The document outlines key concepts of cardiovascular physiology, including cardiac volumes, contractility, and the Frank-Starling relationship, which describes how myocardial stretch affects stroke volume. It explains the physiological mechanisms governing heart function, including neural and hormonal regulation, various reflexes, and the characteristics of cardiac muscle fibers. Additionally, it details methods for measuring cardiac output and the heart's intrinsic and extrinsic controls along with cardiac action potentials.

1. Cardiovascular Physiology

2. CARDIAC VOLUMES
• Stroke Volume: The volume of blood pumped with each heartbeat
– it is determined by
• Preload: gives the volume of blood that the ventricle has available to
pump
• Contractility : the force that the muscle can create at the given length
• Afterload: the arterial pressure against which the muscle will
contract.
– SV=EDV-ESV
• EDV (End Diastolic Volume)- amount of blood collected in a ventricle during
diastole
• ESV(End Systolic Volume)- amount of blood remaining in a ventricle after
contraction
• Ejection fraction: the fraction of EDV pumped with each heart beat
– EF=SV/EDV

3. Preload
• Preload is the ventricular load at the end of
diastole, before contraction has started.
• First described by Starling, a linear
relationship exists between sarcomere length
and myocardial force.

4. Frank-Starling Relationship
• Frank-Starling relationship.
The relationship between
sarcomere length and
tension developed in cardiac
muscles is shown.
• In the heart, an increase in
end-diastolic volume is the
equivalent of an increase in
myocardial stretch;
• Therefore, according to the
Frank-Starling law, increased
stroke volume is generated.

5. Frank-Starling Relationship
• The Frank-Starling relationship is an intrinsic property of
myocardium by which stretching of the myocardial sarcomere
results in enhanced myocardial performance for subsequent
contractions
• Heart muscle expands to maximum during filling.
• Maximal length produces maximum tension on the muscle,
resulting in forceful contraction.
• Therefore, greater filling (more volume entering the heart)
produces greater ejection (more volume leaving).

6. FRANK STARLING PRINCIPLE CONT…
• A family of Frank-Starling curves is shown. A leftward shift of the curve denotes
enhancement of the inotropic state, whereas a rightward shift denotes decreased
inotropy

7. LAPLACE LAW
σ=P×R/2h
σ- wall stress
P- Pressure
R- radius of the ventricle
h – thickness of the ventricle
Wall stress and heart rate are probably the two
most relevant factors that account for changes
in myocardial oxygen demand
• Ellipsoid shape is responsible for the least
amount of stress,therefore when the shape
changes to spherical during contraction, the wall
stress increases.

8. • In response to aortic
stenosis, left ventricular
(LV) pressure increases. To
maintain wall stress at
control levels,
compensatory LV
hypertrophy develops.
• Therefore, the increase in
wall thickness offsets the
increased pressure, and
wall stress is maintained at
control levels

9. CARDIAC OUTPUT
• Cardiac output is the amount of blood pumped by the
heart per unit of time.
• It determined by four factors:
• Two factors that are intrinsic to the heart
• heart rate and
• myocardial contractility
• Two factors that are extrinsic to the heart
• preload and
• afterload

10. Measurement of cardiac output
– Invasive methods
• Fick’s method
• Dye dilution method

11. • Cardiac output in a living
organism can be measured with
the Fick’s principle
• If the oxygen (O2) concentration
in pulmonary arterial blood
(CpaO2), the O2 concentration of
the pulmonary vein (CpvO2), and
the O2 consumption are known,
then cardiac output can be
calculated. pa, Pulmonary artery;
pv, pulmonary vein

12. • The Fick principle is based on the concept of
conservation of mass such that the O2
delivered from pulmonary venous blood (q3)
is equal to the total O2 delivered to
pulmonary capillaries through the pulmonary
artery (q1) and the alveoli (q2).

