regulation of coronary blood flow · regulation of coronary blood flow … a glossary for...

Regulation of Coronary Blood Flow

… A Glossary for Interventionalists

Bernard De Bruyne

Cardiovascular Center Aalst

Belgium

1. General concepts

2. Epicardial vs microvascular compartments

3. Flow-function relationship

4. Coronary autoregulation

ABC of Coronary Physiology for the Interventionalist

Coronary Circulation

Systolic

compression

Cardiac

Myocytes

O2

Driving

Pressure Contractile force

Uniqueness of the Coronary Circulation

No other circulation is so dependent

on the function of the organ it perfuses

Adapted from D.J.G.M. Duncker and Bache R Physiol Rev 2008

Physical

factors

Endo- and paracrine

factors

Noradrenaline Adrenaline

Acethylcholine

adenosine

PO2

Histamine

Bradykinine

Systolic compression Diastolic compression

Arterial Pressure Coronary pressure RAP, LVDP and Pf=0

PCO2, H+, K+

Angiotensine II

α1 α2

β1 β 2

H1

A2

M

H2

AT1

ETB

ET

ETA

ETB 5-HT

TXA2

NO

PGI2

EDHF

M

α2

NO PGI2 EDHF

NO PGI2 EDHF

B2

P2

H1

P2

Endothelium TXA2

5-HT

M

P2

Neuro-humoral

factors

Metabolic

factors

The Control of Myocardial Blood Flow

Extravascular Compressive Forces

Pressure

Aorta

LV

Extravascular Compressive Forces

Pressure

LAD FLOW

Aorta

LV

Extravascular Compressive Forces

Pressure

LAD FLOW

Aorta

LV

Coronary

Pressure

LAD FLOW

RCA FLOW

Extravascular Compressive Forces

Aorta

RV

Pressure

LAD FLOW

RCA FLOW

Extravascular Compressive Forces

Aorta

RV

Pressure

LAD FLOW

RCA FLOW

Extravascular Compressive Forces

Aorta

RV

11

Subepicardium

Subepicardium

Subendocardium

Subendocardium

2.1 μ

2.2 μ

1.9 μ

1.6 μ

Diastole

Systole

Epicardial artery

Intramural artery

Arteriole

Subendocardial plexus

External superficial Spiral muscle

Deep constrictor muscle

Internal superficial Spiral muscle

Endo/Epi flow : 1.2

Systolic Compression

Adapted from D.J.G.M. Duncker and Bache R Physiol Rev 2008

Physical

factors

Endo- and paracrine

factors

Noradrenaline Adrenaline

Acethylcholine

adenosine

PO2

Histamine

Bradykinine

Systolic compression Diastolic compression

Arterial Pressure Coronary pressure RAP, LVDP and Pf=0

PCO2, H+, K+

Angiotensine II

α1 α2

β1 β 2

H1

A2

M

H2

AT1

ETB

ET

ETA

ETB 5-HT

TXA2

NO

PGI2

EDHF

M

α2

NO PGI2 EDHF

NO PGI2 EDHF

B2

P2

H1

P2

Endothelium TXA2

5-HT

M

P2

Neuro-humoral

factors

Metabolic

factors

The Control of Myocardial Blood Flow

0 100 200 300 400 500 0

0.05

0.1

0.15

0.2

0.25

0.3

Regional Myocardial Mass (g)

Cro

ss-S

ect

ion

al L

um

en

al A

rea

(cm

²)

C. Seiler et al Circulation 1992

Relation between Vessel Size and Myocardial Mass

CAD

Normals

Flow

Mass

Pressure

Distance from the ostium

% of value at the ostium

100

Diameter

APEX BASE

About Pressure, Flow, Resistance, and Vessel Size

About Pressure, Flow, Resistance, and Vessel Size

Ref Diam (mm)

% Stenosis for an

Cross Sectional Area of 4 mm²

< 4 mm² = significant stenosis ?

