Cardiovascular Physiology

Overview of the cardiovascular system (CVS)

CVS = heart (pump) + blood vessels (tubes) + blood (fluid)
- blood thought to be consumed by tissues till Harvey (early 17th) proved blood
recirculation including transit via the lung to go from the left to the right cavity
- blood from arteries to the veins via the capillaries, discovered by Malpighi (end 17th)

I. The heart
II. The vasculature
III. The blood
 THE CARDIOVASCULAR SYSTEM
The cardiovascular system is a closed loop. Veins Capillaries Arteries
Drawing conventions:
The heart is a pump that circulates blood - Left heart on the right side
through the system. Arteries take blood
Head and
- oxygenated arterial blood in red
away from the heart, and veins carry Brain vs. venous blood in blue
blood back to the heart. (artificial blue except if cyanosis !
bluish color around the mouth and
Arms under the fingernails)
Systemic circulation
= blood circulating from Pulmonary
veins Ascending arteries
the left side of the heart Pulmonary
Lungs
Superior
to the tissues and back vena cava arteries
to the right side of the Right
Aorta
heart. atrium
Left atrium
Coronary
Pulmonary circulation arteries
Abdominal aorta
= blood circulating from Left ventricle
Right
the right ventricle to the ventricle
Heart
Inferior
lungs and back to the vena cava
left atrium Trunk

A system of valves in Hepatic artery

the heart and veins Hepatic Hepatic portal vein FIGURE QUESTION
vein A portal system is two capillary beds
ensures that the blood Liver Digestive
joined in series. Identify the two
tract
flows in one direction Renal portal systems shown in this figure.
Renal
only. Ascending veins
veins arteries

Descending arteries
Venous valve Kidneys

Pelvis and
Legs

Blood Flows Down a Pressure Gradient (ΔP).

• Blood can flow only if one region develops higher pressure than other regions.
• In humans, the heart creates high pressure when it contracts.
• As blood moves through the system, pressure is lost because friction (= resistance)
between blood and vessel walls.
Venae cavae
Capillaries
Arterioles
Arteries

Venules
Aorta

Veins
Mean systemic blood pressure

100

80
(mm Hg)

60

40

20

0
Transport = primary function of the cardiovascular system

1)
!! If no O2 in the brain:
- for 5-10 seconds à loss of consciousness
- for 5-10 minutes à permanent damages

2)

3)

I. THE HEART

1. Anatomy of the heart

2. Cardiac muscle cells
3. Cardiac excitation-contraction (EC) coupling
4. Cardiac conduction
5. Cardiac cycle
6. Stroke volume, heart rate and cardiac output
 (1/8)
1. Anatomy of the heart

The heart lies in the center of the thorax.

Position of
Sternum semilunar valves

Base of heart
(just behind the sternum)

Apex of heart
(angled down to the left side)

Position
of AV
Diaphragm valves

(2/8)

The heart is on the ventral side of the thoracic

cavity, sandwiched between the lungs.

Trachea
Thyroid gland
Lung
First rib (cut)

Diaphragm Apex of
heart
 (3/8)

A thin layer of pericardial fluid

inside the pericardium
lubricates the external surface of
the heart as it beats within the sac.

The heart itself is composed mostly

of cardiac muscle or myocardium,
covered by thin outer and inner
layers of epithelium
and connective tissues.

Coronary arteries and veins run across the surface of the ventricles,
regulating the blood supply to the heart.

(4/8)
Blood enters each ventricle at the top of the chamber but also leaves at the top;
this is because during development, the tubular embryonic heart twists back on itself.

Functionnaly, this means that the ventricles must contract from the bottom up
so that blood is squeezed out of the top.

In the embryo, the heart develops from a single tube.

(a) Age: embryo, day 25.
The heart is a single tube.
(b) By four weeks of development, (c) Age: one year (arteries not shown)
the atria and ventricles can be
distinguished. The heart begins to
twist so that the atria move on top
of the ventricles.

