Cardiovascular Physiology

Dr. David M. Kamau

Department of Medical Physiology
SOMED, JKUAT
Cardiovascular System Function
• Functional components of the cardiovascular
system:
– Heart
– Blood Vessels
– Blood
• General functions these provide
– Transportation
• Everything transported by the blood
– Regulation
• Of the cardiovascular system
– Intrinsic v extrinsic
– Protection
• Against blood loss
– Production/Synthesis: ANP
• The CVS of humans integrates three basic
functional parts, or organs:
va pump (the heart) that circulates
va liquid (the blood) through a set of
vcontainers/channels (the vessels).
• This integrated system is able to adapt to the
changing circumstances of normal life.
• Demand on the CVS fluctuates widely;
Øbetween sleep and wakefulness,
Øbetween rest and exercise,
Øwith acceleration/deceleration,
ØDuring changes in body position or
Øintrathoracic pressure,
Øduring digestion, and under
Øemotional stress or
ØThermal stress.
To meet these variable demands, the entire system requires sophisticated
and integrated regulation.
THE HEART

• Is a dual pump that drives the blood in two serial

circuits: the systemic and the pulmonary circulations.
• A remarkable pump, weighing ~300 g, drives the
human circulation.
• The heart really consists of two pumps, the left heart,
or main pump, and the right heart, or boost pump.
They operate in series and require a delicate
equalization of their outputs.
• The output of each pump is ~5 L/min, but this can
easily increase 5-fold during exercise.
• During a 75-year lifetime, the two ventricles combined
pump 400 million L of blood (enough to fill a lake 1 km
long, 40 m wide, and 10 m deep).
• The circulating fluid itself is a tissue, kept in a liquid
state by mechanisms that actively prevent cell-cell
adhesion and coagulation.
• With each heartbeat, the ventricles impart the energy
necessary to circulate the blood by generating the pressure
head/gradient that drives the flow of blood through the
vascular system.
• Anatomically, we can divide the vascular system of tubes
into two main circuits: the systemic and the pulmonary
circulations
• The vascular system could also be divided into a
high-pressure part (extending from the contracting
left ventricle to the systemic capillaries) and a low-
pressure part (extending from the systemic capillaries,
through the right hear t, across the pulmonar y
circulation and left atrium, and into the left ventricle in
its relaxed state).
• The vessels respond to changing metabolic
demands of the tissues they supply by directing
blood flow to (or away from) tissues as demands
change.
• The circulatory system is also self-repairing/self
expanding.
• Endothelial cells lining vessels mend the surfaces of existing
blood vessels and generate new vessels (angiogenesis).
• Some of the most important life-threatening human diseases
are caused by:
– failure of the heart as a pump (e.g., congestive heart
failure),
– failure of the blood as an effective liquid organ (e.g.,
thrombosis and embolism), or
– failure of the vasculature either as a competent
container (e.g., hemorrhage) or as an efficient
distribution system (e.g., atherosclerosis).
• Moreover, failure of the normal interactions among these
three organs can by itself elicit or aggravate many human
pathological processes.
Cardiovascular System Function
• To create the “pump” we have to examine
the Functional Anatomy
– Cardiac muscle
– Chambers
– Valves
– Intrinsic Conduction System
Functional Anatomy of the Heart
Cardiac Muscle

• Characteristics
– Striated
– Short branched cells
– Uninucleate
– Intercalated discs
– T-tubules larger and
over z-discs
Functional Anatomy of the Heart
Chambers

• 4 chambers
– 2 Atria
– 2 Ventricles
• 2 systems
– Pulmonary
– Systemic
Functional Anatomy of the Heart
Valves

• Function is to prevent backflow

– Atrioventricular Valves
• Prevent backflow to the atria
• Prolapse is prevented by the chordae
tendinae
– Tensioned by the papillary muscles
– Semilunar Valves
• Prevent backflow into ventricles
Intrinsic Conduction System

• Consists of
“pacemaker” cells
and conduction
pathways
– Coordinate the
contraction of the
atria and ventricles
Lecture Outline
• Cardiovascular System Function
• Functional Anatomy of the Heart
• Myocardial Physiology
– Autorhythmic Cells (Pacemaker cells)
– Contractile cells
• Cardiac Cycle
• Cardiac Output Controls & Blood Pressure
Myocardial Physiology
Autorhythmic Cells (Pacemaker Cells)

• Characteristics of
Pacemaker Cells
– Smaller than conduction myofibers
contractile cells
– Don’t contain many normal contractile
myocardial cell

myofibrils
– No organized
sarcomere structure
• do not contribute to SA node cell
the contractile force AV node cells
of the heart
Myocardial Physiology
Autorhythmic Cells (Pacemaker Cells)

• Characteristics of Pacemaker Cells

– Unstable membrane potential
• “bottoms out” at -60mV
• “drifts upward” to -40mV, forming a pacemaker potential
– Myogenic
• The upward “drift” allows the membrane to reach threshold potential (-
40mV) by itself
• This is due to
1. Slow leakage of K+ out & faster leakage Na+ in
» Causes slow depolarization
» Occurs through If channels (f=funny) that open at negative
membrane potentials and start closing as membrane approaches
threshold potential
2. Ca2+ channels open as membrane approaches threshold
» At threshold additional Ca2+ ion channels open causing more rapid
depolarization
» These deactivate shortly after and
3. Slow K+ channels open as membrane depolarizes causing an
efflux of K+ and a repolarization of membrane
Myocardial Physiology
Autorhythmic Cells (Pacemaker Cells)

