Download 3. Cardiac Output

Definitions
Cardiac Output
Cardiac Output and venous return
Dr Badri Paudel
GMC
–  The quantity of blood pumped into the aorta
each minute
–  measured in milliliters (mL) per minute (min)
or liters (L) per minute
–  normally around 5,000 mL (5 L) per minute
(5,000 mL/min or 5 L/min)
Venous Return
–  The quantity of blood flowing from the veins
into the right atrium each minute
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Cardiac Output (CO)
End-Diastolic Volume – End-Systolic Volume = Stroke Volume
Beat = stroke volume (SV)
= EDV – ESV
= 70 ml
Volume of blood ejected
from one ventricle
End-Diastolic
Volume
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End-Systolic
Volume
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Minute = Cardiac output (CO)
= SV x HR
= 5 liters / min
Minute / square meter of body
surface area
= Cardiac index
= 3.2 liter / min / m26
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Cardiac output (CO) is directly affected by… • heart rate (HR), the number of <mes the heart beats each minute; and • stroke volume (SV), the amount of blood ejected during each beat 4/18/12 Ejection Fraction:
Ø Definition:
It is the ratio of SV compared to EDV.
SV
70
X 100
=
=
EDV
Ø Value:
CO = HR x SV X 100
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Normally it is about 50 – 60 %.
Ø Importance:
•  If HR increases, what will happen to cardiac output? It is used as indicator for myocardial contractility.
•  If SV decreases, what will happen to cardiac output? badri@GMC 7 4/18/12
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Cardiac Reserve
•  During exercise CO (Cardiac Output) may
increase up to 20-25 liters/minute and up to 40
liters/minute during heavy exercise in athletes
•  Cardiac reserve is the difference between the
cardiac output at rest and maximal cardiac
output during heavy exercise.
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IMPORTANT RELATIONSHIPS
Determinants of Cardiac Output
CONTRACTILITY
PRELOAD
(+)
(+)
HEART
RATE
Some definitions
AFTERLOAD
(-)
o 
STROKE
VOLUME
(+)
o 
(+)
o 
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Determining factor:
n 
CARDIAC
OUTPUT
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Preload: the initial stretching of the cardiac
myocytes prior to contraction.
End diastolic volume: the volume of blood in
a ventricle at the end of filling
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Venous return
Preload Pumps up the heart.badri@GMC
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Measurement of Cardiac Output
Some definitions
o 
o 
o 
Afterload: the force the
sarcomere must overcome in
order to shorten during systole
Determining factor:
n 
o 
o 
o 
o 
Aortic pressure
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Electromagnetic flowmeter
Indicator dilution (dye such as cardiogreen)
Thermal dilution
Oxygen Fick Method
CO = (O2 consumption / (A-V O2 difference)
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Fick Principle
O2 Consumption
Cardiac output =
o 
A man has a resting O2 consumption of 250 ml O2/min, a
o 
[O2] pulmonary vein – [O2] pulmonary artery
o 
femoral arterial O2 content of 0.20 ml O2/ml blood, and a
pulmonary arterial O2 content of 0.15 ml O2/ml blood.
o 
o 
CO =
250 ml O2/min
o 
= 5000 ml/min
0.20 ml O2/ml – 0.15 ml O2/ml
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O2 Fick Problem
o 
o 
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If pulmonary vein O2 content = 200 ml O2/
L blood
Pulmonary artery O2 content =
160 ml O2 /L blood
Lungs add 400 ml O2 /min
What is cardiac output?
Answer: 400/(200-160) =10 L/min
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Intrinsic autoregulation
Regulation of Cardiac output
1-Heterometric autoregulation:
Initial Length (Preload):
Extrinsic regulation
* It depends on
- Nervous supply of the heart.
- Hormones or chemical
* It adjust both stroke volume
and heart rate.
Intrinsic regulation
(Auto regulation)
*It is the ability of the heart to
change its stroke volume
independent of nervous
chemical or hormonal factors.
* It include
• 
The major determinant of the force of contraction is the
• 
The end diastolic volume (EDV) is used instead of
• 
The EDV is determined by the preload.
• 
The term preload refers to the degree of passive stress
initial length of the muscle fiber.
length of muscle fiber.
exerted by the volume of blood in the ventricle just
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Heterometric
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autoregulation
Homeometic
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autoregulation
before its contraction.
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Characters of heterometric auto-regulation
Preload
" It is preload phenomena .
" It is of a short duration .
" There is an increase in the length of muscle fiber .
" End diastolic volume ( E.D.V ) increases .
" Stroke volume ( S.V ) increases .
