The goal of this webinar is to provide an overview of the fundamental principles of preload, afterload, contractility and lusitropy (diastolic properties), how these are quantified on the pressure-volume diagram, and how they are affected in heart failure. Links are made to underlying properties of cardiac muscle and ventricular structure. After establishing basic concepts, it will be demonstrated how pressure-volume analysis can lead to a quantitative understanding of how heart and vasculature interact to determine stroke volume, cardiac output and blood pressure. The implications for understanding therapeutic effects will also be discussed. Key Topics: - Preload, Afterload, Contractility and Lusitropy - Cardiac Muscle and Ventricular Structure - Understanding Heart-Vasculature Interactions - PV Loops in Heart Failure - Understanding Therapies and Their Effects on Cardiac Pump Performance

2. InsideScientific is an online educational environment
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3. Cardiovascular Physiology
and Hemodynamics
Daniel Burkhoff MD PhD
Adjunct Associate Professor
Columbia University

4. 4
If your research involves studying the effects of altered
genes, cells, extracellular matrix, drugs, etc, on
cardiovascular properties, there are several key
concepts, indexes and measurement techniques you
should be aware of:
PRELOAD
AFTERLOAD
CONTRACTILITY
LUSITROPY

5. 5
Resources
Harvi
Interactive, simulation-based
textbook for the iPad
iPad 2, 3 and mini (iOS 7)

6. 6
Foundations in Cellular
Physiology

7. 7
The Sarcomere

8. 8
Sarcomere F-L Relation

9. 9
Muscle Heart
Force - Length
Pressure - Volume

10. 10
Integrated Cardiovascular Physiology
Ventricular-Vascular Interactions
Cardiac Output
Arterial Blood Pressures
Venous Blood Pressures

11. 11
Physiology of the
Intact Heart

12. The Cardiac Cycle:
The Classic “Wiggers” Diagram
12

13. 0 25 50 75 100 125 150
0
25
50
75
100
125
150
LV Volume (ml)
LVPressure(mmHg)
MV Closes
AoV Opens
AoV
Closes
MV
Opens
Isovolumic
Contraction
Isovolumic
Relaxation
Filling
Ejection
The Cardiac Cycle
Pressures-Volumes Loop
13

14. LV Volume (ml)
LVPressure(mmHg)
SV
Stroke Volume
End Diastolic Volume
End Systolic Volume
SV = ESV-EDV
EF = SV/EDV
CO=SV.HR
Volumes Retrievable from the PV Loop
ESV EDV
14

15. 0 75 150
0
75
150
LV Volume (ml)
LVPressure(mmHg)
DBP
SBP
Pes
EDP
LAP
Systolic Blood Pressure
End Systolic Pressure
Diastolic Blood Pressure
End Diastolic Pressure
Left Atrial Pressure
15
Pressures Retrievable from the PV Loop

16. 16
Pressure-Volume Relations
The Basics

17. 0 25 50 75 100 125 150
0
25
50
75
100
125
150
LV Volume (ml)
LVPressure(mmHg)
17
Pressure-Volume Loops and Relationships

18. 0 75 150
0
LV Volume (ml)
LVPressure
(mmHg)
10
20
30
End-Diastolic Pressure-Volume Relationship
18
Vo
P = β(eα(V-Vo)-1)

19. 0 25 50 75 100 125 150
0
25
50
75
100
125
150
LV Volume (ml)
LVPressure(mmHg)
Vo
Ees
End-Systolic Pressure-Volume
Relationship
(ESPVR)
Pes = Ees(Ves-Vo)
19
End-Systolic Pressure-Volume Relationship

20. 20
EDPVR and ESPVR define the boundaries within
which the PV Loop sits, independent
of “preload” and “afterload”

21. 21
Preload

22. 22
Sarcomere Isometric F-L Relation

23. 0 50 100 150
0
50
100
150
LV Volume (ml)
LVPressure(mmHg)
Preload:
The load imposed on the ventricle
at the end of diastole. The most
common measures of preload
include end-diastolic volume (EDV)
and end-diastolic pressure (EDP).
23
Preload: Ventricular Level
EDV, EDP

24. 0 50 100 150
0
50
100
150
LVPressure(mmHg)
Increased
Preload
Preload:
The load imposed on the ventricle
at the end of diastole. The most
common measures of preload
include end-diastolic volume (EDV)
and end-diastolic pressure (EDP).
24
Preload: Ventricular Level
LV Volume (ml)

25. 0 50 100 150
0
50
100
150
LVPressure(mmHg)
Decreased
Preload
Preload:
The load imposed on the ventricle
at the end of diastole. The most
common measures of preload
include end-diastolic volume (EDV)
and end-diastolic pressure (EDP).
25
Preload: Ventricular Level
LV Volume (ml)