• Characteristics of Pacemaker Cells

 Myocardial Physiology
Autorhythmic Cells (Pacemaker Cells)

• Altering Activity of Pacemaker Cells

– Sympathetic activity
• NE and E increase If channel activity
– Binds to β1 adrenergic receptors which activate cAMP and
increase If channel open time: Shorter time to threshold
– Causes a more rapid pacemaker potential and faster rate of
action potentials

Sympathetic Activity Summary:

increased chronotropic effects
heart rate
increased dromotropic effects
conduction of APs
increased inotropic effects
contractility
 Myocardial Physiology
Autorhythmic Cells (Pacemaker Cells)
• Altering Activity of Pacemaker Cells
– Parasympathetic activity
• ACh binds to muscarinic receptors
– Increases K+ permeability and decreases Ca2+ permeability
= hyperpolarizing the membrane
» Longer time to threshold = slower rate of action
potentials

Parasympathetic Activity
Summary:
decreased chronotropic effects
heart rate
decreased dromotropic effects
 conduction of APs
decreased inotropic effects
 contractility
Myocardial Physiology
Contractile Cells
• Special aspects
– Intercalated discs
• Highly convoluted and interdigitated
junctions
– Join adjacent cells with
» Desmosomes & fascia adherens
– Allow for syncytial activity
» With gap junctions
– More mitochondria than skeletal muscle
– Less sarcoplasmic reticulum
• Ca2+ also influxes from ECF reducing
storage need
– Larger t-tubules
• Internally branching
– Myocardial contractions are graded!
Myocardial Physiology
Contractile Cells
• Special aspects
– The action potential of a contractile cell
• Ca2+ plays a major role again
• Action potential is longer in duration than a “normal” action
potential due to Ca2+ entry
• Phases
4 – resting membrane potential @ -90mV
0 – depolarization
» Due to gap junctions or conduction fiber action
» Voltage gated Na+ channels open… close at 20mV
1 – temporary repolarization
» Open K+ channels allow some K+ to leave the cell
2 – plateau phase
» Voltage gated Ca2+ channels are fully open (started during initial
depolarization)
3 – repolarization
» Ca2+ channels close and K+ permeability increases as slower
activated K+ channels open, causing a quick repolarization
– What is the significance of the plateau phase?
• A refractory period follows repolarization, during which
concentration of K + and Na + are actively restored to
t h e i r a p p r o p r i a t e s i d e s o f t h e s a r c o l e m m a by
Na +/K + pumps.
• The muscle cell cannot contract again until Na  +  and
K  +  are restored to their resting potential states.
(Absolute via relative refractoriness)
• The refractory period of cardiac muscle is dramatically
longer than that of skeletal muscle.
• This prevents tetanus from occurring and ensures
that each contraction is followed by enough time to
allow the heart chamber to refill with blood
before the next contraction.
Myocardial Physiology
Contractile Cells

• Skeletal Action Potential vs Contractile

Myocardial Action Potential
Myocardial Physiology
Contractile Cells

• Plateau phase prevents summation due to the

elongated refractory period
• No summation capacity = no tetanus
– Which would be fatal
Summary of Action Potentials
Skeletal Muscle vs Cardiac Muscle
Key Points in Cardiac Muscle
Contraction
• Cardiac muscle fibers contract via excitation-contraction
coupling, using a mechanism unique to cardiac muscle
called calcium -induced calcium release (CICR).
• Excitation-contraction coupling describes the process
of converting an electrical stimulus (action potential)
into a mechanical response (muscle contraction).
• C a l c i u m - i n d u c e d c a l c i u m r e l e a s e i nvo l ve s t h e
conduction of calcium ions into the cardiomyocyte,
triggering further release of ions into the cytoplasm.
Events of contraction
• Cardiomyocytes are capable of coordinated contraction,
controlled through the gap junctions of intercalated discs. The
gap junctions spread action potentials to support the
synchronized contraction of the myocardium.
• Pacemaker cells in the SA and AV nodes initiate an action
potential which is conducted around the heart via gap
junctions of the intercalated discs.
• Membrane depolarisation opens voltage-operated calcium
channels (VOCCs) in the T-tubule system and calcium is
released.
• Calcium binds to RyR on the sarcoplasmic reticulum. This
induces conformational changes in a Ca2+ channel which is
closely associated with RyR.
• RyR is activated and opens to release Ca2+ from the SR
stores. This is known as the “calcium spark”.
• Calcium in the cytoplasm then binds to cardiac
troponin-C, which moves the troponin complex away
from the actin binding site. This frees the actin to be
bound by myosin and initiates contraction.
• The myosin head binds to ATP and pulls the actin
filaments toward the center o f th e sa rco m ere,
contracting the muscle.
 Myocardial Physiology
Contractile Cells
• Initiation
– Action potential via pacemaker cells to
conduction fibers
• Excitation-Contraction Coupling
1. Starts with CICR (Ca2+ induced Ca2+ release)
• AP spreads along sarcolemma
• T-tubules contain voltage gated L-type Ca2+
channels which open upon depolarization
• Ca2+ entrance into myocardial cell and opens
RyR (ryanodine receptors) Ca2+ release
channels
• Release of Ca2+ from SR causes a Ca2+
“spark”
• Multiple sparks form a Ca2+ signal

