective tissue weakens and the heart becomes dilated. The heart in
this state is weakened and produces a cardiac function curve with a negative slope as end-diastolic volume
increases.

The cardiac function curve also shifts upward as sympathetic activity increases. In other words, stroke
volume at any given end-diastolic volume increases as sympathetic stimulation increases.
Significance of Starling's law is that it enables the heart to regulate its size under different conditions of
venous return. This is important because as the heart wall expands the tension is greater and it needs to work

harder to generate the same pressure. If the ventricles are too big, heart failure is more likely to occur as the
heart fails to generate enough pressure to maintain cardiac output.
Factors Affecting End-Diastolic Volume
End-diastolic volume is primarily determined by end-diastolic pressure, also called preload. As the preload
increases, end-diastolic volume increases and stroke volume increases according to Starling's law.
Preload is affected by:
1. Filling time which depends upon heart rate.
2. Atrial pressure resulting from venous return and atrial contraction.
A decrease in heart rate tends to increase pre-load and end-diastolic pressure. A rise in atrial pressure also
increases pre-load.
The most important factor influencing venous return is central venous pressure which, in turn, is affected by
many variables. As central venous pressure rises, venous return increases, and this leads to an increase in enddiastolic volume.
Afterload
Afterload is due to arterial pressure which places pressure or a "load" on the ventricular myocardium after a
contraction begins. For the left ventricle, pressure in the aorta during ventricular ejection determines the
afterload. Afterload increases with mean arterial pressure.

Summary of factors affecting stroke volume

Integration of factors affecting cardiac output.