0 25 50 2

3

4

5

About Pressure, Flow, Resistance, and Vessel Size

Anatomy vs Physiology: the Chimeric Link

Waksman et al. JACC 2013

Sarno et al JACC 2009

Guagliumi et al EuroInterv 2013

IVUS OCT

CCT

Statistical (mechanistic) relation but little clinical relation

FFR

Angio

DS

Toth et al EHJ 2014

1. General concepts

2. Epicardial vs microvascular compartments

3. Flow-function relationship

4. Coronary autoregulation

ABC of Coronary Physiology For the Interventionalist

Two-Compartment Model of the Coronary Circulation

The coronary angiogram detects only 5% of the total coronary tree

Epicardial Artery Microvasculature

FFR IMR

CFR

Two-Compartment Model of the Coronary Circulation

Conductance Arteries

<500 µ

Pa

100

MICRO

>500 µ

Resistance Arteries

MACRO

Microvasculature

Two-Compartment Model of the Coronary Circulation

Pressure and Flow Velocity in Normal Coronary Arteries

CFR = 4.15

FFR = 0.98

Adenosine

Conductance Arteries

<500 µ

Pa

100

>500 µ

Resistance Arteries

Microvasculature

Focal Stenosis

MICRO MACRO

Conductance Arteries

<500 µ >500 µ

Resistance Arteries

Microvasculature

Stent

Pa

100

MICRO MACRO

Conductance Arteries

<500 µ

Pa

100

>500 µ

Resistance Arteries

Microvasculature

Focal Stenosis

Diffuse Atherosclerosis

MICRO MACRO

Conductance Arteries

<500 µ

Pa

100

>500 µ

Resistance Arteries

Microvasculature

Diffuse Atherosclerosis

Stent

MICRO MACRO

Conductance Arteries

<500 µ

Pa

100

>500 µ

Resistance Arteries

Microvasculature

Diffuse Atherosclerosis

MICRO MACRO

Normal

Endothelium

Vascular Smooth

Muscle Cell

NO

Guanyl Cyclase

eNOS

L-Arginine

cGMP Relaxation

Mechano-

receptor

Shear stress

of blood flow

ACh Bradykinine

Endothelin

Endothelial Control of vascular tone

Dysfunctional

Endothelium

NO

Guanyl Cyclase

eNOS

L-Arginine

cGMP Constriction

Mechano-

receptor

Shear stress

of blood flow

ACh Bradykinine

Endothelin

Endothelial Control of vascular tone

Vascular Smooth

Muscle Cell

Importance of Maximal Vasodilation

Nitrates Adenosine

Vasospasm Autoregulation

Epicardial = Conductance Arteries > 550 µ

Microvasculature = Resistance

Arteries < 550 µ

Yeung AC et al. N Engl J Med 1991;325:1551-1556.

Endothelial Control of Coronary Blood Flow

Effect of Mental Stress on

the Diameter of Coronary Arteries

1. General concepts

2. Epicardial vs microvascular compartments

3. Flow-function relationship

4. Coronary autoregulation

ABC of Coronary Physiology For the Interventionalist

Adapted from D.J.G.M. Duncker and Bache R Physiol Rev 2008

Physical

factors

Endo- and paracrine

factors

Noradrenaline Adrenaline

Acethylcholine

adenosine

PO2

Histamine

Bradykinine

Systolic compression Diastolic compression

Arterial Pressure Coronary pressure RAP, LVDP and Pf=0

PCO2, H+, K+

Angiotensine II

α1 α2

β1 β 2

H1

A2

M

H2

AT1

ETB

ET

ETA

ETB 5-HT

TXA2

NO

PGI2

EDHF

M

α2

NO PGI2 EDHF

NO PGI2 EDHF

B2

P2

H1

P2

Endothelium TXA2

5-HT

M

P2

Neuro-humoral

factors

Metabolic

factors

The Control of Myocardial Blood Flow

Neuro-humoral factors

Metabolic factors

Endo- and paracrine factors

Physical factors

Endothelium

Multiple, interacting, cumulative, nonlinear mechanisms

Coronary Autoregulation

The Control of Myocardial Blood Flow

Adapted from D.J.G.M. Duncker

Autoregulation

The ability of the heart of maintaining flow constant in case of change of perfusion pressure

without the intervention of any other external mechanism

ETP April 24-26, 2014

ww

w.c

ard

io-a

als

t.b

e

25

50

75

100

125

150

175

200

0 25 50 75 100 125 150 175 200

Coronary Perfusion Pressure (mm Hg)

