This document discusses cardiac output and its regulation. It defines key terms like stroke volume, heart rate, venous return, and cardiac index. It describes how cardiac output is determined by stroke volume and heart rate. It explains factors that affect preload, afterload, contractility, and the Frank-Starling mechanism. It discusses the cardiac function curve and vascular function curve in regulating cardiac output through interactions between the heart and vasculature. It also addresses how cardiac output changes with exercise, sympathetic stimulation, and other physiological conditions.

1. Cardiac Output

2. Learning Outcomes
• Define stroke volume, heart rate, cardiac output, venous
return, mean systemic filling pressure and cardiac index.
State the normal value of each of the above in a healthy
adult at rest.
• State physiological and pathological situations affecting
cardiac output.
• Enumerate the methods for measuring cardiac output. State
the noninvasive methods for estimation of cardiac output
and also the clinical methods for estimation of cardiac
output.
• Explain autonomic influences and exercise on the heart
rate, stroke volume and cardiac output.
• Explain underlying mechanism of bradycardia, and cardiac
output in trained athletes.

3. Learning Outcomes
• Describe the meaning of each of the following term-
preload, after load, myocardial contractility and explain
its clinical significance.
• Describe the relationship between heart rate and the
force of contraction (Bowditch effect), explaining the
underlying mechanism.
• Demonstrate the relation between venous return and
cardiac output. Discuss the regulation of cardiac output.
• Define the frank-starling law of the heart. Explain the
physiologic basis of this law and its significance.
• Describe the relationship between cardiac output and
myocardial oxygen demand and consumption.

4. Basic Theory of
Circulatory Function
 The blood flow to each tissue of the body is almost always precisely
controlled in relation to the tissue needs
 The cardiac output is controlled mainly by the sum of all the local
tissue flows
 Frank-Starling Relationship is the predominant factor in matching
venous return and cardiac output with in physiological limit.
 In general, the arterial pressure is controlled independently of either
local blood flow or cardiac output control

5. Cardiac Output
• Defined as volume of the blood pumped by each ventricle
per minute.
• Normal value in adult male=5-6L/min. (slightly less in
females)
• Can be determined from values of stroke volume and heart
rate
• CO = Stroke volume X heart rate.

6. Stroke Volume:
• The volume blood pumped by the heart with
each beat. SV= EDV-SDV
• Normal Value is 70ml
End-Diastolic Volume End-Systolic Volume
Stroke Volume

7. • Ejection Fraction: fraction of EDV ejected by the
ventricle in each beat;
• Normal Value =60-80%
• Can be calculated using following expression
• Cardiac Index: Cardiac output/ square meter of body
surface area.
• The normal range is about 3.0 – 3.5 L/min/m2
EDV
ESV
EDV
EDV
SV
EF




8. Venous Return
• Amount of blood returning to the heart per unit of time
through the great veins and coronary sinus. [equal to
Cardiac Output]
• Principal determinants of venous return
• 1. Right atrial pressure, backward force to impede
flow of blood from veins into the right atrium.
2. Degree of filling of the systemic circulation [mean
systemic filling pressure]), which forces the systemic
blood toward the heart
• 3. Resistance to blood flow between the peripheral
vessels and the right atrium.

9. Mean systemic filling pressure
• Equilibrated pressure in the
circulation when blood flow
ceases hypothetically.
• Extra blood volume stretches
the walls of the vasculature-
greater will be the mean
circulatory filling pressure.
• Sympathetic stimulation
constricts blood vessels and
increase mean circulatory filling
pressure.

10. Physiological variation cardiac output
1. Age
2. Exercise
3. Anxiety
4. Emotion & excitement
5. Pregnancy
6. After eating
7. Environmental temperature
8. Postural changes

11. Pathological variation cardiac output

12. Methods of measuring cardiac output
Dye injection / dye dilution method.
1.Thermo dilution method.
2.Direct fick’s method.
Physical methods
1.Echocardiography
2.Ballistocardiography

13. • Evan’s blue .
• Prerequisites for
dye.
• Procedure : 5mg of
Evans blue ----
blood sample every
2 sec
Indicator / dye dilution method.

14. FICK’S principle :
Amount of substance taken
up by an organ per unit of
time is equal to arterial level
of the substance minus the
venous level times the blood
flow
Indicator / dye dilution method.

15. Lets find out Cardiac output
A healthy person at rest has an O2 uptake
of 250 ml/min and an arterio-venous O2
content difference of 50 ml/L. Calculate
the cardiac output at rest.