Spark Gif
Myocardial Physiology
Contractile Cells
• Excitation-Contraction Coupling cont…
2. Ca2+ signal (Ca2+ from SR and ECF) binds to troponin to initiate myosin
head attachment to actin
• Contraction
– Same as skeletal muscle, but…
– Strength of contraction varies
• Sarcomeres are not “all or none” as it is in skeletal muscle
– The response is graded!
» Low levels of cytosolic Ca2+ will not activate as many
myosin/actin interactions and the opposite is true
• Length tension relationships exist
– Strongest contraction generated
when stretched between 80 &
100% of maximum (physiological
range)
– What causes stretching?
» The filling of chambers
with blood
Myocardial Physiology
Contractile Cells

• Relaxation
– Ca2+ is transported back into
the SR and
– Ca2+ is transported out of the
cell by a facilitated Na+/Ca2+
exchanger (NCX)
– As ICF Ca2+ levels drop,
interactions between
myosin/actin are stopped
– Sarcomere lengthens
Lecture Outline
• Cardiovascular System Function
• Functional Anatomy of the Heart
• Myocardial Physiology
– Autorhythmic Cells (Pacemaker cells)
– Contractile cells
• Cardiac Cycle
• Cardiac Output Controls & Blood Pressure
Cardiac Cycle
Coordinating the activity

• Cardiac cycle is the sequence of events as

blood enters the atria, leaves the ventricles and
then starts over
• Synchronizing this is the Intrinsic Electrical
Conduction System
• Influencing the rate (chronotropy -time &
dromotropy-AP conduction) is done by the
sympathetic and parasympathetic divisions of
the ANS
Cardiac Cycle
Coordinating the activity

• Electrical Conduction Pathway

– Initiated by the Sino-Atrial node (SA node) which is myogenic at 70-80
action potentials/minute
– Depolarization is spread through the atria via gap junctions and
internodal pathways to the Atrio-Ventricular node (AV node)
• The fibrous connective tissue matrix of the heart prevents further spread of
APs to the ventricles
• A slight delay at the AV node occurs
– Due to slower formation of action potentials
– Allows further emptying of the atria
– Action potentials travel down the Atrioventricular bundle (Bundle of His)
which splits into left and right atrioventricular bundles (bundle branches)
and then into the conduction myofibers (Purkinje cells)
• Purkinje cells are larger in diameter & conduct impulse very rapidly
– Causes the cells at the apex to contract nearly simultaneously
» Good for ventricular ejection
 Cardiac Cycle
Coordinating the activity

• The Electrical
Conduction
Pathway
Cardiac Cycle
Coordinating the activity

• The electrical system gives rise to electrical

changes (depolarization/repolarization) that is
transmitted through isotonic body fluids and is
recordable
– The ECG!
• A recording of electrical activity
• Can be mapped/matched/ to the cardiac cycle
Principles of Pressure and Flow

Two main variables govern fluid movement:

1. Pressure - causes a fluid to flow (fluid dynamics)
– pressure gradient = pressure difference between two points
– measured in mm Hg with a manometer or
sphygmomanometer
2. Resistance - opposes fluid flow
– great vessels have positive blood pressure
– ventricular pressure must rise above this resistance for
blood to flow into great vessels
Pressure Gradients and Flow
• Fluid flows only if it is subjected to more pressure at one point
than another which creates a pressure gradient
• – fluid flows down its pressure gradient from high pressure to
low pressure

