Embed Size (px)
Citation preview
Pathophysiology of Vascular
Function in CKD
Gérard M. LondonGérard M. London
INSERM U970
Hôpital Européen Georges Pompidou
Paris
Arterial Pathophysiology and Cardiovascular
Diseases in CKD
Arteriosclerosis Atherosclerosis
CORONARY ARTERY
↑↑↑↑Systolic BP; ↓↓↓↓Diastolic BP
(Decreased coronary perfusion)
CORONARY ARTERY
DISEASE
Volume*Overload
Adaptive LVH
Maladaptive LVH
Systolic/diastolic dysfunction
HEART FAILURE
SUDDEN DEATH
CEREBROVASCULAR
PERIPHERAL ARTERY
DISEASE*Hgb; AVF; Na+
(Decreased coronary reserve)
Prevalence of discrete plaques on common
carotid artery in control subjects and ESRD
patients
Controls ESRD
Age (years) 48.5 ± 16 51 ± 16 NS
Plaques (%) 17.8% 56.3% < 0.01
Type of plaques
• Calcified 23.1% 91.5% <0.01
• Soft/mixed 77% 9% <0.01
London et al Sem Dial 1999
9
10
11
12
Ca
roti
d a
rter
y d
iam
eter
(m
m)
4.5
5.2
5.8
6.5
Bra
chia
l a
rter
y d
iam
eter
(m
m)
Age related changes in arterial internal diameters
5
6
7
8
20 30 40 50 60 70 80 90
Age (years)
Ca
roti
d a
rter
y d
iam
eter
2.5
3.2
3.8
4.5
20 30 40 50 60 70 80
Age (years)
Bra
chia
l a
rter
y d
iam
eter
Controls
ESRD patients
Controls (r = 0.400; P < 0.01) Controls (r = 0.525;P < 0.01)
ESRD (r = 0.438; P < 0.0001) ESRD (r = 0.277;P = 0.065)
Evolution of Carotid diameter with progression of CKD stages
Briet M. et al Kidney Int 2006
0.80
0.90
1.00
1.10C
om
mon
caro
tid
art
ery
IM
Th
(mm
)
Age related changes in Carotid IMTh
0.40
0.50
0.60
0.70
10 20 30 40 50 60 70 80 90
Age (years)
Com
mon
caro
tid
art
ery
IM
Th
(mm
)
Controls
ESRD patients
Mechanical stresses in the blood vessel
flow Q
R
σθσθσθσθ
circumferential wall stress fluid shear stress
sq = P x R
h
t = 4 µ Q
p R 3
h
Baseline BA diameter (mm) 4.12 ±±±± 0.13 4.56 ±±±±
0.11
< 0.01
BA compliance (m2.kPa–1.10–7) 0.45 ±±±± 0.02 0.37 ±±±± 0.02 < 0.01
BA distensibility (kPa–1.10–3) 3.5 ±±±± 0.22 2.6 ±±±± 0.19 < 0.001
BA incremental elastic modulus (kPa.103) 3.0 ±±±± 0.22 5.0 ±±±± 0.42 < 0.001
Baseline mean flow velocity (cm/s) 4.6 ±±±± 0.40 3.4 ±±±± 0.30 < 0.01
Baseline mean flow (ml/min) 39 ±±±± 4.6 33 ±±±± 3.6 NS
Controls ESRD
Brachial artery characteristics
flow Q
Baseline mean flow (ml/min) 39 ±±±± 4.6 33 ±±±± 3.6 NS
Baseline mean SR (s–1
) 53 ±±±± 2.9 39 ±±±± 3.5 < 0.01
Baseline peak SR (s–1
) 365 ±±±± 23 324 ±±±± 26 < 0.05
Whole blood viscosity
(cPoise) 3.57 ±±±± 0.07 2.79 ±±±±0.06 <0.001
Baseline mean SS
(dynes/cm2)
19 ±±±± 1.15 10.7 ±±±± 1.0 <0.001
Baseline peak SS (dynes/cm2) 129 ±±±± 9 83 ±±±± 5 <0.001
Verbeke et al JASN 2007
t = 4 µ Q
p R
3
Paracrine effect(s) of endothelial MPs predisposing to endothelial dysfunction in vivo
Boulanger, C. M. et al. Hypertension 2006;48:180-186
0
200
400
600
800
1000
0 6 12 18 24 30
Brachial artery shear stress (dynes/cm²)
CD
14
4+
MP
s (e
v/µ
L)
100
1000
10000
0 5 10 15 20 25 30
CD
31
+/4
1-
MP
s (e
v/µ
L)