Superior
vena cava
Pericardial Pharynx
Aortic Left
cavity arches atrium
Artery
Artery Ventricle Inferior
Ventricle vena cava
Atria
Left atrial
primordia Right
Vein Vein ventricle
 (5/8)
Superior view of transverse plane in (b)
Superior Aorta Pulmonary Pulmonary
Bronchus vena Esophagus (segment trunk vein
cava removed) (artery)

Right Right Pericardium Pericardial Left Left

atrium ventricle Sternum cavity ventricle atrium

One-way flow through the heart is ensured by two sets of valves.

(6/8)

Pulmonary valve
Aorta
Aortic valve Left and right sides of the heart are
Right separated by the interventricular
pulmonary Left pulmonary septum, so that blood from one side
arteries arteries does not mix with blood
on the other side.
Superior Left pulmonary
vena cava veins The two sides however contracts
in a coordinated fashion:
first atria contract together,
Right atrium Left atrium then the ventricles contract together.
Flaps of left AV
(bicuspid) valve
(= mitral valve)
Chordae tendineae
Flaps of right
AV (tricuspid) Papillary muscles Papillary muscles provide stability
valve for the chordae (= tendons), but
they cannot actively open or close
Right Left ventricle the AV valves. The valves move
ventricle passively when flowing blood
Inferior pushes on them.
vena cava

Descending aorta
 (7/8)
Heart valves ensure one-way flow in the heart (during contraction)

longitudinal
Transverse
section
section.

VENTRICULAR CONTRACTION

Frontal section During ventricular contraction, Transverse section

the AV valves remain closed
Aorta Mitral (left AV), or
to prevent blood flow
Left atrium bicuspid, valve
backward into the atria.
Aortic Mitral valve
semilunar
valve Chordae
(open) tendineae
(tense) Fibrous
Papillary skeleton
muscles Aortic
(tense) Left ventricle semilunar
(contracted) valve (open)
Pulmonary
semilunar
Tricuspid
valve (open)
« Prolapse » = abnormal condition, (right AV) valve
when the valve is pushed back
into the atrium during ventricle contraction.

(8/8)
Heart valves ensure one-way flow in the heart (during relaxation)

longitudinal
Transverse
section
section.

VENTRICULAR RELAXATION
Frontal section Transverse section

Pulmonary veins
Mitral (left
Semilunar AV), or
valves Mitral valve (open) bicuspid,
valve
(open)
Chordae
tendineae (relaxed)
Papillary muscles Semilunar
(relaxed) valves
(closed)
Left The semilunar valves prevent
ventricle blood that has entered the
(dilated) arteries from flowing back into
Each semilunar valve has three cuplike leaflets
the ventricles during ventricular
that snap closed when blood attempting to flow back
relaxation. into the ventricles fill them. Because of their shape,
these valves do not need connective tendons.
 Two sets of heart valves

Atrioventricular valves between atria and ventricles

Tricuspid valve (right side)

Bicuspid or mitral valve (left side)

Semilunar valves between ventricles and arteries

Pulmonary valve (right)

Aorta valve (left)

… -R-S-T- …
Right Side has Tricuspid

2. Cardiac muscle cells

• Autorhythmic cells, or pacemakers (1% of the myocardium)
= unique property of the heart: its ability to contract without any outside signal
– specialized to generate action potentials spontaneously
– signal for contraction is “myogenic” (originating from the heart itself)
– smaller and fewer contractile fibers compared to contractile cells
– do not have organized sarcomeres, do not contribute to the contractile force

• Contractile cells (99% of the myocardium)

– Striated fibers organized into sarcomeres
Myocardial cell characteristics
- Fibers much smaller than skeletal muscle fibers

Intercalated - Ususally one single nucleus per fiber

disks Myocardial muscle cell - Intercalated disks join neighboring cells end-to-end