13. • The amount of O2 delivered to the pulmonary
capillaries by way of the pulmonary arteries (q1) equals
total pulmonary arterial blood flow (Q) times the O2
concentration in pulmonary arterial blood (CpaO2):
• q1 =Q × CpaO2
• The amount of O2 carried away from pulmonary
venous blood (q3) is equal to total pulmonary venous
blood flow (Q) times the O2 concentration in
pulmonary venous blood (CpvO2):
• q3 =Q × CpvO2

14. q1+q2=q3
Q(CpaO2)+q2=Q(CpvO2)
q2=Q{CpvO2-CpaO2)
Q=q2/(CpvO2-CpaO2)
• Thus, if the CpaO2, CpvO2, and O2 consumption (q2)
are known, then the cardiac output can be determined.

15. Indicator Dilution Method for Measuring
Cardiac Output
• A dye is injected into a large systemic vein or,
preferably, into the right atrium.
• This passes rapidly through the right side of the heart,
then through the blood vessels of the lungs, through
the left side of the heart, and, finally, into the systemic
arterial system.
• The concentration of the dye is recorded as the dye
passes through one of the peripheral arteries

16. • Extrapolated dye concentration
curves used to calculate two
separate cardiac outputs by
the dilution method.
• (The rectangular areas are the
calculated average
concentrations of dye in the
arterial blood for the durations
of the respective extrapolated
curves.)

17. • A total of 5 mg of dye had been injected at the
beginning.
• Average concentration of dye was 0.25 mg/dl of
blood
• Duration of this average value was 12 seconds.
• CO= 5X60/ 0.25X12 =10L/min

18. EXTRINSIC INNERVATION OF THE HEART
• Afferents:
– SYMPATHETIC- the paired superior,
middle and inferior cardiac nerves from
the cervical ganglia and those originating
from the upper 4-5 thoracic ganglia
– PARASYMPATHETIC- the paired vagi
– Form the cardiac plexus
• Efferents:
– Through the C fibres , to the white rami,
to bulbar center
– Responsible for perception of cardiogenic
pain.
– Through Glossopharyngeal and Vagus
nerves

19. NEURAL REGULATION OF CARDIAC
FUNCTION
• The two limbs of the autonomic nervous
system provide opposing input to regulate
cardiac function.

20. • The neurotransmitter of the parasympathetic nervous system is
acetylcholine.
• Parasympathetic innervation of the heart is through the vagal nerve.
• The principal parasympathetic target neuroeffectors are the muscarinic
receptors in the heart.
• Activation of muscarinic receptors
– reduces pacemaker activity,
– slows AV conduction,
– directly decreases atrial contractile force, and
– exerts inhibitory modulation of ventricular contractile force

21. • The neurotransmitter of the sympathetic nervous system is
norepinephrine.
• Norepinephrine released from sympathetic nerve terminals stimulates
adrenergic receptors located in the heart. The two major classes of ARs
are α and β
• Sympathetic receptors:
– All types of β receptors are found in the human heart.
– β1 receptors are the predominant subtype in heart(both atria and
ventricles)
– β2 – atria>ventricles
– β3- ventricles
• β-AR stimulation increases both contraction and relaxation

22. • The two major subpopulations of α-ARs are α1
and α2.
-α₁ receptors-
• α₁A, α₁B, and α₁D subtypes
• Both α₁A and α₁B are positive inotropic
• Cardiac hypertrophy is primarily mediated by α₁A ARs
-α₂ receptors-
• Three subtypes α₂ A, α₂B and α₂C.
• Presynaptic inhibition of NE release

23. HORMONAL REGULATION
• Cardiac hormones: Polypeptides secreted by cardiac tissues
– Natriuretic peptides
– Adrenomedullin
– Angiotensin II
– Aldosterone
• Natriuretic peptides:
– Atrial natriuretic protein- secreted from the atria
– B-type natriuretic peptide- from the venttricles
– Generate cGMP
– Cardiac endocrine response to pressure or volume overload
– Organogenesis of the embryonic heart and CVS
– In patients with chronic heart failure, increases of serum ANP and BNP levels are a
predictor of mortality