r = –0.770
P < 0.0001
r = –0.648
P < 0.0001
A. B.
100
1000
10000
100000
0 5 10 15 20 25 30
Brachial artery shear stress (dynes/cm²)
CD
31
+/4
1+
MP
s (e
v/µ
L)
10
100
1000
10000
100000
0 5 10 15 20 25 30
An
nex
ineV
+ M
Ps
(ev
/µL
)
r = –0.291
P = 0.100r = –0.082
P = 0.672
C. D.
Boulanger Ch et al Hypertension 2007
125
187.5
250E
SS
YS
TS
T-S
tres
s (k
Pa
)
circumferential wall stress
sq = P x R
h
0.0
62.5
Controls
100±16
ESRD patients
111±28 p<0.001
ES
SY
ST
ST
London GM (submitted)
Evolution of Carotid Circumferential wall stress
with progression of CKD stages
Briet M. et al Kidney Int 2006
0.21
0.24
0.26
Control population (n=104)
Circumf.stress = 24.4±6.1
Co
mm
on
Ca
roti
d a
rter
y
rela
tiv
e w
all
th
ick
nes
s (T
h/r
)
0.22
0.25
0.28
ESRD patients (n=163)
Circumf.stress = 28.0±6.1 (p=0.027)
0.14
0.16
0.19
80 100 120 140 160 180 200
Common Carotid artery systolic BP (mm Hg)
Co
mm
on
Ca
roti
d a
rter
y
rela
tiv
e w
all
th
ick
nes
s (T
h/r
)
0.12
0.15
0.18
60 80 100 120 140 160 180 200 220 240
London GM et al (submitted)
R= – 0.154
P= 0.050
R= 0.349
P <0.001
0.21
0.24
0.26
ESRD with absence of
carotid artery calcifications
Co
mm
on
Ca
roti
d a
rter
y
rela
tiv
e w
all
th
ick
nes
s (T
h/r
)
0.22
0.25
0.28
ESRD with
carotid artery calcifications
0.14
0.16
0.19
60 80 100 120 140 160 180 200 220 240
Common Carotid artery systolic BP (mm Hg)
Co
mm
on
Ca
roti
d a
rter
y
rela
tiv
e w
all
th
ick
nes
s (T
h/r
)
0.12
0.15
0.18
60 80 100 120 140 160 180 200 220 240
London GM et al (submitted)
R= - 0.068
P = NS
R=-0.293
P<0.01
Shroff et al Circulation 2008;118:1748-57
2.00
2.50
3.00
3.50
Co
mm
on
Ca
roti
d a
rter
y e
last
ic m
od
ulu
s
Control subjects
ESRD patients
2.00
2.50
3.00
3.50
ESRD carotid calcifications –
ESRD carotid calcifications +
0.00
0.50
1.00
1.50
60 80 100 120 140 160 180 200 220 240
Common Carotid artery systolic BP (mm Hg)
Co
mm
on
Ca
roti
d a
rter
y e
last
ic m
od
ulu
s
0.00
0.50
1.00
1.50
60 80 100 120 140 160 180 200 220 240
London GM et al (submitted)
All categories P<0.00001
Evolution of Carotid elastic modulus with progression of CKD stages
Briet M. et al Kidney Int 2006
5
8
11
14
17
20
10 20 30 40 50 60 70 80 90Age (years)
Ao
rtic
Pu
lse
Wa
ve
Vel
oci
ty (
m/s
)
6
8
11
13
16
18
10 20 30 40 50 60 70 80 90
AGE vs HRPWV
Age (years)
Bra
chia
l P
uls
e W
av
e V
elo
city
(m
/s)
**
**
**-** P < 0.0001
Age (years) Age (years)