- T-ubules larger than those of skeletal muscles and

branching inside the myocardial muscles

- Sarcoplasmic reticulum smaller reflecting that

cardiac muscle depends in part on extracellular
calcium for contraction (more like smooth muscle
cells)

- Mitochondria occupy about one-third the cell

volume of a muscle fiber, reflecting the high energy
demand of these cells

- Cardiac muscles consume 70-80% of the O2

delivered to it by blood, more than twice the
amounts extracted by other cells in the body.
During periods of increased activity, the heart uses
almost all the O2 brought to it by coronary arteries.
As a result, the only way to get more O2 to
exercising heart muscle is to increase the blood
flow.

Intercalated disks
Intercalated disks = cell junctions consisting
of interdigitated membranes, with 2 components:

- Desmosomes (strong connections that tie adjacent

cells together, allowing force created in one cell
to be transferred to the adjacent cell

- Gap junctions = structures that electrically connect

cadiac muscle cells to one another, allowing waves
of depolarization to spread rapidly so that all the
heart muscle cells contract almost simultaneously
3. Cardiac excitation-contraction (EC) coupling
• In cardiac muscle as in skeletal muscle, an action potential initiates EC coupling
but in the heart, it originates spontaneously in pacemaker cells and spreads into
the contractile cells through gap junctions ( ≠ Ach from somatic motor neurons
in skeletal muscle)
– Each of the two types of cardiac muscle cells has a distinctive action potential

• Calcium entry is a key feature of cardiac EC coupling. The process is called

“calcium-induced calcium releases” (CICR). Note that after contraction, calcium
is transported back to the SR but is also removed from the cell via the Na+,Ca2+-
exchanger (NCX)

• Cardiac muscle contraction can be graded (ie, the fiber varies the amount of
force it generates) [in skeletal muscle, contraction in a single fiber is all-or-none]
– Force generated is proportional to number of active crossbridges, itself determined by
how much Ca2+ is bound to troponin
– Sarcomere length (at the beginning of contraction) affects force of contraction.
In the intact heart, stretch on the individual fibers is a function of how much blood is in the
chambers of the heart. The relationship between force and ventricular volume is an important
property of cardiac function; see below)
 EC COUPLING IN CARDIAC MUSCLE
This figure shows the cellular events leading to contraction
and relaxation in a cardiac contractile cell.
Action potential enters
from adjacent cell.
Ca2+ 2 K+ 3 Na+ Ca2+
ECF
ATP NCX Voltage-gated Ca2+
ICF channels open. Ca2+
3 Na+ enters cell.
RyR Ca2+
Ca2+ induces Ca2+ release
through ryanodine
receptor-channels (RyR).
SR L-type Sarcoplasmic
reticulum (SR)
Ca2+ Ca2+
channel Ca2+ stores Local release causes
Ca2+ spark.
ATP
CICR or Summed Ca2+ sparks
Ca2+-induced T-tubule create a Ca2+ signal.
Ca2+ sparks
Ca2+ release
Ca2+ ions bind to troponin
to initiate contraction.
Ca2+ signal Ca2+ Ca2+
Relaxation occurs when
Actin Ca2+ unbinds from troponin.

Ca2+ is pumped back

into the sarcoplasmic
reticulum for storage.

Contraction Relaxation Myosin

Ca2+ is exchanged with
Na+ by the NCX antiporter.

FIGURE QUESTION Na+ gradient is maintained

Using the numbered steps, compare the events shown to EC by the NA+-K+-ATPase.
coupling in skeletal and smooth muscle

ACTION POTENTIAL OF A CARDIAC CONTRACTILE CELL

PX = Permeability to ion X
↓PNa Influx of calcium during phase 2 lengthens the total
+20 duration of a myocardial action potential,
↓PK and ↑ PCa
Membrane potential (mV)

which typically lasts 200 msec or more

0
(vs 1-5 msec in neurons and skeletal muscle)
-20
The longer myocardial action potential helps to prevent
↑ PK and ↓ PCa
-40 the sustained contraction called tetanus (which would
be fatal if it happened in the heart). §
-60 ↑PNa