24. • Adrenomedullin is a recently discovered cardiac hormone that was originally
isolated from pheochromocytoma tissue.
– Positive inotropic and positive chronotropic
– Increase NO- potent vasodilator
• Angiotensin II- key modulator of cardiac growth and function
– Two receptors- AT₁ and AT₂
– AT₁
• Predominant subtype
• Positive chronotropic and inotropic
• Cell growth and proliferation of myocytes and fibroblasts
• Activation of AT1 receptors is directly involved in the development of
cardiac hypertrophy and heart failure
– AT₂
• Antiproliferative
• Most abundant in fetal heart
• Upregulated in response to injury and ischemia

25. CARDIAC REFLEXES
• Cardiac reflexes are fast-acting reflex loops
between the heart and the central nervous
system (CNS) that contribute to
-Regulation of cardiac function and
-Maintenance of physiologic homeostasis.
• Specific cardiac receptors elicit their
physiologic responses by various pathways.

26. • Cardiac receptors are linked to the CNS by myelinated or
unmyelinated afferent fibers that travel along the vagus nerve.
• Cardiac receptors are in the
– atria,
– ventricles,
– pericardium, and
– coronary arteries.
• Extracardiac receptors are located in the
– great vessels and
– carotid artery.

27. Reflexes
1. Baroreceptor Reflex
2. Chemoreceptor Reflex
3. Brain Bridge Reflex
4. Bezold-Jarisch Reflex
5. Valsalva Maneuver
6. Cushing Reflex
7. Occulocardiac Reflex

28. Baroreceptor Reflex (Carotid Sinus Reflex)
• The baroreceptor reflex is responsible for maintenance of
arterial blood pressure.
• Changes in arterial blood pressure are monitored by
circumferential and longitudinal stretch receptors located in
the carotid sinus and aortic arch.
• The nucleus solitarius, located in the cardiovascular center
of the medulla, recieves the impulse from these stretch
receptors through afferent glossopharyngeal and vagus
nerves.

29. • The cardiovascular center in medulla consists of two
functionally different areas;
– LATERALLY & ROSTRALLY- This area is responsible for
increasing blood pressure
– CENTRALLY & CAUDALLY- This area is responsible for
lowering arterial blood pressure.
• Typically, the stretch receptors are activated if
systemic blood pressure is greater than 170 mm of
Hg

30. • The response from depressor system includes
decreased sympathetic activity, leading to decrease in
cardiac contractility, heart rate and vascular tone.
• In addition, activation of the parasymapathetic system
further decreases the heart rate, myocardial
contractility.
• Reverse effects are elicited with the onset of
hypotension

31. • The baroreceptor reflex plays an important
beneficial role during acute blood loss and
shock.
• However, the reflex arch loses its functional
capacity when arterial blood pressure is less
than 50 mm Hg

32. CHEMORECPTOR REFLEX
• Chemosensitive cells are located in the carotid
bodies and the aortic body.
• These cells respond to changes in pH status
and blood O2 tension

33. • At PaO2 < 50 mm Hg or in acidosis
• Chemoreceptors send impulses along the
– sinus nerve of Hering (a branch of the glossopharyngeal
nerve) and
– the tenth cranial nerve to the chemosensitive area of
the medulla.
• This area responds by
– Stimulating the respiratory centers and thereby
increasing ventilatory drive.
– Activation of the parasympathetic system ensues and
leads to a reduction in heart rate and myocardial
contractility.

34. Bainbridge Reflex

35. BEZOLD- JARISCH REFLEX
• The Bezold-Jarisch reflex responds to noxious ventricular
stimuli

36. • Because it invokes bradycardia, the Bezold-Jarisch
reflex is thought of as a cardioprotective reflex.
• This reflex has been implicated in the physiologic
response to a range of cardiovascular conditions
such as
– myocardial ischemia or
– infarction,
– thrombolysis, or
– revascularization and
– syncope.