•  Preload can be defined as the initial stretching of
the cardiac myocytes prior to contraction. It is
related to the sarcomere length at the end of
diastole.
" End systolic volume slightly increases .
" It is usually followed by Homeometric regulation .
Examples of heterometric regulation :
" a - In case of changing position from standing into
supine position e.g. lying in bed.
" b - In the ( early stage ) beginning of muscular
exercise .
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Frank-Starling Relationship
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Preload is directly affected by… • filling <me and • venous return –  LVEDV (left ventricular end-diastolic volume)
–  LVEDP (left ventricular end-diastolic pressure)
–  PCWP (pulmonary capillary wedge pressure)
–  CVP (central venous pressure)
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Preload … • stretches the myocardium so that the myofibers are lengthened before contrac<on resul<ng in a stronger contrac<on, up to a point (above which strength decreases), according to the Frank-­‐Starling law of the heart. •  Because we cannot measure sarcomere length
directly, we must use indirect indices of preload.
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Frank-Starling Mechanism
Frank-Starling Mechanism
•  Allows the heart to readily adapt to changes in
venous return.
•  When venous return to the heart is increased,
ventricular filling increases, as does preload. This
stretching of the myocytes causes an increase in
force generation, which enables the heart to eject
the additional venous return and thereby increase
stroke volume.
•  The Frank-Starling Mechanism plays an important
role in balancing the output of the 2 ventricles.
•  In summary: Increasing venous return and
ventricular preload leads to an increase in stroke
volume.
•  Simply stated: The heart pumps the blood that is
returned to it
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Length-tension curve
(Frank-Starling )
Frank-Starling Mechanism
Stroke volume (SV) (ml)
(related to muscle tension)
Optimal length
Increase
in SV
(Cardiac muscle does
not normally operate
within the descending
limb of the length–
tension curve.)
B1
A1
Normal resting length
Increase
in EDV
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End-diastolic volume (EDV) (ml)
(related to cardiac-muscle fiber length)
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Frank-Starling Mechanism
•  There is no single Frank-Starling Curve for
the ventricle. Instead, there is a family of
curves with each curve defined by the
existing conditions of afterload and
inotropy.
The muscle developed tension is increased upon increasing
the initial length ( preload ) up to certain limit .Further increase
in muscle length beyond this limit depresses the muscle
developed tension and this is not seen in the normal heart but
only
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Frank-Starling Curves
Frank Starling
o 
o 
o 
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Intrinsic regulation of
heart pumping
Increased venous
return leads to
increased stroke
volume
CO=SV x HR
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2-Homeometic autoregulation
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Afterload
q  It follows the heterometric regulation.
•  Afterload can be viewed as the "load" that
the heart must eject blood against.
q  It can occur for long time.
q  It is an after load phenomenon.
q  It is initiated by the increase in aortic
pressure.
•  In simple terms, the afterload is closely
related to the aortic pressure.
q  The increase in myocardial contraction
increase SV by the decrease in ESV.
q  EDV returns to the normal value (not
changed).
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•  LaPlace’s Law
•  More precisely defined in terms of
ventricular wall stress:
Wall Stress
Wall Stress
σ∝
–  LaPlace’s Law: Wall stress = Pr/h
•  P = ventricular pressure
•  R = ventricular radius
•  h = wall thickness
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Afterload is better defined
in relation to ventricular wall stress
Afterload
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Pr
h
P
r
h
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Effects of Afterload
Afterload
•  Afterload is increased by:
–  Increased aortic pressure
–  Increased systemic vascular resistance
–  Aortic valve stenosis
–  Ventricular dilation
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AFerload… • inversely affects stroke volume; and • directly affects end systolic volume; ESV •  What effect will hypertension have on a=erload? •  What effect will hypertension have on stroke volume? 4/18/12
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Heterometric
Homeometeric
q Sequence
Occurs at first (followed
by homeometic
regulation).
Following the
heterometric regulation.
q Onset
Rapid
(Immediate after increase
in VR)
Slow
(after few min)
Short
(few minutes)
Long
(Maintain the elevated
stroke volume for long
time).
No change
q Duration
q EDV
Increase
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Heterometric
q ESV
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Homeometeric
Constant
(or slightly increased)
Decrease
q SV
Increase
Increase
q Stretch of
ventricular
muscle
fibers.
Present
Absent
q Mechanism
Starling law
Increase of the aortic
pressure
Pre load
After load.
q Phenomenon
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Extrinsic regulation
Anrep Effect
•  An abrupt increase in afterload can cause a
modest increase in inotropy.
Ø It is the adjustment of CO via change of heart
rate (HR) and/or stroke volume (SV).
