Mechanistic insights into the relationship between wave reflection and retinal artery flow pulsatility. McDonnell BJ *, Coulson J **, Zagura M***, Munnery I **, Munnery M **, Stohr E*, Shave R*, McEniery CM ¶ , Wilkinson IB ¶ , Cockcroft JR**. *University of Wales Institute, Cardiff. **Wales Heart Research Institute, Heath Hospital, Cardiff. ***University of Tartu, Tartu, Estonia. ¶ Department of Clinical Pharmacology, Addenbrooke’s Hospital, Cambridge.
Transcript
Mechanistic insights into the relationship between wave reflection
and retinal artery flow pulsatility.
McDonnell BJ *, Coulson J **, Zagura M***, Munnery I **, Munnery M **, Stohr E*, Shave R*, McEniery CM ¶, Wilkinson IB ¶, Cockcroft JR**.
*University of Wales Institute, Cardiff. **Wales Heart Research Institute, Heath Hospital, Cardiff.
***University of Tartu, Tartu, Estonia.¶Department of Clinical Pharmacology, Addenbrooke’s Hospital, Cambridge.
Small arteries
Large arteries
Arterioles Capillaries Veins
120
Blood
Pressure
(mmHg)
80
Pulsatile to smooth flow/pressure in the arterial system
Large artery stiffness and microvascular damage
Increased Large artery stiffness
Increased damage to end organs
High PP transmitted to micro-circulation
Increased Pulsatility (PP)
Decline in GFR is More Closely Related to Pulse Pressure than MAP
Fesler et al. J Hypertens 2007;25:1796
Sato et al. Graefe’s Arch Clin Exp Opthalmol. 2006;244:963
Age-related Macular Degeneration is Associated with Increased Central Pressure
What are the determinants of pulsatility????
Determinants of pulsatility
Q: AIx?-The degree to which the incident wave is reflected??
Physiology, Berne and Levy
Systolic Pressure
Diastolic Pressure
Large Artery Stiffness
Stroke Volume
Large artery stiffness and microvascular damage
Increased Large artery stiffness
Increased damage to end organs
High PP transmitted to micro-circulation
Increased Pulsatility (PP)
Large artery stiffness and microvascular damage
Increased Large artery stiffness
Decreased damage to end organs
Decrease PP transmitted to micro-circulation
Increased Pulsatility (PP)
AIx
Relationship between Pulse Pressure and Wave Reflection on retinal artery Pulsatility Ratio
0 10 20 30 40 50 600
0.5
1
1.5
2
2.5
3
3.5
4
PR
AIx (%)
R=-0.33, P=0.011
30 40 50 60 70 80 90 1001
1.5
2
2.5
3
3.5
4
PP (mmHg)
R=0.26, P = 0.04
PR
N=64
Difference in PR between highest and lowest of AIx.
Low AIx High AIx0
0.5
1
1.5
2
2.5
PR
P= 0.032
An increased AIx may have a potentially
beneficial effect in reflecting an otherwise high pulsatile flow wave travelling to the
micro-circulation
Step 2:
Aim of study: • To investigate if wave reflection is directly
related to degree of pulsatility in the retinal artery.
• By reducing/manipulating wave reflection via administration of sublingual GTN.
The Effects of GTN
Methods
• Vascular Measurements: – (Peripheral and Central BP and HR, (using Mobilograph, IEM)– CBP and AIx (using SphygmoCor)
Participants: 9 individuals, aged 63±6 years (3 Males, 6 Females)
-free from CVD and ocular disease and free from taking sympathomimetic compounds.
Measuring of flow oscillations in the retinal artery using:
• Pulsatility Index as a measure of flow wave pulsatility.
PI takes into account Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV) of the flow wave, whilst accounting for Mean Flow Velocity (MV).
Pulsatility Index: PI = (PSV/EDV) / MV
PSV
EDV
Mv
Doppler ultrasound to measure arterial blood flow in the retinal artery
GTN Protocol
All measurements were recorded simultaneously at:
Baseline
ADMINISTRATION OF 500µg of GTN
1min
3min
5min
10min
15mins
Results
Baseline Group Demographics
Age (Years) 63.4 ± 6
Males/females 3/6
Ht (m) 1.60±0.04
Wt (Kg) 75.4± 9.7
BMI (Kg/m2) 29.5±3.4
HR (bpm) 64±6
SBP (mmHg) 140±19
DBP (mmHg) 85±13
MAP (mmHg) 106±14
AIx (%) 38.2±7
aPWV (m/sec) 8.1±1.4
BL 1min 3min 5min 10min 15min20
22
24
26
28
30
32
34
36
38
40
1.4
1.45
1.5
1.55
1.6
1.65
Relationship between changes in AIx and Pulsatility Index
Mean PI
Mean AIx
AIx (%)
PI
P<0.05
P<0.05
10 15 20 25 30 35 40 45 50 550
0.5
1
1.5
2
2.5
3
3.5
4
PI
AIx (%)
R= -0.27, P<0.05
Relationship between AIx and PI
Summary
Evidence suggesting a direct inverse relationship between changes in Wave Reflection and changes in flow Pulsatility in the retinal artery.