37. Valsalva Maneuver

39. Cushing Reflex

40. Oculocardiac Reflex

41. • The incidence of this reflex during ophthalmic
surgery ranges from 30% to 90%.
• Administration of an antimuscarinic drug such
as glycopyrrolate or atropine reduces the
incidence of bradycardia during eye surgery

42. THE CARDIAC MUSCLE
Myocardium has three types of muscle fibers:
I. Cardiac muscles forming the walls of the atria and
ventricles (contractile unit of the heart).
II. Muscle fibres forming the pacemaker which is the site of
origin of cardiac impulse.
III.Muscle fibres forming the conducting system which
transmits the impulse to the various parts of the heart

43. Muscle Fibres which Form the Contractile unit
● Cardiocytes are 10-20 micrometers in
diameter and 50-100 micrometers in
length.
● Cardiac muscle fibers are striated and
involuntary
● Sarcomere of the cardiac muscle has all the
contractile proteins, namely actin, myosin,
troponin and tropomyosin.
● Cardiocytes have a single nucleus and are
short, thick, and branched.

45. ● Exhibit branching
● Adjacent cardiac cells are joined end to end by
specialized structures known as -intercalated discs
● Within intercalated discs there are two types of
junctions
— Desmosomes -to provide additional support and
stability for the cardiac muscle fibers.
— Gap junctions that allow action potential to spread
from one cell to adjacent cells

46. ●Contain Large Mitochondria
●Mechanism of contraction is similar to skeletal muscle cells.
●Cardiac muscle is oxygen dependant, receives oxygen from blood in
coronary arteries.
●Can use various organic fuels; fatty acids, glucose, ketones, and
lactic acid.
●Fatigue resistant- beats continuously from early embryonic stage to
death.

47. Heart function as syncytium
● When one cardiac cell undergoes an action
potential, the electrical impulse spreads to all
other cells that are joined by gap junctions so
they become excited and contract as a single
functional syncytium.
● Atrial syncytium and ventricular syncytium

48. Orientation of cardiac muscle fibres:
● Unlike skeletal muscles,
cardiac muscles have to
contract in more than
one direction.
● Cardiac muscle cells are
striated, meaning they
will only contract along
their long axis.
● In order to get
contraction in two axis,
the fibres wrap around.

49. Cardiac Action Potential
● Action potential in heart initiated by group of specialized
cells called SA node.
● Cardiac action potential is a brief changes in
voltage(membrane potential) across the cell membrane of
the heart cells.
● This is caused by movement of charged ions between the
inside and outside of the cell through protein called ion
channels.

51. SPREAD OF ACTION POTENTIAL THROUGH CARDIAC MUSCLE
● Action potential spreads through cardiac muscle
very rapidly because of the presence of gap
junctions between the cardiac muscle fibers.
● Gap junctions are permeable junctions and allow
free movement of ions and so the action potential
spreads rapidly from one muscle fiber to another
fiber.

52. ii) Muscle fibres forming the pacemaker
● Some of the muscle fibres of heart are modified into a
specialized structure known as pacemaker.
● These muscle fibres forming the pacemaker have less
striation.
● They are named pacemaker cells or P cells.
● Sino-atrial (SA) node forms the pacemaker in human heart.

53. Action Potential
● Depolarization starts very slowly and
the threshold level of –40 mV is
reached very slowly.
● After the threshold level, rapid
depolarization occurs up to +5 mV. It
is followed by rapid repolarization.
● Once again, the resting membrane
potential becomes unstable and
reaches the threshold level slowly

54. Depolarization
● When the negativity is decreased to –40 mV, which is the
threshold level, the action potential starts with rapid
depolarization.
● The depolarization occurs because of influx of more calcium ions

55. Repolarization
● After rapid depolarization, repolarization
starts.
● It is due to the efflux of potassium ions from
pacemaker fibers.
● Potassium channels remain open for a longer
time, causing efflux of more potassium ions.
● It leads to the development of more
negativity, beyond the level of resting
membrane potential. It exists only for a short
period.
● Then, the slow depolarization starts once
again, leading to the development of
pacemaker potential, which triggers the next
action potential.

