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