-80
Prevention of tetanus is important because cardiac
muscle must relax between contractions
-100
so the ventricles can fill with blood !!
0 100 200 300
Time (msec)

Phase* Membrane channels

Na+ channels open (depolarization)

Na+ channels close (initial repolarization)
Ca2+ channels open and fast K+ channels close à resulting in flattening of action potential (plateau)
Ca2+ channels close and slow K+ channels open à rapid repolarization
Resting potential (-90 mV)

*The phase numbers are a convention.

FIGURE QUESTION
Compare ion movement during this action potential to ion
movement of a neuron s action potential
No tetanus in cardiac muscle§

Refractory period = the time following an action potential

during which a normal stimulus cannot trigger a second action potential

In the heart, the long action potential (red curves) means that the
refractory period (yellow background) and the contraction
(-relaxation) (blue curve) end almost simultaneously.

By the time a second action potential can take place, the myocardial cell
has almost completely relaxed. Consequently, no summation occurs.

Reminder:
 ACTION POTENTIALS IN CARDIAC AUTORHYTHMIC CELLS
Autorhythmic cells have unstable membrane potentials called pacemaker potentials.

The pacemaker potential Ion movements during an State of various ion channels
gradually becomes less negative action and pacemaker
until it reaches threshold, potential
triggering an action potential.

20
Ca2+ channels close,
K+ channels open

0
Ca2+ in K+ out Lots of Ca2+
Membrane potential (mV)

channels
open
-20

Threshold
-40
Ca2+ in Some Ca2+
channels open,
If channels close If channels
-60
Net Na+ in If channels open
Pacemaker Action open
potential potential K+ channels close

Time Time Time

In autorhythmic myocardial cells, membrane potential is unstable, it starts at -60 mV and slowly drifts
upward toward threshold (it is called a pacemaker potential, rather than a resting potential since it never
« rests » at a constant value).

These cells contains channels that are different from the channels of other excitable tissues.
At -60 mV, If channels that are permeable to both K+ and Na+ open (f subscript is for « funny »).
Na+ influx exceeds K+ efflux: the net influx of positive charge slowly depolarizes the autorhythmic cells
(similar to what happens in the neuromuscular junction when nonspecific cation channels open)
4. Cardiac conduction
ELECTRICAL CONDUCTION IN MYOCARDIAL CELLS
Autorhythmic cells spontaneously fire action potentials. Depolarizations of the autorhythmic cells
then spread rapidly to adjacent contractile cells through gap junctions.
Action
potentials of
autorhythmic
cells
Action
Electrical potentials of
current contractile
Cells of
sinoatrial cells
(SA) node
Contractile cell

Intercalated disk
with gap junctions

THE CONDUCTING SYSTEM OF THE HEART

Electrical signaling begins in the SA node.

SA node Purple shading in SA node depolarizes.

steps 2–5 represents
AV node depolarization.

Electrical activity goes

rapidly to AV node via
internodal pathways.

THE CONDUCTING Depolarization spreads

SYSTEM more slowly across
OF THE HEART atria. Conduction slows
through AV node.

SA node Depolarization moves

rapidly through the His-
Internodal Purkinje system to the
pathways apex of the heart (4m/sec).

Depolarization wave
spreads upward from
the apex.
AV node

Bundle of His

Bundle
branches Purkinje
fibers

FIGURE QUESTION
What would happen to conduction
if the AV node malfunctioned and
could no longer depolarize?
 As action potentials spread across atria,
they encounter the fibrous skeleton of the heart at the junction of
the atria and ventricles.
This barricade prevents the transfer of electrical signals from the The ejection of blood from the ventricles is aided
atria to the ventricles. by the spiral arrangement of the muscles in the wall.