56. CONTRACTILITY
● CONTRACTILITY -
„ Contractility is ability of the tissue to shorten
in length (contraction) after receiving a stimulus.
● Following are the contractile properties:
○ ALL-OR-NONE LAW „
○ STAIRCASE PHENOMENON „
○ SUMMATION OF SUBLIMINAL STIMULI „
○ REFRACTORY PERIOD

57. ALL-OR-NONE LAW
● According to all-or-none law, when a stimulus is applied,
whatever may be the strength, the whole cardiac muscle
gives maximum response or it does not give any response
at all.
● Below the threshold level, i.e. if the strength of stimulus is
not adequate, the muscle does not give response
● Cause for All-or-none law
All-or-none law is applicable to whole cardiac muscle.
It is because of syncytial arrangement of cardiac muscle.

58. ● First, one stimulus is applied with a
strength of 1 volt and the
contraction is recorded.
● Then, after 20 seconds, the
strength is increased to 2 volt and
the contraction is recorded.
● The procedure is repeated by
increasing the strength every with
an interval of 20 seconds
● Amplitude of all contractions
remains same, irrespective of
increasing the strength of stimulus.
This shows that cardiac muscle
obeys all-or-none law

59. STAIRCASE PHENOMENON or TREPPE PHENOMENON
● When the ventricle is
stimulated at a interval of 2
seconds, without changing
the strength, the force of
contraction increases
gradually for the first few
contractions and then it
remains same.
● Gradual increase in the force
of contraction is called
staircase phenomenon.

60. SUMMATION OF SUBLIMINAL STIMULI
● When a stimulus with a subliminal strength is applied, the quiescent heart
does not show any response.
● When few stimuli with same subliminal strength are applied in succession,
the heart shows response by contraction, due to the summation of stimuli.

61. REFRACTORY PERIOD
● Refractory period is the period in which the muscle
does not show any response to a stimulus.
● It is of two types:
○ 1. Absolute refractory period
○ 2. Relative refractory period.

62. ● Absolute Refractory Period
○ Absolute refractory period is the period during which the muscle does not show
any response at all, whatever may be the strength of the stimulus.
○ It is because, the depolarization occurs during this period. So, a second
depolarization is not possible.
● Relative Refractory Period
○ Relative refractory period is the period during which the muscle shows
response if the strength of stimulus is increased to maximum.
○ It is the stage at which the muscle is in repolarizing state.

63. Refractory Period in Cardiac Muscle
● Cardiac muscle has a long refractory period compared to
skeletal muscle.
● Absolute refractory period extends throughout the
contraction period of cardiac muscle and its duration is
0.27 sec.
● Relative refractory period extends during first half of
relaxation period, which is about 0.26 sec.
● So, the total refractory period is 0.53 sec.

64. Refractory period in beating heart
● When the stimulus is applied during systole, the heart does not
show any response.
● It is because the absolute refractory period extends throughout
systole

65. ● When a stimulus is applied during diastole, the heart contracts because,
diastole is the relative refractory period.
● This contraction is called extrasystole or premature contraction.
● Extrasystole is followed by the stoppage of heart in diastole for a while.
● Temporary stoppage of the heart before it starts contracting is called
compensatory pause.

66. Refractory period in quiescent heart
● When two stimuli are applied
successively in such a way that the
second stimulus falls during
contraction period, the heart
contracts only once.
● It is because of the first stimulus.
There is no response to second
stimulus because systole is the
absolute refractory period.

67. ● However, when a second
stimulus is applied during
diastole, the heart contracts
again and second contraction
superimposes over the first one.
● This shows that the relative
refractory period extends
during diastole

68. Frank-Starling Relationship
• The Frank-Starling relationship is an intrinsic property of
myocardium by which stretching of the myocardial sarcomere
results in enhanced myocardial performance for subsequent
contractions
• Heart muscle expands to maximum during filling.
• Maximal length produces maximum tension on the muscle,
resulting in forceful contraction.
• Therefore, greater filling (more volume entering the heart)
produces greater ejection (more volume leaving).