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Regulation of Coronary Blood Flow
24-04-2104
Dirk J. Duncker
ETP April 24-26, 2014
Regulation of Coronary Blood Flow
• Introduction
• Control of Coronary Resistance Vessels
• Autoregulation: Pressure Flow Relation
• Hemodynamic Effects of a Coronary Stenosis
Duncker & Bache Physiol Rev 2008 Van de Hoeff et al J Mol Cell Cardiol 2012 Laughlin, …., Duncker Compr Physiol 2012 Canty & Duncker Braunwald’s Heart Disease 2014 ETP April 24-26, 2014
Cyclic Compression of the Coronary Microvasculature
Courtesy of Harold Laughlin
Duncker & Merkus 2004
GCV flow (ml/min)
0
80
160
RCA flow (ml/min)
0
10
20
LAD flow (ml/min)
0
60
120
Pressure (mmHg)
0
40
80
120 Ao
LV
RV
Time (s)
0.0 0.4 0.8 1.2
Systole Diastole Systole
ETP April 24-26, 2014
Unique aspects of the coronary circulation
• Cyclic compression of the vasculature
• High resting myocardial metabolic rate
Cardiac muscle 1 ml/min/g flow
Skeletal muscle 0.1 ml/min/g flow
High capillary density
Cardiac muscle 3000-4000/mm2
Skeletal muscle 500-1000/mm2
High oxygen extraction Cardiac muscle 60-80%
Skeletal muscle 20-30%
Myocardial O2 balance during exercise
(%)
(%)
(%)
(ml/m
in/g
)
MVO2 (ml/min/g)
0.0 0.2 0.4 0.6
0.0
0.5
1.0
1.5
2.0
2.5
3.0
90
100
MVO2 (ml/min/g)
0.0 0.2 0.4 0.6
0
10
20
30
40
50
CBF Hct
CVSO2
ArtSO2
*
*
** * *
*
* * * *
Von Restorff et al Pfluegers Arch 1977 ETP April 24-26, 2014
Myocardial O2 consumption (ml/min/g)
Coronary Flow Hematocrit
Coronary flow
[O2]ART - [O2]CV
80%
20%
LV work
Contractility
Heart Rate 60%
20%
20%
Basal metabolism
Contraction 100%
~0%
O2 supply
O2 demand
Myocardial O2 balance
Myocardial O2 balance during exercise
60%
80%
Duncker & Bache Physiol Reviews 2008 Duncker & Bache Physiol Reviews 2008 ETP April 24-26, 2014
Laughlin, Davis,…., Bache, Merkus, Duncker Compr Physiol 2012
Metabolic Vasodilation Exercise
LVMBF = LV Myocardial Blood Flow
ETP April 24-26, 2014
• Darcy’s law
ΔP = Flow x R
Flow =
• Poiseuille’s law
R =
Laws of Hemodynamics
r4 L
r h L = length r = radius h = viscosity R = resistance
Flow
P1 P2
P = pressure
R = resistance
R
8 h L
ΔP R
ΔP
JR Levick An Introduction to Cardiovascular Physiology 2010 ETP April 24-26, 2014
Regulation of Coronary Blood Flow
• Introduction
• Control of Coronary Resistance Vessels
• Autoregulation: Pressure Flow Relation
• Hemodynamic Effects of a Coronary Stenosis
Duncker & Bache Physiol Rev 2008 Van de Hoeff et al J Mol Cell Cardiol 2012 Laughlin, …., Duncker Compr Physiol 2012 Canty & Duncker Braunwald’s Heart Disease 2014 ETP April 24-26, 2014
Chilian et al Am J Physiol 1989
Distribution of Resistance in Coronary Microcirculation
μ
Davis et al APS Handbook of Physiology 2008 Zhang, …, Chilian APS Handbook of Physiology 2008
μ
Control of tissue blood flow
“Blood goes where it is needed” John Hunter 1794
“He must have wondered how blood “knows” where it is needed?” LB Rowell JAP 2004
ETP April 24-26, 2014
The ultimate cardiac challenge Exercise
L S 1 2 3 Exercise (km/h)
4 5
CBF(ml/min)
LV dP/dt
(mmHg/s)
-2500
0
2500
5000
LVP(mmHg)
0
50
100
0
MAP(mmHg)
50
100
100
150
50
Rest Exercise at 5 km/h
Duncker et al. Circ Res 1998 Duncker & Merkus J Physiol 2007 Duncker & Bache Physiol Rev 2008 Laughlin, …, Duncker Compr Physiol 2012 ETP April 24-26, 2014
Neurohumoral influences Extravascular influences
NE
ACh
compression
Endothelial influences
histamine
bradykinin
ANG II
Endo- en Paracrine influences
PO2
adenosine
Metabolic influences
ANG I ANG II
bET-1 ET-1
ETA ETB
L-Arg NO PGI2
cAMPcGMP
Endothelium
Smooth Muscle
Cardiomyocyte
ADP
P2Y
shear stress
AA
adenosine
A2
O2• -
O2
O2
CO2
EDHF
ATP
KCa
AT1
ß2
H2O2
KCa
α1
α2
Erythrocytes
O2
NO
ATP
NE
H1
P2XH1
ETB
B2M
H2
M
AChNEKV
TXA2 5HT
TXA25HT
ACE
Platelets
TXA2 5HT