Consequently, the AV node is the only pathway through which As these muscles contract, they pull the apex and base
action potentials can reach the contractile fibers of the ventricle. of the heart closer together, squeezing blood out
This is necessary since blood is pumped out the ventricles of the openings at the top of the ventricles
through openings at the top of the chambers.

A second function of the AV node is to slow down the

transmission of action potentials slightly. This delay allows the
atria to complete their contraction before ventricular contraction
begins.

Pacemakers set the heart rate

• Sinoatrial (SA) node
– the quickest, so the leader
– sets the pace of the heartbeat at 70 bpm
– if damaged, slower pacemakers can take over
– AV node (50 bpm)
– Purkinje fibers (25–40 bpm)

• Complete heart block = disruption of the conduction of electrical signals from

the atria to the ventricles through the AV node
– Rate of contraction of ventricles (35 bpm) < rate of atria (70 bpm); may need to re-set artificially
the heart’s rhythm by a surgically implanted pacemaker

• Fibrillation (disorganized contraction)

– Atrial fibrillation, often asymptomatic but can lead to serious consequences such as
stroke, if not treated
– Ventricular fibrillation, immediate life-threatening emergency, requires electrical
shock to create a depolarization that triggers action potentials in all cells
simultaneously, coordinating them again
The electrocardiogram

Recording electrical activity of the heart by placing electrodes

on the skin’s surface is possible since salt solutions
such as NaCl-based extracellular fluid, are good conductors.

ECG shows the summed electrical activity generated

by all cells of the heart.

Walter Einthoven recorded the first ECG in 1887.

Einthoven s triangle
ECG electrodes attached to both arms and the leg form a triangle.
Each two-electrode pair constitutes one lead, with one positive and
one negative electrode. An ECG is recorded from one lead at a time.

The direction of deflection of the ECG trace indicates the relationship between the direction of the vector of
the electrical current flow and the axis of the lead.

An upward deflection on an ECG means A downward deflection means the A vector that is perpendicular to the
the current flow vector is toward the current flow vector is toward the axis of the electrode causes no
positive electrode. negative electrode. deflection (baseline)

Lead 1 Lead 1 Lead 1

ECG goes up. ECG remains at baseline.

mV mV mV
ECG goes down.

Time Time Time

The electrocardiogram
ECG ≠ single action potential

• ECG = extracellular recording that represents the sum of

multiple action potentials
• Amplitude of the signal = 1 mV (reduced by the time the
action potential (110 mV) reaches the surface of the body)
• Direction of the ECG is not indicative of a depolarization or a
repolarization. The direction of the ECG trace reflects only the
direction of the current flow relative to the axis of the lead.

A single contractile myocardium action potential:

• The action potential of this ventricular cell is an intracellular

recording made by placing one electrode inside the cell and
a ground electrode outside the cell.
110
mV • The action potential has much greater amplitude because it
is being recorded close to the source of the signal.

• An upward deflection represents depolarization and a

1 sec downward one represents repolarization.

ECG : waves and segments

Waves = deflections above or below the baseline
Segments = sections of baseline between two waves
Intervals = combinations of waves and segments

5 mm
25 mm = 1 sec
An electrocardiogram is divided into waves (P, Q, R, S, T),
segments between the waves (the P-R and S-T segments,
for example), and intervals consisting of a combination of
waves and segments (such as the PR and QT intervals).
This ECG tracing was recorded from lead I.

