This document discusses cardiovascular physiology, beginning with an overview of the cardiac cycle and events in the cycle. It then covers determinants of myocardial performance including preload, afterload, contractility, and heart rate. Pressure-volume loops are introduced as a way to assess ventricular function. Physiological and pathological hypertrophy are compared. Key aspects covered include the Wiggers diagram, Frank-Starling mechanism, Anrep effect, Bowditch phenomenon, and formulas for calculating cardiac values.

1. Dr.Praveen Nagula ,1st Year PG

2. Carl John Wiggers
Otto Frank
Sir Thomas Lewis
Ernest H Starling

3. William Harvey
Adolf Eugen Fick
Willem Einthoven

4. Introduction
Principal function of cardiovascular system is to deliver oxygen
and nutrients to and remove carbon dioxide and wastes from
metabolizing tissues.
It is by two specialized circulations in series
1.a low resistance pulmonary driven by right heart
2.a high resistance systemic driven by left heart
Systolic pressure in the vascular system refers to the
peak pressure reached during the systole,not the mean
pressure.
The diastolic pressure refers to the lowest pressure during
diastole.

5. WIGGERS DIAGRAM
EVENTS IN CARDIAC CYCLE
DETERMINANTS OF MYOCARDIAL PERFORMANCE
PRESSURE VOLUME LOOP
PHYSIOLOGICAL VS PATHOLOGICAL HYPERTROPHY

6. Wiggers diagram
The X axis is used to plot time,
The Y axis contains all of the following on a single grid:
Blood pressure
Aortic pressure
Ventricular pressure
Atrial pressure
Ventricular volume
Electrocardiogram
Arterial flow (optional)
Heart sounds (optional)
JVP
Illustration of the coordinated events makes it easier to correlate
the changes during the cardiac cycle.

10. WIGGERS DIAGRAM
EVENTS IN CARDIAC CYCLE
DETERMINANTS OF MYOCARDIAL PERFORMANCE
PRESSURE VOLUME LOOP
PHYSIOLOGICAL VS PATHOLOGICAL HYPERTROPHY

12. Cardiac cycle
• The cardiac cycle describes pressure,volume and flow
phenomena in the ventricles as a function of time.
• Similar for both LV and RV except for the timing,levels of
pressure.

13. Mechanical events in Cardiac cycle
• Systole
• Isovolumic contraction
• Maximal ejection
• Reduced ejection
• Diastole
• Isovolumic relaxation
• Rapid filling phase
• Slow filling phase /diastasis
• Atrial systole

14. LV
RELAXATION
• Isovolumic
contraction(b)
• Maximal
Ejection( c)
LV
CONTRACTION
• Isovolumic
relaxation(e)
• Start of relaxation and
reduced ejection (d)
• Rapid phase(f)
• Slow filling
(diastasis)(g)
• Atrial systole or
booster(a)
LV FILLING
• The letters are arbitrarily allocated so that atrial systole(a) coinicides with the a wave and (c ) with the c wave of JVP.

15. LV contraction
• Actin myosin contraction triggered by arrival of Calcium ions at
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•
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•
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contractile proteins.
ECG – peak of R wave
LV pressure >LA pressure (10-15mm Hg)
Followed approx. 50msec by M1.
Delay of M1 – inertia of the blood flow – valve is kept open.
Isovolumic contraction as volume is fixed.
Increased pressure as more fibers enter contractile state.
LV pressure >Aorta – Aortic valve opens – silent event
clinically.

17. • Phase of rapid ejection:
• Pressure gradient across the aortic valve
• Elastic properties of aorta,arterial tree (systolic expansion)
• LV pressure rises to peak and then falls.

19. LV relaxation
• Activated phospholamban causes calcium transfer into SR.
• Decreases contractile apparatus function – phase of reduced ejection –
blood flow from LV to aorta decreases but maintained by aortic recoil
– WINDKESSEL EFFECT*.
• Aortic valve closes as LV pressure drops
• Isovolumic relaxation
• Mitral valve opens – clinically silent event.
† Giovanni Borelli,Stephen Hales,Fick(mathematical foundation).
†WINDKESSEL in german AIRCHAMBER or elastic resorvoir.

