Download Cardiac Action Potential

Chapter 17
Cardiac Function
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Cardiovascular Anatomy
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Primary function of the heart is to reduce
the driving force that propels blood through
the vessels of the circulatory system
Cardiac dysfunction can lead to abnormal
function or death of cells throughout the
body
Cardiovascular disease is the leading
cause of mortality in the United States
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Cardiovascular Anatomy (Cont.)
Heart
 Located in the mediastinum
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Base
Apex
Cardiac valves control the direction of
blood flow through the heart
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Mitral
Tricuspid
Pulmonic
Aortic
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Cardiovascular Anatomy (Cont.)
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Cardiovascular Anatomy (Cont.)
Heart
 Papillary muscles prevent the valve
leaflets from bending backward into the
atria during ventricular contraction
 Heart muscle
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Endocardium
Epicardium
Pericardium
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Cardiovascular Anatomy (Cont.)
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Cardiovascular Anatomy (Cont.)
Circulatory System
 Right-sided heart chambers pump
deoxygenated (venous) blood through the
lungs
 Left-sided heart chambers pump
oxygenated blood through the systemic
circulation
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Cardiovascular Anatomy (Cont.)
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Cardiac Cycle
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Each heartbeat is composed of a period of
ventricular contraction (systole) followed
by a period of relaxation (diastole)
Closure of the AV valves causes the first
heart sound, S1
Closure of the semilunar valves causes
the second heart sound, S2
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Cardiac Cycle (Cont.)
Isovolumic Contraction
 Following atrial systole the ventricles
contract, causing intraventricular pressure
to rise and the AV valves to close (S1)
 Volume remains constant during this
phase
 Rate of rise in pressure is an indication of
contractility
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Cardiac Cycle (Cont.)
Ventricular Ejection
 Contraction results in a rapid rise in
ventricular pressure > aortic pressure,
forcing the aortic valve to open with rapid
ejection of blood from the ventricle
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Cardiac Cycle (Cont.)
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Stroke volume (SV) is the amount of blood
ejected with each contraction of the
ventricle (SV = EDV – ESV)
End-diastolic volume is the volume of
blood in the ventricle prior to ejection
End-systolic volume is the amount of blood
that remains in the ventricle after ejection
Ejection fraction = SV/EDV
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Cardiac Cycle (Cont.)
Isovolumic Relaxation
 Begins with semilunar valve closure in
response to falling ventricular pressures
and ends when the AV valves open to
allow ventricular filling
 Ventricular blood volume remains constant
during this phase
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Cardiac Cycle (Cont.)
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Cardiac Cycle (Cont.)
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Cardiac Cycle (Cont.)
Atrial Events
 The atria have 3 characteristic waves:
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a wave corresponds to atrial contraction
c wave represents the AV valve bulging during
ventricular contraction
v wave corresponds to atrial filling
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Cardiac Cycle (Cont.)
Aortic and Pulmonary Artery Events
 Arterial pressures fall to their lowest value
just prior to semilunar valve opening =
diastolic blood pressure
 Arterial pressure reaches its maximum
during ventricular ejection = systolic
pressure
 Dicrotic notch reflects closure of the
semilunar valves
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Coronary Circulation
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Coronary arteries supply blood to the heart
muscle
Right and left coronary arteries are located
in the sinuses of Valsalva
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Coronary Circulation (Cont.)
Anatomy of the Coronary Vessels
 Left main coronary artery divides into left
anterior descending and circumflex
branches
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Left anterior descending supplies the septal,
anterior, and apical areas
Circumflex supplies the lateral and posterior
left ventricles
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Coronary Circulation (Cont.)
Regulation of Coronary Blood Flow
 Driving pressure and vascular resistance
to flow
 Ohm’s law—an increase in driving
pressure increases flow, whereas an
increase in resistance reduces flow
 Coronary driving pressure equals aortic
blood pressure (ABP) minus right atrial
pressure (RAP)
(P) = ABP – RAP
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Coronary Circulation (Cont.)
Coronary Vascular Resistance
 Two major determinants:
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Coronary artery diameter adjusted by
autoregulation, ATP-sensitive potassium
channels, nitric oxide levels, and autonomic
nervous system
Varying degree of external compression due to
myocardial contraction/relaxation (most
coronary blood flow occurs during diastole)
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Cardiac Myocytes
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Two general types
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Working cells with mechanical pumping
functions
Electrical cells that transmit electrical impulses
Both produce and transmit action
potentials
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Cardiac Myocytes (Cont.)
Myocyte Structure
 Myocytes behave as a syncytium because
they are jointed by gap junctions within the
intercalated disks that permit the flow of
ions from one cell to the next
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Sarcolemma—T tubules
Sarcoplasmic reticulum—calcium ions—
ryanodine receptors
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Cardiac Myocytes (Cont.)
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Cardiac Myocytes (Cont.)