KATPKCa
KATP
ECE eNOS COX-1 CYP450
PCO2, H+, K+
IP
α2
Control of Coronary Microvascular Tone
Duncker & Bache Physiol Reviews 2008 ETP April 24-26, 2014
Neurohumoral influences Extravascular influences
NE
ACh
compression
Endothelial influences
histamine
bradykinin
ANG II
Endo- en Paracrine influences
PO2
adenosine
Metabolic influences
ANG I ANG II
bET-1 ET-1
ETA ETB
L-Arg NO PGI2
cAMPcGMP
Endothelium
Smooth Muscle
Cardiomyocyte
ADP
P2Y
shear stress
AA
adenosine
A2
O2• -
O2
O2
CO2
EDHF
ATP
KCa
AT1
ß2
H2O2
KCa
α1
α2
Erythrocytes
O2
NO
ATP
NE
H1
P2XH1
ETB
B2M
H2
M
AChNEKV
TXA2 5HT
TXA25HT
ACE
Platelets
TXA2 5HT
KATPKCa
KATP
ECE eNOS COX-1 CYP450
PCO2, H+, K+
IP
α2
Duncker & Bache Physiol Reviews 2008
Control of Coronary Microvascular Tone
ETP April 24-26, 2014
Regulation of Coronary Blood Flow
• Introduction
• Control of Coronary Resistance Vessels
• Autoregulation: Pressure Flow Relation
• Hemodynamic Effects of a Coronary Stenosis
Duncker & Bache Physiol Rev 2008 Van de Hoeff et al J Mol Cell Cardiol 2012 Laughlin, …., Duncker Compr Physiol 2012 Canty & Duncker Braunwald’s Heart Disease 2014 ETP April 24-26, 2014
Autoregulation
The ability of the heart to maintain flow constant in the face of a change in perfusion pressure
without the intervention of any other external mechanism
ww
w.c
ard
io-a
als
t.b
e
ETP April 24-26, 2014 (Courtesy of Bernard De Bruyne)
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
)
Rubio and Berne, Prog CV Disease 1975
Coronary Autoregulation
ETP April 24-26, 2014 (Courtesy of Bernard De Bruyne)
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
)
Rubio and Berne, Prog CV Disease 1975
Autoregulatory Range
ww
w.c
ard
io-a
als
t.b
e
ETP April 24-26, 2014 (Courtesy of Bernard De Bruyne)
Zhang, Rogers, Merkus, … Chilian APS Handbook of Physiology 2008
Davis et al APS Handbook of Physiology 2008
μ
μ
Coronary Pressure-Flow Relation
Canty & Duncker Braunwald’s Heart Disease 2014 ETP April 24-26, 2014
ΔP = Flow x R
Rmin = ΔP/Flowmax
Cmax = 1/Rmin = Flowmax/ΔP
P = pressure
R = resistance
C = conductance
Coronary Pressure-Flow Relation
Canty & Duncker Braunwald’s Heart Disease 2014 ETP April 24-26, 2014
Coronary Pressure-Flow Relation Subendocardial Vulnerability
Canty & Duncker Braunwald’s Heart Disease 2014 ETP April 24-26, 2014
20
Coronary Flow-Function Relation Subendocardial vulnerability
ETP April 24-26, 2014 Canty Circ Res 1988; Canty et al Circulation 1990
Regulation of Coronary Blood Flow
• Introduction
• Control of Coronary Resistance Vessels
• Autoregulation: Pressure Flow Relations
• Hemodynamic Effects of a Coronary Stenosis
Duncker & Bache Physiol Rev 2008 Van de Hoeff et al J Mol Cell Cardiol 2012 Laughlin, …., Duncker Compr Physiol 2012 Canty & Duncker Braunwald’s Heart Disease 2014 ETP April 24-26, 2014
Coronary Pressure-Flow Relation
Canty & Duncker Braunwald’s Heart Disease 2014 ETP April 24-26, 2014
Stenosis
PAORTA
PDISTAL
ETP April 24-26, 2014
Coronary velocity
Pressure Derived Fractional Flow Reserve, FFR
Coronary (Pd)
Aortic (Pao)
Adenosine
CFR= 2.2
FFR= Pd/Pao = 105/133 = 0.78
ETP April 24-26, 2014
Canty & Duncker Braunwald’s Heart Disease 2014
Assessment of Coronary Reserve
Flow velocity wire
Pressure wire
PET/MRI/CT Perfusion
Regulation of Coronary Blood Flow
• Introduction
• Control of Coronary Resistance Vessels
• Autoregulation: Pressure Flow Relations
• Hemodynamic Effects of a Coronary Stenosis
Duncker & Bache Physiol Rev 2008 Van de Hoeff et al J Mol Cell Cardiol 2012 Laughlin, …., Duncker Compr Physiol 2012 Canty & Duncker Braunwald’s Heart Disease 2014 ETP April 24-26, 2014
Coronary Pressure-Flow Relation Influence of Coronary Microvascular Disease
ETP April 24-26, 2014 Canty & Duncker Braunwald’s Heart Disease 2014