Regulation of Coronary Blood Flow - European Society of ... · Regulation of Coronary Blood Flow...

Regulation of Coronary Blood Flow

23-04-2015

Dirk J. Duncker

Div Experimental Cardiology, Thoraxcenter

Erasmus MC, University Medical Center Rotterdam

The Netherlands

ETP April 23-25, 2015


• 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 et al Compr Physiol 2012 Duncker et al Prog Cardiovasc Dis 2015

ETP April 23-25, 2015

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 23-25, 2015

Unique aspects of the coronary circulation

• Cyclic compression of the vasculature

• High ‘resting’ myocardial metabolic rate

Cardiac muscle flow 1.0 ml/min/g

Skeletal muscle flow 0.1 ml/min/g

High myocardial capillary density

Cardiac muscle 3000-4000/mm2

Skeletal muscle 500-1000/mm2

High myocardial oxygen extraction Cardiac muscle 60-80%

Skeletal muscle 20-30%

ETP April 23-25, 2015

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

Myocardial O2 consumption (ml/min/g)

Coronary Flow Hematocrit

ETP April 23-25, 2015

Laughlin, Davis,…., Bache, Merkus, Duncker Compr Physiol 2012

Metabolic Vasodilation Exercise

LVMBF = LV Myocardial Blood Flow

ETP April 23-25, 2015

• 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 5th Edition 2009 ETP April 23-25, 2015


• Introduction





ETP April 23-25, 2015

Chilian et al Am J Physiol 1989

Distribution of Resistance in Coronary Microcirculation

μ

ETP April 23-25, 2015

Davis et al APS Handbook of Physiology 2008 Zhang, …, Chilian APS Handbook of Physiology 2008

μ

ETP April 23-25, 2015

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 23-25, 2015

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 et al JMCC 2012 ETP April 23-25, 2015

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 23-25, 2015

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

ETP April 23-25, 2015 Laughlin et al Compr Physiol 2012


• Introduction





ETP April 23-25, 2015

Autoregulation

The ability of the heart to maintain flow constant in the face of a change in perfusion pressure

…while myocardial metabolism remains unchanged

ETP April 23-25, 2015

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

ETP April 23-25, 2015 (Courtesy of Bernard De Bruyne) 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

)

Rubio and Berne, Prog CV Disease 1975

Autoregulatory Range

ETP April 23-25, 2015 (Courtesy of Bernard De Bruyne)

Coronary Pressure-Flow Relation

Duncker et al Prog Cardiovasc Dis 2015 ETP April 23-25, 2015

Flowmax / ΔP = Conductancemax








• Introduction


• Autoregulation: Pressure Flow Relations



ETP April 23-25, 2015

Stenosis

PAORTA

PDISTAL

ETP April 23-25, 2015

Coronary velocity

Pressure Derived Fractional Flow Reserve, FFR

Coronary (Pd)

Aortic (Pao)

Adenosine

CFR= 2.2

FFR= Pd/Pao = 105/133 = 0.78

Canty & Duncker Braunwald’s Heart Disease 2014

Stenosis

PAORTA

PDISTAL

ETP April 23-25, 2015


Assessment of Coronary Reserve

80%



Flow velocity wire

PET/MRI/CT Perfusion

80%




80%



Pressure wire

80%



Flow velocity wire

Pressure wire


80%


• Introduction


• Autoregulation: Pressure Flow Relations



ETP April 23-25, 2015

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