16. Physical Methods
• Echocardiography:
• Non invasive
• Movement of ventricular valve and septum
Doppler & Echocardiography to measure velocity &
volume of flow through valves
Evaluate EDV , ESV, CO & valvular defects.

17. Factor Affecting Cardiac Output

18. Cardiac
Output
Determinants of Cardiac Output
Heart Rate Preload
Afterload
Contractility

19. Increased sympathetic stimulation
Positive inotropic effect
Increased
force of
contraction
Increased
rate of
contraction
Vasoconstriction
of blood vessel
Increased
conduction
Increased
SV
HR Increased
VR

20. Major Factors Increasing Heart Rate and Force of
Contraction

21. Major Factors Decresing Heart Rate and Force of
Contraction

22. Cardiac
Output
Determinants of Cardiac Output
Heart Rate Preload
Afterload
Contractility

23. Preload
• 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.
• Sarcomere length cannot be measured directly, hence
indirect indices of preload includes:
– LVEDV (left ventricular end-diastolic volume)
– LVEDP (left ventricular end-diastolic pressure)
– PCWP (pulmonary capillary wedge pressure)
– CVP (central venous pressure)

24. Determinants of Preload
 Venous Return
 Venous Blood Pressure
 Total Blood Volume
 Respiration
 Exercise/Muscle contraction
 Gravity
 Venous compliance
 Filling time (Heart rate)
 Ventricular compliance
 Atrial contraction
 Inflow or outflow resistance
 Ventricular systolic failure

25. Frank-Starling Mechanism
• Frank starling law: within physiological limit force of contraction
is directly proportional to initial length of muscle fiber.
• Ventricular muscle is complaint -130 ml but in cardiomyopathies.
Pericardial effusion , cardiac tampnode…?
• Simply stated: Heart pumps the blood that is returned to it
• Increased venous return causes
– increase in ventricular filling increases [Increased preload]
– Stretching of the myocytes causes an increase in force generation,
– heart to eject the additional venous return
• increase stroke volume.

26. Frank-Starling Mechanism
 Allows the heart to readily
adapt to changes in venous
return.
 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.

27. Cardiac
Output
Determinants of Cardiac Output
Heart Rate Preload
Afterload
Contractility

28. Afterload
 Force against which ventricular muscle shortens
 Consequence of aortic compliance and increased total
peripheral resistance.
 Hypertension increases the afterload : the left ventricle has
to work harder to overcome the elevated arterial peripheral
resistance.
 In simple terms, the afterload is closely related to the
aortic pressure.

29. Afterload: Determinants
 Ventricular radius
 compliance of large arteries
 total peripheral vascular resistance,
 blood viscosity
 intra-arterial volume.
 Increased systemic vascular resistance
 Aortic valve stenosis
 systemic arteriolar resistance is the most important factor
regulating afterload,

30. Cardiac
Output
Determinants of Cardiac Output
Heart Rate Preload
Afterload
Contractility

31. Contractility
• Also called as Inotropy.
• Inherent property of the
myocardium to contract
independently of changes
in afterload or preload.
• Decrease in contractility
causes decrease in SV but
increase LVEDP [B]
• Increase in contractility
results in increase SV and
decrease in LVEDP [C]

32. Factors Regulating Inotropy
(-)
Para-
sympathetic
Activation
(+)
Afterload
(Anrep)
(-)
Systolic
Failure
(+)
Heart
Rate
(Treppe)
(+)
Catechol-
amines
(+)
Sympathetic
Activation
Inotropic
State
(Contractility)

33. Summary of factors affecting
myocardial contractility

34. Ancillary Factors

35. Other Factors
• Affect the Venous System and Cardiac Output
– Gravity
– Muscular pump and Venous Valves
– Respiratory pump

36. Gravity
– Venous pooling may significantly reduce CO

37. • Respiratory pump / Intra thoracic
pressure
• During Inspiration- increase in VR
• During Expiration-decrease in VR
• Changes in pressure & diameter of
IVC
• Diaphragm descent causes
increased intra-abdominal
pressure.
• blood flow into right atrium
increases
Effects of Respiration

38. Muscular Activity and Venous Valves
• Skeletal muscle relaxes
• Negative pressure created in
venous segment
• Distal valve open and blood
sucked up.

39. REGULATION OF CARDIAC OUTPUT

40. Because the cardiovascular system is a closed loop
Venous Return = Cardiac Output
Hence Cardiac Output regulation is consequence of
interactions between the cardiac function and vascular
function.