6
8
10
12
14
16
10 20 30 40 50 60 70 80 90
Age (years)
Ao
rtic
Pu
lse
Wa
ve
Vel
oci
ty (
m/s
)
10
Pu
lse
Wave
vel
oci
ty (
m/s
)Aortic and arm pulse wave velocities as as function of age
20 40 60 80
5
Pu
lse
Wave
vel
oci
ty (
m/s
)
Age
Arm
Aorta
Avolio et al Circulation 1983
Characteristics of arterial system in controls and ESRD patients
Controls ESRD
•Peripheral/femoral PWV (m/s) 11.0 ±1.75 11.20 ±1.80
Age (years) 48.5 ± 16 51 ± 16 Age (years) 48.5 ± 16 51 ± 16
•Aortic PWV (m/s) 9.70 ±1.80 10.60 ±2.5**
0.00
0.25
0.50
0.75
1.00
0.0 50 100 150 200 250Follow-up (months)
CV
Su
rviv
al
0.00
0.25
0.50
0.75
1.00
0.0 50 100 150 200 250Follow-up (months)
CV
Su
rviv
al
Aortic PWV Brachial PWV
χχχχ²=72.8
P<0.00001
χχχχ²=1.78
P=0.411
<9.7m/s
>9.7 m/s
>12 m/s
Follow-up (months) Follow-up (months)
0.00
0.25
0.50
0.75
1.00
0.0 50 100 150 200 250Follow-up (months)
CV
Su
rviv
al
Femoral PWV
χχχχ²=2.34
P=0.310
1st tertile
2nd tertile
3rd tertile
Pannier et al Hypertension 2005
*
*
400
Ca
(m
mo
l/k
g)
Aorta (r=0.84)
Correlation between age and arterial calcium (Ca) concentration
in the aorta and internal iliac artery in nonuremic control subjects
**
* *
****
****
**
**
**** *
* * **** *** *******0
200
20 40 60 80
Ca
(m
mo
l/k
g)
AGE (years)
Internal Iliac (r=0.75)
Ibels et al. Am J Med 1979
12.5
15.0
17.5
20.0
Ao
rtic
PW
V (
ms)
Correlation between aortic calcification score and
aortic PWV in ESRD patients
5.0
7.5
10.0
12.5
0 4 8 12 16 20 24
Abdominal aortic calcification score
Ao
rtic
PW
V (
ms)
r = 0.754
P < 0.0001
Pannier et al. Artery 2007
50
75
100
125
150
175
200
225
250
5 8 11 14 17 20
Aortic PWV (m/s)
Ao
rtic
sy
sto
lic
BP
(m
m H
g)
40
53
65
78
90
103
115
128
140
5 8 11 14 17 20
Aortic PWV (m/s)
Dia
sto
lic
BP
(m
m H
g)
Aortic PWV (m/s) Aortic PWV (m/s)
20
38
55
73
90
108
125
143
160
5 8 11 14 17 20
Aortic PWV (m/s)
Ao
rtic
pu
lse
pre
ssu
re (
mm
Hg
)
20
40
60
80
100
120
140
160
5 7 9 11 13 15 17 19 21Aortic PWV (m/s)C
om
mon
caro
tid
art
ery P
uls
e p
res.
(m
m H
g)
20
40
60
80
100
120
140
160
-10 -6 -2 2 6 9 13 17 21CCA Augmented pressure (mm Hg)
(wave reflection)
Com
mon
caro
tid
art
ery P
uls
e p
res.
(m
m H
g)
R = 0.633
P < 0.0001
R = 0.784
P < 0.00001
(wave reflection)
20
40
60
80
100
120
140
160
0.55 0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95Systemic reflection coefficientC
om
mon
caro
tid
art
ery P
uls
e p
res.