•  The mechanism of the Anrep Effect is not
fully understood.
Ø It acts through either autonomic nerve supply of
the heart and/or hormones (chemicals) in the
blood.
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Heart Rate is directly
affected by factors
called chronotropic
agents (or factors).
These factors may be
positive or negative.
Extrinsic regulation
Hormonal (chemical)
regulation
Nervous regulation
Parasympathetic NS
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PosiKve chronotropic agents… • increase heart rate and • include epinephrine, norepinephrine and beta agonists (e.g., isoproterenol). 4/18/12
Sympathetic NS
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NegaKve chronotropic agents… • decrease heart rate and • include acetylcholine (ACh) and beta antagonists (e.g., propranolol). •  What effect will sympathe@c nerve impulses have on heart rate? badri@GMC
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•  What effect will parasympathe@c nerve impulses have on heart rate? badri@GMC
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Effects of Heart Rate
on Cardiac Output
Heart Rate
Cardiac Output
•  Changes in heart rate are generally more
important quantitatively in producing
changes in cardiac output than are changes
in stroke volume
•  Changes in heart rate alone inversely affect
stroke volume
Heart Rate
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Heart Rate
–  The decrease in SV is greater than the increase
in HR (decreased filling time)
•  At low HR
–  decrease in HR is greater than decrement in SV
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Heart rate regulation:
The SA node is the normal pace maker of the heart that set the heart
rate during rest at average rate=70 beats/minute
The autonomic nervous system supply of the heart:
•  The atria (SA node and AV node) are supplied by the
parasympathetic nervous system (The vagus nerve) and the
sympathetic nervous system (Dual supply from both divisions of
A.N.S)
•  The ventricles are mainly supplied by the sympathetic nervous
system. There is very little Parasympathetic supply of the
ventricles
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Bowditch (Treppe) Effect
•  At high HR
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(Increased by Pacing)
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•  An increase in heart rate will also cause positive
inotropy (Bowditch effect, Treppe or “staircase”
phenomenon).
•  This is due to an increase in intracellular Ca++
with a higher heart rate:
–  More depolarizations per minute
–  Inability of Na+/K+-ATPase to keep up with influx of
Na+, thus, the Na+-Ca++ exchange pump doesn’t
function as well
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Area affected:
Parasympathetic stimulation
Sympathetic stimulation
1-SA Node
Decrease heart rate
Increase heart rate
2-Atrial muscle
Decrease contractility
Increase contractility
3-AV Node
Decrease excitability
(increase AV node delay)
Increase excitability
(decrease AV node delay)
4-Ventricles
conductive
system
No effect
Increase conduction through
His bundle and purkinje cells
5-Ventricle muscle No effect
Increase contractility
6-Adrenal medulla No effect
Increase epinephrine
secretion which enhance
sympathetic stimulation on
heart
7-Veins
Increase venous return (by
vasoconstriction of veins)
which increase cardiac
contraction
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(Frank-Starling mechanism)
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No effect
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Effect Of ANS on HR:
Threshold
potential
Heart rate
Sympathetic
activity
(and epinephrine)
Parasympathetic
activity
Threshold
potential
= Inherent SA node pacemaker activity
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4/18/12= SA node pacemaker activitybadri@GMC
on parasympathetic stimulation
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= SA node pacemaker activity on sympathetic stimulation
Stroke volume
The parasympathetic and sympathetic nervous systems act together on
heart rate in antagonistic (opposing) way, during rest the
parasympathetic nervous system dominate more than the sympathetic
nervous system
Extrinsic
control
Strength of
cardiac contraction
What happen if all autonomic nerves to the heart are cut?