Co

ron

ary

Blo

od

Flo

w (

mL

/min

)

Coronary Autoregulation

Rubio and Berne, Prog CV Disease 1975

25

50

75

100

125

150

175

200

0 25 50 75 100 125 150 175 200

Coronary Perfusion Pressure (mm Hg)

Co

ron

ary

Blo

od

Flo

w (

mL/

min

)

Autoregulatory Range

Rubio and Berne, Prog CV Disease 1975

25

50

75

100

125

150

175

200

0 25 50 75 100 125 150 175 200

Coronary Perfusion Pressure (mm Hg)

Initial Pressure

Autoregulatory Range

Co

ron

ary

Blo

od

Flo

w (

mL

/min

)

Rubio and Berne, Prog CV Disease 1975

F = P

Repi + Rmyo

Rmyo

Pa

F

Repi

Pv

K. Lance Gould, 1974

0 25 50 75 100 % Area Stenosis

25

50

75

100

% C

ontr

ol F

low

Flow, Pressure, and Resistance

F = P

Repi + Rmyo

Rmyo

Pa

F

Repi

Pv

K. Lance Gould, 1974

0 25 50 75 100 % Area Stenosis

25

50

75

100

% C

ontr

ol F

low

Flow, Pressure, and Resistance

F = P

Repi + Rmyo

Rmyo

Pa

F

Repi

Pv

K. Lance Gould, 1974

0 25 50 75 100 % Area Stenosis

25

50

75

100

% C

ontr

ol F

low

Flow, Pressure, and Resistance

F = P

Repi + Rmyo

Rmyo

Pa

F

Repi

Pv

K. Lance Gould, 1974

0 25 50 75 100 % Area Stenosis

25

50

75

100

% C

ontr

ol F

low

Flow, Pressure, and Resistance

F = P

Repi + Rmyo

Rmyo

Pa

F

Repi

Pv

K. Lance Gould, 1974

0 25 50 75 100 % Area Stenosis

25

50

75

100

% C

ontr

ol F

low

Flow, Pressure, and Resistance

De Bruyne et al, 1996

• Proximal LAD stenosis (n = 26)

• Normal LV systolic function

• PET fow measurements (15O-labeled water) at rest

Autoregulation

Distal Coronary Pressure (mm Hg)

0

1

2

3

4

5

30 40 50 60 70 80 90 100 110 120 130

Pressure-Flow Relationship

At Rest: Autoregulation

Hyperemic Coronary Perfusion Pressure

( % of normal )

Hyp

ere

mic

Co

ron

ary

Blo

od

Flo

w

( %

of

No

rmal

)

40

50

70

80

90

100

0

10

20

30

60

40 50 70 80 90 100 0 10 20 30 60

Adapted from D.J.G.M. Duncker and Bache R Physiol Rev 2008

Physical

factors

Endo- and paracrine

factors

Noradrenaline Adrenaline

Acethylcholine

adenosine

PO2

Histamine

Bradykinine

Systolic compression Diastolic compression

Arterial Pressure Coronary pressure RAP, LVDP and Pf=0

PCO2, H+, K+

Angiotensine II

α1 α2

β1 β 2

H1

A2

M

H2

AT1

ETB

ET

ETA

ETB 5-HT

TXA2

NO

PGI2

EDHF

M

α2

NO PGI2 EDHF

NO PGI2 EDHF

B2

P2

H1

P2

Endothelium TXA2

5-HT

M

P2

Neuro-humoral

factors

Metabolic

factors

The Control of Myocardial Blood Flow

Adenosine

Pressure-Flow Relationship

During Maximal Vasodilation

Hyperemic Coronary Perfusion Pressure

( % of normal )

Hyp

ere

mic

Co

ron

ary

Blo

od

Flo

w

( %

of

No

rmal

)

40

50

70

80

90

100

0

10

20

30

60

40 50 70 80 90 100 0 10 20 30 60

Autoregulation

Vasodilation

People who wish to treat patients with CAD without coronary physiology must settle for

a suboptimal treatment