(m
m H
g)
R = – 0.595
P < 0.00001
measured pressure wave
Pressure wave analysis
forward/incident pressure wave
reflected pressure wave
pulse wave velocity
Reflected Wave
SPTI DPTI SPTI DPTISPTI DPTI SPTI DPTI
200
Left
ventricular
Correlation between left ventricular mass
and aortic pulse wave velocity
150
100
Aortic pulse wave velocity (cm/sec)
ventricular
mass (g/m2)
500 1000 1500 2000
r = 0.52
p < 0.001
150
London et al KI 1989
175
200
225
250
Su
ben
do
card
ial
via
bil
ity
ra
tio
n (
DP
TI/
SP
TI)
r = -0.406
P<0.0001
75
100
125
150
5 7 9 11 13 14 16 18 20
Aortic PWV (m/s)
Su
ben
do
card
ial
via
bil
ity
ra
tio
n (
DP
TI/
SP
TI)
Pre
ssu
re (
mm
Hg)
Pre
ssu
re (
mm
Hg)
Cyclic high and
pulsatile pressure
Continuous low
pressure
Microcirculation
Arterial system as « hydraulic filter »
Flo
w (m
ls)
Flo
w (m
ls)
Cyclic highly
pulsatile flowContinuous flow
and perfusion
AortaMicrocirculation
capillaries
Arterial
Compliance
Peripheral
Resistance
Left
ventricle
A. SystoleIn normally compliant arterial system
important part of the stroke volume
is stored in the arteries during ventricular
systole stretching the arterial walls
SYSTOL
EArterial
Compliance
Peripheral
Resistance
Leftventricle
B. DiastoleDuring ventricular diastole the previously
stretched arterial walls recoils with
the stored volume insuring continuous
perfusion of tissues and organs
Oxygen Limitation Model
Smaller FractionSmaller Fraction
of O2 Available
for Metabolism
O2
Extraction
Capillary
Transit Time
Blood
Velocity
(NOT capillary
recuitment) Normally 2-3 seconds
Hanon O et al. Stroke 2005;36:2193
Scuteri A et al. J Hypertens 2007;25:1035
Correlation Between CCr (C-G formula) and
Aortic PWV
20
25
30
r = –0.30
P<0.0001
Aort
ic P
WV
(m
/s)
5
10
15
0 50 100 150 200
Creatinine clearance
(mL/min/m²)
Aort
ic P
WV
(m
/s)
Bortolotto et al KI 2001
Arterial Impedance Gradients
Zc-characteristic impedance; Zr-peripheral resistance
PfP
bPt
( )f
b
CR
CR
P
P
ZZ
Z-Z=
+=ΓΓΓΓCoefficientReflection
Zc ZR
Aorta Peripheral arteries
Resistance vessels
Pf P
tPb
PWV=6 m/s PWV=10 m/s
PWV=12 m/s PWV=11 m/s
Pressure transmission in the presence of arterial stiffness gradients
120
100
80
Pre
ssu
re m
m H
g
Aorta
PWV 6 m/sResistance
vessels
Large arteries
PWV=10 m/s
Incident pressure
Reflected pressure
Terminal pressure
Microvascular
network
80
5
Pre
ssu
re m
m H
g
Pressure transmission in “low peripheral resistance” organs (kidney; brain)
when arterial stiffness gradient is decreased or abolished
140
120
80
Pre
ssu
re m
m H
g
Aorta
PWV 11 m/sResistance
vessels
Large arteries
PWV=10 m/sMicrovascular
network
80
5
Pre
ssu
re m
m H
g