• Events that occur on left side of heart

– when ventricle relaxes and expands (pre-load in ventricle) //
its internal pressure falls
– if bicuspid valve is open, blood flows into left ventricle
– when ventricle contracts, internal pressure rises
– AV valves close, pressure in ventricle rises, the aortic valve is
pushed open (overcoming after-load) and blood flows into
aorta from left ventricle
• Opening and closing of valves are governed by
these pressure changes
– AV valves limp when ventricles are relaxed
– semilunar valves are under pressure from blood
in pulmonary trunk and aorta at time when
ventricles are relaxed (after load)
Operation of Heart Valves
Heart Sounds
Auscultation - listening to sounds made by the body
• First heart sound (S1), louder and longer “lubb”,
occurs with closure of AV valves, turbulence in •
the bloodstream, and movements of the heart
wall
• Second heart sound (S2), softer and sharper
“dupp”occurs with closure of semilunar valves,
turbulence in the bloodstream, and movements of
the heart wall
• S3 - rarely heard in people over 30
Cardiac Cycle
• Mechanical function of the heart can be
described by the pressure, volume, and
flow changes that occur within it during
one cardiac cycle.
• A cardiac cycle is defined as one complete
sequence of contraction and relaxation.
• The normal mechanical events of a cycle
of the left heart pump are correlated in the
figure in the next slide.
• Cardiac cycle phases:
A) diastole;
B) systole that is divided into three periods;
C) isovolumetric contraction;
D) ejection, and
E) isovolumetric relaxation.
Phases of the Cardiac Cycle
• Systole = period of contraction
• Diastole = period of relaxation
• Cardiac Cycle is alternating periods of systole and
diastole
• Phases of the cardiac cycle
1. Rest
• Both atria and ventricles in diastole
• Blood is filling both atria and ventricles due to low pressure
conditions
2. Atrial Systole
• Completes ventricular filling
3. Isovolumetric Ventricular Contraction
• Increased pressure in the ventricles causes the AV valves to
close… why?
– Creates the first heart sound (lubb)
• Atria go back to diastole
• No blood flow as semilunar valves are closed as well
Cardiac Cycle
Phases
• Phases of the cardiac cycle
4. Ventricular Ejection
• Intraventricular pressure overcomes aortic pressure
– Semilunar valves open
– Blood is ejected
5. Isovolumetric Ventricular Relaxation
• Intraventricular pressure drops below aortic pressure
– Semilunar valves close = second heart sound (dup)
• Pressure still hasn’t dropped enough to open AV valves so
volume remains same (isovolumetric)
Back to Atrial & Ventricular Diastole
 VENTRICULAR DIASTOLE:
LEFT PUMP
• The diastolic phase of the cardiac cycle begins with the
opening of the atrioventricular (AV) valves.
• The mitral valve opens when left ventricular pressure
decreases below left atrial pressure and the period of
ventricle filling begins
• Blood that had previously accumulated in the atrium
behind the closed mitral valve empties rapidly into the
ventricle and this causes an initial decrease in atrial
pressure.
• Later, the pressures in both chambers slowly increase
together as the atrium and ventricle continue passively
filling with blood returning to the heart through the veins.
• Atrial contraction is initiated near the end of ventricular
diastole by the depolarization of the atrial muscle
cells, which causes the P wave of the
electrocardiogram.
• As the atrial muscle cells develop tension and shorten,
atrial pressure rises and an additional amount of blood
is forced into the ventricle (atrial primer pump action).
VENTRICULAR SYSTOLE
• Begins when the action potential breaks through the AV
node and sweeps over the ventricular muscle resulting
in the QRS complex of the electrocardiogram.
• Contraction of the ventricular muscle cells causes
intraventricular pressure to increase above that in the
atrium, causing abrupt closure of the AV valve.
• Pressure in the left ventricle continues to increase
sharply as the ventricular contraction intensifies. When
the left ventricular pressure exceeds that in the
aorta, the aortic valve opens.
• The period of time between mitral valve closure and
aortic valve opening is referred to as the
isovolumetric contraction phase because, during this
interval, the ventricle is a closed chamber with a fixed
volume.
• Ventricular ejection begins with the opening of the aortic
valve.
• In early ejection, blood enters the aorta rapidly and
causes the pressure there to rise.
• Pressure builds simultaneously in both the ventricle and
the aorta as the ventricular muscle cells continue to
contract in early systole.
• This interval is often called the rapid ejection period.
• Left ventricular and aortic pressures ultimately reach a
maximum called peak systolic pressure. At this point,
the strength of ventricular muscle contraction begins to
wane.
• Muscle shortening and ejection continue, but at a
reduced rate.
• Aortic pressure begins to decrease because blood is leaving the
aorta and large arteries faster than blood is entering from the left
ventricle.
• Throughout ejection, there are very small pressure differences
between the left ventricle and the aorta because the aortic valve
orifice is so large that it presents very little resistance to flow.
• Eventually, the strength of the ventricular contraction diminishes
to the point where intraventricular pressure decreases below
aortic pressure.
• This causes abrupt closure of the aortic valve. A dip, called the
incisura or dicrotic notch, appears in the aortic pressure trace
because a small volume of aortic blood must flow backward to fill the aortic
valve leaflets as they close
• After aortic valve closure, intraventricular pressure decreases
rapidly as the ventricular muscle relaxes.
• For a brief interval, called the isovolumetric relaxation phase,
the mitral valve is also closed. Ultimately, intraventricular
pressure decreases below atrial pressure, the AV valve opens,
and a new cardiac cycle begins.
• NB. Atrial pressure progressively increases during ventricular
systole because blood continues to return to the heart and fill
the atrium.
• The increased atrial pressure at the end of systole promotes rapid
ventricular filling once the AV valve opens to begin the next heart
cycle.
• The ventricle reaches its minimum at the time of aortic
valve closure (end-systolic volume-EDV).
• The amount of blood ejected from the ventricle during a single