P wave: atrial depolarization

P-R segment: conduction through AV
node and AV bundle
QRS complex: ventricular +1
depolarization R R

T wave: ventricular repolarization

Millivolts

(atrial repolarization incorporated

into the QRS complex) P-R S-T
segment segment
S
P wave Q T wave

FIGURE QUESTION
1. If the ECG records at a speed of
25 mm/sec, what is the heart
rate of the person?
(1 little square = 1 mm) PR interval QT interval QRS complex
 Today, a 12-lead ECG is the standard for clinical use (quick, painless and non invasive)
ECG tracing (various combinations of the 3 limb electrodes + 6 electrodes placed on the chest and trunk)

...
§ > Normal rate = tachycardia
§ < Normal rate = bradycardia
§ irregular rhytm = arrhythmia
§ if one or more P waves without initiating
a QRS complex = heart block

§ if long QT interval = long QT syndrome;

LQTS may occur as a side effect of some drugs
due to a delayed repolarization of the heart.
It increases the risk of « torsades de pointe »,
a form of irregular heartbeat originating from the
ventricles that may lead to sudden death.

5. Cardiac cycle

Each cardiac cycle has 2 phases:

- Diastole = time during which cardiac muscle relaxes
- Systole = time during which cardiac muscle contracts
- Atria and ventricles do not contract and relax at the same time

Hydraulic rules:
- Blood flows from area of higher pressure to one of lower pressure
- Contraction increases pressure while relaxation decreases pressure
- The left side of the heart creates higher pressure than the right side which sends blood
through the shorter pulmonary circuit.

Heart sounds (Lub-Dup !):

- First sound S1 = vibration following closure of the AV valves …. Lub !
- Second sound S2 = vibration following closure of semilunar valves …. Dub !
Stethoscope allows to listen to the heart through the chest wall.
 CORRELATION BETWEEN AN ECG AND ELECTRICAL EVENTS IN THE HEART
The figure shows the correspondence between electrical
events in the ECG and depolarizing (purple) and
repolarizing (peach) regions of the heart. START P wave: atrial
depolarization
P

End
R

Mechanical events P-Q or P-R segment:

conduction through
( ) of the cardiac cycle T AV node and AV
P bundle
lag slightly behind
the electrical signals. QS P

Atria contract

T wave:
ventricular Repolarization
repolarization ELECTRICAL
R EVENTS
OF THE
T CARDIAC
P
CYCLE
QS

P Q wave
Repolarization
S-T segment Q
R

P R wave
R
QS

Ventricles contract R P

Q
P S wave

QS

The heart cycles between contraction Atria are filling with blood from the veins.
(systole) and relaxation (diastole). Late diastole—both sets of
chambers are relaxed and As the ventricles relax, AV valves open.
ventricles fill passively. Blood flows by gravity from the A to the V.

The volume of blood in V does not change, START

but the pressure decreases since V relax.

Isovolumic ventricular
relaxation—as ventricles
relax; pressure in ventricles Atrial systole—Atrial contraction
falls, blood flows back into forces a small amount (20% tot) of
cusps of semilunar valves additional blood into ventricles.
and snaps them closed (DUP!).
Since there are no one-way valves
AV valves remain closed tole to block backward flow, a small
because pressure of V, amount of blood is forced backward
although falling, into the veins.
is still higher than
pressure of A.

DUP !
tole

S1

S2

ial dias
Practically, low-pressure blood ric ular sys
that fills the arteries is pushed further
in the vasculature.

Ventricular ejection— Isovolumic ventricular

as ventricular pressure contraction—first phase of
rises and exceeds ventricular contraction pushes
pressure in the arteries, LUB ! AV valves closed (LUB!) but
the semilunar valves does not create enough pressure
open and blood is to open semilunar valves.
ejected.
At the same time, atria relax and when pressure The volume of blood in V does not change, but
falls below that in the veins, blood fills A again. the pressure increases since V continue to contract.
Pressure-volume curves
Moving from A to B, C, D and back to A
represents time passing as the heart fills
with blood then contracts.
A’ B C D A A’ B

Stroke volume
120
D EDV = End-diastolic volume (= max vol. of blood = 135ml) – point B
ESV ESV = End-systolic volume (= blood left in the heart = 65 ml) – point D
Left ventricular pressure (mm Hg)