Reflected pressure Incident pressure
Reflected pressure
Terminal pressure
0.80
0.85
0.90
0.95S
yst
emic
Ref
lect
ion
Co
effi
cien
t
0.60
0.65
0.70
0.75
0.80
0.70 0.80 0.90 1.00 1.10 1.20 1.30
(Aortic PWV/Brachial PWV)0.5
Sy
stem
ic R
efle
ctio
n C
oef
fici
ent
r= -0.46
P<0.0001
London GM (submitted)
0.75
0.82
0.88
0.95S
yst
emic
ref
lect
ion
co
effi
cien
t
0.55
0.62
0.68
0.75
10 20 30 40 50 60 70 80 90Age (years)
Sy
stem
ic r
efle
ctio
n c
oef
fici
ent
London GM (submitted)
r = -0.455
P <0.001
50
60
70D
ista
nce
fro
m t
he
aort
a t
o r
efle
ctin
g s
ites
( %
of
bod
y h
eigh
t )
r = 0.165
P = 0.014
20
30
40
10 20 30 40 50 60 70 80 90Age (years)
Dis
tan
ce f
rom
th
e aort
a t
o r
efle
ctin
g s
ites
( %
of
bod
y h
eigh
t )
London GM (submitted)
Characteristics of arterial system in controls and ESRD patients
Controls ESRD
•Forward pressure (mm Hg) 38 ± 11 44 ± 16**
•Wave reflection (% of PP) 17 ±17 25 ±15***
•Reflected pressure (mm Hg) 11 ± 6 14 ± 8*
•Reflected wave arrival time (ms) 128 ±15 108 ± 16**
•Zr (dynes.s.cm-5) 2309 ±530 2260 ±1175
•Zc (dynes.s.cm-5) 179 ± 52 214 ±103**
•ΓΓΓΓ (reflection coefficient) 0.85 ± 0.04 0.81 ±0.06**
•Aortic PWV (m/s) 9.70 ±1.80 10.60 ±2.5**
•Peripheral/femoral PWV (m/s) 11.0 ±1.75 11.20 ±1.80
*P<0.05; **P<0.01; ***P<0.001ESRD: fmin=4.62Hz ; Control: fmin=3.90Hz
1.2
1.4
1.6
1.8A
ort
ic P
WV
/fem
ora
l P
WV
(ra
tio
)
P < 0.01
0.4
0.6
0.8
1.0
Controls
0.84±0.15
ESRD
0.97±0.25
Ao
rtic
PW
V/f
emo
ral
PW
V (
rati
o)
*Peak flow
Flow debt repayment=B/A
Fore
arm
blo
od
flo
w m
l/100 m
l/m
in
30
40
Schematic representation of reactive hyperemic response in the human
forearm after five minutes of ischemia
0 1 2 3 4 5 6 7 8 9 10 11
baseline occlusion postocclusion Time,min
******A = Flow debt mL/100 mL
*
******* ***** * ** *
Duration of hyperemia
B = Excess hyperemic flow
ml/100ml
Fore
arm
blo
od
flo
w m
l/100 m
l/m
in
0
10
20
30
*
0
40
80
120
160
200
240
6 8 10 12 14 16 18
AoPWV (M/S)
Flo
w d
ebt
rep
ay
emen
t (%
)
0
40
80
120
160
200
240
6 8 10 12 14 16 18
AoPWV (M/S)
Du
rati
on
of
va
sod
ila
tion
(s)
0
2
4
6
8
10
12
6 8 10 12 14 16 18
AoPWV (M/S)
Min
ima
l re
sist
an
ce (
arb
itra
ry u
nit
s)
AoPWV (M/S) AoPWV (M/S)
0
200
400
600
800
1000
1200
1400
1600
1800
6 8 10 12 14 16 18
AoPWV (M/S)
Ma
xim
al
blo
od
flo
w (
% f
rom
ba
seli
ne)
100
120
140
160P
ost
isch
emic
Flo
w d
ebt
rep
ay
emen
t (%
)r = 0.391
P <0.0001
20
40
60
80
0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95
Systemic Reflection Coefficient
Po
stis
chem
ic F
low
deb
t re
pa
yem
ent
(%)
London GM (submitted)
Arterial changes in CKD
• Premature Aortic Aging: increased diameter
and stiffness.