41. Cardiac Function Curve
• Demonstrate relationship between
cardiac output of the left ventricle and
right atrial pressure.
• Essentially a frank starling curve, shows
its dependence with Right atrial
pressure, venous return, end-diastolic
volume, and end-diastolic fiber length.
• Differ form frank starling curve because
“cardiac output instead of ventricular
stroke volume” is plotted against
changes in “right atrial pressure”

42. Cardiac Function Curve
• When right atrial pressure is
below 0, cardiac output is 0, [too
little blood in the cardiac
chambers to generate pressure
during systole].
• When right atrial pressure
increases above +4 mm Hg,
cardiac output is maximum.
[maximal filling of the ventricle].

43. Cardiac Function Curve
• effect of increasing heart
rate on cardiac output.
• Modest increases in heart rate
facilitate cardiac output,
despite a shorter ventricular
filling time, due to the
Bowditch effect.
• However, large increases in
heart rate shorten filling time
so much that cardiac output
decrease.

44. Cardiac Function Curve
• Hypereffective or hypoeffective
ventricle alter cardiac output at
particular Rt Atrial Pressure.
• Increased sympathetic activity,
hypertrophied ventricle, low after
load ventricle is hypereffective
• A hypoeffective ventricle is
present
• Increased parasympathetic or
inhibition of sympathetic
stimulation,
• the ventricle is damaged,
• increased afterload.

45. Vascular Function Curve
• Also called vascular function curve
• This curve shows inverse relation between venous return & right
atrial pressure.
• As right atrial (venous) pressure increases, venous return decreases
and vice versa.
• When right atrial pressure equals to mean systemic filling pressure,
venous return is zero, since there is no pressure difference to drive
blood flow.
Cardiac
Output

46. Vascular Function Curve
• venous return between a right atrial pressure of 0 mmHg and -8
mmHg is not significant.
• More negative right atrial pressure tends to suck together the walls
of the large veins near the heart, which limits any further increase
in blood flow.
Cardiac
Output

47. Vascular Function Curve
• Take home message: This relationship is determined by vascular
properties:
R (peripheral resistance), arterial compliance[Ca ] and Venous
Compliance [Cv] and and Mean systemic filling Pressure [Psf.]
Cardiac
Output

48. Resistance to Vascular Return (RVR)
• The slope of the linear portion of the vascular function curve is 1/RVR.
• For typical physiological values of Psf = 7 mm Hg, Pv = 2 mm Hg, and
Q = 5 L/min:
Cardiac
Output
Slope
(Psf - Pv )
Q
= RVR
(7- 2 mmHg)
5 L/min
=1 mmHg·min/L

49. Vascular Function Curve
Effects of Changes in Resistance to Vascular Return (RVR)
• As the resistance in vascular
bed increases, the slope
decreases.
• This means that a given
change in [right atrial] venous
pressure causes a change in
venous return.
• Maximal venous return is
when resistance is low.
Cardiac
Output

50. • intercept at 0 mmHg right atrial
pressure [point A ] shows the
“normal” cardiac output and
venous return [near 5 L/min].
• If blood volume by increased by
20%, only vascular function
curve shifts to right and causes
• Psf increases to about 16 mm
Hg,
• right atrial pressure is at 7
mm Hg, and cardiac output is
~13 L/min.
Normal Cardiac Output & effect of increased
Blood Volume

51. • Cardiac output and vascular
function curves shift during a
increased sympathetic activity
causes the cardiac function
curve to shift upwards and to
the left, while the vascular
function curve shifts upwards
and to the right.
• Opposite effects during spinal
Anesthesia
Cardiac Output during Sympathetic
Stimulation and spinal Anesthesia

52. Sympathetic stimulation results
1. Increased cardiac contractility
2. Increased heart rate
3. Decreased venous compliance
4. Increased total peripheral
resistance.
Cardiac output just rises to 10
L/min during sympathetic
stimulation.
Cardiac Output during Sympathetic
Stimulation

53. • Cause cardiac output to increase to ~20
L/min
• Venous return curve shift
considerably different than during
sympathetic stimulation ???
• Afterload decreases as arterioles in
skeletal muscle dilate.
• Increase in venous return contributed by
skeletal muscle pump
• Cumulative effects in addition to the
actions of the sympathetic nervous
system.
Cardiac Output during Exercise

54. Cardiac output & myocardial oxygen demand
• At rest coronary blood flow is 250 ml /min. 70- 80%
oxygen is utilized.
• During exercise coronary blood flow is 4-5 times more
with 100% oxygen is utilization.
• Increased coronary blood flow by sympathetic
stimulation -
1. Increased activity of heart.
2. Increased cardiac output.
3. Increased mean arterial pressure.
4. Coronary vasodilation –hypoxia ,fall in PH