Conclusion
Wave reflection may have a protective effect on the pulsatile flow wave transmitted to the microvasculature.
Acknowledgements:
• Prof John Cockcroft• Mrs Margaret Munnery• Dr James Coulson• Mr Iain Munnery• Maksim Zagura
• Dr Ian Wilkinson• Dr Carmel McEniery• Dr Kaisa Maki-Petaja
Wales Heart Research Institute, Heath Hospital, Cardiff:
Vascular Research Unit, Addenbrooke’s Hospital, Cambridge:
McEniery CM. Curr Hypertens Rep. 2009;11:253-9
Effects of Antihypertensive Drugs on Central Pressure, Wave Reflection and Aortic PWV
High PWV with High Wave Reflection = Low Pulsatility in Microcirculation
High PWV with Low Wave Reflection = HIGH Pulsatility in Microcirculation
Effect of aortic stiffness on retinal artery Pulsatility Ratio
4 6 8 10 12 14 16 18 200
0.5
1
1.5
2
2.5
3
3.5
4
R² = 0.285596292950341
PR
aPWV (m/s)
Percentage change in PI and AIx from baseline
AIx@5mins PI@5mins
-180
-130
-80
-30
20
Percentage change in PI and AIx from baseline
%
P=0.04
1min 3min 5min 10min 15min
-14
-12
-10
-8
-6
-4
-2
0
0
0.02
0.04
0.06
0.08
0.1
0.12
0.14
0.16
The Relationship Between Changes in AIx and PI from Base-line
DPI DAIx
Del
ta A
Ix
Delta P
I
*
*
* P<0.05
Effect of aPWV and AIx on the microvasculature
Elastic Segment Muscular Segment
Macrocirculation Microcirculation
Elastic Segment Muscular Segment
Macrocirculation Microcirculation
Effect of aPWV and AIx on the microvasculature
Elastic Segment Muscular Segment
Macrocirculation Microcirculation
Effect of aPWV and AIx on the microvasculature
Aims and objectives:
1. To determine the relationship between aPWV, AIx and pulsatility in the retinal artery.
2. To investigate whether individuals with high PWV’s and low AIx have higher pulsatility in the microcirculation than individuals with low PWV’s and high AIx.
Aims and objectives:
1. To determine the relationship between aPWV, AIx and pulsatility in the retinal artery.
Microvasculardamage
Large vessel stiffening
↑ MAP ↑ PP
Increased PWV was associated with increased microalbuminuria in the general population
Hoorn study
Methods Participants: • 62 individuals, aged 39-83 years
– free from CVD and ocular disease – and free from taking sympathomimetic compounds.
Macrovascular measurements:• Peripheral and Central BP• Augmentation Index (SphygmoCor)• Aortic PWV (carotid – femoral) (SphygmoCor)
Microvascular measurements:• Retinal Artery Pulsatility Ratio (PR)• Retinal Artery Resistance Index (RI)
(Retinal Artery Doppler Ultrasound)
Methods II Doppler ultrasound to measure arterial
blood flow in the retinal artery
Pulsatility Index:
PI = (PSV/EDV) / mean flow velocity
Resistance index:
RI = (Peak systolic velocity- End diastolic velocity)/Peak systolic velocity
Peak Systolic Velocity
End Diastolic Velocity
Taken from Baxter et al. Opthalmol. Vis. Sci.1992
Results
Summary• Significant relationship between increased
CF PWV and increased pulsatility in the retinal artery.
• Increased wave reflection was inversely related to increased pulsatility in the retinal artery.
• Individuals with high PWV and low AIx had significantly higher pulsatility in the retinal artery compared to individuals with low PWV and high AIx.
Future Research
Effects of Atenolol on PI and AIx??????
BL 1min 3min 5min 10min 15min0
5
10
15
20
25
30
35
40
0
100
200
300
400
500
600
700
Relationship between AIx and acceleration to peak systolic velocity
![Coulson, Andrea and Bonner, James (2015) Living Wage ...€¦ · Coulson, Andrea and Bonner, James (2015) Living Wage Employers : evidence of UK Business Cases. [Report] , This version](https://static.documents.pub/doc/80x56/5ec6515512933a21da5ee19d/coulson-andrea-and-bonner-james-2015-living-wage-coulson-andrea-and-bonner.jpg)