The heart rate will be 100/minute,which is he inherent rhythm of the
SA (which is the SA Node discharge when it is free from the normal
inhibitory dominant parasympathetic effect at rest)
Intrinsic control
Sympathetic activity
(and epinephrine)
A Cardiovascular control center in the brain stem coordinates the
autonomic activity to the heart, if heart rate is to be increased this
center control the increase in sympathetic activity and at same time
decrease the parasympathetic activity and vice versa
End-diastolic
volume
Intrinsic control
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Venous return
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Resting heart without sympathetic:
End-diastolic volume
135 ml
Sympathetic stimulation can increase stroke volume and cardiac output by:
A-Increase force of contraction:
-Under sympathetic stimulation with the EDV=135 ml___The Stroke volume
will be 100 ml and End Systolic Volume(ESV)=35 ml only
-Sympathetic stimulation shift the Frank-Starling curve up and to the left and
according to the degree of sympathetic stimulation is the degree of the
shift up to a maximal increase in strength of contraction 100% greater than
resting strength
Stroke volume
70 ml
B-Increase venous return:
Sympathetic stimulation also cause vasoconstriction of the veins which
squeezes more blood from the veins to the heart (=more filling) which in
turn increase EDV and stroke volume
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End-systolic volume
65 ml
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Shift of Frank-Starling curve up and to the left
by sympathetic stimulation:
Sympathetic stimulation:
End-diastolic volume
135 ml
Frank-Starling curve on
sympathetic stimulation
Normal Frank-Starling
curve
Stroke volume
100 ml
End-systolic volume
35 ml
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Effects of increased sympathetic
stimulation on Cardiac output
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Effects of increased parasympathetic
stimulation on Cardiac output
Increased venoconstriction
Increased venous return
Increased preload
Increased force of
ventricular contraction
Increased slope of
Pace maker potential
Increased heart rate
decreased force of
atrial contraction
decreased slope of
Pace maker potential
decreased heart rate
Increased stroke volume
Decreased ventricular filling
Increased
decreased
cardiac output
cardiac output
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Cardiac output
Heart rate
•  Filling Kme is inversely related to heart rate; as heart rate increases, filling <me decreases. •  Chronotropic agents affect filling <me, thus they affect EDV. However, these agents may also affect contrac<lity such that the effects on stroke volume are less straighMorward. Stroke volume
Extrinsic
control
Intrinsic control
Parasympathetic
activity
Sympathetic
activity (and
epinephrine)
End-diastolic
volume
Intrinsic control
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Venous return
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4/18/12 badri@GMC •  What effect will increased heart rate have on stroke volume (if other factors stay the same)? 66 11
2- Hormonal (chemical) regulation
q  Glucagon hormone: Causes increase of CO. It
has +ve inotropic action (increases SV and CO).
q  Catecholamine: Causes increase CO (Its actions
similar to sympathetic stimulation).
q  Digitalis drug: Causes increase of CO (It has
+ve inotropic action).
q  Thyroxin hormone: Causes increase CO by
increasing the number and sensitivity of B1 receptors
to catecholamine.
q  Acetyl choline: Causes decrease CO (Action
similar to parasympathetic stimulation).
q  Insulin hormone: Causes increase of CO. It has +ve
inotropic action (increases SV and CO).
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Contractility
Extrinsic factors Affecting
Myocardial Contraction
Force ( Inotropic Factors )
Contractility
•  The inherent capacity of the myocardium to
contract independently of changes in afterload
or preload.
•  Changes in contractility are caused by intrinsic
cellular mechanisms that regulate the
interaction between actin and myosin
independent of sarcomere length.
•  Increased rate and/or quantity of Calcium
delivered to myofilaments during contraction
•  Alternate name is inotropy.
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PosiKve inotropic agents… •  increase contrac<lity and •  epinephrine, norepinephrine and cardiac glycosides (e.g., digitalis) •  What effect will epinephrine have on stroke volume? 4/18/12
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NegaKve inotropic agents… •  decrease contrac<lity and •  include calcium channel blockers (e.g., verapamil). •  What effect will blocking calcium channels have on stroke volume? 4/18/12
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Extrinsic factors Affecting Myocardial
Contraction Force ( Inotropic Factors )
1) Nervous Factors:
Sympathetic stimulation increases strength of
contraction (positive inotropic factor ) through its
Ca ++ raising effect .
b) Parasympathetic stimulation has a negative
inotropic effect due to its intracellular Ca++
lowering action (opposite to sympathetic).
2) Neurohormones:
a. Epinepherine & norepinepherine : are povitive
inotropic factors (similar to sympathetic) .
b. Acetyl choline : is negative inotropic factor
(similar to parasympathetic).
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3) ECF ions:
Effects of variations in Ca++ and K + ions:
a. Ca++ infusion (intravenous) may stop the heart
during systole (Ca++ rigor).
b. Effects of hyperkalaemia: Depresses cardiac
contractility and may stop the heart during diastole
so increased K + ions have a negative inotropic
effect
4) Drugs :
Digitalis used in the treatment of heart failure is the
most important of all; it acts through inhibition of Na+
K+ ATP ase & thus Na+ ions accumulate inside the
cells & stimulate Na+ Ca++ exchanger (between
intracellular Na+ & extracellular Ca++) which
increases the intracellular Ca++ concentration
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Factors Regulating Inotropy
(+)
(-)
Parasympathetic
Activation
(+)
Afterload
(Anrep)
Sympathetic
Activation
Inotropic
State
(Contractility)
(-)
(+)
Catecholamines
(+)
Heart
Rate
(Treppe)
Systolic
Failure
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