Structure of the Contractile Apparatus
 Striation due to organized structure of the
proteins of the contractile apparatus
 Actin and myosin proteins form contractile
apparatus; are arranged in contractile units
called sarcomeres

Z disks (Z line)
 I band
 A band
 M line
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Cardiac Myocytes (Cont.)
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Cardiac Myocytes (Cont.)
Characteristics of Contractile Filaments
 Thick filaments
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Myosin
• Enzymatic activity and splits ATP
• Titin
Thin filaments
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Actin
• Tropomyosin
• Troponin
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Molecular Basis of Contraction
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All myocytes of the chamber must shorten
simultaneously to produce a forceful
contraction
Specialized cells of the conduction system
coordinate myocardial contraction
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Molecular Basis of Contraction
(Cont.)
Overview of Contraction
 Excitation-contraction coupling:
Depolarization causes ion channels of the
plasma membrane and T tubules to open
allowing sodium and calcium entry and
release of calcium from the SR. Presence
of free calcium in the sarcoplasm results in
contraction.
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Molecular Basis of Contraction
(Cont.)
Sliding Filament/Cross-Bridge Theory of
Muscle Contraction
 Contraction of cardiac muscle by
shortening of individual sarcomeres due to
increased overlap of actin and myosin
filaments
 Myosin heads bind to specific sites on
actin and pull the thin filaments toward the
center of the sarcomere
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Molecular Basis of Contraction
(Cont.)
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Molecular Basis of Contraction
(Cont.)
Sliding Filament/Cross-Bridge Theory of
Muscle Contraction
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ATP hydrolysis provides the energy for crossbridging and affects affinity of myosin for actin
Myosin has high affinity for actin when ADP and Pi
are bound; low affinity when ATP is bound
Myosin cycles between high- and low-affinity
states, making and breaking cross-bridges with
the actin filament
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Molecular Basis of Contraction
(Cont.)
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Molecular Basis of Contraction
(Cont.)
Role of Calcium in Muscle Contraction
 Contraction is dependent on adequate
calcium ions in the cytoplasm
 Muscle relaxation (lusitropy) is due to
removal of calcium from the cytoplasm
 This is an energy-requiring process
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Molecular Basis of Contraction
(Cont.)
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Molecular Basis of Contraction
(Cont.)
Energy of Muscle Relaxation
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Significant energy required to pump calcium ions
out of the cytoplasm
Membrane pumps in the sarcolemma and SR
actively move calcium out of the sarcoplasm
against a concentration gradient
Sarcolemma has 2 different calcium pumps
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One that requires ATP
One that uses the potential energy of the sodium
gradient to remove calcium
SR calcium pumps (SERCAs) require ATP
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Cardiac Energy Metabolism
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Uses energy from ATP hydrolysis to drive
energy-requiring functions
Accomplished by glycolytic and oxidative
reactions
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Cardiac Energy Metabolism
(Cont.)
Oxygen Utilization
 Creatine phosphate (CP)—storage form of
ATP
 CP an immediately available source of
energy
 Under conditions of low ATP availability,
CP is converted to ATP by the enzyme CK
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Cardiac Energy Metabolism
(Cont.)
Substrate Utilization
 Primary energy substrates are fatty acids
and glucose
 Able to use lactate and ketones when they
accumulate in the circulation
 Able to use a variety of substrates to
produce ATP under varying metabolic
conditions
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Cardiac Electrophysiology
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Heart is rhythmically activated by action
potentials
Action potentials are generated and
transmitted by a specialized conduction
system
Many cardiac disorders result from
disturbances in electrical function that
produce abnormal conduction pathways,
dysrhythmias, and conduction blocks
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Cardiac Electrophysiology (Cont.)
Cardiac Resting Potential
 Resting cardiac cells are negatively
charged on the inside
 Difference in potassium ion concentration
across the cell membrane determines
resting membrane potential
 Increase in extracellular potassium
hypopolarizes the cell while a decrease
hyperpolarizes the cell
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Cardiac Electrophysiology (Cont.)
Cardiac Action Potential
 Depolarization of cardiac cells to a
threshold point results in activation of
voltage-sensitive ion channels in the
membrane
 Action potential in atrial and ventricular
cells has 5 characteristic phases
 Atrial action potentials are shorter due to
reduced phase 2
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Cardiac Electrophysiology (Cont.)
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Cardiac Electrophysiology (Cont.)
Rhythmicity of Myocardial Cells
 Automaticity refers to intermittent,
spontaneous generation of action
potentials
 The rate of rhythmic discharge is
determined by the relative influx of sodium
and calcium, versus the efflux of
potassium
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Cardiac Electrophysiology (Cont.)
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Cardiac Electrophysiology (Cont.)
Specialized Conduction System of the
Heart
 Normal excitation of the heart
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SA node
Atrial internodal pathways
AV node
Bundle of His
Ventricular bundle branches
Purkinje fibers
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Cardiac Electrophysiology (Cont.)