• Accelerated in the presence of calcifications
• Lost or Impairement of Hydraulic Filter : high
Systolic and Pulse pressure in Aorta and Central
arteries (LVH poor Coronary perfusions), and
abnormal pressure transmission to microcirculation
(impaired vasodilation)
0.50
0.75
1.00
Common Carotid Pulse Pressure and Cardiovascular mortality
in ESRD patients(log rank p<0.0001)
Ca
rdio
va
scu
lar
free
ev
ents
PPcc <50 mm Hg
PPcc≦≦≦≦75 mm Hg
P<0.05
P<0.00001
0.00
0.25
0.50
0.0 28 56 84 112 140
Follow-up (months)
Ca
rdio
va
scu
lar
free
ev
ents
Cox model: P=0.0049
adjusted for age and mean BP
PPcc≧≧≧≧70 mm Hg
P<0.001
Safar et al Hypertension 2002
Aix
Aix
Amplification
Aorta Peripheral artery
Tsh forward wave
reflected wave
recorded wave
50
100
150
(mm
Hg
)
Superimposed simultaneous phasic recording of aortic (Ao),left ventricular (LV) pressures and coronary blood flow (CBF)
(Buckeberg et al. Circ Res. 1972)
100
Ao
DPTIDPTI
Ao
DPTIBP
(mm
Hg
)
0
LVSTTI
100
LA or PA
WedgeSTTI
(mm
Hg
)C
BF
(ml/
min
)
Effects of age on arterial stiffness and wave reflections
For males (circle and solid lines) and females (squares and dashed line)
Augmentation index
Augmented pressure
Carmel M. McEniery et al .JACC 2005;46:1753
1.6
1.8
2.0
2.2
2.4
Ao
rtic
ta
per
ing
(Ao
rtic
ro
ot/
ao
rtic
bif
urc
ati
on
)P = 0.03
0.8
1.0
1.2
1.4
1.6
Controls
1.76±0.24
ESRD
1.64±0.3
Ao
rtic
ta
per
ing
(Ao
rtic
ro
ot/
ao
rtic
bif
urc
ati
on
)
0
40
80
120
160
200
240
6 8 10 12 14 16 18
AoPWV (M/S)
Flo
w d
ebt
rep
ay
emen
t (%
)
0
40
80
120
160
200
240
6 8 10 12 14 16 18
AoPWV (M/S)
Du
rati
on
of
va
sod
ila
tion
(s)
0
2
4
6
8
10
12
6 8 10 12 14 16 18
AoPWV (M/S)
Min
ima
l re
sist
an
ce (
arb
itra
ry u
nit
s)
AoPWV (M/S) AoPWV (M/S)
0
200
400
600
800
1000
1200
1400
1600
1800
6 8 10 12 14 16 18
AoPWV (M/S)
Ma
xim
al
blo
od
flo
w (
% f
rom
ba
seli
ne)
0
40
80
120
160
200
240
0.60 0.70 0.80 0.90 1.00 1.10 1.20 1.30 1.40
(AoPWV/FTPWV)0.5
0
50
100
150
200
250
300
350
400
0.60 0.70 0.80 0.90 1.00 1.10 1.20 1.301.40(AoPWV/FTPWV)0.5
Tim
e to
flo
w d
ebt
rep
ayem
ent
(s)
Flo
w d
ebt
rep
ay
emen
t (%
)
(AoPWV/FTPWV)
0
200
400
600
800
1000
1200
1400
1600
1800
0.60 0.70 0.80 0.90 1.00 1.10 1.20 1.30 1.40
(AoPWV/FTPWV)0.5
(AoPWV/FTPWV)
Maxim
al
blo
od
flo
w (
% f
rom
base
lin
e)
100
120
140
160P
ost
isch
emic
Flo
w d
ebt
rep
ay
emen
t (%
)r = 0.391
P <0.0001
20
40
60
80
0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95
Systemic Reflection Coefficient
Po
stis
chem
ic F
low
deb
t re
pa
yem
ent
(%)
London GM (submitted)
Clinical Characteristics
Controls (n=59) ESRD (n=121) P-value
Age (yrs) 48±±±±13 51±±±±15 NS
Weight (kg) 76±±±±15 64±±±±13 <0.0001
Height (m) 1.70±±±±0.11 1.64±±±±0.11 <0.001
Systolic BP (mmHg) 144±±±±21 152±±±±30 0.020
Diastolic BP (mm Hg) 86±±±±14 83±±±±15 NS
Mean BP (mm Hg) 105±±±±15 106±±±±18 NS
Pulse Pressure(mm Hg)
58±±±±15 68±±±±24 <0.0001
Coronary Artery Calcification in Young Dialysis Patients
100
1000
10000
Calc
ific
ati
on
Sco
re*
59
0.1
1
10
0 5 10 15 20 25 30 35
Age (years)
Calc
ific
ati
on
Sco
re*
N=39
*Determined by EBT.
