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Cardiovascular Physiology

and Hemodynamics

Daniel Burkhoff MD PhD Adjunct Associate Professor

Columbia University

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

Resources

Harvi Interactive, simulation-based

textbook for the iPad

iPad 2, 3 and mini (iOS 7)

6

Foundations in Cellular

Physiology

7

The Sarcomere

8

Sarcomere F-L Relation

9

Muscle Heart

Force - Length

Pressure - Volume

10

Integrated Cardiovascular Physiology Ventricular-Vascular Interactions

Cardiac Output

Arterial Blood Pressures

Venous Blood Pressures

11

Physiology of the

Intact Heart

The Cardiac Cycle: The Classic “Wiggers” Diagram

12

0 25 50 75 100 125 150 0

25

50

75

100

125

150

LV Volume (ml)

LV

Pre

ss

ure

(m

mH

g)

MV Closes

AoV Opens

AoV

Closes

MV

Opens

Iso

vo

lum

ic

Co

ntr

ac

tio

n

Iso

vo

lum

ic

Rela

xa

tion

Filling

Ejection

The Cardiac Cycle Pressures-Volumes Loop

13

LV Volume (ml)

LV

Pre

ss

ure

(m

mH

g)

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

0 75 150 0

75

150

LV Volume (ml)

LV

Pre

ss

ure

(m

mH

g)

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

Pressure-Volume Relations The Basics

0 25 50 75 100 125 150 0

25

50

75

100

125

150

LV Volume (ml)

LV

Pre

ss

ure

(m

mH

g)

17

Pressure-Volume Loops and Relationships

0 75 150 0

LV Volume (ml)

LV

Pre

ss

ure

(mm

Hg

)

10

20

30

End-Diastolic Pressure-Volume Relationship 18

Vo

P = β(eα(V-Vo)-1)

0 25 50 75 100 125 150 0

25

50

75

100

125

150

LV Volume (ml)

LV

Pre

ssu

re (

mm

Hg

)

Vo

Ees

End-Systolic Pressure-Volume

Relationship

(ESPVR)

Pes = Ees(Ves-Vo)

19

End-Systolic Pressure-Volume Relationship

20

EDPVR and ESPVR define the boundaries within

which the PV Loop sits, independent

of “preload” and “afterload”

21

Preload

22

Sarcomere Isometric F-L Relation

0 50 100 150 0

50

100

150

LV Volume (ml)

LV

Pre

ssu

re (

mm

Hg

)

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

0 50 100 150 0

50

100

150

LV

Pre

ssu

re (

mm

Hg

)

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)

0 50 100 150 0

50

100

150

LV

Pre

ssu

re (

mm

Hg

)

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)

0 50 100 150 0

50

100

150

LV

Pre

ssu

re (

mm

Hg

)

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

Afterload

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

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

0 50 100 150 0

50

100

150

LV Volume (ml)

LV

Pre

ssu

re (

mm

Hg

) 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 resis­tance (TPR):

TPR = (MAP-CVP)/CO

30

Afterload: Impact on LV Performance

0 50 100 150 0

50

100

150

LV Volume (ml)

LV

Pre

ssu

re (

mm

Hg

)

Increased

TPR

31

Afterload: Impact on LV Performance

Despite constant preload

and contractility:

Increased TPR

• Increased pressure

• Decreased SV

0 50 100 150 0

50

100

150

LV Volume (ml)

LV

Pre

ssu

re (

mm

Hg

)

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

0 50 100 150 0

50

100

150

LV Volume (ml)

LV

Pre

ssu

re (

mm

Hg

)

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

Contractility

35

Contractility: The concept applied to Isolated Muscle

36

Contractility: The concept applied to the Left Ventricle

0 50 100 150 0

25

50

75

100

125

150

LV Volume (ml)

LV

Pre

ss

ure

(m

mH

g)

Ees Ees

37

Contractility

38

Lusitropy Diastole

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

Lusitropy: Passive Diastolic Properties

41

Lusitropy: Passive Diastolic Properties

42

Lusitropy: Passive Diastolic Properties

The EDPVR shifts leftward: • Hypertrophic cardiomyopathies

• Infiltrative diseases (amyloid, sarcoid)

• Restrictive cardiomyopathy

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

Lusitropy: The Rate of Relaxation

Isovolumic

Relaxation

τ LVP

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

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

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

Cardiac Performance cardiac output, blood pressure, etc

Determined by the interaction between

the heart and vascular systems

48

SUMMARY

PRELOAD

AFTERLOAD

CONTRACTILITY

LUSITROPY

49

Harvi Interactive, simulation-based

textbook for the iPad

iPad 2, 3 and mini (iOS 7)

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