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Cardiac Electrophysiology (Cont.)
Autonomic Regulation of Rhythmicity
 Sympathetic innervation is widespread to
all areas of the heart
 Parasympathetic innervation via the vagus
is localized to the SA and AV nodal areas
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Right vagus nerve supplies SA node
Left vagus nerve supplies AV node
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Cardiac Electrophysiology (Cont.)
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Sympathetic activation increases heart
rate (chronotropic effect), speed of
conduction (dromotropic effect), and force
of contraction (inotropic effect) via binding
of NE to β receptors
Parasympathetic stimulation results in
reduction in heart rate, and speed of action
potential conduction via binding of
acetylcholine to muscarinic receptors
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Electrocardiography
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As action potentials spread throughout the
myocardium, electrical current is
transmitted to the body surface
A recording of these electrical currents is
called an electrocardiogram (ECG)
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P wave corresponds to atrial depolarization
QRS complex represents ventricular
depolarization
 T wave reflects ventricular repolarization
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Electrocardiography (Cont.)
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Electrocardiography (Cont.)
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Determinants of Cardiac Output
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Measure of the amount of blood pumped
out of the heart each minute
Normal resting cardiac output is 5-6
L/minute
Cardiac index is a measure of cardiac
output relative to body surface area
CO = stroke volume x heart rate
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Determinants of Cardiac Output
(Cont.)
Determinants of Heart Rate
 Influence by autonomic nervous system—
release of norepinephrine increases rate
 Baroreceptors detect fall in blood pressure
and transmit to CNS—parasympathetic
system inhibition and cardia sympathetic
nerve activation increase heart rate
 Atrial or ventricular overdistention
suppresses parasympathetic influence;
increases heart rate
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Determinants of Cardiac Output
(Cont.)
Determinants of Stroke Volume
 The volume of blood in the heart (preload)
 The contractile capabilities (contractility)
 Impedance opposing ejection of blood
from the ventricle (afterload)
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Determinants of Cardiac Output
(Cont.)
Volume of Blood in the Heart (Preload)
 Frank-Starling law: increased preload
stretches the sarcomere, resulting in more
forceful contraction
 There are limits to the improvement in SV
with increased diastolic filling
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Determinants of Cardiac Output
(Cont.)
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Determinants of Cardiac Output
(Cont.)
Contractile Capabilities of the Heart
(Contractility)
 The amount of contractile proteins in the
muscle cells
 Availability of ATP
 Availability of free calcium ions in the
cytoplasm
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Determinants of Cardiac Output
(Cont.)
Impedance to Ejection from the Ventricle
(Afterload)
 Aortic valve narrowing can significantly
increase afterload
 Increase in afterload increases pressure
work and requires greater tension
development within the walls of the
chamber (wall stress)
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Determinants of Cardiac Output
(Cont.)
Cardiac Workload
 Oxygen requirements of the heart are
determined by amount of energy (ATP)
exerted to perform its pumping function
 Increases in the 4 determinants of CO are
the major determinants of energy needs
 High afterload is most detrimental because
it increases cardiac workload without
increasing CO
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Endocrine Function of the Heart
Secretion of Natriuretic Peptides
 Atrial natriuretic peptide synthesized by
myocytes and released in response to
atrial stretch
 B-type natriuretic peptide produced and
released by ventricles in response to
chronic overdistention
 ANP and BNP cause enhanced excretion
of sodium and water by the kidneys
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Tests of Cardiac Function
Electrocardiography
 Provides graphic illustration of the
electrical currents generated by cardiac
cells
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Standard bipolar limb leads I, II, III
Unipolar augmented leads aVR, aVL, aVF
12-lead ECGs
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Tests of Cardiac Function (Cont.)
Magnetic Resonance Imaging and
Computed Tomography
 Useful for imaging cardiac structures
 May identify:
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Myocardial thickening
Pericardial sac disease
Valvular structures
Congenital malformations
Coronary plaque burden
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Tests of Cardiac Function (Cont.)
Echocardiography
 Uses reflected sound waves to provide an
image of cardiac structure and motion
within the chest
 Useful in diagnosis of heart enlargement,
valvular disorders, collections of fluid in the
pericardial space, cardiac tumors, and
abnormalities in left ventricular motion
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Tests of Cardiac Function (Cont.)
Nuclear Cardiography
 Radioactive substances injected into the
bloodstream are used to trace the patterns
of blood flow in the heart
 Assesses the adequacy of blood flow to
cardiac tissues
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Tests of Cardiac Function (Cont.)
Cardiac Catheterization/Coronary
Angiography
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A catheter is passed from the femoral or brachial
artery into the aorta
Used to directly measure pressures within cardiac
chambers; visualize chamber size, shape, and
movement; sample for blood oxygen content in
various heart regions; measure CO and EF; and
visualize and manage coronary artery
obstructions
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