20. LV filling
• Rapid filling phase – active diastolic relaxation of LV.
• LA- LV pressures equalize - diastasis.
• LA booster atrial systole – important in exercise and LVH.
• First phase of diastole –isovolumic phase – no ventricular
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filling.
Most of ventricular filling –rapid filling phase.
Diastasis -5%
Final atrial booster phase -15%.
The sucking effect of ventricle – myosin is pulled into the
space between the two anchoring segments of titin.
Dominant backward pressure wave –diastolic coronary
filling.

23. Physiologic systole,diastole
• It is related to the events occuring at the cellular level ,by
change of pressure and the electrical events.
• Physiological systole –start of isovolumic contraction to the
peak of ejection phase.
• Physiological diastole – commences as pressure falls.
• Fits well in pressure volume curve .

24. Cardiological systole,diastole
• It is related to the valve closures.
• Systole – M1-A2
• Thereby starts later than physiological systole and ends later.
• Diastole – A2-M1

26. Protodiastole
• Proto –means original,first
• The period of start of ventricular relaxation.
• Lasts until the semilunar valves are closed.
• It is 0.04 sec.

28. ECHO cardiac cycle
Rapid filling phase of diastole
Atrial systole

30. Phonocardiogram
A graphic recording of cardiac
sound
A specially designed
microphone on the chest wall.
Sound waves amplified,
filtered and recorded.
Doppler Echocardiography has
replaced the
phonocardiography

31. Carotid Pulse Tracing (CPT)
Reflects the pressure and possible small volume changes
in a segment of the carotid artery with each cardiac cycle.
P (percussion wave) is the first peak and is related to aortic
ejection. 80 msec after the first heart sound.
T (tidal wave) is the second wave and occurs late in
systole.
D (dicrotic notch) coincides with aortic closure (A2), plus
the traveling time of the pulse to the neck (.01-.05 sec).

33. Causes of Abnormalities in the Carotid Pulse

34. Jugular Venous Pulse tracing

35. JUGULAR VENOUS PULSE
Reflects volume change in the internal jugular vein and
closely resembles the pressure changes in the right atrium.
A wave atrial contraction.
C wave onset of ventricular contraction.
X descent atrial diastole.
V wave atrial filling before AV valves open.
Y descent AV valves open filling of the ventricles.

36. Apex cardiogram

37. Apex cardiogram
Records low-frequency vibrations over the apical impulse.
Deflections not delayed.
A –atrial contraction.
C –onset of LV contraction.
E – peak of the ascent (initial ejection from LV to aorta)
O – opening of the mitral valve.
RF –rapid filling wave
SF – slow filling wave.

39. WIGGERS DIAGRAM
EVENTS IN CARDIAC CYCLE
DETERMINANTS OF MYOCARDIAL PERFORMANCE
PRESSURE VOLUME LOOP
PHYSIOLOGICAL VS PATHOLOGICAL HYPERTROPHY

40. Determinants of myocardial mechanical
performance
3 main determinants
Loading conditions
(preload,afterload)
Contractile state
Heart rate

41. Preload
• Wall stress at the end of diastole – maximum resting
length of sarcomere.
• Increasing LVEDV increases SV in ejecting beats,increases
LV pressure in isovolumic beats.
• Modulation of ventricular performance by changes in
preload with constant afterload –heterometric
autoregulation,operates on a beat –to beat basis.

42. Frank Starling mechanism
• Starling – venous pressure in RA – heart volume
• Within physiological limits – the larger the volume of the heart
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–greater the energy of its contraction – the greater the amount of
chemical change at each contraction.
LV volume – Cardiac Output
Stroke volume related to LVEDV – modern version
Real time 3D ECHO – global LV volume,endocardial function
LV volume surrogate markers – LVEDP ,PCWP.

43. • Frank – greater the initial LV volume – more rapid rate of rise –
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greater the peak pressure reached –faster the rate of relaxation.
An important compensatory mechanism that maintains stroke
volume,when there is myocardial dysfunction or excessive
afterload.
Atria also exhibit frank starling curve – exercise.(resistance to
early diastolic filling).
Passive P-V relationship is exponential.
Chronic volume overload – EDPVR – rightward.
Chronic pressure overload –EDPVR - leftward.
Increased diastolic filling –Starling.
Increased inotropic effect – Frank

44. Afterload
Exact definition – wall stress during LV ejection.
Tension in the LV wall that resists ventricular ejection or as the
arterial input impedance.
In clinical practice the arterial blood pressure is often taken as
synonymous with afterload while ignoring aortic compliance
(increase in stiff aorta).