26. 0 50 100 150
0
50
100
150
LVPressure(mmHg)
Decreased
Preload
Increased
Preload
The different loops are
obtained with different
preloads, but constant
contractility and afterload.
26
Preload: Ventricular Level
LV Volume (ml)

27. 27
Afterload

28. 28
Afterload: Intact Ventricle
• There are several different indexes of
ventricular afterload, each with its own
merits and drawbacks:
• Myocardial wall stress
• Arterial Pressure
• Arterial Resistance
• Arterial Impedance

29. 29
Afterload: Total Peripheral Resistance
• Conceptually, for the intact LV, a measure of afterload should
provide a quantitative index that uniquely characterizes the
arterial system independent of preload and contractility
• Such an index can be derived from the
relationship between pressure and flow
through the system
• One index, total peripheral resistance
(TPR), is based on Ohms law and is
simply the ratio between mean pressure
across the system and mean flow:
TPR = (MAP-CVP)/CO
MAP
CVP
Flow

30. 0 50 100 150
0
50
100
150
LV Volume (ml)
LVPressure(mmHg)
Afterload: The mechanical load
on the ventricle during ejection.
Under normal physiological
conditions, this is determined by
the arterial system. The most
common index of afterload is total
peripheral resis-tance (TPR):
TPR = (MAP-CVP)/CO
30
Afterload: Impact on LV Performance

31. 0 50 100 150
0
50
100
150
LV Volume (ml)
LVPressure(mmHg)
Increased
TPR
31
Afterload: Impact on LV Performance
Despite constant preload
and contractility:
Increased TPR
• Increased pressure
• Decreased SV

32. 0 50 100 150
0
50
100
150
LV Volume (ml)
LVPressure(mmHg)
Decreased
TPR
32
Afterload: Impact on LV Performance
Despite constant preload
and contractility:
Increased TPR
• Increased pressure
• Decreased SV
Decreased TPR
• Decreased SV
• Increased pressure

33. 0 50 100 150
0
50
100
150
LV Volume (ml)
LVPressure(mmHg)
Decreased
TPR
Increased
TPR
33
Afterload: Impact on LV Performance
Despite constant preload
and contractility:
The pressure-volume loop
falls within the boundaries
established by the
ESPVR and EDPVR

34. 34
Contractility

35. 35
Contractility:
The concept applied to Isolated Muscle

36. 36
Contractility:
The concept applied to the Left Ventricle

37. 0 50 100 150
0
25
50
75
100
125
150
LV Volume (ml)
LVPressure(mmHg)
Ees
Ees
37
Contractility

38. 38
Lusitropy
Diastole

39. The EDPVR is
nonlinear and
defines the boundary
for the position of the
end-diastolic
pressure-volume
point of the PV loop:
Ped= β(eα(Ved-Vo)-1)
39
Lusitropy:
Passive Diastolic Properties

40. 40
Lusitropy:
Passive Diastolic Properties

41. 41
Lusitropy:
Passive Diastolic Properties

42. 42
Lusitropy:
Passive Diastolic Properties
The EDPVR shifts leftward:
• Hypertrophic cardiomyopathies
• Infiltrative diseases (amyloid, sarcoid)
• Restrictive cardiomyopathy

43. 43
Lusitropy:
The Rate of Relaxation
The decay of pressure during
the isovolumic relaxation phase
of diastole follows a roughly
exponential time course.
P = e-t/τ
Active relaxation can therefore
be characterized by τ, the time
constant of relaxation.
Isovolumic
Relaxation
LVP

44. 44
Lusitropy:
The Rate of Relaxation
Isovolumic
Relaxation
τLVP
The decay of pressure during
the isovolumic relaxation phase
of diastole follows a roughly
exponential time course.
P = e-t/τ
Active relaxation can therefore
be characterized by τ, the time
constant of relaxation.

45. 45
τ is influenced by:
• Contractile element isoforms
• Heart Rate
• τ decreases significantly as heart rate increases
• Energy Supply
• τ increases significantly during myocardial
ischemia
• β Stimulation
• τ decreases significantly with β-adrenergic
stimulation or any drugs that increase ATP
Lusitropy:
The Rate of Relaxation

46. 46
Lusitropy
• Passive diastolic properties: the extent of
relaxation
• Characterized by the EDPVR
• Compliance
• Stiffness
• Capacitance
• Active relaxation: the rate of relaxation
• Indexed by τ
• Impact on cardiac performance highly
dependent on heart rate
• Concept of “incomplete relaxation”

47. 47
Cardiac Performance
cardiac output, blood pressure, etc
Determined by the interaction between
the heart and vascular systems

48. 48
SUMMARY
PRELOAD
AFTERLOAD
CONTRACTILITY
LUSITROPY

49. 49
Harvi
Interactive, simulation-based
textbook for the iPad
iPad 2, 3 and mini (iOS 7)

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