beat, the stroke volume, is equal to ventricular EDV minus
ventricular ESV.
• During the early, most rapid phase of systolic ejection, the
aorta distends because more blood is being put into it from
the left heart than is leaving it to the systemic organs.
• That distension is caused by the increasing pressure within the
aorta.
• During the later, weakening phase of cardiac ejection, the
opposite is true (decreasing pressure).
• The overall result is that the aortic pressure reaches a maximum
value (systolic pressure) near the middle of ventricular systole.
• During diastole, the arterial pressure is maintained by the elastic
recoil of walls of the aorta and other large arteries.
• Nonetheless, aortic pressure gradually decreases during diastole as
the aorta supplies blood to the systemic vascular beds.
• The lowest aortic pressure, reached at the end of diastole, is called
diastolic pressure.
• The difference between diastolic and peak systolic pressure in the
aorta is called the arterial pulse pressure.
• Typical values for systolic and diastolic pressures in the aorta are
120 and 80 mm Hg, respectively, with a pulse pressure of 40 mm
Hg.
• At a normal resting heart rate of about 70 beats/min, the heart
spends approximately two thirds of the cardiac cycle in diastole
and one third in systole.
• When increases in heart rate occur, both diastolic and systolic
intervals become shorter.
• Action potential durations are shortened and conduction
velocity is increased.
• Contraction and relaxation rates are also enhanced.
• This shortening of the systolic interval tends to blunt the
potential adverse effects of increases in heart rate on diastolic
filling time.
RIGHT PUMP
• Because the entire heart is served by a single electrical excitation
system, similar mechanical events occur almost simultaneously
in both the left heart and the right heart.
• Both ventricles have synchronous systolic and diastolic periods and the
valves of the right and left heart normally open and close nearly
in unison.
• Because the two sides of the heart are arranged in series in the
circulation, they must pump the same amount of blood and therefore
must have the same cardiac output.
• The major difference between the right and left pumps is in the
magnitude of the peak systolic pressure.
• The pressures developed by the right heart are considerably
lower than those for the left heart because the pulmonary vessels
provide considerably less resistance to blood flow than that offered
collectively by those of the systemic organs.
• Therefore, less arterial pressure is required to drive the cardiac
output through the lungs than through the systemic organs.
• Typical pulmonary artery systolic and diastolic pressures are 25
and 8 mm Hg, respectively.
• The pressure pulsations that occur in the right atrium are
transmitted in retrograde fashion to the large veins near the
heart.
• These pulsations can be visualized in the neck over the jugular
veins in a recumbent individual.
Cardiac cycle—right heart
• They are collectively called the jugular venous pulse, and can
provide clinically useful information about the heart.
• Right atrial contraction produces the first pressure peak, called
the a wave.
• The c wave, which follows shortly thereafter, coincides with the
onset of ventricular systole and is caused by an initial bulging
of the tricuspid valve into the right atrium.
• Right atrial pressure decreases after the c wave because of atrial
relaxation and a downward displacement of the tricuspid valve
during ventricular emptying.
• Right atrial pressure then begins to increase toward a third peak,
the v wave , as the central veins and right atrium fill behind a
closed tricuspid valve with blood returning to the heart from the
peripheral organs.
• With the opening of the tricuspid valve at the conclusion of
ventricular systole, right atrial pressure again decreases as
blood moves into the relaxed right ventricle.
• Shortly afterward, right atrial pressure begins to increase once
more toward the next a wave as returning blood fills the central
veins, the right atrium, and right ventricle together during
diastole.
HEART SOUNDS
• Heart sounds, which occur in the cardiac cycle, are normally
heard by auscultation with a stethoscope placed on the chest.
• The first heart sound, S1, occurs at the beginning of systole
because of the abrupt closure of the AV valves, which
produces vibrations of the cardiac structures and the blood in
the ventricular chambers.
• S1 can be heard most clearly by placing the stethoscope over the
apex of the heart. It occurs immediately after the QRS complex
of the electrocardiogram.
• The second heart sound, S2 , arises from the closure of the
aortic and pulmonic valves at the beginning of isovolumetric
relaxation. This sound is heard at about the time of the T wave
in the electrocardiogram.
• The pulmonic valve usually closes slightly after the aortic valve.
• Because this discrepancy is enhanced during the inspiratory
phase of the respiratory cycle, inspiration causes what is
referred to as the physiological splitting of the second heart
sound.
• The discrepancy in valve closure during inspiration may range
from 30 to 60 milliseconds.
• One of the factors that leads to prolonged ejection of the right
ventricle during inspiration is that the decreased intrathoracic
pressure that accompanies inspiration transiently enhances
venous return and diastolic filling of the right heart. This extra
filling volume will be ejected but a little extra time is required.
• The third and fourth heart sounds, when present, along with S1
and S2 , produce what are called gallop rhythms (resembling
the sound of a galloping horse).
• When present, the S3 occurs shortly after S2 during the period
of rapid passive ventricular filling and, in combination with
heart sounds S1 and S2, produces what is called ventricular
gallop rhythm.
• Although S3 may sometimes be detected in normal children, it
is heard more commonly in patients with left ventricular
failure.
• The S4, which occasionally is heard shortly before S1, is
associated with atrial contraction and rapid active filling of the
ventricle.
• Thus, the combination of S1 , S2 , and S4 sounds produces an
atrial gallop rhythm.
• The presence of S4 often indicates an increased ventricular
diastolic stiffness, which can occur with several cardiac disease
states.
CARDIAC CYCLE PRESSURE–VOLUME & LENGTH–TENSION
RELATIONSHIPS