A!B: Atrial pressure > Ventricle pressure,

DUP ! mitral valves opens (point A), atrial blood flows into ventricle,
80 volume of the ventricle increases but pressure remains constant,
C
then with atrial contraction (A’àB), pressure increases a little
ONE
CARDIAC B!C : Ventricular contraction, mitral valve closes, so that blood
CYCLE has nowhere to go and pressure increases (isovolumic)
40
C!D: Ventricle pressure > aorta pressure,
aortic valves open (point C), pressure continues to increase
LUB !
START EDV as the ventricle contracts further, but volume decreases
B as blood is pushed out into the aorta
A Aʹ
D!A: Ventricle relaxes, ventricular pressure decreases,
0 65 100 135
when ventricle pressure < aortic pressure, semilunar valve closes,
Left ventricular volume (mL) blood has nowhere to go, ventricular relaxation continues
(isovolumic)

THE WIGGERS DIAGRAM (electrical and mechanical events of the cardiac cycle)
This diagram follows left heart and aortic pressures, left ventricular volume, and the ECG through one cardiac cycle.

Time (msec)
0 100 200 300 400 500 600 700 800
QRS
QRS
complex
complex
Electro-
cardiogram T
P P
(ECG)

120

iii
90 Aorta Dicrotic notch
i: mitral valve closes (LUB!)
Pressure ii
(mm Hg)
60
Left
ventricular
$$$
ii: aortic valve opens
iii: aortic valve closes (DUP!)
pressure
iv: mitral valve opens

30 Left atrial
pressure iv

0 i
Heart
sounds
S1 S2
135
EDV
Left
ventricular
volume (mL)

65 ESV
Atrial Ventricular Ventricular Atrial
systole systole diastole systole

Atrial systole Isovolumic Ventricular Early Late Atrial systole

ventricular systole ventricular ventricular
contraction diastole diastole
 6. Stroke volume, heart rate and cardiac output

• ESV or end-systolic volume (volume of blood after contraction)

– 65 mL
– safety margin ; with a more forceful contraction, the heart can decrease its ESV
• EDV or end-diastolic volume (volume of blood before contraction)
– 135 mL
• SV or stroke volume (volume of blood pumped by one ventricle during a contraction)
– EDV – ESV = stroke volume (135 – 65 = 70 mL, more exactly ‘mL per beat’)
– can increase to as much as 100 mL during exercise
• HR or heart rate (beat per min)
– Average resting heart : 70 bpm (higher in children than in adults)
– Trained athletes at rest : 50 bp
– Someone excited or anxious : >125 bpm
• CO or cardiac output (volume of blood pumped by one ventricle in a given period of time)
– CO = HR × SV
– Average CO = 5 L/min (72 bpm x 70 mL/beat)
– It means that every minute, at rest, one side of the heart pumps all the blood of the body
– CO is the same for both ventricles (if mismatched, blood pools in the circulation behind the weaker
ventricle)

Heart rate is modulated by the autonomic nervous system

Heart rate is initiated by autorhythmic cells in the SA node but is modulated by neural and hormonal inputs.

- tonic control of the heart dominated by the parasympathetic branch

(if all autonomic input to the heart is blocked, spontaneous depolarization rate
of the SA node = 90-100 times per min)
- two means to increase heart rate:
- reducing the parasympathic activity
- stimulating the sympathic activity (activation of beta-1 receptor with catecholamines
leading to cAMP production and binding to the cyclic nucleotide-gated channel If)
 Autonomic control of heart rate

via K+ and via If and

Ca2+ channels, Ca2+ channels,
respectively respectively
§ §

§ also through alteration of the rate of conduction through the AV node

Stroke Volume
directly related to the force of contraction, itself affected by 2 parameters:

- the length of muscle fiber* at the beginning of the contraction (determined by EDV)
The longer the muscle fiber/sarcomere when a contraction begins,
the greater the tension develops (Frank Starling law).*

- the contractility of heart**(= ability to contract at any given fiber length)

Contractility is a function of calcium interaction with the contractile filaments.**
 The Frank-Starling law*