45. Anrep effect
• Homeometric autoregulation
• Under experimental conditions
sudden marked increase in aortic
pressure is produced,LVEDP initially
rises and the stroke volume then
recovers.
• Increased LV wall tension –
increases Cytosolic Na - Calcium

47. Heart rate
• Rate that would give maximal
mechanical performance of an
isolated muscle strip , also
determined by the need for
adequate time for diastolic filling.
• Normally – pacing rates of 150/min
–tolerated.
• During exercise – 170/min
• LVH – 100-130/min

49. Bowditch phenomenon
Treppe effect
Positive inotropic effect of activation
Force freqeuncy relation
• “increased heart rate – increases force of ventricular contraction”
HR – negative staircase effect
• More rapid stimulation – more sodium and calcium ions enter the
myocardial cell that can be handled by sodium pump and the
mechanisms for calcium exit - decreased force.
 Clinical implications
AF with varying interval.
In HF – phenomenon is muted or lost.
Post extrasystolic potentiation ,inotropic effect of paired pacing –
increased contractile state.
•

51. Contractility
• It is the inherent capacity of the myocardium to contract
independently of changes in the preload and afterload.
• An increased contractile function –assosciated with
greater degree of relaxation – LUSITROPIC effect
• Important regulator of My02 uptake
• Increased contractile function – exercise,adrenergic
stimulation,digitalis,other inotropic agents.

52. Ventricular relaxation
Four factors are of chief interest in influencing relaxation.
1.cytosolic calcium must fall to cause the relaxation
phase(ATP,phospholamban).
2.the inherent viscoelastic properties of the
myocardium.(hypertrophy)
3.increased phosphorylation of troponin I enhances the rate of
relaxation.
4.systolic load influences relaxation(increased systolic load,increased
lusitropic effect)(Brutsaert).
Impaired relaxation is an early event of angina pectoris(decreased
ATP –decreased early diastole filling).
-dp/dt = (rate of isovolumetric relaxation)*
*Glanz method P(t)= P0e-t⁄τE +Pα

53. Diastolic stiffness
 Diastole is the summation of processes
by which the heart loses its ability to
generate force and shorten and returns
to its precontractile state.
 Chamber stiffness is quantified from the
relationship between diastolic LV
pressure and volume.
 Volume dependent (slope of the tangent
drawn to the PV curve)
 Volume independent(intrinsic,extrinsic)
 Diastolic LV stress( ) and strain( ).
 Strain is the deformation of the muscle
produced by an applied force and is
expressed as percent change in length
from unstressed length.

55. Time varying elastance concept
Ventricular volume and loading are altered under conditions of
unvarying contractility.(frank starling preparations are load
independent).
At any time t,following the onset of contraction,the P-V relation
is linear
P(t) = E(t)-{V(t)-Vo},E –time varying elastance,Vo is volume at
zero pressure or dead volume.
Ventricle behaves like a spring with a stiffness(elastance) that
increases during contraction,decreases during relaxation.
PVA area bounded by the LV P-V loop is a measure of the total
mechanical energy of LV contraction.

57. Formulae
Ejection fraction = (stroke volume/end diastolic volume 100).
Wall tension = (P.r)/2h(P pressure,r radius,h wall thickness)
EA = PES/SV , [E- effective arterial resistance,PES-end systolic
pressure,SV- stroke volume}.
EA/Ees ratio (index of ventriculo arterial coupling,pump
performance).
Fick equation VO2 = Q(AVO2)
 V/ P = compliance. P/ V =stiffness
Cardiac output = stroke volume HR
PVA = PE+SW
PE = PES(VES-V0)/2 – PED(VED-V0)/4
PVA MV02

58. PRESSURES (mm Hg)
Right atrium mean
0-5
wave
Normalavalues
1-7
Right ventricle peak systolic/end diastolic
17-32/1-7
Pulmonary artery peak systolic/end diastolic
17-32/1-7
v wave
1-7
mean
9-19
PCWP
4-12
LA mean
4-12
a wave
4-15
v wave
4-15
LV peak systolic/end diastolic
90-140/5-12
Aorta peak systolic/end diastolic
90-140 /60-90
mean
70-105
Resistance (dynes/cm2) SVR
900-1400
PVR
40-120
Oxygen consumption index (L-min/m2)
115-140
Cardiac index (L-min/m2)
2.8-4.2