• Intraventricular pressure and

volume are intimately linked
to the tension and length of
the cardiac muscle cells in the
ventricular wall.
• Figure A & B show the
correspondence between a
ventricular pressure–volume
loop and a cardiac muscle
length–tension loop during
one cardiac cycle respectively
• Cardiac muscle length–tension behavior is the underlying basis for ventricular
function.
• Each major phase of the ventricular cardiac cycle has a
corresponding phase of cardiac muscle length and tension
change.
• During diastolic ventricular filling, for example, the progressive
increase in ventricular pressure stretches the resting cardiac
muscle to greater lengths along its resting length-tension curve
and causes a corresponding increase in muscle tension.
• End-diastolic ventricular pressure is referred to as ventricular
preload because it sets the end-diastolic ventricular volume and
therefore the resting length of the cardiac muscle fibers at the
end of diastole.
• At the onset of systole, the ventricular muscle cells develop
tension isometrically (during the isovolumetric contraction phase)
and intraventricular pressure increases accordingly.
• After the intraventricular pressure increases sufficiently to open
the outlet valve, ventricular ejection begins as a consequence of
ventricular muscle shortening.
• Systemic arterial pressure is often referred to as the ventricular
afterload because it determines the tension that must be
developed by cardiac muscle fibers before they can shorten (to
counter resistance).
• NB: Other factors influence the actual wall tension required to
eject blood from the ventricle eg end-diastolic volume, velocity
of contraction and viscosity of the blood.
• During cardiac ejection, cardiac muscle is simultaneously
generating active tension and shortening (i.e., an afterloaded
isotonic contraction).
• The stroke volume is determined by how far ventricular muscle
cells are able to shorten during contraction.
• This depends on the length–tension relationship of the cardiac muscle cells
and the load against which they are shortening (preload and afterload).
• Once shortening ceases and the output valve closes, the cardiac
muscle cells relax isometrically.
• Ventricular wall tension and intraventricular pressure decrease
in unison during isovolumetric relaxation.
CARDIAC OUTPUT & ITS DETERMINANTS
• Cardiac output (CO) is the volume (liters) of blood pumped by
each of the ventricles per minute.
• It is an extremely important cardiovascular variable that is continuously
adjusted so that the cardiovascular system operates to meet the
body’s moment-to-moment circulatory needs.
• From rest to strenuous exercise, for example, the cardiac output
of an average person will increase from approximately 5.5 to
about 15 L/min.
• The extra cardiac output provides the exercising skeletal muscles
with the additional nutritional supply needed to sustain an
increased metabolic rate.
• To understand the cardiovascular system’s response to all other
physiological or pathological demands placed on it, we must
understand what deter mines, and therefore controls,
cardiac output.
• Cardiac output is the product of heart rate and stroke volume
(CO = HR × SV).
• Therefore, all changes in cardiac output must be produced by
changes in heart rate and/or stroke volume.
• Fa c t o r s i n f l u e n c i n g h e a r t r a t e d o s o by a l t e r i n g t h e
characteristics of the diastolic depolarization of the pacemaker
cells.
• Recall that variations in activity of the sympathetic and parasympathetic
nerves leading to cells of the sinoatrial (SA) node constitute the most
important regulators of heart rate. (How?)
• These neural inputs have immediate effects (within one beat)
and therefore can cause very rapid adjustments in cardiac
output.
INFLUENCES ON STROKE VOLUME
EFFECT OF CHANGES IN VENTRICULAR PRELOAD:
STARLING’S LAW OF THE HEART
• The volume of blood that the heart ejects with each beat can
vary significantly.
• One of the most important factors responsible for these
variations in stroke volume is the extent of cardiac filling during
diastole.
• This concept is known as Starling’s law of the heart. This law
states that, with other factors equal, stroke volume increases as cardiac filling
increases.
• This phenomenon is based on the intrinsic mechanical
properties of myocardial muscle.
• Increasing muscle preload increases the extent of shortening
during a subsequent contraction with a fixed total load. An
increased preload is accompanied by increased initial muscle fiber length.
• Increases in ventricular preload increase both end-diastolic
volume and stroke volume almost equally.
• One for m of hear t failure called diastolic failure is
characterized by an abnormally stiff ventricle and a disturbance
in the relationship between cardiac filling pressure and end-
diastolic volume. In this situation, diastolic filling is limited,
stroke volume is reduced, cardiac output is inadequate, and
function of the cardiovascular system is compromised.
EFFECT OF CHANGES IN VENTRICULAR AFTERLOAD

• Increased afterload, at constant preload, has a negative effect

on cardiac muscle shortening because muscle cannot shorten
beyond the length at which its peak isometric tension-
generating potential equals the total load upon it.
• Thus, shortening must stop at a greater muscle length when
afterload is increased.
• Normally, mean ventricular afterload is nearly constant,
because mean arterial pressure (resistance) is held within tight
limits by cardiovascular control mechanisms.
• In many pathological situations such as hypertension (high
blood pressure) and aortic valve obstruction, ventricular
function is adversely influenced by abnormally high ventricular
afterload (resistance).
• When this occurs, stroke volume may be decreased because end-
systolic volume is increased.
EFFECT OF CHANGES IN CARDIAC MUSCLE CONTRACTILITY
• Activation of the sympathetic nervous system results in release of
NE from cardiac sympathetic ner ves, which increases
contractility of the individual cardiac muscle cells.
• T h i s r e s u l t s i n a n u p wa r d s h i f t o f t h e p e a k i s o m e t r i c
length–tension curve.
• As shown in figure A overleaf, such a shift results in an increase in
shortening of a muscle contracting with constant preload and total
load.
• Thus, as shown in figure B, the NE released by sympathetic nerve
stimulation increases ventricular stroke volume by decreasing the end-systolic
volume without directly influencing the end-diastolic volume.
• In addition to these changes in the extent of myocyte shortening,
an increase in contractility will also cause an increase in the rates of myocyte
tension development and of shortening. This will result in an increase in
the rate of isovolumetric pressure development (dP/dt) and the
rate of ejection during systole.
Effect of norepinephrine (NE) on afterloaded contractions on cardiac muscle (A) and on
ventricular stroke volume (B).
• In addition to these changes in the extent of myocyte
shortening, an increase in contractility also causes an increase in
the rates of myocyte tension development and of shortening.
• This results in an increase in the rate of isovolumetric pressure
development (dP/dt) and the rate of ejection during systole.
• Systolic failure is characterized by a severely depressed ability of the
cardiac muscle cells to produce tension and shorten.
• In this situation, systolic contraction is limited, stroke volume is
reduced, cardiac output is inadequate, and function of the
cardiovascular system is compromised.
SUMMARY OF DETERMINANTS OF CARDIAC OUTPUT