Goodman WG et al. N Engl J Med. 2000;342:1478-1483.
Calcification scores nearly doubled
in a majority of patients with
positive initial scan when
rescanned at 20 months
Effect of arterial stiffness on timing of forward
and reflected Waves
Systolic
Augmentation
Pressure (Aix)
PWV 8 m/sec PWV 12 m/sec
Negative
Aix
Positive
Aix
.
Forward-traveling wave Backward-traveling reflected wave Actual (composite) wave
T T
T - traveling time of pressure wave to reflecting sites and back
measured pressure wave
Pressure wave analysis
forward/incident pressure wave
reflected pressure wave
pulse wave velocity
Oxygen Limitation Model
Smaller FractionSmaller Fraction
of O2 Available
for Metabolism
O2
Extraction
Capillary
Transit Time
Blood
Velocity
(NOT capillary
recuitment) Normally 2-3 seconds
1.2
1.4
1.6
1.8A
ort
ic P
WV
/fem
ora
l P
WV
(ra
tio
)
P < 0.01
0.4
0.6
0.8
1.0
Controls
0.84±0.15
ESRD
0.97±0.25
Ao
rtic
PW
V/f
emo
ral
PW
V (
rati
o)
1.6
1.8
2.0
2.2
2.4
Ao
rtic
ta
per
ing
(Ao
rtic
ro
ot/
ao
rtic
bif
urc
ati
on
)P = 0.03
0.8
1.0
1.2
1.4
1.6
Controls
1.76±0.24
ESRD
1.64±0.3
Ao
rtic
ta
per
ing
(Ao
rtic
ro
ot/
ao
rtic
bif
urc
ati
on
)
0
40
80
120
160
200
240
6 8 10 12 14 16 18
AoPWV (M/S)
Flo
w d
ebt
rep
ay
emen
t (%
)
0
40
80
120
160
200
240
6 8 10 12 14 16 18
AoPWV (M/S)
Du
rati
on
of
va
sod
ila
tion
(s)
0
2
4
6
8
10
12
6 8 10 12 14 16 18
AoPWV (M/S)
Min
ima
l re
sist
an
ce (
arb
itra
ry u
nit
s)
AoPWV (M/S) AoPWV (M/S)
0
200
400
600
800
1000
1200
1400
1600
1800
6 8 10 12 14 16 18
AoPWV (M/S)
Ma
xim
al
blo
od
flo
w (
% f
rom
ba
seli
ne)
0
40
80
120
160
200
240
0.60 0.70 0.80 0.90 1.00 1.10 1.20 1.30 1.40
(AoPWV/FTPWV)0.5
Fem
ora
l art
ery P
WV
(m
/s)
0
50
100
150
200
250
300
350
400
0.60 0.70 0.80 0.90 1.00 1.10 1.20 1.301.40(AoPWV/FTPWV)0.5
Tim
e to
flo
w d
ebt
rep
ayem
ent
(s)
(AoPWV/FTPWV)
0
200
400
600
800
1000
1200
1400
1600
1800
0.60 0.70 0.80 0.90 1.00 1.10 1.20 1.30 1.40
(AoPWV/FTPWV)0.5
(AoPWV/FTPWV)
Maxim
al
blo
od
flo
w (
% f
rom
base
lin
e)
Traub, O. et al. Arterioscler Thromb Vasc Biol 1998;18:677-685
Mechanical stresses in the blood vessel
flow Q
R
σθσθσθσθ
circumferential wall stress fluid shear stress
sq = P x R
h
t = 4 µ Q
p R 3
h
100
120
140
160P
ost
isch
emic
Flo
w d
ebt
rep
ay
emen
t (%
)r = 0.391
P <0.0001
20
40
60
80
0.60 0.65 0.70 0.75 0.80 0.85 0.90 0.95
Systemic Reflection Coefficient
Po
stis
chem
ic F
low
deb
t re
pa
yem
ent
(%)
London GM (submitted)