59. WIGGERS DIAGRAM
EVENTS IN CARDIAC CYCLE
DETERMINANTS OF MYOCARDIAL PERFORMANCE
PRESSURE VOLUME LOOP
PHYSIOLOGICAL VS PATHOLOGICAL HYPERTROPHY

60. Pressure volume loop
• Best of the current approaches to the assessment of the
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contractile behaviour of the intact heart.
Es,the pressure – volume relationship .
Changes in the slope of this line joining the different Es points
are generally good load independent index of the contractile
performance of the heart.
Enhanced inotropic effect, Es shifted upward and to the left.
Lusitropic effect shifted Es downward and to right.
The P-V relationship is linear in smooth muscle,curvilinear in
cardiac muscle(exponential).

64. Atrial Pressure Volume Loop

65. Atrial function
1.Blood receiving reservoir chamber
2.contractile chamber (booster pump)
3.conduit
4.volume sensor of the heart (ANP) – diuresis.
5.mechanoreceptors (Bainbridge reflex –
VR -
HR).
Rapid atrial repolarization – increased Ito ,I K Ach.
During atrial pacing,the preload is increased and the atria are
distended,so that the volume part of the loop is small and the
pressure part of the loop is much enlarged.

66. Pressure volume loop diagram
in various pathological
scenarios

67. INCREASED AFTERLOAD
EXERCISE
INCREASED PRELOAD
INOTROPIC EFFECT
HEART RATE

69. WIGGERS DIAGRAM
EVENTS IN CARDIAC CYCLE
DETERMINANTS OF MYOCARDIAL PERFORMANCE
PRESSURE VOLUME LOOP
PHYSIOLOGICAL VS PATHOLOGICAL HYPERTROPHY

70. Physiologic ,pathological hypertrophy

71. Meerson,studied the cardiac hypertrophic response to
experimental constriction of aorta.- compensatory
hypertrophy.
 Increased wall stretch,as a result of an increased
intraventricular LV pressure (Systolic stress correction
hypothesis,Grossman)- myocytes grow in width and
thicken.
Response to a sustained
LV pressure overload
Beneficial
hypertrophy
ERK,Akt(protein kinaseB)
Pathological
hypertrophy
P38MAPkinase,JNK,TGF-B

72. Chronic elevation of the preload was associated with Akt
activation without fibrosis,little apoptosis,better function,and
lower mortality.
Chronic elevation of afterload (AS) caused maladaptive
hypertrophy,increased fibrosis,rapid failure,increased mortality.
Increased release of angiotensin II from myocardium.
TGF B maldaptive hypertrophy in AS (diastolic dysfunction)
Cardiac steatosis in insulin resistance – increased TG

74. Isometric versus isotonic contraction
An isometric exercise is a form of exercise involving the static
contraction of a muscle without any visible movement in the
angle of the joint.
The term "isometric" combines the Greek words "isos" ("equal"
or "same") and "metron" ("distance" or "measure"), meaning
that in these exercises the length of the muscle and the angle of
the joint do not change, though contraction strength may be
varied.
 This is in contrast to isotonic contractions, in which the
contraction strength does not change, though the muscle length
and joint angle do.

76. WIGGERS DIAGRAM
EVENTS IN CARDIAC CYCLE
DETERMINANTS OF MYOCARDIAL PERFORMANCE
PRESSURE VOLUME LOOP
PHYSIOLOGICAL VS PATHOLOGICAL HYPERTROPHY
RV CARDIAC CYCLE

77. RV cycle

79. References
1.Ganong’s Review of Medical Physiology,24th Edition.
2.Guyton and Hall,Textbook of Medical Physiology.
3.Best and Taylor’s Physiological Basis of Medical
Practice,13th edition.
4.HURST’S,THE HEART ,13th edition
5.Braunwald’s Heart Disease,9th edition
6.Circulation Journal.
7.European Heart Journal.

80. THE WONDERFUL DAY
11-12-13