• Heart rate is controlled by chronotropic influences on the

spontaneous electrical activity of SA nodal cells.
• Cardiac parasympathetic nerves have a negative chronotropic effect, and
sympathetic nerves have a positive chronotropic effect on the SA node
• Stroke volume is controlled by influences on the contractile
performance of ventricular cardiac muscle—in particular its degree of
shortening in the afterloaded situation.
• The three distinct influences on stroke volume are contractility,
preload, and afterload.
• Increased cardiac sympathetic nerve activity increases stroke
volume by increasing the contractility of cardiac muscle (a
positive inotropic effect)
• Increased arterial pressure decreases stroke volume by
increasing the afterload on cardiac muscle fibers.
• Increased ventricular filling pressure increases end-
diastolic volume, which tends to increase stroke volume
through Starling’s law of the heart.
• It is important to note that both heart rate and stroke volume
are subject to more than one influence. Thus, the fact that
increased contractility tends to increase stroke volume should
not be taken to mean that, in the intact cardiovascular system,
stroke volume is always high when contractility is high.
• For example, following blood loss thru hemorrhage, stroke
volume may be low in spite of a high level of sympathetic nerve
activity and increased contractility.
• Because arterial pressure is normal or low following hemorrhage,
the low stroke volume associated with severe blood loss must be
(and is) the result of low cardiac filling pressure.
Influences on Cardiac Output
 SUMMARY OF SYMPATHETIC NEURAL INFLUENCES ON
CARDIAC FUNCTION
• Effects of the sympathetic NS on the electrical and mechanical
properties of cardiac muscle, and thus on cardiac pumping
ability, are initiated by the interaction of NE with β1-adrenergic
receptors on cardiac muscle cells.
• This results in a cascade of events involving the Gs activation
of adenylate cyclase, formation of cAMP, and activation of
PKA with subsequent phosphorylation of many molecules that
play key regulatory roles in intracellular processes.
• T hese cellular events combine to evoke the following
improvements in pumping capabilities of the heart:
1. an increase in heart rate (positive chronotropic effect) by activating the
inward-going sodium If current in SA nodal cells.
2. a decrease in cardiac action potential duration by early activation of the
delayed iK current in cardiac myocytes, which minimizes the detrimental
effect of high heart rates on diastolic filling time.
 3. an increase in the rate of action potential conduction,
particularly evident in the AV node (positive dromotropic
effect), by altering conductivity of gap junctions;
4. an increase in cardiac contractility (positive inotropic effect)
by activating the iCa2+ current and increasing Ca2+ release from
the sarcoplasmic reticulum, which increases the contractile
ability of cardiac muscle at any given preload; and
5. an increase in rate of cardiac relaxation (positive lusitropic
effect) by increasing Ca2+ uptake by the sarcoplasmic
reticulum, which also helps minimize the detrimental effect of
high heart rates on diastolic filling time.
• Most catecholamine influences on the heart are a result of
increases in sympathetic neural activity.
• Although circulatng catecholamines of adrenal origin can
potentially evoke similar effects, their concentrations are
normally so low that their contributions are negligible.
• Specific drugs called β1-adrenergic receptor
blockers (antagonists) block all the effects of
catecholamines from whatever source on cardiac
muscle.
• These drugs may be useful in the treatment of
cor onar y ar ter y disease to thwar t increased
metabolic demands placed on the heart by
activity of sympathetic nerves.
MYOCARDIAL OXYGEN CONSUMPTION
• In many pathological situations, such as severe coronary
atherosclerosis, oxygen requirements of myocardial tissue exceed
the capacity of coronary blood flow to deliver oxygen to the
heart muscle.
• This mismatch can result in severe chest pain or discomfort called
angina pectoris.
• It is important to understand what factors determine energy costs, and
therefore the myocardial oxygen consumption, because reduction of
oxygen demand may be of significant clinical benefit to
the patient.
• Because the heart derives its energy almost entirely from
aerobic metabolism, myocardial oxygen consumption is
directly related to myocardial ATP use.
• The basal metabolism of the heart tissue (energy consumed in
cellular processes other than contraction such as energy-dependent ion
pumping) normally accounts for about 25% of myocardial ATP
use and therefore myocardial oxygen consumption in a resting
individual.
• The processes associated with muscle contraction account for about
75% of myocardial energy use.
• Primarily, this reflects ATP splitting associated with cross-bridge
cycling during the isovolumetric contraction and ejection phases of the
cardiac cycle (phases when ATP is majorly utilized-work done)
• Some ATP is also used for Ca2+ sequestration at the
termination of each contraction
• The energy expended during the isovolumetric contraction phase
of the cardiac cycle accounts for the largest portion (~50%) of
total myocardial oxygen consumption despite the fact that the
