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
Systole
Diastole
Systole
120
Ao
Pressure
(mmHg)
80
LV
40
RV
0
LAD flow
(ml/min)
120
60
0
Courtesy of Harold Laughlin
RCA flow
(ml/min)
20
10
0
GCV flow
(ml/min)
160
80
0
0.0
ETP April 24-26, 2014
Duncker & Merkus 2004
0.4
0.8
Time (s)
1.2
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
(%)
*
2.5
*
2.0
(%)
*
1.5
50
* *
*
40
*
100
0.5
0.0
ArtSO2
90
30
1.0
(%)
(ml/min/g)
Hct
Hematocrit
CBF Flow
Coronary
3.0
CVSO2
20
10
0
* *
* *
0.0 0.2 0.4 0.6
0.0 0.2 0.4 0.6
MVOMyocardial
MVO
2 (ml/min/g)O consumption
(ml/min/g)
2 (ml/min/g)
2
ETP April 24-26, 2014
Von Restorff et al Pfluegers Arch 1977
Myocardial O2 balance during exercise
60%
100%
Contraction
20%
O2 demand
20%
Myocardial
O2 balance
~0%
80%
Heart Rate
60%
Contractility
LV work
Basal metabolism
Coronary flow
80%
O2 supply
20%
ETP April 24-26,
2014Physiol Reviews 2008
Duncker
& Bache
[O2]ART - [O2]CV
Duncker & Bache Physiol Reviews 2008
Metabolic Vasodilation
Exercise
LVMBF = LV Myocardial Blood Flow
ETP April 24-26, 2014
Laughlin, Davis,…., Bache, Merkus, Duncker Compr Physiol 2012
Laws of Hemodynamics
• Darcy’s law
ΔP = Flow x R
Flow = ΔP
R
• Poiseuille’s law
R= 8 hL
 r4
ETP April 24-26, 2014
ΔP
P1
P2
  Flow  
R
P = pressure
R = resistance
L
h
r
L = length
r = radius
h = viscosity
R = resistance
JR Levick An Introduction to Cardiovascular Physiology 2010
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
Distribution of Resistance in Coronary Microcirculation
μ
Chilian et al Am J Physiol 1989
μ
Davis et al APS Handbook of Physiology 2008
Zhang, …, Chilian APS Handbook of Physiology 2008
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
Rest
MAP
(mmHg)
Exercise at 5 km/h
100
50
100
LVP
(mmHg)
50
0
5000
LV dP/dt
(mmHg/s) 2500
L
S
1 2 3 4
Exercise (km/h)
5
0
-2500
CBF
(ml/min)
150
100
50
0
ETP April 24-26, 2014
Duncker et al. Circ Res 1998
Duncker & Merkus J Physiol 2007
Duncker & Bache Physiol Rev 2008
Laughlin, …, Duncker Compr Physiol 2012
Control of Coronary Microvascular Tone
Neurohumoral influences
Extravascular influences
compression
NE
Endo- en Paracrine influences
ANG II
ACh
histamine
PCO2, H+, K+
bradykinin
adenosine
Endothelial influences
PO2
Metabolic influences
Platelets
ETP April 24-26, 2014
Erythrocytes
Duncker & Bache Physiol Reviews 2008
shear stress
Metabolic influences
Control of Coronary Microvascular Tone
Platelets
Erythrocytes
shear stress
NO
O2
TXA2 5HT
ATP
P2Y
Endothelium
ECE
TXA2
5HT
M
ACh
α1
NE
5HT
L-Arg
ETB
ETA
NO
PGI2
AA
ETB
cGMP
H1
H2
P2X
KCa
KATP
H2O2
cAMP
O2
A2
KATP
KCa
CO2
ATP
Cardiomyocyte
ETP April 24-26, 2014
O2• -
EDHF
IP
Smooth Muscle
α2
B2
H1
COX-1 CYP450
ANG II
AT1
α2
M
eNOS
ET-1
bET-1
ACE
ANG I
TXA2
ß2
KCa
KV
NE
adenosine
ADP
O2
Duncker & Bache Physiol Reviews 2008
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
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
ETP April 24-26, 2014 (Courtesy of Bernard De Bruyne)
www.cardio-aalst.be
Autoregulation
Coronary Autoregulation
200
150
125
www.cardio-aalst.be
Coronary Blood Flow (mL/min)
175
100
75
50
25
0
25
50
75
100
125
150
175
200
Coronary Perfusion Pressure (mm Hg)
ETP April 24-26, 2014 (Courtesy of Bernard De Bruyne)
Rubio and Berne, Prog CV Disease 1975
Autoregulatory Range
200
150
125
www.cardio-aalst.be
Coronary Blood Flow (mL/min)
175
100
75
50
25
0
25
50
75
100
125
150
175
200
Coronary Perfusion Pressure (mm Hg)
ETP April 24-26, 2014 (Courtesy of Bernard De Bruyne)
Rubio and Berne, Prog CV Disease 1975
μ
Davis et al APS Handbook of Physiology 2008
μ
Zhang, Rogers, Merkus, … Chilian APS Handbook of Physiology 2008
Coronary Pressure-Flow Relation
ΔP = Flow x R
Rmin = ΔP/Flowmax
Cmax = 1/Rmin = Flowmax/ΔP
P = pressure
R = resistance
C = conductance
ETP April 24-26, 2014
Canty & Duncker Braunwald’s Heart Disease 2014
Coronary Pressure-Flow Relation
ETP April 24-26, 2014
Canty & Duncker Braunwald’s Heart Disease 2014
Coronary Pressure-Flow Relation
Subendocardial Vulnerability
20
ETP April 24-26, 2014
Canty & Duncker Braunwald’s Heart Disease 2014
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
ETP April 24-26, 2014
Canty & Duncker Braunwald’s Heart Disease 2014
Stenosis
PDISTAL
PAORTA
ETP April 24-26, 2014
Pressure Derived Fractional Flow Reserve, FFR
FFR= Pd/Pao = 105/133 = 0.78
Aortic (Pao)
Coronary (Pd)
Coronary velocity
CFR= 2.2
Adenosine
ETP April 24-26, 2014
Assessment of Coronary Reserve
Flow velocity wire
PET/MRI/CT Perfusion
Pressure wire
Canty & Duncker Braunwald’s Heart Disease 2014
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