• Frank-Starling law (Otto Frank (german) and Ernest Starling (british))

– as stretch of the ventricular wall increases, so does stroke volume,
in other words, stroke volume increases as EDV increases

• EDV is determined by venous return (= the amount of blood that enters the heart
from the venous circulation), itself affected by 3 parameters:
– Skeletal muscle pump = compression of veins returning blood to the heart
(particularly in the legs; helping when exercising but no assistance during periods of sitting
or standing motionless)
– Respiratory pump = pressures changes in the abdomen and thorax during
breathing (as chest expands and diaphragm moves toward the abdomen, the thoracic
cavity enlarges and develops a subatmospheric pressure that decreases the pressure in
thoracic veins whereas pressure increases on the abdominal veins)
– Sympathetic innervation of veins = constriction of veins

• Preload = degree of myocardial stretch before contraction begins

The Starling curve*

The force (tension) created by a striated muscle is directly related to the starting
length of the sarcomere

relationship validated
for cardiac muscle by O. Frank

As additional blood
enters the heart,
the heart contracts
more forcefully
and ejects more blood
(= the Frank-Starling law)

within « physiological » limits:

The mechanism described by the Frank-Starling law contributes to avoid differences in CO

between the two ventricles. If [CO]RV > [CO]LV : blood volume increases in the pulmonary
circulation! increased venous return ! increased [EDV]LV ! increased [stroke volume]LV
Contractility**

Inotropic agent
= any chemical that affects contractility

– Positive inotropism
= increased force of contraction
ex: epinephrine, norepinephrine and digitalis

– Negative inotropism
= decreased force of contraction

CATECHOLAMINES INCREASE CARDIAC CONTRACTION**

Phospholamban is a regulatory protein that alters sarcoplasmic reticulum Ca2+–ATPase activity.

Epinephrine
and
norepinephrine

bind to
Contractility is a function
of calcium interaction with β1-receptors
the contractile filaments.
that activate

cAMP second
messenger system

resulting in phosphorylation of

Voltage-gated Ca2+ channels Phospholamban

Open time increases ↑ Ca2+-ATPase on SR

↑ Ca2+ entry from ECF ↑ Ca2+stores in SR Ca2+ removed from cytosol faster

Shortens Ca-troponin
↑ Ca2+ released
binding time
KEY
SR = Sarcoplasmic
reticulum Shorter
More forceful duration
ECF = Extracellular
contraction of contraction
fluid

‘+ inotropism’ ‘+ chronotropism’
Afterload and ejection fraction

• Afterload = combined load of EDV and arterial resistance during ventricular

contraction
Increased afterload is found in pathological situations including hypertension and loss of
stretchability (compliance) in the aorta.
If increased afterload becomes a chronic situation, the myocardial cells hypertrophy, resulting in
increased thickness of the wall (together with an increased need of O2 and ATP)

• As indicators of afterload, one may consider

– Measurements of arterial blood pressure (tensiometer)
– Ejection fraction = % EDV ejected with one contraction (echocardiography)
– SV/EDV à 70 ml/135ml = 52%
– With exercise, if SV increases to 100 ml, ejection fraction increases to 74%

STROKE VOLUME AND HEART RATE DETERMINE CARDIAC OUTPUT

CARDIAC OUPTUT

is a function of

Heart rate CO = HR x SV Stroke volume

determined by determined by

Rate of depolarization Force of contraction in

in autorhythmic cells ventricular myocardium

is influenced by

Decreases Increases increases

Contractility End-diastolic
volume
Sympathetic
Due to
innervation and which varies with
parasympathetic
epinephrine
innervation
increases Venous constriction Venous return

aided by

FIGURE QUESTIONS
Which step(s) is (are) controlled
by ACh? By norepinephrine? Skeletal muscle Respiratory
Which tissue(s) has (have) muscarinic pump pump
receptors? β1-receptors?