heart does no external work during this period.
• The energy needed for isovolumetric contraction is mainly
dependent on the intraventricular pressure that must develop during this
time, that is, on the cardiac afterload (to overcome systemic arterial
resistance).
• Cardiac afterload therefore is a major determinant of
myocardial oxygen consumption.
• Reductions in cardiac afterload can produce clinically significant
reductions in myocardial energy requirements and therefore
myocardial oxygen consumption (thus check against O2 mismatch).
• Energy utilization during isovolumetric contraction is actually more
directly related to isometric wall tension development than to intraventricular
pressure development.
• Wall tension is related to intraventricular pressure and to
ventricular radius through the law of Laplace (T = P × r).
• Consequently, reductions in cardiac preload (i.e., end-diastolic volume, radius)
tend to reduce the energy required for isovolumetric contraction (less costly
energy-wise).
• It is during the ejection phase of the cardiac cycle that the heart
actually performs external work and the energy the heart expends
during ejection depends on how much external work it is doing. In a
fluid system, work (force × distance) is equal to pressure
(force/distance2 ) × volume (distance3).
• The external physical work done by the left ventricle in one beat,
that is, the stroke work, is equal to the area enclosed by the left
ventricular pressure–volume loop.
• Stroke work is increased either by an increase in stroke volume
(increased “volume” work) or by an increase in afterload
(increased “pressure” work).
• In terms of ATP utilization and oxygen consumption, increases
in the pressure work of the heart are more costly than increases in volume
work.
• Therefore, reductions in afterload are especially helpful in
reducing the myocardial oxygen requirements for doing external
work.
• Changes in myocardial contractility has important
consequences on the oxygen requirement for basal metabolism,
isovolumic wall tension generation, and external work.
• Heart muscle cells use more energy in rapidly developing a given tension
and shortening by a given amount than in doing the same thing more slowly.
• Also, with increased contractility, more energy is expended in
active Ca2+ transport.
• The net result of these influences is often referred to as the
“energy wasting” effect of increased contractility.
• Heart rate is one of the most important deter minants of
myocardial oxygen consumption because the energy costs per
minute must equal the energy cost per beat times the number of
beats per minute.
• In general, it is more efficient (i.e., less oxygen is required) to
achieve a given cardiac output with low heart rate and high stroke
volume than with high heart rate and low stroke volume.
• This appears to be related to the relatively high energy cost of the
isovolumetric pressure development phase of the cardiac cycle. The
less pressure (wall tension) developed and the less often pressure development
occurs, the less energy used.
SELF/GROUP TEST
1. You are listening to your patient’s heart sounds and have identified the systolic
and diastolic intervals. Four of the conditions listed below exist during the same
phase of the cardiac cycle and one does not. Which one is the odd one?
A) The mitral valve is open.
B) The ST segment of the ECG is occurring.
C) The “v” wave of the jugular venous pulse has just occurred.
D) Ventricular volume is rapidly increasing.
E) Aortic pressure is decreasing
2. Your patient has coronary artery disease with significant occlusion of the left
anterior descending coronary artery. Although all of the following will increase
cardiac work, which of the following will be most likely to result in an attack of
angina pectoris?
A) high heart rates
B) elevated arterial blood pressures
C) increased end-diastolic volume
D) low arterial blood pressure
E) increased cardiac contractility
3. A drug is given that blocks cardiac β1-adrenergic receptors. What will be
the direct consequences of this drug on the heart?
A) Heart rate will increase.
B) The PR interval of the ECG will shorten.
C) Metabolic demands will be reduced.
D) Coronary flow rate will increase.
E) Cardiac contractility will increase.
4. A cannula is placed in the pulmonary artery (PA) of a normal healthy
individual and pressure is reported to be 25/8 mm Hg. Which of the
following can be surmised from these values?
A) RV systolic pressure is 25 mm Hg; PA diastolic pressure is 8 mm Hg.
B) RV systolic pressure is 25 mm Hg; left atrial pressure is 8 mm Hg.
C) RV systolic pressure must be significantly higher than 25 mm Hg.
D) RV diastolic pressure must be significantly higher than 8 mm Hg.
E) Pulmonary capillary pressure is 8 mm Hg
5. An individual has an autonomic nervous system dysfunction in
which cardiac parasympathetic nerve activity abruptly increases
while cardiac sympathetic activity decreases. Which of the following
situations is most likely to occur?
A) LV end-diastolic volume will increase.
B) Cardiac output will increase.
C) Heart rate will increase.
D) LV end-systolic volume will decrease.
E) Coronary blood flow will increase.
Cardiac Cycle
Phases
Cardiac Cycle
Blood Volumes & Pressure
Cardiac Cycle
Putting it all together!